[In Process Citation]

I BRAZILIAN GUIDELINES ON CARDIOVASCULAR PREVENTION

Sociedade Brasileira de Cardiologia • ISSN-0066-782X • Volume 101, Nº 6, Suppl. 2, December 2013www.arquivosonline.com.br

I BrazIlIan GuIdelInes on

CardIovasCular PreventIon

This guideline shall be referred as:

Simão AF, Precoma DB, Andrade JP, Correa Filho H, Saraiva JFK, Oliveira GMM, Murro ALB, Campos A, Alessi A, Avezum Junior A, Achutti AC, Miguel ACMG, Sousa ACS, Lotemberg AMP, Lins AP, Falud AA, Brandão AA, Sanjuliani AF, Sbissa AS, Alencar Filho AC, Herdy AH, Polanczyk CA, Lantieri CJ, Machado

CA, Scherr C, Stoll C, Amodeo C, Araújo CGS, Saraiva D, Moriguchi EH, Mesquita ET, Fonseca FAH, Campos GP, Soares GP, Feitosa GS, Xavier HT, Castro I, Giuliano ICB, Rivera IV, Guimaraes ICB, Issa JS, Souza JRM, Faria Neto JR, Cunha LBN, Pellanda LC, Bortolotto LA, Bertolami MC, Miname MH, Gomes MAM, Tambascia M, Malachias MVB, Silva MAM, Izar MC, Magalhães MEC, Bacellar MSC, Milani M,

Wajngarten M, Ghorayeb N, Coelho OR, Villela PB, Jardim PCBV, Santos Filho RD, Stein R, Cassani RSL, D’Avila RL, Ferreira RM, Barbosa RB, Povoa RMS, Kaiser SE, Ismael SC, Carvalho T, Giraldez VZR,

Coutinho W, Souza WKSB.

A JOURNAL OF BRAZILIAN SOCIETY OF CARDIOLOGY - Published since 1948www.arquivosonline.com.br

Editorial Board

BrazilAdib D. Jatene (SP)Alexandre A. C. Abizaid (SP)Alfredo José Mansur (SP)Álvaro Avezum (SP)Amanda G. M. R. Sousa (SP)André Labrunie (PR)Andrei Sposito (DF)Angelo A. V. de Paola (SP)Antonio Augusto Barbosa Lopes (SP)Antonio Carlos C. Carvalho (SP)Antônio Carlos Palandri Chagas (SP)Antonio Carlos Pereira Barretto (SP)Antonio Cláudio L. Nóbrega (RJ)Antonio de Padua Mansur (SP)Ari Timerman (SP)Armênio Costa Guimarães (BA)Ayrton Klier Péres (DF)Ayrton Pires Brandão (RJ)Barbara M. Ianni (SP)Beatriz Matsubara (SP)Braulio Luna Filho (SP)Brivaldo Markman Filho (PE)Bruce B. Duncan (RS)Bruno Caramelli (SP)Carisi A. Polanczyk (RS)Carlos Alberto Pastore (SP)Carlos Eduardo Negrão (SP)Carlos Eduardo Rochitte (SP)Carlos Eduardo Suaide Silva (SP)Carlos Vicente Serrano Júnior (SP)Celso Amodeo (SP)Charles Mady (SP)Claudio Gil Soares de Araujo (RJ)Cleonice Carvalho C. Mota (MG)Dalton Valentim Vassallo (ES)Décio Mion Jr (SP)Denilson Campos de Albuquerque (RJ)Dikran Armaganijan (SP)Djair Brindeiro Filho (PE)Domingo M. Braile (SP)Edmar Atik (SP)Edson Stefanini (SP)Elias Knobel (SP)Eliudem Galvão Lima (ES)Emilio Hideyuki Moriguchi (RS)Enio Buffolo (SP)

Eulógio E. Martinez Fº (SP)Evandro Tinoco Mesquita (RJ)Expedito E. Ribeiro da Silva (SP)Fábio Sândoli de Brito Jr. (SP)Fábio Vilas-Boas (BA)Fernando A. P. Morcerf (RJ)Fernando Bacal (SP)Flávio D. Fuchs (RS)Francisco Antonio Helfenstein Fonseca (SP)Francisco Laurindo (SP)Francisco Manes Albanesi Fº (RJ)Gilmar Reis (MG)Gilson Soares Feitosa (BA)Ínes Lessa (BA)Iran Castro (RS)Ivan G. Maia (RJ)Ivo Nesralla (RS)Jarbas Jakson Dinkhuysen (SP)João Pimenta (SP)Jorge Ilha Guimarães (RS)Jorge Pinto Ribeiro (RS)José A. Marin-Neto (SP)José Antonio Franchini Ramires (SP)José Augusto Soares Barreto Filho (SE)José Carlos Nicolau (SP)José Geraldo de Castro Amino (RJ)José Lázaro de Andrade (SP)José Péricles Esteves (BA)José Teles Mendonça (SE)Leopoldo Soares Piegas (SP)Luís Eduardo Rohde (RS)Luiz A. Machado César (SP)Luiz Alberto Piva e Mattos (SP)Lurildo Saraiva (PE)Marcelo C. Bertolami (SP)Marcia Melo Barbosa (MG)Marco Antônio Mota Gomes (AL)Marcus V. Bolívar Malachias (MG)Maria Cecilia Solimene (SP)Mario S. S. de Azeredo Coutinho (SC)Maurício I. Scanavacca (SP)Mauricio Wajngarten (SP)Max Grinberg (SP)Michel Batlouni (SP)Nabil Ghorayeb (SP)Nadine O. Clausell (RS)Nelson Souza e Silva (RJ)

Orlando Campos Filho (SP)Otávio Rizzi Coelho (SP)Otoni Moreira Gomes (MG)Paulo A. Lotufo (SP)Paulo Cesar B. V. Jardim (GO)Paulo J. F. Tucci (SP)Paulo J. Moffa (SP)Paulo R. A. Caramori (RS)Paulo R. F. Rossi (PR)Paulo Roberto S. Brofman (PR)Paulo Zielinsky (RS)Protásio Lemos da Luz (SP)Renato A. K. Kalil (RS)Roberto A. Franken (SP)Roberto Bassan (RJ)Ronaldo da Rocha Loures Bueno (PR)Sandra da Silva Mattos (PE)Sergio Almeida de Oliveira (SP)Sérgio Emanuel Kaiser (RJ)Sergio G. Rassi (GO)Sérgio Salles Xavier (RJ)Sergio Timerman (SP)Silvia H. G. Lage (SP)Valmir Fontes (SP)Vera D. Aiello (SP)Walkiria S. Avila (SP)William Azem Chalela (SP)Wilson A. Oliveira Jr (PE)Wilson Mathias Jr (SP)

ExteriorAdelino F. Leite-Moreira (Portugal)Alan Maisel (United States of American)Aldo P. Maggioni (Italy)Cândida Fonseca (Portugal)Fausto Pinto (Portugal)Hugo Grancelli (Argentina)James de Lemos (United States of American)João A. Lima (United States of American)John G. F. Cleland (England)Maria Pilar Tornos (Spain)Pedro Brugada (Belgium)Peter A. McCullough (United States of American)Peter Libby (United States of American)Piero Anversa (Italy)

Scientific Director

Luiz Alberto Piva e Mattos

chief eDitor Luiz Felipe P. Moreira

ASSociAteD eDitorS

clinicAl cArDiology José Augusto Barreto-Filho

SurgicAl cArDiology

Paulo Roberto B. Evora

interventioniSt cArDiology Pedro A. Lemos

PeDiAtric/congenitAl cArDiology Antonio Augusto Lopes

ArrhythmiAS/PAcemAker Mauricio Scanavacca

non-invASive DiAgnoStic methoDS Carlos E. Rochitte

BASic or exPerimentAl reSeArch Leonardo A. M. Zornoff

ePiDemiology/StAtiSticS

Lucia Campos Pellanda

ArteriAl hyPertenSion

Paulo Cesar B. V. Jardim

ergometricS, exerciSe

AnD cArDiAc rehABilitAtion

Ricardo Stein

firSt eDitor (1948-1953)

† Jairo Ramos

President Jadelson Pinheiro de Andrade

Vice-President Dalton Bertolim Précoma

President Elect Angelo Amato Vincenzo de Paola

Administrative Director Marcelo Souza Hadlich

Financial Director Eduardo Nagib Gaui

Government Liaison Director Daniel França Vasconcelos

Communication Director Carlos Eduardo Suaide Silva

Assistance Quality Director José Xavier de Melo Filho

Scientific Director Luiz Alberto Piva e Mattos

Cardiovascular Health Promotion Director - BSC/Funcor Carlos Alberto Machado

State / Regional Liaison Director Marco Antonio de Mattos

Specialized Department Director Gilberto Venossi Barbosa

Information Technology Director Carlos Eduardo Suaide Silva

Research Director Fernando Bacal

Chief Editor of the Brazilian Archives of Cardiology Luiz Felipe P. Moreira

BSC Journal Editor Fábio Vilas-Boas Pinto

Epidemiological Project Council Coordinator David de Pádua Brasil

Social Action Coordinators Alvaro Avezum Junior Ari Timerman

New Project Council Coordinator Glaucia Maria Moraes Oliveira

Use of New Technology Council Coordinator Washington Andrade Maciel

Young Cardiologist Inclusion Council Coordinator Fernando Augusto Alves da Costa

Clinical Practice Quality and Patient Safety Council Coordinator Evandro Tinoco Mesquita

Standardization and Guideline Council Coordinator Harry Correa Filho

Continuing Education Council Coordinator Antonio Carlos de Camargo Carvalho

Emergency Care and Sudden Death Committee Manoel Fernandes Canesin Nabil Ghorayeb Sergio Timerman

Cardiovascular Prevention Committee Antonio Delduque de Araujo Travessa Sergio Baiocchi Carneiro Regina Coeli Marques de Carvalho

Strategic Planning Committee Fabio Sândoli de Brito José Carlos Moura Jorge Walter José Gomes

Member Assistance Committee Maria Fatima de Azevedo Mauro José Oliveira Gonçalves Ricardo Ryoshim Kuniyoshi

International Liaison Committee Antonio Felipe Simão João Vicente Vitola Oscar Pereira Dutra

Presidents of State and Regional Brazilian Societies of Cardiology

BSC/AL - Alfredo Aurelio Marinho Rosa

BSC/AM - Jaime Giovany Arnez Maldonado

BSC/BA - Augusto José Gonçalves de Almeida

BSC/CE - Eduardo Arrais Rocha

BSC/CO - Hernando Eduardo Nazzetta (GO)

BSC/DF - Renault Mattos Ribeiro Junior

BSC/ES - Antonio Carlos Avanza Junior

BSC/GO - Luiz Antonio Batista de Sá

BSC/MA - Magda Luciene de Souza Carvalho

BSC/MG - Maria da Consolação Vieira Moreira

BSC/MS - Sandra Helena Gonsalves de Andrade

BSC/MT - José Silveira Lage

BSC/NNE - Aristoteles Comte de Alencar Filho (AM)

BSC/PA - Claudine Maria Alves Feio

BSC/PB - Alexandre Jorge de Andrade Negri

BSC/PE - Silvia Marinho Martins

BSC/PI - Ricardo Lobo Furtado

BSC/PR - Álvaro Vieira Moura

BSC/RJ - Glaucia Maria Moraes Oliveira

BSC/RN - Carlos Alberto de Faria

BSC/RS - Justo Antero Sayão Lobato Leivas

BSC/SC - Conrado Roberto Hoffmann Filho

BSC/SE - Eduardo José Pereira Ferreira

BSC/SP - Carlos Costa Magalhães

BSC/TO - Adalgele Rodrigues Blois

Brazilian Society of Cardiology

Presidents of the Specialized Departaments and Study Groups

BSC/DA - Hermes Toros Xavier (SP)

BSC/DCC - Evandro Tinoco Mesquita (RJ)

BSC/DCM - Orlando Otavio de Medeiros (PE)

BSC/DCC/CP - Estela Suzana Kleiman Horowitz (RS)

BSC/DECAGE - Abrahão Afiune Neto (GO)

BSC/DEIC - João David de Souza Neto (CE)

BSC/DERC - Pedro Ferreira de Albuquerque (AL)

BSC/DFCVR - José Carlos Dorsa Vieira Pontes (MS)

BSC/DHA - Weimar Kunz Sebba Barroso de Souza (GO)

BSC/DIC - Jorge Eduardo Assef (SP)

BSC/SBCCV - Walter José Gomes (SP)

BSC/SBHCI - Marcelo Antonio Cartaxo Queiroga Lopes (PB)

BSC/SOBRAC - Adalberto Menezes Lorga Filho (SP)

BSC/DCC/GAPO - Daniela Calderaro (SP)

BSC/DCC/GECETI - João Fernando Monteiro Ferreira (SP)

BSC/DCC/GEECABE - Luis Claudio Lemos Correia (BA)

BSC/DCC/GEECG - Carlos Alberto Pastore (SP)

BSC/DCP/GECIP - Angela Maria Pontes Bandeira de Oliveira (PE)

BSC/DERC/GECESP - Daniel Jogaib Daher (SP)

BSC/DERC/GECN - José Roberto Nolasco de Araújo (AL)

Arquivos Brasileiros de Cardiologia

Filiada à Associação Médica Brasileira

Volume 101, Number 6, Supplement 2, December 2013

Indexing: ISI (Thomson Scientific), Cumulated Index Medicus (NLM), SCOPUS, MEDLINE, EMBASE, LILACS, SciELO, PubMed

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Summary

Foreword ..............................................................................................................................................page 1

Introduction ........................................................................................................................................page 1

1. Risk stratiication ........................................................................................................................page 2Cardiovascular risk stratiication for atherosclerosis prevention and treatment .........................................page 2Risk stratiication in stages .......................................................................................................................page 2Phase 1 - Presence of significant atherosclerosis or its equivalent ..........................................................page 2Phase 2 - Risk score ..................................................................................................................................page 2Phase 3 - Aggravating Factors...................................................................................................................page 5Phase 4 - Risk stratification by lifetime ....................................................................................................page 5

2. Smoking ..........................................................................................................................................page 7Smoking Prevention ..................................................................................................................................page 7Primordial smoking prevention .................................................................................................................page 7Factors contributing to the initiation of smoking .......................................................................................page 7Strategies to ight smoking initiation .........................................................................................................page 8How to treat the psychological dependence on smoking ...........................................................................page 8Tools that help to evaluate and understand patient proile: .......................................................................page 9Pharmacological Treatment of Smoking ...................................................................................................page 9Nicotine replacement therapy ...................................................................................................................page 10Transdermal nicotine ................................................................................................................................page 10Oral use nicotine - nicotine gum or lozenges ..........................................................................................page 10Bupropion chloride ..................................................................................................................................page 10Varenicline tartrate ...................................................................................................................................page 10Second-line medications ..........................................................................................................................page 11Nortriptyline .............................................................................................................................................page 11Associations of anti-tobacco drugs ............................................................................................................page 11

3. Diet, supplements and vitamins ..........................................................................................page 11Introduction ...............................................................................................................................................page 11Carotenoids ...............................................................................................................................................page 11Vitamin E ...................................................................................................................................................page 12Vitamin C ..................................................................................................................................................page 12Vitamin D ..................................................................................................................................................page 12Vitamins B and folate ................................................................................................................................page 13Omega-3 polyunsaturated fatty acids of marine origin (Docosahexaenoic (DHA) and

Eicosapentaenoic (EPA) ..............................................................................................................page 13Omega-3 polyunsaturated fatty acids of vegetable origin ..........................................................................page 13

4. Obesity and overweight ............................................................................................................page 14Introduction ...............................................................................................................................................page 14Primary Prevention ....................................................................................................................................page 14Secondary Prevention ...............................................................................................................................page 14Drug therapy ............................................................................................................................................page 15Bariatric surgery .......................................................................................................................................page 15

5. Arterial Hypertension ................................................................................................................page 15Deinition and classiication (VI DBH) ........................................................................................................page 16Blood pressure measurements ..................................................................................................................page 16Routine initial evaluation of the hypertensive patient ................................................................................page 16

Identification of subclinical target-organs injuries...................................................................................page 16Prevention ................................................................................................................................................page 17Primary prevention of SAH .......................................................................................................................page 18Non-pharmacological measures ................................................................................................................page 18Diets .........................................................................................................................................................page 18Sodium .....................................................................................................................................................page 18Alcohol .....................................................................................................................................................page 18Physical activity ........................................................................................................................................page 18Weight Control .........................................................................................................................................page 19Control of psychosocial stress ..................................................................................................................page 19Multidisciplinary team .............................................................................................................................page 19Other non-pharmacological strategies for blood pressure control..........................................................page 19Drug measures for hypertension prevention ..............................................................................................page 19Treatment decision-making and risk category ...........................................................................................page 19Pharmacological treatment .......................................................................................................................page 19Therapeutic targets ...................................................................................................................................page 20

6. Dyslipidemia .................................................................................................................................page 20Non-pharmacological treatment of dyslipidemia .......................................................................................page 21Pharmacological treatment of dyslipidemia ..............................................................................................page 22Statins .......................................................................................................................................................page 22Ezetimibe ..................................................................................................................................................page 23Resins .......................................................................................................................................................page 23Niacin .......................................................................................................................................................page 23Fibrates .....................................................................................................................................................page 23Omega 3 Fatty Acids.................................................................................................................................page 24

7. Diabetes ..........................................................................................................................................page 24Prevention .................................................................................................................................................page 24

8. Metabolic Syndrome .................................................................................................................page 25Metabolic Syndrome deinition ..................................................................................................................page 25Prevalence of metabolic syndrome in different population groups ............................................................page 25Cardiovascular and Metabolic Risks Associated with MS ...........................................................................page 25Risk Factors for Metabolic Syndrome ........................................................................................................page 26Prevention of Metabolic Syndrome ............................................................................................................page 26Weight reduction ......................................................................................................................................page 26Abdominal obesity ...................................................................................................................................page 27Healthy diet ..............................................................................................................................................page 27Physical Exercise .......................................................................................................................................page 27Changes in life style versus drug therapy ...................................................................................................page 27

9. Physical activity, exercises and sports ...............................................................................page 27Concepts and most relevant expressions ...................................................................................................page 27Major Acute and Chronic Effects of Exercise ..............................................................................................page 27Epidemiological Rationale of Physical Activity Beneits ............................................................................page 27Risks of Physical Activity, Physical Exercise and Sports Practice ...............................................................page 29Physical Exercise Prescription ..................................................................................................................page 29Formal and Informal Physical Activity: Strategies to Encourage Referral, Implementation and Adherence ................................................................................................................................page 30

10. Psychosocial risk factors ......................................................................................................page 30Deinitions and Impact ..............................................................................................................................page 30Assessment of psychosocial risk factors ...................................................................................................page 31Signiicance of Interventions on the Psychosocial Risk Factors .................................................................page 31“Ten strategic steps” to improve counseling for behavioral change ............................................................page 31Future Directions .......................................................................................................................................page 32Adherence to cardiovascular disease prevention strategies: life style and medication ...............................page 32Definition .................................................................................................................................................page 32Impact ......................................................................................................................................................page 32Causes ......................................................................................................................................................page 32Evaluation .................................................................................................................................................page 33Interventions ............................................................................................................................................page 33

11. Childhood and adolescence ................................................................................................page 34Dyslipidemia .............................................................................................................................................page 34Epidemiology in Brazil..............................................................................................................................page 34Screening ..................................................................................................................................................page 34Reference values ......................................................................................................................................page 34Treatment .................................................................................................................................................page 34Change in life style ...................................................................................................................................page 34Drug therapy ............................................................................................................................................page 35Obesity ......................................................................................................................................................page 38Definition and Epidemiology....................................................................................................................page 38Prognosis ..................................................................................................................................................page 38Diagnosis ..................................................................................................................................................page 38Prevention and Treatment ........................................................................................................................page 38Systemic Arterial Hypertension .................................................................................................................page 38Physical activity .........................................................................................................................................page 40

12. Legislation and prevention of risk factors for cardiovascular diseases ...........page 42Introduction ...............................................................................................................................................page 42

13. Topics in prevention ................................................................................................................page 45Autoimmune diseases and cardiovascular disease ...................................................................................page 45Inluenza and cardiovascular disease ........................................................................................................page 46Chronic Kidney Disease .............................................................................................................................page 47Obstructive Artery Disease ........................................................................................................................page 48Socioeconomic Factors .............................................................................................................................page 48Obstructive sleep apnea ............................................................................................................................page 49Erectile dysfunction ...................................................................................................................................page 50Periodontitis ..............................................................................................................................................page 50

References ..........................................................................................................................................page 51

I Brazilian Guidelines on Cardiovascular

Prevention

develoPment Sociedade Brasileira de Cardiologia (Brazilian Society of Cardiology)

Board of standardIzatIons and GuIdelInes

Antônio Carlos Sobral Sousa, Harry Correa Filho, Iran Castro, Marcus Vinícius Bolivar Malachias, Mário Sérgio de Carvalho Bacellar

CoordInator of the Board of standardIzatIons and GuIdelInes

Harry Correa Filho

CoordInator Antônio Felipe Simão

PresIdent of the BrazIlIan soCIety of CardIoloGy

(2012-2013 term)Jadelson Pinheiro de Andrade

edItorIal Board

Harry Correa Filho, Antônio Felipe Simão, Dalton Bertolim Précoma, Gláucia Maria Moraes de Oliveira

edItors

Jadelson Pinheiro de Andrade, Andrei de Carvalho Sposito, Dalton Bertolim Précoma, Jose Francisco Kerr Saraiva, Oscar Pereira Dutra e Gláucia Maria Moraes de Oliveira

The guideline should be cited as:Simão AF, Précoma DB, Andrade JP, Correa Filho H, Saraiva JFK, Oliveira GMM et al. Sociedade Brasileira de

Cardiologia. I Diretriz Brasileira de Prevenção Cardiovascular. Arq Bras Cardiol. 2013: 101 (6Supl.2): 1-63

Correspondence to:Sociedade Brasileira de Cardiologia

Av. Marechal Câmara, 360/330 – Centro – Rio de Janeiro – CEP: 20020-907 e-mail: [email protected]

DOI: 10.5935/abc.2013S012

Work GrouPs

Group 1 - Risk Stratification

Coordinator: Francisco Antonio Helfenstein Fonseca. Participants: Sergio Emanuel Kaiser, Marcelo Chiara Bertolami, Maria Cristina O Izar e Emilio H Moriguchi.

Group 2 - Smoking

Coordinator: Aristoteles Comte de Alencar Filho. Participants: Aloyzio Achutti, Carla Janice Lantieri, Jaqueline Scholz Issa, Silvia Cury Ismael.

Group 3 - Diet, Supplements and Vitamins

Coordinator: Raul Dias dos Santos Filho. Participants: Ana Maria Pita Lotemberg, Ana Carolina Moron Gagliardi, Roberta Lara Cassani, Marcio Hihoshi Miname.

Group 4 - Obesity and Overweight

Coordinator: Carlos Scherr. Participants: Walmir Coutinho, Adriana Campos, Ana Paula Lins.

Group 5 - Arterial Hypertension

Coordinator: Marcus Vinícius Bolivar Malachias. Participants: Weimar Kunz Sebba Barroso de Souza, Celso Amodeo, Paulo Cesar Brandão Veiga Jardim, Luiz Aparecido Bortolotto, Rui Manuel dos Santos Povoa.

Group 6 - Dyslipidemia

Coordinator: Jose Rocha Faria Neto. Participants: Andre Arpad Faludi, Carolina Stoll, Hermes Toros Xavier, Marcelo Chiara Bertolimi, Viviane Z. Rocha.

Group 7 - Diabetes

Coordinator: Otávio Rizzi Coelho. Participants: Jose Roberto Matos de Souza.

Group 8 - Metabolic Syndrome

Coordinator: Andréa Araujo Brandão. Participants: Emilia Moriguchi, Maria Eliane Campos Magalhães, Walmir Coutinho, Alexandre Alessi, Antonio Felipe Sanjuliani.

Group 9 - Physical Activity

Coordinator: Artur Haddad Herdy. Participants: Claudio Gil Soares de Araujo, Mauricio Milani, Nabil Ghorayeb, Ricardo Stein, Tales de Carvalho

Group 10 - Psychosocial Factors

Coordinator: Mauricio Wajngarten. Participants: Alvaro Avezum Junior, Carise Anne Polanczyk, Evandro Tinoco Mesquita, Gilson Soares Feitosa.

Group 11 - Childhood and Adolescence

Coordinatora: Isabela de Carlos Back Giuliano. Participants: Lucia Campos Pellanda, Ivan Romero Rivera, Maria Alayde Mendonça R.Rivera.

Group 12 - Legislation

Coordinator: Carlos Alberto Machado. Participants: Antonio Silveira Sbissa, Marco Antonio Mota Gomes, Geniberto Paiva Campos, Lucelia Batista N. Cunha, Lenildo de Moura and Romero Bezerra Barbosa.

Group 13 - Topics in Prevention

Coordinator: Glaucia Maria Moraes de Oliveira. Participants: Roberto Muniz Ferreira, Paolo Branco Vilela and Gabriel Porto Soares.

Names Members

Participated in clinical studies and / or

experimental trials supported by

pharmaceutical or equipment related to the

guideline in question

Has spokenat events

or activitiessponsoredby industry

related to theguideline in

question

It was (is)advisory board

member ordirector of a

pharmaceuticalor equipment

Committeesparticipated

in completionof research

sponsored byindustry

Personal orinstitutional aidreceived from

industry

Produced scientiicpapers

in journalssponsored by

industry

It shares the

industry

Adriana Campos Junqueira de Souza No No No No No No No

Alexandre Alessi No No No No No No No

Álvaro Avezum Junior No No No

Population Health Research Institute,

McMaster University, Hamilton, Canada

No No No

Aloyzio Cechella Achutti No No No No No No No

Ana Carolina Moron Gagliardi No No No No No No No

Ana Maria Pita Lotemberg No No No No No No No

Ana Paula Machado Lins No No No No No No No

Andre Arpad Falud No No No No No No No

Andrea Araújo Brandão No

Servier, Biolab, Astra Zeneca, Novartis,

Chiesi, Daiichi Sankyo

Biolab, Servier No Servier, Daiichi Sankyo, Biolab

Medley, Biolab, Servier, Astra

Zeneca, Novartis, Daiichi Sankyo

No

Antônio Felipe Simão No No No No No No No

Antônio Felipe Sanjuliani No No No No No No No

Antônio Silveira Sbissa No No No No No No No

Aristóteles Comte Alencar Filho No No No No Biolab, Pizer, Bayer No No

Artur Haddad Herdy No No No No No No No

Carise Anne Polanczyk No No No No No No No

Carla Janice Lantieri No No No No No No No

Carlos Alberto Machado No No No No No No No

Carlos Scherr No Coca-Cola, Unilever No No

Novartis, Biolab, Astrazeneca,

Bayer, Ache,MSD, Boehringer

MSD, Nycomed No

Carolina Stoll No No No No No No No

Celso Amodeo astra zeneca, Biolab, ache, novartis, Sankyo, Takeda

astra zeneca, Biolab, ache, novartis,

Sankyo, Takeda


Sankyo, Takeda


Sankyo, Takeda

astra zeneca, Biolab, ache,

novartis, Sankyo, Takeda

astra zeneca, Biolab, ache,

novartis, Sankyo, Takeda

No

Cláudio Gil Soares de Araújo No No No No No No No

Dalton Bertolim Precoma No No No No No No No

Denise Saraiva No No No No No No No

Emílio H. Moriguchi Pizer Biolab, Daiichi-Sankyo, MSD Merck, Daiichi-Sankyo No Merck, Daiichi-

Sankyo, Biolab Biolab No

Evandro Tinoco Mesquita No No No No No No No

Francisco Antônio Helfenstein Fonseca

Novartis, Aché, Libbs, MSD, AstraZeneca, Torrent, Novartis No No Novartis No

AstraZeneca, Novartis, Biolab,

Aché, Pizer, BMS, Libbs, MSD, Nestlé, Hypermarcas

No

Continuation

Geniberto Paiva Campos No No No No No No No

Gabriel Porto Soares No No No No Novartis Aché, Bristol No

Gilson Soares Feitosa No No No No No No No

Gláucia Maria Moraes de Oliveira No No No No No No No

Harry Correa Filho No No No No No No No

Hermes Toros Xavier Pizer, AstraZeneca

Aché, Amgen, AstraZeneca,

Biolab, Chiesi, MSD, Novartis, Pizer,

Torrent

Amgen, MSD, Torrent No Amgen, MSD, Torrent

Aché, Amgen, AstraZeneca, Biolab, Chiesi, MSD, Novartis, Pizer, Torrent.

No

Isabela de Carlo Back Giuliano No No No No No No No

Ivan Romero Rivera No No No No No No No

Isabel Cristina Britto Guimaraes No No No No No No No

Jadelson Pinheiro de Andrade No No No No No No No

Jaqueline Scholz Issa PizerPizer,

Johnson&Johnson, Glaxo-Smith Kline

No No No No No

Jose Francisco Kerr Saraiva AstraZeneca, Daichii Sankyo

AstraZeneca, Boheringer, Pizer,

BMS, Chiesi, Daichii Sankyo

Boheringer, Pizer, BMS, NovoNordisk AstraZeneca No

Novartis, Nova Quimica,

BoheringerNo

José Roberto Matos de Souza No No No No No No No

José Rocha Faria Neto Astra Zeneca, Daichi SankyoAstra Zeneca, Daichi Sankyo, Boehringer

Ingelheim, MSDNo No No MSD No

Lucelia Batista N. Cunha No No No No No No No

Lucia Campos Pellanda No No No No No No No

Luiz Aparecido Bortolotto No No No No No No No

Marcelo Chiara Bertolami

MSD, Astrazeneca, Schering-Plough, Pizer, Novartis

MSD, Astrazeneca, Biolab, Pizer,

Novartis, Aché, Novaquímica,

Novonordisk, Bayer, Libbs

No No NoMSD, Pizer,

Novaquímica, Aché

No

Márcio Hihoshi Miname No No No No No No No

Marco Antônio Mota Gomes No No Biolab, Servier, Omron Torrent

Biolab, Daiichi Sankyo, Novartis,

Takeda

Biolab, Torrent, Novartis No

Marcus Vinícius Bolivar Malachias No

Servier, Boehringer-Ingelheim, Torrent,

AstraZeneca, Pizer, Novartis

No No NoServier, Nova

Química, Libbs, Bayer

No

Maria Alayde Mendonça da Silva No No No No No No No

Maria Cristina de Oliveira Izar

Amgen, Genzyme, Novartis, Aché, MSD, Aegerion,

Unilever, Libbs

MSD, Aché, Aegerion, UNILEVER No No Aegerion Torrent,

Genzyme, Libbs No

Maria Eliane Campos Magalhães No AstraZeneca, Pizer,

MSD No No Pizer, AstraZeneca Nova Química No

Maurício Milani No No No No No No No

Maurício Wajngarten No No No No No No No

Nabil Ghorayeb No No No No No No No

Continuation

Otávio Rizzi Coelho Improve Pizer e Bayer Pizer, Novo Nordisk e Biolab No Takeda, Bayer e

Pizer AstraZeneca No

Paolo Blanco Villela No No No No No No No

Paulo César Brandão Veiga Jardim Servier Novartis, Biolab,

Aché No No No Novartis, Biolab, Aché No

Raul Dias dos Santos Filho

Pizer, Astra Zeneca, ISIS, MSD, Roche

Pizer, Astra Zeneca, biolab, BMS,

Aegerion, Novartis, MSD

Pizer,Astra Zeneca, BMS, Biolab,

Aegerion, Genzyme, Boehringer

nao Genzyme, Aegerion, Biolab, Sanoi, MSD Biolab, MSD No

Ricardo Stein No No No No No No No

Roberta Soares Lara Cassani No Gomes da Costa No No No No No

Roberto Luiz D'Avila No No No No No No No

Roberto Muniz Ferreira No No No No No No No

Romero Bezerra Barbosa No No No No No No No

Rui Manuel dos Santos Povoa No No No No No No No

Sérgio Emanuel Kaiser No MSD, Abbott, Farmasa No No No Novaquimica,

Medley No

Silvia Cury Ismael No No No No No No No

Tales de Carvalho No No No No No No No

Viviane Zorzanelli Rocha Giraldez No No No No No No No

Walmir Coutinho No No No No No No No

Weimar Kunz Sebba Barroso de Souza No No No No No No No

Definitions for grade of recommendation and level of evidence:

Grade of recommendation

Class I: Conditions for which there is conclusive evidence, or in its absence, general agreement that the procedure is safe and useful / effective.

Class II: Conditions for which there is conflicting evidence and/or divergence of opinion about safety and usefulness/efficacy of the procedure.

Class IIa: Weight or evidence/opinion in favor of the procedure. Approved by most professionals.

Class IIB: safety and usefulness/efficacy less well established, with no predominance of opinions in favor of the procedure.

Class III: Conditions for which there is evidence and / or consensus that the procedure is not useful / effective and in some cases may be harmful.

Level of Evidence

Level A: Data obtained from multiple consistent randomized trials of good size, and/or robust meta-analysis of randomized clinical trials.

Level B: Data obtained from less robust meta-analysis, from a single randomized trial or nonrandomized trials (observational studies).

Level C: Data obtained from consensual experts’ opinion.

It is noteworthy that levels of evidence classified as B or C cannot be interpreted as weak recommendations. There are many consensus recommendations; therefore, with a degree of recommendation I, level of evidence C (experts’ opinions). On the other hand, some indications considered controversial (recommendation grade II) may be supported by randomized controlled trials (Level of evidence A).

Guidelines

I Brazilian Guidelines on Cardiovascular Prevention

Arq Bras Cardiol. 2013; 101(6Supl.2): 1-63

ForewordWhen we analyze the epidemiology of Cardiovascular

Diseases, we observe it has the same behavior in the beginning of this century that major epidemics had in the past centuries.

This becomes clear when we look at the data from the World Health Organization (WHO) in recent decades, showing that, of 50 million deaths, Cardiovascular Diseases (CVD) accounted for 30% of this mortality, i.e., 17 million individuals1,2.

The identification of risk factors with higher population prevalence allowed well-conducted cardiovascular prevention programs in several countries such the United States, Canada, Finland, United Kingdom, Australia and Japan, to be able to significantly reduce mortality from cardiovascular diseases3.

Based on this epidemiological profile, the identification of risk factors and the outcome of these programs application, the World Health Organization established as its goal decrease by 25% the Noncommunicable Chronic Diseases (NCDs), among them the CVDs, by the year of 20254.

In line with this global proposal and considering that the epidemiological reality in Brazil also discloses alarming rates of 30% of deaths from CVDs, among all other related causes, the Board of Directors of the Brazilian Society of Cardiology (SBC), during its current term, decided to draft the “National Cardiovascular Prevention Program” and implement it in the country aiming to modify this epidemiological reality.

Several arms of the National Cardiovascular Prevention Program are already being applied in Brazil, with international effects, such as the “Carta do Rio”5, created and signed jointly by SBC and the main Cardiology Societies in the world and published on their sites and Cardiology journals. The “SBC goes to school” program, the Brazilians Cardiovascular Registries6, the Agreement on Cooperation between the SBC/OPAS/MS for the application of the TECA A and TECA B program7, the Agreement on Cooperation with State and Municipal Health Secretariats for the training of Public Health8 physicians and the Agreement on Cooperation between SBC/CNBB/Ministry of Health, are some of these examples that have already started to show impact of results, being disseminated in Brazil and in international forums.

The proposal of creating the I Brazilian Guideline for Cardiovascular Prevention of the Brazilian Society of Cardiology is another important step in this program.

With this document, SBC offers to Brazilian Cardiology an important tool for the standardization of procedures regarding Cardiovascular Prevention in Brazil.

Our acknowledgments to all those who contributed for the creation of this guideline, which will certainly be a relevant milestone in the National Cardiovascular Prevention Program of SBC.

Jadelson P. Andrade

President SBC - 2012/2013 Term

IntroductionEver since the Brazilian Society of Cardiology (SBC)

established as its goal, following the example of the World Health Organization (WHO), to reduce cardiovascular mortality by 25% by the year 2025, it became clear the need to create the I Brazilian Guideline of Cardiovascular Prevention9.

The first step taken in this direction was the “Carta do Rio” (Letter from Rio), a document prepared during the course of Brazil III Prevent & I Latin America Prevent, held in the city of Rio de Janeiro in December 20125.

CVDs will increase the disability-adjusted life years (DALYs) of 85 million patients to 150 million worldwide by 2020, leading to a noticeable decrease in global productivity10,11.

The WHO estimates that three quarters of cardiovascular mortality can be reduced with appropriate changes in life style, and that is the great challenge of all existing CV prevention guidelines9.

Therefore, we need to adopt governmental measures associated with institutional measures and of the organs responsible for health prevention in our country at all levels. SBC is doing its part in this process.

The I Brazilian CV Prevention Guideline has this goal: to discuss the necessary measures to be adopted as a practical guide for the routine practice of the Brazilian cardiologist.

The bases of prevention have their roots in CV epidemiology and evidence-based Medicine. Based on that, the team of editors and contributors of the I Brazilian CV Prevention Guideline elected 13 items as the foundation of this guideline, which will be proposed and discussed throughout the document.

Antonio Felipe Simão - Coordinator

1

Guidelines



1. Risk stratification

Cardiovascular risk stratiication for atherosclerosis prevention and treatment

An acute coronary event is the first manifestation of atherosclerotic disease in at least half the individuals with this complication. Thus, the identification of asymptomatic individuals that are more susceptible is crucial for effective prevention, with the correct definition of therapeutic goals11. To estimate the severity of cardiovascular disease (CVD), the so-called risk scores and algorithms based on regression analyses of population studies were created, through which the overall risk identification is substantially improved.

Among the existing algorithms, the Framingham risk score (FRS)12, the Reynolds Risk Score (RRS)13-14, the Global Risk Score (GRS)15 and the Lifetime Risk (LRS)16-18, are options that will be discussed later.

The FRS estimates the probability of occurrence of myocardium infarction or death from coronary heart disease in a 10-year period in individuals with no prior diagnosis of clinical atherosclerosis12. Although this risk estimate is subject to corrections according to epidemiological indicators of the studied population, the FRS appropriately identifies individuals with high and low risks, the RRS includes C-reactive protein (CRP) and family history of premature coronary heart disease and estimates the probability of myocardial infarction, stroke, death and revascularization in 10 years13,14. The GRS estimates the risk of myocardial infarction, cerebrovascular accident (CVA), peripheral vascular insufficiency and heart failure in 10 years15. The LRS assesses the probability of an individual to have an ischemic event after 45 years of age16-18. The calculation of the LRS considers that the individual belongs exclusively to one of the following categories: a) those with no risk factors, or all optimal risk factors at age 45; b) those that have one or more non-optimal risk factors; c) those with one or more high risk factors; d) those with one of the main risk factors; e) those with two or more of the main risk factors16-18.

The combination of these various scores allows a better risk estimate. The justification for the use of a short-term score and another long-term one is the fact that most women and young adult men are at the range of low predicted short-term risk; however, part of these will remain low risk, while others will have predicted high risk throughout life. Thus, the risk approach through lifetime can be used to improve the motivation of individuals with low predicted short-term risk, but with predicted high risk in the long term to intensify changes in life style and control risk factors.

This guideline recommends the use of the GRS15 for risk assessment in 10 years and the LRS16-18 to estimate risk throughout life in individuals over 45 years.

Note: All other scores can be used as risk stratification tools.

Risk stratiication in stagesThe risk stratification proposed by this Guideline proposes

four stages:

Phase 1 - Presence of significant atherosclerosis or its equivalent

The risk of atherosclerotic disease is estimated based on the joint analysis of characteristics that increase the individual’s likelihood of developing the disease. Therefore, the most evident risk identification factor is the previous manifestation of the disease itself. Thus, the first phase in risk stratification is the identification of clinical manifestations of atherosclerotic disease or its equivalent (such as diabetes mellitus type 1 or 2, or significant chronic kidney disease, even in primary prevention) (Chart 1.1). Individuals thus identified, both men and women, have a higher than 20% risk in 10 years to have new cardiovascular events19 or a first cardiovascular event19.

The patient that falls into one of these categories does not require additional steps for risk stratification and is automatically considered to be high risk.

High-risk conditions are those shown in Table 1.120.

Phase 2 - Risk score

The Global Risk Score (GRS)15 (http://www.zunis.org/FHS_CVD_Risk_Calc_2008.htm ) must be used in the initial evaluation in individuals that were not included in the high-risk conditions (Tables 1.2 , 1.3 , 1.4 , 1.5).

Individuals considered LOW RISK by this Guideline are those with probability < 5% to have major cardiovascular events (coronary artery disease - CAD, stroke, peripheral obstructive arterial disease or heart failure) in 10 years. Patients classified in this category with family history of premature cardiovascular disease will be reclassified to intermediate risk.

Individuals considered INTERMEDIATE risk are men with calculated risk ≥ 5% and ≤ 20% and women with calculated risk ≥ 5 % and ≤ 10% occurrence of any of the aforementioned events12,20,21.

Individuals are considered HIGH risk are those with calculated risk > 20% for men and > 10% for women in a 10-year period21.

Table 1.1 – Criteria for identiication of patients with high risk of coronary events (Phase 1)20

• Coronary artery atherosclerotic disease, peripheral arterial, cerebrovascular or peripheral obstructive disease, with clinical manifestations (cardiovascular events), and also in the subclinical form documented by diagnostic methodology.

• Revascularization procedures.

• Diabetes mellitus type 1 and type 2.

• Chronic Kidney Disease.

2

Guidelines



Table 1.2 – Scoring according to overall risk for women19,20

Points Age (years) HDL-C TC SBP (untreated) SBP (treated) Smoking Diabetes

-3 < 120

-2 60+

-1 50-59 < 120

0 30-34 45-49 < 160 120-129 No No

1 35-44 160-199 130-139

2 35-39 < 35 140-149 120-129

3 200-239 130-139 Yes

4 40-44 240-279 150-159 Yes

5 45-49 280+ 160+ 140-149

6 150-159

7 50-54 160+

8 55-59

9 60-64

10 65-69

11 70-74

12 75+

Points Total

HDL-C: high-density lipoprotein cholesterol; TC: total cholesterol; SBP: systolic blood pressure.

Table 1.3 – Overall cardiovascular risk in 10 years for women19,20

Points Risk (%) Points Risk (%)

≤ -2 <1 13 10.0

-1 1.0 14 11.7

0 1.2 15 13.7

1 1.5 16 15.9

2 1.7 17 18.5

3 2.0 18 21.6

4 2.4 19 24.8

5 2.8 20 28.5

6 3.3 21+ > 30

7 3.9

8 4.5

9 5.3

10 6.3

11 7.3

12 8.6

3

Guidelines



Table 1.4 – Scoring according to overall risk for men19,20

Points Age (years) HDL-C TC SBP (untreated) SBP (treated) Smoking Diabetes

-2 60+ < 120

-1 50-59 < 120

0 30-34 45-49 < 160 120-129 No No

1 35-44 160-199 130-139

2 35-39 < 35 200-239 140-159 120-129

3 240-279 160+ 130-139 Yes

4 280+ 140-159 Yes

5 40-44 160+

6 45-49

7

8 50-54

9

10 55-59

11 60-64

12 65-69

13

14 70-74

15 75+

Points Total

HDL-C: high-density lipoprotein cholesterol; TC: total cholesterol; SBP: systolic blood pressure.

Table 1.5 – Overall cardiovascular risk in 10 years for men19,20

Points Risk (%) Points Risk (%)

≤ -3 ou menos <1 13 15.6

-2 1.1 14 18.4

-1 1.4 15 21.6

0 1.6 16 25.3

1 1.9 17 29.4

2 2.3 18+ >30

3 2.8

4 3.3

5 3.9

6 4.7

7 5.6

8 6.7

9 7.9

10 9.4

11 11.2

12 13.2

4

Guidelines



Phase 3 - Aggravating Factors

For intermediate-risk individuals, aggravating factors should be used, which, when present (at least one) reclassify the individual for high-risk condition. (Chart 1.1)22 and the criteria for metabolic syndrome according to the International Diabetes Federation (IDF) (Chart 1.2)23,24.

The diagnosis of metabolic syndrome requires the presence of abdominal obesity as an essential condition and two or more of the criteria shown out in Chart 1.223,24.

Phase 4 - Risk Stratification by Lifetime

Aiming to reduce the burden of cardiovascular disease, the overall risk calculation in 10 years has been emphasized. However, it has been observed that many individuals considered low risk in 10 years, are actually high risk throughout the lifetime. The cardiovascular disease estimation using the lifetime risk stratification allows stratifying more comprehensively the burden of

cardiovascular disease in the general population at the present time and in the future, as it takes into account the risk of cardiovascular disease as the individual ages. This tool can assist in public health policies, allowing projections of global cardiovascular disease burden of in the population. This guideline recommends the use of the Lifetime Risk Score in individuals at low to intermediate risk after 45 years of age.

Table 1.6 classifies risk factors, according to the control and/ or their importance as optimal, non-optimal, high and main.

Table 1.7 and Table 1.8 show the calculation of LRS for men and women, respectively, after 45 years of age, based on the exposure to these factors throughout the lifetime.

The risk predicted by the lifetime > 39% in men and > 20.2% in women characterizes a high-risk condition for the lifetime25,26.

The algorithm in Figure 1 summarizes and aids in cardiovascular risk stratification.

Chart 1.1 – Aggravating risk factors12

• Family history of early coronary artery disease (male first-degree relative < 55 years-old or female first-degree relative < 65 years-old). • Criteria of metabolic syndrome according to the International Diabetes Federation24,25 .• Microalbuminuria (30-300 mg/min) or macroalbuminuria (> 300 mg/min).• Left ventricular hypertrophy.• High-sensitivity C-reactive protein > 3 mg/L.• Evidence of subclinical atherosclerotic disease:

– carotid stenosis/thickening > 1mm26;– coronary calcium score > 100 or > 75th percentile for ageo or sex27;– ankle-brachial test < 0.9.

Chart 1.2 – Diagnostic criteria for metabolic syndrome23,24

Criteria Deinition

• Abdominal obesity

• Men

• Caucasian of European origin and African descendants • ≥94

• South Asians, Native Americans and Chinese • ≥90

• Japanese • ≥85 cm

• Women

• Caucasian of European origin, African descendants, South Asians, Native Americans and Chinese • ≥80 cm

• Japanese • ≥90 cm

• Triglycerides • ≥150 mg/dL

• HDL-cholesterol

• Men • <40 mg/dL

• Women • <50 mg/dL

• Blood pressure

• Systolic • ≥ 130 mmHg or treatment for arterial hypertension

• Diastolic • ≥ 85 mmHg or treatment for arterial hypertension

• Glycemia • Fasting ≥100 mg/dL

5

Guidelines



Table 1.6 – Classiication of risk factors, according to their control and/or importance19,20

Risk factor Optimal risk factors 1 Non-optimal risk factors High risk factors Main risk factors

Total Cholesterol <180 mg/dl 180-190 mg/dl 200-239 mg/dl > 240 mg/dl

Systolic blood pressure Non-treated <120 mmHg Non-treated 120-139 mmHg Non-treated 140-159 mmHg Treatment for SAH or non-treated SBP ≥ 160 mmHg

Diastolic blood pressure Non-treated <80 mmHg Non-treated 80-89 mmHg Non-treated 90-99 mmHg Treatment for SAH or Non-treated DBP≥ 100 mmHg

Smoking No No No Yes

Diabetes No No No Yes

SBP: systolic blood pressure; DBP: diastolic blood pressure; SAH: systemic arterial hypertension.

Table 1.7 – Risk of fatal and nonfatal cardiovascular events by Lifetime in men, according to the exposure to risk factors throughout life19,20

Variable Situation according to risk factors

All optimal risk factors≥ 1 non-optimal

Risk factor≥ 2 High risk factors 1 Main risk factor ≥ 2 Main risk factors

Percentage risk (95% CI)

Risk after 45 years

Fatal CAD or non-fatal AMI 1.7 (0-4.3) 27.5 (15.7-39.3) 32.7 (24.5-41.0) 34.0 (30.4-37.6) 42.0 (37.6-46.5)

Fatal or nonfatal stroke 6.7 (1.4-11.9) 7.7 (5.0-10.4) 8.5 (6.9-15.6) 8.4 (7.5-9.4) 10.3 (9.0-11.7)

Death from cardiovascular disease 9.1 (0-18.6) 13.1 (9.9-16.3) 15.3 (13.3-17.3) 20.7 (19.4-22.2) 32.5 (30.5-34.5)

Total of events related to atherosclerotic CVD

1.4 (0-3.4) 31.2 (17.6-44.7) 35.0 (26.8-43.2) 39.6 (35.7-43.6) 49.5 (45.0-53.9)

CAD: coronary artery disease; AMI: acute myocardial infarction; CVD: cardiovascular disease.

Table 1.8 – Risk of fatal and nonfatal cardiovascular events by Lifetime in women, according to exposure to risk factors throughout life19,20

Variable Situation according to risk factors

All optimal risk

factors

≥ 1 non-optimal risk factors

≥ 2 high-risk factors 1 main risk factor≥ 2 main risk

factors

Percentage risk (95% CI)

Risk after 45 years

Fatal CAD or non-fatal AMI 1.6 (0-4.3) 9.3 (3.0-15.6) 9.3 (5.0-13.7) 12.7 (10.3-15.0) 21.5 (17.5-25.5)

Fatal or nonfatal stroke 8.3 (3.8-12.8) 8.9 (6.5-11.3) 9.1 (7.5-10.9) 9.1 (7.9-15.9) 11.5 (9.5-13.5)

Death from cardiovascular disease 4.8 (0.8-8.7) 4.9 (3.1-6.7) 6.9 (5.4-8.3) 11.2 (9.9-12.5) 21.9 (19.4-24.5)

Total of events related to atherosclerotic CVD

4.1 (0-8.2) 12.2 (4.6-19.7) 15.6 (10.3-20.9) 20.2 (17.2-23.2) 30.7 (26.3-35.0)

Table 1.9 – Classiication of recommendation and level of evidence for risk stratiication in cardiovascular prevention

Recommendation ClassLevel of

evidence

• Clinical manifestations of atherosclerotic disease or equivalents (type 1 or 2 diabetes mellitus and signiicant chronic kidney disease), even in primary prevention, have a risk > 20% in 10 years of new cardiovascular events or of the irst cardiovascular event I A

• Patients classiied as intermediate-risk with a family history of early cardiovascular disease will be reclassiied as high-risk IIa B

• Men with a calculated risk for any of the events cited ≥5% and ≤20% and women with that calculated risk ≥5% and ≤10% are considered intermediate-risk

I A

• Men with a calculated risk >20% and women with that calculated risk >10% are considered high-risk I A

• For individuals at intermediate risk, aggravating factors should be used, and when present (at least one) reclassify the individual as high-risk (Class IIa recommendation, level of evidence B)

IIa B

• Use of risk according to lifespan for low- and intermediate-risk individuals aged >45 years IIa B

6

Guidelines



2. SmokingThere are over 1 billion smokers worldwide and 80% of

them live in low-and middle-income countries, where the burden of tobacco-related diseases and death is heavier. It is estimated that current smokers consume about 6 trillion cigarettes every year27.

Approximately 50% of avoidable deaths among smokers could be prevented if the addiction was abolished, with most of these deaths being caused by CVD. The relative risk of myocardial infarction is two-fold higher among smokers aged > 60 years and five-fold higher among those aged < 50 years, when compared with nonsmokers. Tobacco consumption has declined in the general population, but showed an increase among individuals of low socioeconomic status and among women. In women, its deleterious effects appear to be stronger, being related to accelerated nicotine metabolism, with greater relevance in women that make concurrent use of oral contraceptives28.

Smoking prevention

The Framework Convention on Tobacco Control (FCTC) was the first international public health treaty in the history of the World Health Organization and represented a response instrument of the 192 countries members of the World Health Assembly to the growing smoking epidemic worldwide27.

In 1989, approximately 32% of the population aged 15 and older were smokers, according to the National Survey on Health and Nutrition/IBGE. Data from the household survey called Special Smoking Survey (PeTab) disclosed that in Brazil in 2008 there were around 25 million smokers and 26 million former smokers. The prevalence of smokers was 17.2% of the population aged 15 or older in 2008, demonstrating the decline occurred during these 20 years. However, data from

the Surveillance of Risk Factors and Protection against Chronic Diseases Telephone Survey (VIGITEL) released in April 2012, showed a further decline to 14.8% of smokers in Brazil, aged > 18 years. Among men, the percentage of smokers was 18.1% and among women, 12 %. Among those who smoked 20 or more cigarettes a day, 5.4% were men and 3.3% women. Men, in contrast, stop smoking more frequently: 25% said they were former smokers, while 19% of women said they were smokers in the past. The capital cities with the most smokers are Porto Alegre (23%), Curitiba (20%) and São Paulo (19%). The Northeast region has the capital cities with lowest incidence of smoking among their residents: Maceió (8%), João Pessoa, Aracaju and Salvador (all 9%)29.

Primordial smoking prevention

Primordial prevention of smoking is understood as preventing the initiation of smoking. The earlier an individual starts smoking, the more likely he or she will become an adult smoker. After one year, children inhale the same amount of nicotine per cigarette as adults; they also experience symptoms of dependence and abstinence30; such dependence can develop very rapidly in children. Approximately 80% of all individuals who start smoking in adolescence will continue to do so into adulthood, and a third of these will die prematurely because of smoking-related diseases31,32.

Factors that contribute to the initiation of smoking

1. Attitudes and beliefs - a study with adolescents33 showed that 40% of those who had never smoked became experimenters and 8% had the habit of smoking for 4 consecutive years. The firm decision of not smoking was the strongest predictor to prevent smoking. Attitudes that lead to smoking are influenced by several factors:

Figure 1 – Algorithm for cardiovascular risk stratiication19,20

ORS: overall risk stratiication; CAD: coronary artery disease; CV: cardiovascular

ORS < 5% in men and womenORS ≥ 5% and ≤20% in men or

≤ 10% in women

HIGH RISKINTERMEDIATE

RISK

HIGH RISK

Ifrisk based on lifespan• >39% for men or• > 20.2 % for women,• High risk of CV events

If family history of early CAD, reclassifyUse aggravating: if an aggravating factor

is present

LOW RISKINTERMEDIATE

RISK

Risk based on lifespan

High-risk condition present or ORS > 20% in men and > 10%

in women

7

Guidelines



the influence of friends and family, social pressure among adolescents, age, false conception (adolescents tend to overestimate the frequency of smoking of adults and underestimate their own); advertising33.

2. Nicotine addiction - Nicotine is a highly addictive substance and many individuals develop dependence within days or weeks of exposure. Young individuals are more vulnerable to nicotine addiction than adults34,35.

3. Depression: most studies show an association between the presence of depression and initiation of smoking, although it is unclear whether the association is causal36.

4. Inadequate school performance: truancy and poor school performance are associated with the initiation and continuity of smoking34,35.

5. Adverse experiences: parental separation or divorce, physical emotions, emotional, physical or sexual abuse; growing up with an addicted, mentally ill or convict family member36.

6. Substance abuse: there is a high frequency of current smoking among adolescents who use illicit drugs38. Thus, every adolescent that smokes should be seen as, potentially, engaged in other risky behaviors37.

Strategies to ight smoking initiation38

One way to address the primordial prevention is by age groups, observing, for each group, the top five items (5 As):

Group 0-4 years: ask parents and other family members about their smoking habits; advise them to keep the environment free of tobacco smoke; the message should include information about the risks to parents and children, as well as the importance of the parental role model for the children; assess the willingness to cooperate among the parents and other family members; assist parents in their attempt to stop smoking, by providing your own assistance material and/or referring them to their own physicians; arrange a visit within 3 months if a family member is a smoker; check on the progress of the parents in each subsequent pediatric visit.

Group 5-12 years: ask children about how it feels when someone nearby is smoking and what they do about it; also, if they consider it dangerous to smoke and if they think they will smoke when they are older, and moreover, if they have tried smoking or if they have friends who smoke, advise children not to try smoking, praise them for remaining a non-smoker and/or free of exposure to cigarette smoke; remind them about the negative effects of tobacco in the short term, such as a reduction of smell and athletic capacity, as well as risks to personal health (e.g., asthma exacerbation); advise parents to stop smoking and provide clear anti-smoking information to their children; assess the risk factors for smoking initiation or progression of smoking regularly, including the level of experimentation, smoking among friends, depressive symptoms, school performance and adverse experiences; assist parents in their attempts to quit smoking, help the children to develop skills to refuse smoking and tobacco exposure; assist parents in

their efforts to prevent smoking in their children through parental style and firm antismoking messages; arrange visit within 1-2 months for any child who has tried smoking or has clear risk factors to do so, referring them as required in cases of social or learning difficulties, as well as mental disorder cases.

Group of adolescents and young adults: ask the adolescents about their smoking behavior, confidentially, about friends who are smokers and about light cigarettes; advise adolescences to quit smoking, reinforcing the risks to personal health and danger of addiction; praise adolescences that are not smoking and remind them about the health risks; assess the motivation and symptoms of tobacco dependence among adolescents who are smoking; assess the risk factors for smoking initiation among those that are not smoking; assist teenagers who are smoking in their attempt to quit smoking, including nicotine replacement and by referring if necessary; assist parents in their efforts to prevent the initiation of smoking in their children through parenting style and firm antismoking information; arrange a visit within a month for each adolescent that is smoking, supporting their attempt to stop smoking or assessing the motivation and barriers to stop smoking; refer them as necessary, if risk factors such as social or learning difficulties or signs of mental disorders are identified.

Primordial cardiovascular prevention includes avoiding the establishment of modifiable cardiovascular risk factors including smoking and building effective strategies in order to promote cardiovascular health of individual and the population. For this purpose, the joint action of multidisciplinary teams (doctors, nurses, psychologists, physical educators, educators, nutritionists, social workers, communicators, managers) is necessary, as well as of intersectorial actions (family, school, government, society experts, university), continuously and simultaneously.

How to treat the psychological dependence on smoking

There are two types of approach:

Basic Approach (AAAPA) where the goal is to ask if the individuals smoke, assess the profile of smokers, advise them to quit, prepare them for smoking cessation and arrange follow-up for smoking cessation. This approach should always be performed by the doctor during a routine consultation, lasting at least 3 minutes and a maximum of 5 minutes, on average, at each visit that the patient does. The patient should be questioned and asked systematically at every consultation and return visit on the evolution of the cessation process. This approach is indicated for all smokers. A meta-analysis involving 29 studies showed that cessation rates were 19.9% for those who were submitted to medical intervention39.

Specific intensive approach: is carried out by health professionals available and trained to perform a more detailed follow-up with the patient, including the physician. In this case, the professional should have a structured program available to the patient with scheduled sessions (eight sessions in group/individual) and national reference medication will be used for treatment of smoking, as well as cognitive-behavioral approach. If possible, patients should be followed up to one year of

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Guidelines



treatment. Cognitive behavior is a psychological approach based on dealing with the automatic thoughts that smokers have and that lead them to seek cigarette smoking39.

In cognitive-behavioral approach, the most often used behavioral techniques are: self-observation, control of stimuli or triggers that lead to smoking (phone, computer, alcoholic beverages, bathroom, car), identification and learning of functional thought patterns, relaxation and deep breathing techniques, deferral and pattern interruption, assertiveness training (so that patients may face situations where they feel tempted to smoke), self-instruction (in which participants are taught to argue with themselves about the situation that tries to trick them into smoking) and troubleshooting, so that the patients are taught about appropriate ways to solve a problematic situation39.

Tools that help in evaluating and understanding patient proile:• Prochaska and DiClemente Scale for change in behavior:

this scale brings a model that allows assessing what stage of change in behavior the patient is, clearly and objectively. Smoking cessation is a dynamic process that is repeated over time and has different stages. At each stage, the individual uses different cognitive and behavioral processes40. The authors propose five different stages in this process: precontemplation, characterized by the absence of intention to change behavior, i.e., the individual does not perceive, in this case, the act of smoking as a problem; contemplation implies some awareness of the problem. It is perceived, there is intention to change, but there is no concept of when, or commitment to do it; preparation is a stage prior to the action. There is a clear intention to change; the individual has already taken some initiatives towards change, but the action is not yet effective; action is a change of behavior to try to resolve the problem. The individual spends time looking for treatments and promotes changes that should be long-lasting and maintenance is the stage at which such changes should be consolidated, encompassing everything that was gained at the stage of action. The stages occur non-linearly, i.e., spirally, which means that each stage that is not maintained leads to the initial stage.

• Motivational Interviewing: It is a viable alternative for the treatment of addictive behaviors, within brief interventions, as the initial impact seems to influence the motivation for change in behavior. Strategies for motivational interviewing: provide advice, remove barriers/ help with obstacles, provide alternative choices to smoking, decrease the undesirable aspect of the behavior, practice empathy, give feedback, clarify goals and actively help and provide care for relapse prevention - abstinence coping41.

• Fagerström Scale: it is an assessment scale that allows checking the degree of physical dependence on nicotine. It should be used in the initial evaluation of smokers when they come for treatment. In case of need for medication, it helps define the best medication and how much of it should be taken42.

In this case, it is noteworthy that one should not consider using the medication only in cases where Fagerström score is > 5. It is now known by scientific studies that a very low Fargeström score means that the psychological addiction is very high and in this case, the medication helps by reducing abstinence symptoms42.

• Reasons for Smoking Scale: is a scale that allows assessing in which situations the smoker uses cigarettes. Is related to physical, psychological dependence and conditioning and helps clarify the risk situations in everyday life for the smoker. This scale assesses: stimulation, handling (ritual), pleasure derived from smoking , tension reduction/relaxation, physical addiction, habit/automatism and social smoking. These items must be worked throughout the intensive process of smokers’ approach43,44.

Pharmacological Treatment of Smoking

There is consistent evidence that anti-tobacco drugs increase the success rate in smoking cessation37. Their use doubles or even quadruples the possibilities of abstinence37. Nicotine replacement therapy (NRT), bupropion and varenicline are considered first-line treatment for smoking and are recommended for prescription in national45 and international37 guidelines. Other drugs such as Nortriptyline, despite their proven efficacy, have side effects and contraindications that may limit their use37, and are therefore considered second-line treatment.

Some drugs appear as promising agents for smoking cessation because somehow, they have an effect on different brain circuits involved in nicotine dependence46. However, systematic reviews have not demonstrated the expected efficacy. These include the lack of consistency regarding results with the use of clonidine47, Naltrexone48, serotonin reuptake inhibitors49 and anxiolytics50. That is a quite different situation when compared to the first-line drugs, of which efficacy has been by acting primarily on the dopaminergic system, known to be related to the mesolimbic and reward systems50, crucial in the withdrawal and dependence process.

There are no defined criteria to choose among them. In clinical practice, prescription is made considering specific drug contraindications, product availability in the public healthcare system, patients’ financial availability for drug acquisition, professional clinical experience, among others, with no well-structured technical selection criteria. In some services, assessment of nicotine dependence and previous attempts at medication use are part of an algorithm used to define the choice of the first-line drug for the start of treatment, but this is limited to local experience52,53 and, therefore, there are no subsidies to support the standardized choice of drug.

The prescription of anti-smoking drugs is critical to improving the effectiveness of smoking cessation treatment, as also are key consultations of accompanying and encouraging the promotion of changes in habits and behavior of patients53,54.

The main characteristics of anti-tobacco first-line drugs are described below.

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Nicotine replacement therapy

Nicotine is primarily responsible for the dependence attributed to cigarettes and nicotine replacement therapies have used since 1984 in the treatment of smoking cessation. Forms of nicotine replacement therapy (NRT) currently used and available in Brazil are transdermal and oral (tablets and gum). They are both effective in smoking cessation, are often used in association and can double the success rate when compared to placebo55.

Transdermal nicotine

• Effectiveness compared with placebo: (RR: 1.9; 95% CI: 1.7-2.2).

• Rate of abstinence at 6 months (RR: 23.4; 95% CI: 21.3 - 25.8).

• Dose: 21 mg, 14 mg, 7 mg.

• Presentation: transdermal adhesive patches.

• Route (s) of administration: transdermal use with daily replacement.

• Treatment regimen: use of each presentation for 4 weeks on average, with progressive dose reduction. Example: (21, then 14, then 7 mg/day).

• Care in the administration: application on the upper chest, or anterior, posterior and lateral superior arm regions.

• Adverse reactions: itching and redness at the application site, nausea, dizziness and tachycardia with overdose.

• Contraindications: dermatological diseases that prevent adhesive application, 15-day period after acute myocardial infarction episode, pregnancy and breastfeeding.

• Overdose (toxicity): nausea, dizziness, tachycardia and hypertensive crisis.

Oral use nicotine - nicotine gum or lozenges

• Efficacy when compared with placebo: (RR: 2.2; 95% CI: 1.5 -3.2).

• Rate of abstinence at 6 months: (RR: 26.1; 95% CI: 9.7-33.6).

• Doses: 2 and 4 mg.

• Presentation: chewing gum or lozenges.

• Route of administration: Oral.

• Treatment regimen: when there is intense desire to smoke, replacing cigarettes (1-15 gums/day).

• Care in the administration: drinking a glass of water before use to neutralize the oral pH, due to the alteration caused by the consumption of food and removal of food waste, which may decrease absorption through the oral mucosa.

• Adverse reactions: nicotine gum may cause pain in the temporomandibular joint, when chewed fast and incessantly, as well as oropharyngeal irritation and nausea when chewed quickly and often. Nicotine lozenges can cause irritation of the oropharynx and nausea when chewed, rather than dissolved in the mouth, or when there is excessive use.

• Contraindications:

– Nicotine gum - Incapacity to chew, active peptic ulcer, 15 days after AMI.

– Nicotine lozenges - active peptic ulcer, 15 days after AMI.

– Overdose (toxicity): nausea, dizziness, tachycardia and hypertensive crisis.

Bupropion hydrochloride

Bupropion is an inhibitor of dopamine and norepinephrine reuptake that has shown to be effective in smoking cessation37,56,57 by reducing nicotine withdrawal symptoms. Being an antidepressant, it helps in controlling depressive symptoms that may arise during the process of smoking cessation.

• Efficacy compared to placebo (RR: 2.0; 95% CI: 1.8 -2.2).

• Rate of abstinence at 6 months - (RR: 24.2; 95% CI: 22.2-26.4).

• Presentation: Extended Release Tablets 150 mg.

• Route of administration: Oral.

• Dose schedule: 1 tablet daily for 4 days, then increase to 1 tablet twice daily with a minimum interval of 8 hours between doses.

• Care in the administration: avoid nightly administration to minimize the risk of insomnia.

• Adverse effects: dry mouth, insomnia (discontinued sleep), constipation, abdominal pain, dizziness.

• Contraindications:

– Absolute: risk of seizure (history of seizures, epilepsy, febrile seizures in childhood, known abnormalities in the electroencephalogram (EEG); alcoholism, use of monoamine oxidase inhibitor (MAOI) in the last 14 days, cerebrovascular disease, central nervous system (CNS) tumor and head trauma.

• Warnings/Precautions: The combination of bupropion and nicotine replacement, mainly in the form of adhesive patches, can raise blood pressure and its concomitant use with alcohol use may predispose to seizures.

• Overdose (toxicity): convulsions.

Varenicline tartrate

Varenicline37,58 is a partial agonist of the nicotinic receptor in the central nervous system. Among the first-line drugs for the treatment of smoking, varenicline is the most effective medication59,60.

• Efficacy compared to placebo (RR: 3.1; 95% CI: 2.5-3.8).

• Rate of abstinence at 6 months (RR: 33.2; 95% CI: 28.9-37.8).

• Dose: 0.5 and 1 mg tablets of varenicline tartrate.

• Route of administration: oral.

• Treatment regimen: Start with 0.5 mg once a day. On the 4th day prescribe 0.5 mg twice a day. On the 7th day, prescribe 1 mg twice a day. Prescribe for 12 to 24 weeks.

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Varenicline therapy does not require immediate smoking cessation. Smoking cessation is recommended after the 14th day of the start of medication.

• Adverse reactions: The most expected side effect with the use of this substance is nausea (30% of patients), which is minimized by ingesting the medication after meals and with a glass of water. Less than 6% of patients stop the medication for this reason.

• Contraindications: Absolute - patients with end-stage renal failure, pregnant and breastfeeding women. Dose adjustment is necessary in patients with severe renal failure (see table of adjustment).

• Care in the administration: One must be cautious when prescribing it to patients with a history of psychiatric illnesses such as severe depression, bipolar disorder and panic disorder. Although no causal association has been shown and considering that smokers have higher risk of depression and suicidal thoughts61, the Food and Drug Administration (FDA) in 200962, warned against the possibility of mood alterations, agitation and suicidal thoughts among varenicline users and therefore, it is not recommended for patients with nonstabilized psychiatric disorders63.

In 2011, Sigh63 carried out a meta-analysis with some studies on varenicline use, warning of a possible risk of cardiovascular events among users. After careful analysis of the study, it was concluded that a significant number of patients using varenicline in randomized studies were not included in the meta-analysis and showed no cardiovascular event. A more comprehensive meta-analysis was performed64 including all studies with varenicline and no increased risk of cardiovascular events was observed in the varenicline versus placebo group. The safety and efficacy of varenicline were evaluated and demonstrated by Rigotti et al.65, in a randomized and placebo-controlled trial in patients with cardiovascular disease.

• Overdose (toxicity): nausea, dizziness, vomiting.

Second-line medications

Nortriptyline

Nortriptyline is a tricyclic antidepressant that blocks noradrenaline reuptake in the central nervous system. It is a second-line drug in the treatment of smoking. The FDA has not yet approved its use for this purpose because, although its efficacy is similar to that obtained with NRT or bupropion, there is greater risk of side effects37,56. The recommended

dose is 25 mg/day as a single dose, with gradual increase up to 75 to 100 mg/day. The use is not recommended in patients with structural heart disease of any kind, due to the risk of inducing arrhythmias and conduction disturbances.

Associations of anti-tobacco drugs

The effectiveness of first-line anti-tobacco drugs is between 20% and 25% for nicotine replacement therapy and Bupropion, not exceeding 35% with varenicline37. Some studies on the combination of adhesive nicotine patches and oral nicotine have shown improved results. A meta-analysis of nine studies56 that combined a nicotine patch with a rapid nicotine-release agent (gum, spray, lozenges) showed that the combination was more effective than a single type of NRT (RR: 1.34; 95% CI: 1:18-1:51).

The combination of NRT and bupropion was more effective than bupropion alone in the meta-analysis of four studies53

(RR: 1.24; 95% CI: 1.06 -1.45).

The association between varenicline and bupropion seems to be the most effective of all66; however, randomized studies67 of greater consistency are in progress to demonstrate such indication.

3. Diet, supplements and vitamins

Introduction

Although they can modulate a number of physiopathological mechanisms associated with atherosclerosis, prospective studies failed to show any benefits in the intake of vitamins and omega 3 fatty acids in the form of supplementation in cardiovascular disease (CVD) prevention. More information is needed about vitamin D and alpha-linoleic acids, but in the light of current knowledge, one cannot recommend the use of these supplements to prevent CVDs. Summaries of recommendations for the intake of these supplements can be found in Tables 3.1 to 3.3.

Carotenoids

Carotenoids are a class of over 600 compounds, responsible for the yellow, red and orange pigments in plants, with α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin being the ones most often found in foods. Known mainly as precursors of vitamin A, carotenoids are also important suppressors of free radicals and act as potent antioxidants68.

Table 2.1 – Degree of recommendation and level of evidence for the treatment of smoking on cardiovascular prevention

Recommendation Class Level of Evidence

• Smoking is an independent risk factor for cardiovascular disease and, therefore, should be avoided I B

• Passive exposure to tobacco smoke increases the risk of cardiovascular disease and should be avoided I B

• Pharmacological treatment of smoking Nicotine replacement therapy Bupropion hydrochloride Varenicline tartrate

IIII

AAAA

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Table 3.1 – Summary of recommendations for non-consumption of vitamin supplements in cardiovascular disease prevention

Indication Class Level of Evidence

There is no evidence of beneit of vitamin A or beta-carotene supplementation in the primary or secondary prevention of cardiovascular disease

III A

Vitamin B and folic acid supplementation is not effective in primary or secondary cardiovascular disease prevention III A

There is no evidence of vitamin C supplementation beneit for prevention, progression or death from cardiovascular disease II A

Vitamin D supplementation is not recommended for cardiovascular disease prevention in individuals with normal blood levels of this vitamin. Likewise, there is no evidence that supplementation in individuals with vitamin D deiciency will prevent CVD

III C

Table 3.2 – Recommendations for consumption of products rich in omega-3 fatty acid


Supplementation with omega-3 of marine origin (2-4 g/day) or even higher doses should be recommended for severe hypertriglyceridemia (> 500 mg/dL), with risk of pancreatitis, refractory to non-pharmacological measures and drug therapy

I A

At least 2 ish meals a week as part of a healthy diet should be recommended to reduce cardiovascular risk. This recommendation is particularly directed to high-risk individuals such as those who have already had myocardial infarction

I B

EPA + DHA supplementation is not recommended for individuals at risk of cardiovascular disease using preventive evidence-based treatments

III A

Evidence for a role of carotenoids in CVD came from studies that showed that increased consumption of fruits and vegetables was associated with lower risk of cardiovascular disease69.

A series of retrospective longitudinal and prospective studies identified an inverse association between intake of carotenoids and the risk of CVD69. However the effect of carotenoids is complex and probably not due to a single compound alone.

In contrast, prospective randomized trials showed no benefit of supplementation with carotenoids for CVD70,71.

Therefore, the use of supplements with carotenoids, beta-carotene or others is not recommended. Instead of that, efforts should be directed at the increased consumption of fruits and vegetables rich in this nutrient.

Vitamin E

Vitamin E is the main fat-soluble antioxidant in the human body and is present in a complex of four isomers (α, β, γ, δ - tocopherol). Interest in the potential benefit of vitamin E on the risk of CVD was related to its antioxidant capacity and the possibility of modifying the oxidized low-density lipoprotein (oxLDL), particularly involved in atherogenesis72. However, prospective randomized trials such as the ATBC, CHAOS, GISSI, and HOPE showed no benefits of vitamin E supplementation on CVD70,71,73. Despite a solid theory of the molecular basis of oxidative stress and its role in atherosclerosis, these trials do not support the use of supplemental vitamin E in the prevention of CVD, with its consumption being more effective and safe when obtained from foods. Therefore, vitamin E supplementation is not recommended for the cardiovascular disease prevention.

Vitamin C

Vitamin C or ascorbic acid is soluble in water and a very effective antioxidant, as it easily loses electrons. The theory of free radicals in the aging process elucidates its role in the progression of chronic diseases74.

Although supported by observational studies, randomized controlled trials do not support a role of vitamin C supplementation in primary or secondary prevention of cardiovascular diseases74. Thus, vitamin C supplementation for the prevention of cardiovascular disease is not recommended.

Vitamin D

Vitamin D is a fat-soluble nutrient that has several functions in the body, with the main one being bone metabolism. However, vitamin D has many other functions and the use of vitamin D supplements for the prevention and treatment of a wide range of diseases has increased considerably in the last decade76.

Its two main forms are vitamins D2 (ergocalciferol) and D3 (cholecalciferol). Vitamin D3 can be synthesized by humans by the skin cells after exposure to UV-B radiation from sunlight. In the absence of sunlight, vitamin D intake is crucial. Vitamin D and dietary supplements are absorbed by the intestine and then converted into 25-hydroxyvitamin D3 [25 (OH) D] in the liver, and 1,25 dihydroxyvitamin D3 [1,25 (OH) 2D3], the active form of vitamin D, in the kidney.

Zittermann et al.76 summarized the underlying mechanisms for a possible role of vitamin D in the prevention of coronary disease. These include inhibiting the proliferation of vascular smooth muscle, suppression of vascular calcification, the downregulation of proinflammatory cytokines, increased

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regulation of anti-inflammatory cytokines and the effect of the vitamin D as an endocrine downregulator of the renin-angiotensin system.

Low concentrations of circulating vitamin D have been associated with hypertension, obesity, diabetes mellitus and metabolic syndrome; additionally, vitamin D deficiency has been associated with risk of cardiovascular disease in recent studies76,77.

There is evidence of a role of vitamin D in CVD in ecological studies, with an increase in heart disease events with the geographical latitude, i.e., associated with less exposure to sunlight, considering that vitamin D concentrations decrease with the latitude. Several prospective studies have investigated the serum concentration of 25-hydroxy (OH) vitamin D in relation to cardiovascular diseases, showing biased results for the association of low concentrations of this marker and increased risk for cardiovascular disease77-78. While the protective effect of vitamin D in cardiovascular events is supported by epidemiological evidence, there is insufficient evidence to date to recommend supplementation for the prevention of cardiovascular disease. Thus, vitamin D supplementation for cardiovascular disease prevention is not recommended.

Vitamins B and Folate

Evidence of an association between CVD and vitamin B were demonstrated by the effect of these vitamins on the reduction of homocysteine79,80. Homocysteine, an amino acid that contains sulfur, is a metabolite indirectly produced during the demethylation of methionine. Prospective studies have shown an independent association, albeit of modest intensity, between serum homocysteine levels and CVD risk80. A number of factors have been identified as being associated with elevated homocysteine levels. These include inadequate intake of folic acid, vitamins B6 and/or B12, preexisting atherosclerotic disease, drinking coffee, smoking, alcohol consumption, diabetes, use of antiepileptic drugs or methotrexate, renal failure, rheumatoid arthritis, hypothyroidism and cystathionine beta-synthase and methylenetetrahydrofolate reductase mutations.

Randomized prospective studies with large number of cardiovascular events failed to show any benefit of folate and B complex supplementation in reducing homocysteine levels and CVD prevention80.

The discrepancy between the results of epidemiological studies and clinical trials may be due in part to the inclusion of different populations and the use of foods fortified with folic acid in some countries.

The supplementation of folic acid or B complex is not recommended for cardiovascular disease prevention.

Omega-3 polyunsaturated fatty acids of marine origin

(docosahexaenoic (DHA) and eicosapentaenoic acid (EPA)

The omega-3 fatty acids of marine origin, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have several effects on different physiological and metabolism aspects that may influence the chance of developing cardiovascular diseases 81,82. While it is generally agreed that the regular

consumption of fish rich in omega-3 fatty acids is part of a healthy diet, the recommendation of supplementing the diet with fish oil capsules is surrounded by controversy, generated by the conflicting results of clinical trials83-86.

Clinical trials have show that supplementation with 2 g to 4 g of EPA/DHA a day can lower the levels of triglycerides (TG) by 25% to 30%, slightly increase HDL-C levels (1% to 3%) and increase LDL-C by 5% to 10%86. The capacity to reduce the levels of TG is dose-dependent, with a reduction of approximately 5% to 10% for each 1 g of EPA/DHA consumed daily, being higher in individuals with higher baseline TG levels .

In a meta-analysis of 36 randomized clinical trials, supplementation with fish oil (median dose of 3.7 g/day) was shown to reduce systolic blood pressure by 3.5 mmHg and diastolic by 2.4 mmHg87. The reduction of adrenergic tone and systemic vascular resistance is a proposed mechanism.

Despite early evidence suggesting a protective effect of fish and omega-3 fatty acids of marine origin on cardiovascular events87, especially in individuals that already had cardiovascular disease, recent studies have shown no benefit of supplementation with omega-3 in individuals who had already shown or not manifestations of atherosclerotic disease83,84. One possible reason is related to the population profile, especially regarding the more frequent use of medications known to be protective (e.g., statins, beta-blockers, angiotensin-converting enzyme inhibitors), the more aggressive control of traditional risk factors and the higher number of revascularization procedures in more contemporary studies. Thus, it is debatable whether omega-3 fatty acids can bring real added benefits when the patient is managed according to current recommendations.

As most studies evaluated EPA and DHA in combination, currently there is not enough evidence to support separate recommendations for each of these fatty acids.

EPA and DHA supplementation is not recommended for cardiovascular disease prevention.

Omega-3 polyunsaturated fatty acids of vegetable origin

The alpha-linolenic fatty acid (ALA) has shown inconsistent effects on lipid levels88,89. In a systematic review and meta-analysis of 14 randomized controlled trials with ALA supplementation, no significant effect was observed on total cholesterol, LDL-C or triglycerides, showing a minimal effect on HDL-C (reduction of 0.4 mg/dL)90.

Specifically, the effects of flaxseed in experimental animals varied from nil to slight lipid decrease and a review suggested a triglyceride-lowering effect of the consumption of large amounts of flaxseed oil in humans90. Observational studies suggest a modest reduction in the risk of CVD with ALA consumption90. Data from the alpha-omega study showed no benefits of ALA supplementation for CVD prevention in individuals who had experienced previous cardiovascular disease85. However, further studies on ALA supplementation for CVD prevention are needed90. ALA supplementation is not recommended for cardiovascular disease prevention.

Recommendations for consumption and supplementation of ALA are shown in Table 3.3.

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4. Obesity and overweight

Introduction

In recent decades, Brazil has gone through a process called nutritional transition91, a concept that refers to secular changes in the patterns of nutrition and nutritional status, major alterations in food intake and physical activity patterns as a result of economic, social, demographic and sanitary changes92.

In Brazil, the prevalence of overweight and obesity has increased continuously from 1974 to the present day among adults of both genders. However, from 2002-2003 the prevalence of overweight, which was higher among women, became higher among men, increasing from 18.5% to 50.1% in all regions except the Northeast, while it increased from 28.7% to 48% among women93.

During a 34-year period, the prevalence of obesity increased more than four-fold for men (from 2.8% to 12.4%) and more than two-fold for women (8% to 16.9 %)94,95. Brazil currently ranks fourth among countries with the highest prevalence of obesity96 and for the first time the number of overweight adults will exceed the number of low weight ones96. In children and adolescents, there is a significant increase in overweight and obesity, regardless of gender and social class, and a significant proportion of obese children will become obese adults.

Obesity, with its multifactorial characteristic, is one of the prevalent factors to explain the increased burden of noncommunicable chronic diseases (NCDs), as it is often associated with cardiovascular diseases such as hypertension, dyslipidemia, type 2 diabetes, osteoarthritis and certain types of cancer, and it is also considered an important condition that predisposes to mortality96,97.

Primary prevention

It is important to identify at which biological time it is possible to prevent weight gain. For women, the time of greatest risk of weight gain appears to be the reproductive age, specifically pregnancy and the first two years after delivery97,98. Among children and adolescents, excessive weight gain prevention was expected, precisely because it is a growth phase that requires extra energy, while the possibility of energy expenditure is higher compared to other stages of life. However, these potential facilitators do not seem to outweigh factors associated with obesity and that are responsible for the growth of this epidemic also in these age groups and stages of life99.

In this sense, it is important to highlight the so-called “obesogenic environment”, i.e.: the role of the food industry,

fast food chains, advertising and TV programs, movies, video games, in conclusion, situations that make children more sedentary and exposed to excessive consumption. The most appropriate interventions should combine environmental and behavioral changes100-102.

Children and adolescents: see specific chapter.

Adults

Among adults, several studies have shown the decline in the consumption of rice and beans, increased intake of processed products (mainly cookies and soft drinks), excessive consumption of sugar, the systematic increase in fat and low intake of fruit and vegetables (FV), a situation of unfavorable trends for a healthy eating pattern and directly associated with the increase in NCDs, in which obesity is one of the most important, a situation similar to that observed in the preceding age groups103,104.

The recommendations are as follows:

• Three meals (breakfast, lunch and dinner) and two healthy snacks a day. Do not skip meals. Avoid snacking between meals.

• Pay attention to food labels and choose those with lower amounts of trans fats.

• Avoid soft drinks and processed juices, cakes, pastries and cookies, sweet desserts and other sugared foods.

• Give preference to water consumption between meals.

• Do at least 30 minutes of physical activity every day.

• However, those with a tendency to obesity or family profile should do 45-60 minutes of moderate-intensity physical activity a day; those who were obese and lost weight should do 60-90 minutes to prevent regaining weight.

• Even in the elderly physical activity and exercise can prevent weight gain and obesity105.

• Avoid excessive consumption of alcoholic beverages106.

Secondary Prevention

The proposed intervention at this level aims at modifications in life style and other actions, for children as well and for adolescents and adults.

It is often considered an acceptable strategy to achieve weight reduction necessary at the beginning of the process. This daily reduction may promote reduction of approximately 500 g a week107.

Intensification of physical exercising such as walking, cycling, swimming, aerobics, 30 to 45 minutes 3-5 times a week can contribute to the reduction of cardiovascular risk

Table 3.3 – Recommendation for consumption of products rich in omega-3 fatty acids of vegetable origin


Encourage the consumption of omega-3 polyunsaturated fatty acids of vegetable origin as part of a healthy diet can be recommended to reduce cardiovascular risk, although the real beneit of this recommendation is debatable and the evidence is not conclusive

IIb B

ALA supplementation is not recommended for cardiovascular disease prevention III B

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Table 4.1 – Summary of recommendations for obesity and overweight in the primary prevention of cardiovascular disease


Three meals (breakfast, lunch and dinner) and two healthy snacks a day. II A

Pay attention to food labels and choose those with lower amounts of trans fats. II A

Avoid soft drinks and processed juices, cakes, pastries and cookies, sweet desserts and other sugared foods. I A

Give preference to water consumption between meals. II A

Do at least 30 minutes of physical activity every day. I A

Those with a tendency to obesity or family proile should do 45-60 minutes of moderate-intensity physical activity a day; those who were obese and lost weight should do 60-90 minutes to prevent regaining weight.

I A

Avoid excessive consumption of alcoholic beverages. I A

Table 4.2 – Summary of recommendations for obesity and overweight in the secondary prevention of cardiovascular disease


Diet with a caloric reduction of about 500 kcal/day I A

Intensiication of physical exercises such as walking, cycling, swimming, aerobics, 30-45 minutes 3-5 times a week I A

Minimize sedentary activities such as sitting for long periods watching television, playing at computer or video games I B

Encourage healthy eating habits for children and adolescents I B

Use of sibutramine for weight loss in patients with cardiovascular disease III B

Bariatric surgery for selected patients I B

factors. It is important to increase the lean mass, thus the combination of aerobic exercise with the isometric/static ones is crucial.

Sedentary activities, such as sitting for long periods watching television, at the computer or playing video games should be minimized. In addition, one should have physical activity during the work period, for instance, take the stairs instead of the elevator, take a walk at lunchtime, and encourage healthy eating habits for children and adolescents.

Thus, the recommended amount of weight loss and the schedule to determine this loss may vary depending on the degree of obesity and the characteristics and severity of the complications and other features related to individuals and their life style.

Drug therapy

There are two drugs approved for the treatment of obesity in Brazil: Orlistat and Sibutramine. Sibutramine, although approved in Brazil, should not be used in patients with CVD107. Both promote modest weight loss, in a sustainable manner, and are indicated for the long-term treatment of obesity in conjunction with a reduced-calorie eating plan and regular physical activity.

Bariatric surgery

Comorbidities associated with obesity showed improvement after bariatric surgery. The Adelaide study showed that 60% of

patients who initially had comorbidities related to obesity were able to stay drug-free for three years after the surgery108, 109.

Surgical intervention is an option for carefully selected patients with clinically severe obesity (body mass index [BMI] ≥ 40 kg/m² without comorbidities or 35 kg/m² with comorbidities) when clinical treatments have failed.

Multidisciplinary follow-up of the patient due to possible nutritional changes is required.

5. Arterial hypertensionSystemic arterial hypertension (SAH) is the most important

risk factor for the development of coronary artery disease, heart failure, cerebrovascular disease, chronic kidney disease and atrial fibrillation110,111 and has been associated with the development of cognitive deficit and dementia112.

Mortality from CVD increases progressively with increasing levels of blood pressure (BP) from 115/75 mmHg, in a linear, independent and continuous manner113.

In a decade, approximately 7.6 million deaths worldwide were attributed to hypertension (54 % from stroke and 47% from ischemic heart disease [IHD]), mostly in low and medium economic development and more than 50% in individuals aged between 45 and 69 years114.

Considering BP values ≥ 140/90 mmHg, 22 studies found hypertension prevalence in the adult population between 22.3% and 43.9% (mean 32.5%), with more than 50% between 60 and 69 years and 75% > 70 years115-118.

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Deinition and classiication (VI DBH119)

Blood pressure measurements

At the first assessment, the measures must be taken in both arms and in case of different results, the arm with the higher value should be used as reference in subsequent measurements. Individuals should be investigated for arterial disease in the presence of pressure differences between the upper limbs > 20/10 mmHg for systolic/diastolic pressures, respectively120.

At least three measurements should be carried out at each visit and a one-minute interval between them is suggested121,122. The mean of the last two should be considered the actual BP. If the systolic and/or diastolic pressures obtained show a greater than 4 mmHg difference, new measurements should be performed until a smaller difference is obtained.

The recommended manner to measure blood pressure is in the sitting position. Measurements in the supine and orthostatic positions must be made at least in the first assessment in all individuals and in all assessments in the elderly, diabetics, patients with dysautonomia, alcoholics and/or those using antihypertensive medication (Table 5.1).

The ABMP (ambulatory blood pressure monitoring), HBPM (home blood pressure monitoring) and SMBP (self-measured blood pressure) are important tools in the investigation of patients with suspected hypertension or for treatment control. It is recommended, whenever possible, to measure BP outside the office to confirm a diagnosis, identify white-coat hypertension and masked hypertension, in addition to the anti-hypertensive treatment control123,124.

Routine initial evaluation of the hypertensive patient

Basic routine complementary tests for hypertension should include: urinalysis; serum potassium; serum creatinine and estimated glomerular filtration rate using formulas126,127; fasting glucose, total cholesterol, HDL-C, triglycerides, serum uric acid and conventional electrocardiogram (ECG)119.

The supplementary assessment for hypertensive patients may include119:

Table 5.1 – Classiication of blood pressure according to the casual ofice measurements (> 18 years)

Classiication Systolic pressure (mmHg) Diastolic pressure (mmHg)

Optimal < 120 < 80

Normal < 130 < 85

Borderline* 130-139 85-89

Stage 1 hypertension 140-159 90-99

Stage 2 hypertension 160-179 100-109

Stage 3 hypertension ≥ 180 ≥ 110

Isolated systolic hypertension ≥ 140 < 90

When the systolic and diastolic pressures are at different categories, the higher one should be used to classify blood pressure.

* Normal-high pressure or pre-hypertension are equivalent terms in the literature.

a) Chest radiography: recommended for patients with suspected heart failure when other tests are not available and to assess pulmonary and aortic involvement.

b) Echocardiogram: hypertensive patients stages 1 and 2, without left ventricular hypertrophy on ECG, but with two or more risk factors; hypertensive patients with suspected heart failure.

c) Microalbuminuria in a single urine sample (by urinary albumin/creatinine ratio): hypertensive diabetic patients, hypertensive patients with metabolic syndrome and hypertensive patients with two or more risk factors.

d) Ultrasound of the carotid arteries: patients with carotid murmur, with signs of cerebrovascular disease, or atherosclerotic disease in other territories.

e) Exercise testing: suspected stable coronary heart disease, patient with diabetes, or family history of coronary disease in patients with controlled blood pressure.

f) Glycated hemoglobin: in patients with metabolic syndrome, diabetic or glucose intolerant individuals. When it is not possible to assess glycated hemoglobin, we suggest the oral glucose tolerance test in patients with fasting glucose between 100 and 126 mg/dL.

g) ABPM, HBPM and SMBP, according to the conventional indications for the methods.

h) Evaluation of arterial stiffness by pulse wave velocity or other methods, if available.

i) Investigation of secondary hypertension, as indicated by history, physical examination or by the initial laboratory assessment.

Identification of subclinical target-organ injuries

a) ECG with LVH (Sokolow-Lyon > 35 mm; Cornell > 28 mm -0 for males (M); > 20 mm – for females [F]);

b) Echocardiogram with LVH (LV mass > 134 g/m2 in M or 110 g/m2 in F);

c) intima-media thickness of the carotid artery > 0.9 mm or presence of atheroma plaque;

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Guidelines



Table 5.2 – Initial routine assessment of the hypertensive patient119


Urinalysis I C

Serum potassium I C

Serum creatinine I B

Estimated glomerular iltration rate I B

Fasting glucose I C

Total cholesterol, HDL-C, serum triglycerides I C

Serum uric acid I C

Conventional ECG I B

HDL-C- colesterol da lipoproteína de alta densidade por High-density lipoprotein cholesterol

Table 5.3 – Supplementary assessment for hypertensive patients119

Recommendation Class Level of evidence

Chest radiography IIa C

Echocardiogram - hypertensive patients stages 1 and 2 without LVH on the ECG IIa C

- hypertensive patients with suspected HF I C

Microalbuminuria - hypertensive and diabetic patients I A

- Hypertensive patients with metabolic syndrome I C

- Hypertensive patients with two or more risk factors I C

Carotid ultrasound IIa B

Exercise test for suspected coronary artery disease IIa C

Glycated hemoglobin IIa B

Pulse wave velocity IIb C

LVH, left ventricular hypertrophy, ECG, electrocardiogram, HF-heart failure

d) ankle-brachial index < 0.9;

e) estimated creatinine clearance < 60 mL/min/1.72 m2;

f) low glomerular filtration rate or creatinine clearance (< 60 mL/min);

g) microalbuminuria 30-300 mg/24 hours or albumin/creatinine ratio > 30 mg per g;

h) assessment of arterial stiffness by pulse wave velocity > 12 m/s125, 126.

Prevention

Clinical studies demonstrated that the detection, treatment and control of hypertension are crucial to reducing cardiovascular events. A meta-analysis of 354 clinical trials showed that the reduction in morbidity and mortality is proportional to the decrease in blood pressure, both systolic and diastolic, and may reduce decrease by 46% the occurrence of myocardial infarction and by 63% the number of strokes 127. In Brazi l ,

Chart 5.1 – Calculation of creatinine clearance and glomerular iltration rate and interpretation of values for classiication of chronic kidney disease according to NKF121

• Estimated glomerular iltration rate (eGFR) by the Cockcroft-Gault formula122: eGFR (mL/ min) = [140 - age] x weight (kg)/serum creatinine (mg/dL) x 72 for men; for women, multiply the result by 0.85.

• Glomerular iltration rate by the MDRD formula123 at www.kidney.org/professional / KDOQI / guidelines_ckd. • Interpretation124:

– Normal kidney function: > 90 mL/ min with no other changes in urinalysis; – Kidney disease Stage 1: > 90 mL/min with changes in urinalysis; – Kidney disease Stage 2: 60-90 mL/min; – Kidney disease Stage 3: 30-60 mL/min; – Kidney disease stage 4-5: < 30 mL/min.

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Guidelines



14 population studies performed in the last fifteen years, with 14,783 individuals (BP < 140/90 mmHg) showed low rates of BP control (19.6%)116-118.

Primary prevention of SAH

Hypertension can be prevented or postponed. Changes in life style are enthusiastically recommended for primary prevention of SAH, notably in individuals with borderline BP levels. Such life style adjustments reduce BP, as well as cardiovascular mortality128.

Healthy life style habits should be adopted since childhood and adolescence, respecting the regional, cultural, social and economic characteristics of individuals. The main non-pharmacological recommendations for primary prevention of hypertension are: healthy diet, low sodium and alcohol intake, adequate intake of potassium, fight against sedentary life style and smoking and maintain body weight control. Such recommendations are indicated for the prevention of hypertension as adjuvants to drug treatment for hypertension129.

Non-pharmacological measures

Diets

The DASH (Dietary Approaches to Stop Hypertension) dietary pattern, rich in fruits, vegetables, fiber, minerals and low-fat dairy products, has a significant impact in BP reduction. A high degree of adherence to this type of diet reduced by 14% the development of hypertension. The benefits on the BP have been associated with high intake of potassium, magnesium and calcium in this nutritional pattern. The DASH diet also enhances the effect of dietary guidelines for weight loss, also reducing cardiovascular risk biomarkers130,131.

The Mediterranean diet is also associated with BP reduction. High consumption of fruits and vegetables was found to be inversely proportional to the BP levels, even with a higher percentage of fat. Replacement of excess carbohydrates in this diet by unsaturated fat induces a more significant BP reduction132,133.

Vegetarian diets are inversely associated with the incidence of cardiovascular diseases. This is explained by the lower amount of nutrients consumed, such as saturated fat and cholesterol. However, these diets are deficient in micronutrients such as iron, vitamin B12 and calcium and supplementation is needed to meet current recommendations. Micronutrient deficiencies often seen in lactovegetarians have been identified as factors predisposing to SAH in adults following this type of diet. A relevant fact is the observation that vegetarians have, in general, lower BMI, which, regardless of the type of diet, is associated with lower BP134,135.

Sodium

The maximum amount considered to be healthy for daily ingestion of sodium chloride (table salt) is 5 g (corresponding to 2 g of Sodium)136,137. In practice, it is recommended the consumption of no more than 3 shallow teaspoons of salt (3 g), which added to 2 g of salt already present in foods, would come to a total of 5 g.

Alcohol

In hypertensive subjects, alcohol intake, acutely and dose-dependently, reduces BP, but elevation occurs a few hours after alcohol consumption. Given the controversy regarding the safety and cardiovascular benefit of low doses, as well as the harmful use of alcohol in society, it should be recommended to those who have the habit of drinking alcoholic beverages not to exceed 30 g of ethanol per day, for men, preferably non-habitually, with half of that amount being indicated to women138,139. The maximum daily amounts suggested for the most common types of alcoholic drinks are two cans (350 x 2 = 700 mL) or 1 bottle (650 mL) of beer; 2 150 mL glasses or 1 300 mL glass of wine, two 50 mL doses of whiskey, vodka or distilled liquor.

Physical activity

The regular practice of aerobic physical activity such as walking for at least 30 minutes a day, 3 times/week, is indicated

Table 5.4 – Non-pharmacological treatment of hypertensive patients119


Diet - DASH I A

- Mediterranean I B

- Vegetarian IIa B

Sodium - daily intake of 2 g I A

Alcohol - no more than 30 g of alcohol a day I B

Physical activity - 30 minutes/day/3 times a week (minimum) I A

Weight control - BMI between 18.5 and 24.9 kg/m2 I A

Psychosocial stress control IIa B

Multidisciplinary team I B

DASH = Dietary Approaches to Stop Hypertension BMI- body mass index.

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Guidelines



for the prevention, whereas, for treatment, daily supervised exercise is recommended140. Resistance exercises may be associated with aerobics141.

Weight control

Individuals should maintain body weight within the normal range (BMI between 18.5 and 24.9 kg/m2) and abdominal circumference measures below 102 cm for men and 90 cm for women142,143.

Control of psychosocial stress

Different techniques of stress management have been assessed, but with conflicting results. Meditation, music therapy, biofeedback, yoga, and other stress management techniques, were able to slightly reduce BP in hypertensive individuals144.

Multidisciplinary team

Considering that hypertension is a multifactorial clinical syndrome, rely on the support of the multidisciplinary support team for hypertensive patients is a desirable conduct, whenever possible145.

Other non-pharmacological strategies for blood pressure control

Specific strategies, such as using slow-breathing techniques146, the use of CPAP (continuous positive airway pressure) in case of obstructive sleep apnea syndrome147 and bariatric surgery for advanced obesity148 have shown significant impact in reducing blood pressure.

Drug measures for hypertension prevention

The TROPHY149 and PHARAO150 studies evaluated the efficacy and safety of antihypertensive drugs in hypertension prevention. The drug strategy based on the blocking of the renin-angiotensin system was well tolerated and prevented the development of hypertension in young high-risk populations. However, to date, no previously performed study showed enough power to determine the indication of drug treatment for individuals with borderline BP with no evidence of cardiovascular disease.

Treatment decision-making and risk category

Hypertensive patients must be classified based on their mean level of blood pressure and presence or not of associated risk factors, target-organ lesions and established cardiovascular or renal disease.

The therapeutic decision-making should be based on risk stratification, as shown in Chart 5.2 below:

Pharmacological treatment

Drug treatment of hypertension significantly alters the prognosis, regardless of the antihypertensive drugs used both in monotherapy and in combination. Several randomized trials and meta-analyses have demonstrated the benefits of reducing blood pressure levels on cardiovascular morbidity and mortality. Several clinical trials showed reduction of relevant outcomes in studies with diuretics, beta-blockers (BB), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs) AT1 receptor and calcium-channel antagonists (CCAs)151. As monotherapy controls BP in less than 1/3 of hypertensive individuals, most clinical trials used associations of drugs for blood pressure control, demonstrating that the benefits achieved do not depend on the drug classes used.

According to the VI Brazilian Guidelines on Hypertension, treatment should be started with monotherapy in stage 1 patients with low or moderate risk and drug combinations in stages 2 or 3, or stage 1 with high or very high risk (Figure 5.1)119.

Regarding the recommended drug associations, one should always take into account the patients’ comorbidities; however, in general, the best associations in terms of effectiveness are drugs that inhibit the renin-angiotensin-aldosterone system (ACEIs or ARBs) with calcium channel antagonists or diuretics152.

1. Diuretics: are effective in lowering blood pressure levels, showing evidence in reducing morbidity and mortality. Thiazide diuretics (hydrochlorothiazide, chlorthalidone, indapamide) are indicated. Potassium-sparing diuretics (amiloride and triamterene) have low diuretic effect, but when combined with thiazides or loop diuretics, they are useful in preventing hypokalemia153. Spironolactone has greater antihypertensive effect than the other potassium-sparing diuretics, being especially indicated for resistant hypertension cases.

2. Calcium-channel antagonists: are effective in reducing morbidity and mortality. Sustained release drugs are indicated due to the reduction of events and even superiority in reducing stroke154. Dihydropyridines are the most often indicated, as they have greater antihypertensive effect.

3. Beta-blockers: are effective in reducing blood pressure; however, in some meta-analyses, the first and second-generation drugs, when used alone, promoted less protection against stroke in individuals older than 55 years. They are well indicated in special situations such as arrhythmias, coronary artery disease and heart failure. Clinical trials with carvedilol, metoprolol,

Chart 5.2 – Treatment decision-making

Risk category Consider

No additional risk Isolated non-medical treatment

Low additional risk Isolated non-medical treatment for up to 6 months. If goal is not reached, associate medical treatment

Medium, high and very high additional risk Non-drug + drug treatment

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Guidelines



Figure 5.1 – Hypertension treatment algorithm according to the VI Brazilian Guidelines on Hypertension119.

Stage 1 Hypertension Stage 2 and 3 Hypertension

Low and moderate CV risk High and very high CV risk

MonotherapyAll classes of antihypertensive drugs,

except for direct vasodilators

CombinationsTwo antihypertensive drugs of different classes and at low doses

Inadequate response or intolerable adverse events

Increase the monotherapy dose

Change monotherapy Add 2nd drugIncrease association

doseChange drug association

Add 3rd drug

Inadequate response

Add other antihypertensive drugs

bisoprolol and nebivolol have shown significant reduction in cardiovascular mortality and morbidity in patients with heart failure, regardless of age155.

4. ACEIs or ARBs: Both classes are very useful in the treatment of most hypertensive patients, especially in populations with high cardiovascular risk or with comorbidities. Several clinical trials demonstrated beneficial effects in heart failure, in the prevention of cerebrovascular accidents and in patients with diabetes mellitus with renal impairment. ARBs are equivalent to ACE inhibitors in relation to coronary events, but superior in cerebrovascular protection156,157.

5. Other agents: a) aliskiren, a direct inhibitor of renin, showed to be effective in reducing blood pressure levels and useful in combination with diuretics or calcium-channel blockers. However, the association with other ACEIs or ARBs proved deleterious; b) central action agents and alpha-adrenergic blockers are more useful in multiple combinations158.

Blood pressure goals that are recommended according to the “2013 ESH/ESC Guidelines for the management of arterial hypertension” are < 140 mmHg for systolic blood pressure (SBP) and < 90 mmHg for diastolic blood pressure (DBP). An exception is made for diabetic patients, for which DBP < 85 mmHg is recommended. The SBP recommendation for patients with nephropathy and proteinuria is < 130 mmHg159.

Therapeutic targets

Blood pressure goals to be achieved, according to the VI Brazilian Guidelines on Hypertension, are shown in the Chart 5.3119.

6. DyslipidemiaHigh cholesterol can be considered a major modifiable

risk factor for coronary artery disease (CAD)160,161 and its control, mainly of the low-density lipoprotein cholesterol (LDL-C) levels, brings great benefit in reducing cardiovascular outcomes such as infarction and death from coronary heart disease160.

After patient risk stratification (previously discussed), the primary and secondary therapeutic goals to be achieved in the treatment of dyslipidemia are established, according to the overall risk (low, intermediate or high). The primary goal to be achieved is the recommended LDL-C level and the secondary one, the recommended non-HDL (high-density lipoprotein) cholesterol level, calculated by subtracting HDL-C from total cholesterol, representing the serum concentration of atherogenic lipoproteins (Table 6.1). Specific goals are determined for patients at high and intermediate risk. Patients at low cardiovascular risk should have individualized goals according to clinical decision and the reference values of the lipid profile (Table 6.2).

Chart 5.3 – BP goals to be achieved according to individual characteristics

Category Consider

• Hypertensive patients stages 1 and 2 with low and medium cardiovascular risk < 140/90 mmHg

• Hypertensive patients and borderline behavior with high and very high cardiovascular risk, or 3 or more risk factors, DM, MS or TOL

130/80 mmHg

• Hypertensive patients with renal failure and proteinuria > 1.0 g/L 130/80 mmHg

DM - diabetes melito; SM - síndrome metabólica; LOA - lesões em órgãos-alvo por DM - Diabetes Mellitus, MS - metabolic syndrome; TOI – target-organ injuries

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Guidelines



In relation to hypertriglyceridemia, patients with triglyceride levels > 500 mg/dL should receive drug therapy to reduce the risk of pancreatitis. Those with levels between 150 and 499 mg/dL should receive individualized treatment according to the clinical decision, based on cardiovascular risk and associated conditions. There are no proposed goals for HDL-C, for apolipoproteins or lipoprotein (a) [Lp (a)] (Table 6.3).

Non-pharmacological treatment of dyslipidemia

Nutrition therapy, weight loss and physical activity should be recommended to all patients. Taking into account that the serum levels of cholesterol and triglycerides are correlated with increased consumption of cholesterol, carbohydrates, saturated fatty acids and trans fatty acids, patients should be advised on

food selection, preparation, the amount to be consumed and possible substitutions. Dietary recommendations are shown in Chart 6.1. In the treatment of hypercholesterolemia, the reduction in the intake of saturated fatty acids and trans fatty acids and intake of phytosterols (2-3 g/day) have a major impact. Soluble fiber intake has less impact than the previous measures, but has also shown to be effective in reducing cholesterol. Less impressive results are obtained with the increase in physical activity, weight reduction and soy protein intake160,161.

In the treatment of hypertriglyceridemia, the reduction of weight, alcohol, simple sugars and carbohydrate intake has a great impact. Increased physical activity and the replacement of saturated fatty acids by mono- and polyunsaturated ones have a moderate impact on serum levels of triglycerides160,161.

Table 6.1 – Lipid Goals according to cardiovascular risk19

Risk level Primary goal (mg/dL) Secondary goal (mg/dL)

HIGH LDL-C < 70 Non-HDL-C < 100

INTERMEDIATE LDL-C < 100 Non-HDL-C < 130

LOW Individualized goal Individualized goal

* Patients at low CV risk should receive individualized advice, with goals established by reference values of the lipid proile (shown in Table 6.2), with focus on the prevention and control of other CV risk factors.

Table 6.2. – Reference values of lipid proile for adults19

Lipids Values (mg/dl) Category

LDL-C

< 100100 – 129130 – 159160 – 189

≥ 190

OptimalDesirableLimítrofe

HighVery high

Non-HDL-Cholesterol

< 130130 − 159160 − 189

≥ 190

OptimalDesirable

HighVery high

Table 6.3 – Recommendations for the nonpharmacological treatment of dyslipidemia in cardiovascular prevention19

Indication ClassLevel of

evidence

Control LDL-C I A

Meet the recommended LDL-C level (primary goal) I A

No goals proposed for HDL-C I A

Reduce the intake of saturated fatty acids and trans fatty acids, and consume phytosterols (2-3 g/day) and soluble ibers I A

Increase physical activity I A

Reduce body weight and increase the ingestion of soy proteins; replace saturated fatty acids with mono- and polyunsaturated fatty acids I B

Meet the recommended non-HDL-cholesterol level (secondary goal) II A

Use proper therapy when triglyceride levels > 500 mg/dL to reduce the risk of pancreatitis, and use individualized therapy when triglyceride levels are between 150 and 499 mg/dL

II A

No goals proposed for apolipoproteins or lipoprotein(a) II A

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Guidelines



Table 6.4 – Recommendations for the drug treatment of dyslipidemias19


Statins as a irst-choice drug in primary and secondary prevention I A

Use of ibrates alone or in combination with statins for prevention of microvascular disease in type 2 diabetics I A

Association of ezetimibe or resins to statins when LDL-C goal is not achieved IIa C

Association of niacin to statins III A

Use of omega 3 fatty acids for cardiovascular prevention III A

Chart 6.1 – Dietary Recommendations for reducing hypercholesterolemia19

Prefer Consume moderatelyConsume occasionally at low

amounts

• Grains • Whole grains• Reined bread, rice and pasta,

cookies, sugary cereals• Sweet breads, cakes, pies,

croissants

• Vegetables • Raw or cooked vegetables• Vegetables prepared with

butter or cream

• Legumes • All, including soy and soy protein

• Fruit • Fresh or frozen fruit • Dried fruit, jelly, jam, ice cream

• Sweets and sweeteners • Non-caloric sweeteners • Honey, chocolate, sweets • Cakes and ice-cream

• Meat and ish • Lean and oily fish, chicken without the skin

• Lean beef cuts, pork, seafood• Frankfurters, salami, bacon,

ribs, tripe

• Dairy products and eggs • Nonfat milk and yogurt and egg whites• Semi-skimmed milk, white

cheese and skim dairy products

• Yellow, creamy cheeses, egg yolks, full-fat milk and dairy products

• Sauces for cooking and seasoning

• Vinegar, ketchup, mustard, nonfat sauces

• Vegetable oils, light margarines, salad dressing and mayonnaise

• Butter, shortening, pork fat, trans fats, coconut oil

• Nuts and seeds • All • Coconut

• Food preparation • Grilled, cooked or steamed foods • Roast and stir-fried foods • Fried foods

Pharmacological treatment of dyslipidemia

The drugs available for the treatment of dyslipidemias are statins (inhibitors of hydroxy-methyl-glutaryl coenzyme A [HMG-CoA] reductase), ezetimibe, resins or bile acid sequestrants, niacin, fibrates and omega-3 fatty acids. Lomitapide and mipomersen are drugs that have been approved for use in some countries in the treatment of the homozygous form of familial hypercholesterolemia, but not yet in Brazil. New drugs such as PCSK9 inhibitors are currently undergoing phase III clinical trials.

Statins

Statins should be used as the first-choice drug in primary and secondary prevention, as they constitute the most clinical-trial validated therapy in reducing cardiovascular events. There is a reduction in the risk of death from all causes by 10% and CAD mortality by 20% for each 40 mg/dL reduction in LDL-C with statins19,162-165.

The reduction in LDL-C varies greatly between types of statins used and this difference has been primarily related to the initial dose (Figure 6.1). Every time the dose of any of the statins is doubled, the additional mean reduction in LDL-C will be 6% to 7%.

Adverse effects with statins are rare164,165. Myalgia with or without increase in creatine kinase (CK) levels occurs in approximately 10% of patients and may occur weeks or years and after the start of the treatment. CK alterations are observed in approximately 3% of patients and rabdomyolysis is extremely rare164,165. The risk of myopathy can be reduced by avoiding interactions with niacin, fibrates (particularly gemfibrozil), calcium-channel blockers (diltiazem, verapamil), macrolides (azithromycin, clarithromycin, erythromycin), azole antifungals (fluconazole, itraconazole, ketoconazole), anti-retroviral protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir, saquinavir), immunosuppressors (cyclosporine, tacrolimus), nefazodone, sildenafil and digoxin166,167. CK levels up to 5 times the upper limit of normal are considered acceptable. One should consider treatment discontinuation when levels are above this acceptable limit (5 to 10 times the upper limit), as well as in the presence of persistence of muscle symptoms. In these situations, lower doses or other statins may be tried.

A significant increase in liver enzymes (more than 3 times the reference value ) occurs in about 1% of patients, but it is usually reversible, even without therapy interruption167. Regarding liver toxicity, temporary discontinuation is advised with increases higher than three times the reference value

22

Guidelines



of transaminases and permanent suspension in cases with active liver disease or severe hepatic dysfunction. The stable transaminase increases in patients with no evidence of acute illness and no complaints, as frequently observed in hepatic steatosis, are not contraindications for the start of statin therapy.

Due to the previously stated reasons, CK and liver transaminases (especially Alanine transaminase [ALT]) must be measured before starting the treatment and after 6-12 weeks. New measurements can be performed after statin dose modifications, after combination with other drugs with interaction potential or according to clinical criteria.

Ezetimibe

The addition of ezetimibe is recommended when the LDL-C goal is not achieved with statin therapy, remembering that statins should be used at the highest tolerated dose to achieve target LDL-C before choosing combination therapy. Ezetimibe reduces serum levels of LDL-C by 10% to 25% and associated with statins, it decreased cardiovascular events in patients with degenerative aortic stenosis and chronic kidney disease when compared with placebo168,169. Compared with statin monotherapy, a study is currently testing the added benefit of ezetimibe associated with statin.

Resins

Resins can be associated with statins when the LDL-C goal is not achieved despite the use of potent statins at effective doses. However, there is no study that has demonstrated clinical benefit of this measure. The reduction in LDL-C is dose-dependent, ranging from 5% to 30% at doses of 4-24 g/day, which may cause an increase in triglycerides in individuals with severe hypertriglyceridemia

(> 400 mg/dL). In Brazil only cholestyramine is available, tested against placebo, with a 19% reduction in the primary combined endpoint of death from coronary heart disease and myocardial infarction170.

Niacin

Niacin is used to reduce triglycerides and increase HDL-C levels, but no cardiovascular benefits of niacin in combination with statins have been observed in patients within the recommended LDL goal. The Coronary Drug Project170,171,172, performed in the 1970s, demonstrated that treatment with niacin in its crystalline form can reduce the incidence of cardiovascular events172. Treatment with more tolerable formulations, such as the niacin extended-release formulations, reduced medio-intimal thickness even in patients using statins.

However, two recent clinical trials have not demonstrated the benefit of adding niacin to effective statin therapy with or without ezetimibe171,172.

Fibrates

Fibrates are also used to reduce triglycerides and increase HDL-C. There is evidence of microvascular disease prevention (retinopathy and nephropathy) in type 2 diabetic patients with the use of fibrates, either alone or in association with statins173,174.

Regarding cardiovascular events, monotherapy with fibrates has shown inconsistent results in clinical trials and association of fibrate and statins has not demonstrated any benefits. In patients with hypertriglyceridemia, particularly those with low HDL-C, some macrovascular benefit is possible, as suggested in the subgroup analysis, but this possibility requires confirmation.

Figure 6.1. – Mean reduction of LDL-C with statins19,161-163.

20 40 20 4080 10 20 40 80 10 20 40 80 10 20 40 80 5 1 2 410

0

-15

-30

-45

-60

Fluvastatina Pravastatina Sinvastatina Atorvastatina Rosuvastatina PitavastatinaFluvastatin Pravastatin Simvastatin Atorvastatin Rosuvastatin Pitavastatin

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Guidelines



The risk of myopathy increases with the combination of fibrates and statins and simvastatin and other drugs metabolized by cytochrome P450 should be avoided; use gemfibrozil should not be used due to the marked increase in the risk of rhabdomyolysis.

Omega 3 Fatty Acids

Omega-3 (ω-3) fatty acids are polyunsaturated fats obtained from fish oil and certain plants and nut oils. Fish oil contains both docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), but vegetable oils contain predominantly alpha-linoleic acid (ALA). At higher doses (4 to 10 g per day) they slightly reduce triglycerides and increase HDL-C levels, but they may also increase LDL-C and meta-analyses have shown no benefit in the reduction of clinical events175, and, therefore, they are not recommended for cardiovascular prevention.

7. Diabetes The projection of 300 million adults with diabetes

mellitus (DM) in the world in 2030, with the current range of more than 180 million diagnosed individuals, arouses the urgent need to act on prevention at global level. Developing countries have the highest incidences, which account for two thirds of cases worldwide176. In Brazil, regional data indicate high rates of DM prevalence in the adult population, reaching 13.5% in some cities177. The 2010 census indicated 128 million adults, which may represent a current population of up to 17 million individuals with DM. These numbers are increasing due to factors such as population growth and aging, urbanization, sedentary life style and increasing obesity.

U.S. figures in 2012 point to a total of 245 billion dollars in costs, including direct medical costs of 176 billion and 69 billion with the decrease in the productivity of affected individuals178. The cost of treating an individual with diabetes was 2.3 higher than in those without diabetes in the healthcare service. Compared to 2007, total expenditures were 47% higher, according to the same survey.

The metabolic control in individuals with the disease is becoming one of the biggest challenges for public health services179, so the development of effective and viable public health service programs for the primary prevention of type 2 diabetes in the population at risk is necessary to control both the incidence of type 2 diabetes, as well as for secondary prevention of its metabolic complications.

Prevention

Changes in life style, such as diet adjustments180 and aerobic exercises181 have shown benefits in the management of blood glucose and weight. The indisputable association of obesity and overweight with increased prevalence of diabetes puts weight control as the primary target for the control of the diabetes epidemic182. Weight loss is independently associated with the restoration of normal glucose regulation in pre-diabetic individuals, as demonstrated in the Diabetes Prevention Program (DPP) study183. Simple measures such as reducing fat intake to less than 30% of total daily calories and total daily calories with regular physical activity can lead to a decrease of 5-7% of the weight in the long term. The diet should result in a deficit of daily calories from 500 to 1,000 Kcal, which usually results in a weekly loss of 450-900 grams, reaching a total of 8% weight loss in 6 months184.

The recommended physical activity is at least 150 minutes of moderate to intense aerobic activity per week or 90 minutes divided into at least three times a week, avoiding more than two days without physical activity185.

It is worth mentioning that weight loss is recommended for all overweight or obese individuals who are at risk of developing diabetes. Changes in life style are the primary means of reducing the risk, through weight decrease and regular physical activities. Regular physical activity is an important mechanism to maintain the ideal weight and improve insulin sensitivity and glycemic control, favorably affecting complicating factors such as hypertension and dyslipidemia and increased aerobic capacity.

Table 7.1 outlines interventions on diet and physical activity.

Table 7.1 – Interventions on diet and physical activity in diabetes for cardiovascular disease prevention


At least 150 minutes of moderate exercise associated with moderate diet and energy restriction to prevent DM in individuals at risk

I A

Due to the effects of insulin resistance in obesity, weight loss is an important therapeutic goal in individuals at risk of developing DM.

I A

Reducing fats to less than 30% of the energy intake and decrease energy intake in overweight individuals I A

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Guidelines



8. Metabolic syndrome

Metabolic syndrome deinitionThe metabolic syndrome (MS) has received increasing

attention not only by the impact of each of its diagnostic components, but mainly because the presence of cardiovascular risk factors has been increasingly prevalent.

There are several versions of the definition of MS, but adopts the criterion of this Policy will set the positioning of several international organizations about tema186.

The diagnosis of MS requires the presence of three or more of the criteria set out in Chart 8.1.

Prevalence of metabolic syndrome in different

population groups

Information on the prevalence of MS is still limited and incomplete187 and depend on the criteria used for its definition, justifying the implementation of treatment and especially, prevention strategies188,189,190.

In the U.S., analysis of data from the National Health and Nutrition Examination Survey (NHANES, 1988-1994) of 8,814 individuals of both genders older than 20 years showed a prevalence of MS (non-adjusted and adjusted for age) of 21.8% and 23.7%, respectively, according to the criteria of the National Cholesterol Education Program - Adults Treatment Panel III (NCEP - ATP III). An increase in prevalence was observed with age: 6.7% (20-29 years) and 43.5% and 42% (60-69 years and 70 years), with little difference between the genders (24% M and 23.4% F, respectively)189. Data from NHANES of 2003-2006 showed even higher non-readjusted prevalence rates (34%) when compared with 1988-1994: 29.2% in individuals ≥ 20 years. Among adults (20-39 years), the prevalence of MS increased from 10.8% (1988-1994) to 15.6% (2003-2006) in women and 15.7% (1998-1994) to 20.3 % (2003-2006) in men189.

A Finnish study of 1,025 individuals aged 65 to 74 years followed for 13 years assessed the prevalence of MS by six

different diagnostic criteria and found rates ranging from 22.5% (European Group for the Study of Insulin Resistance [EGIR]) to 66.4% (American College of Endocrinology [ACE])191, while a Swedish study in nondiabetic individuals found rates of 21.9%, 20.7% and 18.8% according to the criteria of the International Diabetes Federation (IDF), NCEP-ATPIII and EGIR, respectively192.

In Japan, Nanri et al.192 found that MS prevalence in adult men and women in 2007 of 26.9 % and 9.9%, respectively, while Sakurai et al.194, in cohort studies with 812 participants and using three different diagnostic criteria (IDF, Japanese Society of Internal Medicine [JSIM] and American Heart Association and the National Heart, Lung and Blood Institute [AHA/ NHLBI]), obtained values of 44%, 37.1% and 67.7%, respectively194.

The Transition and Health Impact in North Africa (TAHINA) Project, with 4,654 individuals (1,840 men and 2,814 women) aged 35 to 74 years described an overall MS prevalence of 30 % with the NCEP-ATP III criteria (36.1% in women and 20.6% in men). In both genders, the prevalence increased with age and was higher in residents of urban areas195.

The Bogalusa study assessed young adults aged 19 to 39 years from a semi-rural community in America, with 61% females and 39% males (80% whites and 20% blacks) and found an overall prevalence of MS of 12.2% (14.9% in men and 10.4% in women), with no difference between the several ethnic groups (12.8% in whites and 9.6% in blacks). However, black men had higher prevalence than white women (15.4% vs. 5.8%)190.

In Brazil, the data are still scarce, particularly on young individuals. Literature review of eight studies with adolescents (10-19 years) using the MS criteria of the World Health Organization (WHO) or the NCEP-ATPIII described MS prevalence of 4.2% to 15.4% (NCEP-ATPIII) and from 4.5% to 38.7% (WHO), with triglyceride elevation being the most frequently altered component (4% to 75%), while glucose alterations were less frequently observed196. In the Rio de Janeiro study, the presence of aggregation of several cardiovascular risk factors and MS was also observed and strongly correlated with blood pressure197.

Cardiovascular and Metabolic Risks Associated with MS

The evaluation of patients according to their metabolic profile, with early recognition of associated risk factors, is desirable to identify and treat patients at high cardiovascular and metabolic risk. In general, MS is associated with a two-fold higher risk of cardiovascular diseases such as myocardial infarction, cerebrovascular accident (stroke) and cardiovascular mortality, and one and a half-fold higher risk of death from any cause198.

The risk of developing cardiovascular disease associated with MS has been demonstrated in meta-analyses, with relative risk ranging from 1.53 to 2.18199-201.

The physiopathological mechanism by which MS increases cardiovascular risk is still under debate; however, there is strong evidence that insulin resistance is the main factor. The progression of insulin resistance to hyperinsulinemia

Chart 8.1 – Diagnostic criteria for metabolic syndrome

Criteria Deinition

• Abdominal obesity

• Men • ≥94 cm

• Women • ≥80 cm

• Triglycerides • ≥150 mg/dL

• HDL-cholesterol

• Men • <40 mg/dL

• Women • <50 mg/dL

• Blood pressure

• Systolic• ≥ 130 mmHg or treatment for arterial

hypertension

• Diastolic • ≥ 85 mmHg or treatment for arterial hypertension • Glycemia • Fasting glycemia ≥ 100 mg/dL

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Guidelines



and hyperglycemia triggers peripheral vasoconstriction and sodium retention. There is a higher production of liver levels of triglycerides, low density lipoprotein cholesterol (LDL-C), apolipoprotein B and dense and concentrated LDL-C, a situation that predisposes to atherosclerosis. This unfavorable situation in relation to lipids leads to a systemic prothrombotic and proinflammatory state. With central obesity, adipocytes secrete mediators such as tumor necrosis factor alpha (TNF-alpha) and leptin, and, independently, obesity leads to hypertension, dyslipidemia and increased insulin resistance186.

There is a strong association between MS and the development of diabetes, which intensifies as the number of MS components increases. The relative risk of developing diabetes is 2.1 according to the definition of the ATPIII and 3.6 using the WHO definition, in which insulin resistance should be present202-206.

Risk Factors for Metabolic Syndrome

Several risk factors for the development of MS have been identified by cross-sectional, prospective and case-control studies, with important differences being found according to the definition used in the diagnosis207.

Some factors are associated with the prevention of a component of MS, without necessarily preventing the other components or reducing the incidence of the syndrome as a whole. The frequency of pre-school activities, for instance, was associated with a lower incidence of hypertension in adult life, but did not protect against the other MS components207.

Some studies identified multiple determinants of MS, including age, male gender, low educational level, physical inactivity, family history of diabetes and hypertension and inadequate protein intake208.

Poor physical fitness and excess adiposity during adolescence also correlated with increased risk for MS in the adult life209. Many studies correlated sedentary behavior with MS risk210. Nutritional factors seem to be related to MS. The frequent consumption of dairy products, such as milk and yogurt, appears to protect against the development of the syndrome211. Excessive consumption of fructose as an artificial sweetener is related to the development of MS in humans and animals212. Soft drink consumption, even the sugar-free type, has also

been associated with increased risk of MS213. However, fruit consumption seems to protect against MS212.

Several ethnic and environmental factors appear to modulate the impact of some of the risk factors for MS. In the Tunisian population, the prevalence was higher among women than among men. In both genders the prevalence increased with age, but the impact of this factor was higher among women. The urban population had a higher prevalence than the rural one, with greater risk among individuals with higher educational level214.

Filipino women living in the United States showed a greater impact of waist circumference as a component of MS. Women of the same ethnic group living in the Philippines showed low levels of HDL cholesterol as the factor of greatest impact on MS216.

Several psychological disorders also appear to contribute to MS. Depressive symptoms in North Americans police officers were correlated with higher prevalence of MS217. In a case-control study performed in India, it was also demonstrated a higher prevalence of MS among patients with schizophrenia than among controls218.

Prevention of Metabolic Syndrome

There are scarce data in the literature regarding the prevention of MS through pharmacological or non-pharmacological measures in the same theoretically healthy population. The experts’ recommendations pointed out that prevention strategies for MS must be the same used in the non-pharmacological treatment of the syndrome.

For individuals without MS or type 2 diabetes mellitus (DM2) or cardiovascular disease, but with glucose tolerance impairment or the presence of some components of MS (individuals with metabolic risk) there is evidence that changes in life style may prevent MS and/or DM2 (Table 8.1).

Weight reduction

For those with metabolic risk that are overweight or have abdominal obesity, a reduction of 5% to 10% of total weight in one year followed by weight loss maintenance is recommended. Those who are not overweight should maintain their weight. Weight reduction should be achieved

Table 8.1 – Interventions in metabolic syndrome for cardiovascular disease prevention


The reduction of 5% to 10% of weight in one year is recommended, followed by weight loss maintenance I B

Diet low in total and saturated fats, as well as trans-fats, which includes adequate amounts of iber I B

Physical activity for a period of no less than 30 min/day, preferably 45-60 min/day, 5 days/week I B

Individuals with impaired glucose tolerance undergoing drug therapy may show more significant reduction in the incidence of MS or DM2

I B

For individuals with metabolic risk and waist circumference higher than the recommended limits, a reduction of 5% to 10% of weight in one year is recommended

IIa B

The ingestion of less than 7% of total calories from saturated fat and less 200 mg/day of cholesterol in the daily diet is suggested

IIa B

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by means of a formal program changes life style and physical activity must understand and caloric intake adequate219-222.

Abdominal obesity

Individuals with metabolic risk and abdominal circumference higher than the recommended limits should follow the recommendations of the previous item223-225.

Healthy diet

It is recommended that all individuals, with and without metabolic risk, have a diet that is low in total and saturated fat, as well as trans-fat, which includes adequate amounts of fiber. The intake of less than 7% of total calories from saturated fat and less than 200 mg/day of cholesterol in the daily diet is suggested225-227.

There is no consensus on the optimal amount of carbohydrates that the diet should contain. It is recommended that individuals with metabolic risk substantially increase the amount of fibers, unprocessed grains and unsaturated fats in their diets and avoid foods with a high glycemic index225 -227.

Physical exercise

A regular program of moderate physical activity is recommended for patients with metabolic risk, which should be performed for a period of no less than 30 min/day, but preferably 45-60 min/day, for at least five days / week. These activities can be brisk walks or more extenuating exercises223 -227.

Changes in life style versus drug therapy

Individuals with impaired glucose tolerance may have more significant reduction in the incidence of MS or DM2 using an adequate diet and exercise program, when compared to the ones that use pharmacological therapy (metformin or glitazones). The main reasons for choosing changes in life style rather than the use of drugs in these patients with glucose intolerance include: changes in life style are at least as effective in reducing the incidence of metabolic syndrome or type 2 diabetes as drugs; there are few data in the literature about the long-term safety of the use of these drugs in this group of individuals, the cost-effectiveness of drug therapy in this population has not been adequately evaluated223-227.

9. Physical activity, exercise and sportsPhysically active individuals tend to be healthier, have

higher quality of life and life expectancy 228. Physical activity, physical exercise and sports integrate the medical approach for the prevention of cardiovascular diseases (CVDs).

Concepts and most relevant expressions

Physical activity, exercise and sports are correlated, but distinct terms. Physical activity can be defined as any bodily movements produced by skeletal muscles that result in energy expenditure229. In practical terms, it can be classified into occupational or work-related (including housework), transportation or leisure. The leisure physical activity

encompasses those eminently recreational or sports-related (sports practice), with rules, scores, winners, losers and activities focused on physical fitness and health promotion. This last subgroup of physical activity, more structured and with a clearly defined purpose of performance and/or health improvement, is conventionally called “exercise” (for sub-classifications or types of exercise, consult other specific guidelines of the Brazilian Society of Cardiology [SBC])230. According to this concept, the cardiologist will very likely prescribe exercise, and not just physical activity to their patients.

Some degree of physical activity is necessary for the individual’s survival and autonomy. While there is a clear trend of young individuals to move more than the elderly, levels of physical activity, specifically exercise, vary from person to person and this variability increases with advancing age. Thus, regular physical exercises begin gradually, from immobility to higher levels, with longer and more frequent durations231.

Individuals are classified into five options: sedentary (or very little active or inactive), somewhat active, moderately active (or simply active), more or very active and very active (or exceptionally active). Tables 9.1 and 9.2 show the recommended levels of weekly physical exercise for health promotion and illustrate examples of how to classify the patterns of exercise and sports for a child or adolescent, the latter incorporating the matter of the need to define separate criteria according to different age ranges and the estimated average energy expenditure per hour (MET/h) in several examples of physical activity, exercise and sports situations. Further details and suggestions for a more objective quantification of the patterns of exercise and sports in a given patient can be found in another SBC publication232.

Physical fitness is characterized by a series of conditions that allow the individual to perform their daily activities and have sufficient physical capacity to exercise or be physically active229. Physical fitness comprises five components: aerobic status, muscle strength/power, flexibility, balance and body composition.

Major Acute and Chronic Effects of Exercise

For a more objective analysis of the beneficial effects of physical exercise for health, they can be divided into acute (or responses) and chronic (or training)235. The acute effect is one that dissipates quickly and can be an immediate action after a single session or last for up to 24 hours (thus being classified as subacute). The improvement in the flow-mediated response regarding the endothelial function is an example of a single acute effect of the exercise session. The chronic effect is achieved through repeated acute/subacute effects. It can be evaluated at rest, even some time after the last exercise session. The bradycardia observed in athletes that practice predominantly aerobic modalities is an example of a chronic effect. On the other hand, the repetition of responses may generate a chronic effect, such as the decrease in blood pressure levels.

Epidemiological Rationale of Physical Activity BeneitsThere is consistent epidemiological evidence on the

relevance of aerobic physical fitness for health233-239, indicating that the components of aerobic fitness, together or separately, may be associated with clinical prognosis and life expectancy

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Guidelines



Table 9.1 – Recommended levels of physical activity for health promotion and maintenance (adapted from Powell KE et al.228)

Characteristics of the exercise Health beneits Comment

< 150 min/week of mild to moderate intensity Some Some exercise is certainly preferable to a sedentary life style

150-300 min/week of moderate intensity Substantial Longer duration and / or higher intensity exercise confers greater beneits

> 300 min/week of moderate to high intensity AdditionalCurrent scientiic information does not clearly deines an upper limit for the

beneits or to become harmful for an apparently healthy given individual

Table 9.2 – Examples of Physical Exercise Proile Classiication in childhood (adapted from Balassiano DH et al.232)

Score Deinition Childhood/Adolescence

0 Sedentary or very little active Eventual cycling, frequent absenteeism from school physical education

1 Somewhat active Normal attendance at physical education classes and short and intermittent periods of sports or dancing practice

2 Active or moderately active Regular participation, most of the time, in small gyms or dance or ighting classes in gyms and itness centers

3 More or very active Regular and frequent participation in several sporting activities on most days of the week

4 Very active and competitiveParticipation, during most of the time, in trainings and/or competitions or regular and frequent practice of

predominantly aerobic exercises

Chart 9.1 – Main effects of exercise

AcuteEndothelial fucntionCardiac outputMuscle blood lowCoronary blood lowProteção enzimática antioxidativaInsulin sensitivityBaroreceptor sensitivityLipolysis

ChronicEndothelial fucntionMaximum VO

2

Telomere lengthAntioxidant enzymatic protectionInsulin sensitivityBaroreceptor sensitivityJoint lexibility and mobilityMuscle mass, strength and power

Resting metabolic rateVasoactive substances (bradykinin, NO)Growth hormoneProtein synthesis

Better control of body weightBone massTrabecular bone structureNitrogen economy (protein-sparing effect)

GlycemiaAutonomic systemArterial hypertensionInlammatory markersPostprandial hyperlipemiaPulse wave velocityHormones ghrelin and NP γ (appetite regulators)

Glycated hemoglobinResting and submaximal exercise heart rate Pulse pressure in exerciseAutonomic systemArterial stiffnessLipemiaRisk of degenerative cognitive diseases (dementia, Alzheimer’s)Anxiety and symptoms associated with depressionRisk of falls in elderly

VO: Oxygen consumption; NO: nitric oxide.

of middle-aged and elderly individuals240,241,242. This ratifies the recommendations of national243 and international244 guidelines, contemplating the regular practice of aerobic exercises combined with muscle strength ones, such as weight lifting. Additionally, stretching and flexibility exercises should be part of a more complete and comprehensive program245.

Regarding the regular practice of physical exercises, the greatest benefit occurs when sedentary individuals are compared with those that perform no or only very little exercise, as the positive impact of abandoning the sedentary life style is very significant. However, when the varying degrees

of aerobic physical fitness are compared in an increasing scale, one can observe the decreased risk of cardiac death and death from all causes. The higher the level of aerobic fitness, the lower the risk of overall and cardiovascular mortality and morbidity in both healthy individuals and in patients with CVD233,234,236,238,243.

Several studies have identified the effectiveness of regular exercise on the prevention of hypertension and on blood pressure levels246 in patients with systemic hypertension247, probably due to a more favorable autonomic modulation and local vasodilator effect on the smooth muscle of the arterial wall. These beneficial

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Guidelines



effects occur and are added to those of the antihypertensive drugs, often resulting in a reduction of the medication dose. The effects of reducing blood pressure through exercise occur immediately after and last up to several hours after it. Thus, similar to what occurs with the drugs, this action on the cardiovascular system needs to be repeated periodically for the benefit to be maintained chronically. In recent years, in opposition to past dogmas, performing muscle strengthening exercises also became accepted and even recommended within the broader approach of physical exercise for CVD prevention248. Recent evidence suggests that dyslipidemic individuals with higher cardiorespiratory fitness, even without the use of statins, have a lower risk than those with lower fitness using the medication. Those with higher aerobic fitness that used statins showed less mortality from all causes249. Recently, the hypothesis that the concomitant use of statins would have the potential to reduce some of the benefits resulting from physical training has emerged250.

Risks of Physical Activity, Physical Exercise and Sports Practice

Healthy individuals have an extremely low risk of dying as a result of regular exercise practice. A study of more than 20,000 physicians carried out for a mean time of 12 years found that the risk of a fatal event in asymptomatic individuals between 40 and 84 years of age was approximately 1/1.5 million exposures to exercise (during and within 30 minutes immediately post-exercise)251. Thus, the recommendation to be physically active is very safe. However, only 30% of our population exercises regularly as recommended252. The use of the joint guidelines of the Brazilian Societies of Cardiology and Exercise Medicine and Sports253 is recommended, which establish objective and detailed criteria for pre-participation assessment in exercise programs or in sports activities appropriate for different age groups and for the presence or absence of coronary risk factors and/or CVD.

Recent reviews and some observational studies253,254 have identified increases in biochemical indicators and alterations in cardiac images, suggesting the presence of myocardial dysfunction induced by long training periods and repeated competitions in long-lasting aerobic events (usually more than 4 hours) in a small portion of these individuals255,256.

Clinical and/or demographic characteristics should be identified that can indicate a higher probability of developing these alterations and whether there is a safe limit regarding the amount and intensity of exercise253,254.

Physical Exercise Prescription

Exercises may be prescribed concerning their characteristics such as type (aerobic, muscular strength, flexibility), modality (walking, running, biking, dancing), duration (performance time), weekly frequency and intensity adjustment.

Aerobic exercises should be performed at least five times a week, for at least 30 minutes, continuously or with intervals, in order to significantly reduce cardiovascular events and contribute to risk factor control253.

In general, the intensity should be moderate, which can be prescribed using the methods listed in Table 9.1. Previously sedentary patients can start exercising at the lower limit of the prescribed intensity and increase it with regular practice253. As for physically active patients, according to individual assessment, they can perform exercises at more intense levels, with a minimum duration of 20 minutes, three times a week, being a safe activity and one that brings additional benefits.

The muscular resistance or strength training exercises are also beneficial for cardiovascular and musculoskeletal health. They should be performed at least twice a week, at moderate intensity, involving large muscle groups of the upper limbs, trunk and lower limbs. Their performance can be carried out with free weights, ankle weights, resistance bands and weight machines. The intensity of the load can be adjusted so that one is able to perform the exercises with 8 to 15 repetitions per series253.

Stretching and flexibility exercises can result in musculoskeletal benefits, quality of life improvement and prevention of falls in elderly individuals and may even be performed with these purposes. In these exercises, one attempts to achieve maximum range of motion, to the point of mild discomfort and statically maintaining the position for 10 to 30 seconds. The types of stretching can be general or individualized, based on specific assessments such as the Flexitest25.

Table 9.3 – Methods of prescription of moderate-intensity aerobic physical exercises253

Method Description

Subjective sensation of effort (Borg)Performing the exercises with self-perceived exertion as “medium/moderate, or somewhat heavy.”

2 to 4 in the Borg scale 0-10 or 10-13 in the scale 6-20.

Speech TestingPerforming the exercises at an intensity where one feels somewhat breathless, but controlled, so that one can complete a

sentence without pausing.

Using the HR peak percentagePerforming the exercises at an intensity that reaches 60% to 85% of peak HR*

Target HR=peak HR x percentage

Use of HR reserve (Karvonen)Performing the exercises at an intensity that reaches 50% to 80% of HR reserve (HR peak * - HR rest)

Target HR = HR rest + (HR peak* - resting HR) x percentage

Use of ventilatory thresholds in Cardiopulmonary Testing

Performing the exercises at an intensity between the ventilatory thresholds 1 and 2 (anaerobic threshold and respiratory compensation point)

* It is preferable to use the HR peak obtained at a maximal exercise test, as there may be individual variations that can lead to errors in predicting HR by age, especially in patients using medications with negative chronotropic effect4,6.

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Guidelines



The performance of aerobic and non-aerobic fitness evaluations allows a better prescription of physical exercise to attain the best results and, through risk stratification and search for occult heart disease, minimize the risks of greater intensity exercises257.

The initial assessment consists of clinical history, physical examination and electrocardiogram (ECG). More detailed assessments should be individualized, with exercise stress test, cardiopulmonary test, anthropometric, muscle strength and flexibility assessment253. At the initial assessment, we can quantify the functional deficit against the desirable level and establish goals to be reached257,258. It is essential for the patient to undergo re-evaluation, in order to encourage their dedication, as well as measure their evolution during the period. The benefits are proportional to the achieved gains257-259.

Formal and Informal Physical Activity: Strategies to Encourage Referral, Implementation and Adherence

Although health benefits occur with relatively low-intensity activities, resulting from informal everyday actions such as walking, climbing stairs, cycling and dancing, ideally they should also occur with the regular practice of physical exercises (formal activities), which makes it easier to achieve the optimal amount of physical activity, equal to or more than 2,000 kcal per week (Chart 9.2)260.

The referral to structured services of physical activity and cardiac rehabilitation is very important and can significantly impact the health of the population261.

It is necessary to implement comprehensive strategies established through simultaneous actions, such as, for instance, increased physical activity in school programs; transportation policies and systems that favor displacements through walking, cycling and public transportation; public education, including educational campaigns for the population; sports organization at several levels (school, work, community, etc.), with proposals that encourage and enable the practice of sports throughout life, from childhood to old age261.

10. Psychosocial risk factors

Deinitions and impactLow socioeconomic status, lack of social support, stress at

work and in family life, depression, anxiety, hostility and Type D personality are psychosocial risk factors for cardiovascular diseases (CVDs) that hinders adherence to a healthy life style, guidelines and treatments. Often, several psychosocial risk factors coexist. Thus, subjects or populations of low socioeconomic status and/or with chronic stress are more likely to experience depression, hostility and social isolation. Furthermore, CVDs can weaken patients and trigger disorders such as depression and anxiety, creating a pernicious cycle. Among the mechanisms connecting psychosocial factors with CVDs are inappropriate behaviors (inappropriate life style and poor treatment adherence), barriers to health care access and biological alterations (on endocrine, autonomic, hemostatic, inflammatory, endothelial activity, etc.)262.

Socioeconomic status: several prospective studies and systematic reviews have shown that men and women with low socioeconomic status, low educational level, low income, low social status jobs, low social support or living in poor residential areas have increased cardiovascular risk263.

Depression: several systematic reviews and meta-analyses have shown that the clinical symptoms of depression and depressive mood increase the incidence and worsen the prognosis of coronary artery disease. Perceived social support seems to reduce, and the lack of it, to increase the negative influence of depression264,265.

Anxiety: large epidemiological studies indicate that panic attacks increase the risk of cardiovascular event incidence, whereas anxiety, generalized phobia and panic attacks can worsen the evolution of established CVDs. In spite of some contradictory data, two recent meta-analyses have confirmed that anxiety is an independent risk factor for the incidence of coronary artery disease and adverse events after myocardial infarction266.

Chart 9.2 – Time required for a 70-kg individual to achieve weekly caloric expenditure of 2,000 kcal in some activities (approximate values )

Activity Time per week Time per day (7x week) Time per day (5x week)

Walking on level surfaces 6h 50min 1h10min

Bike riding 7h30min 1h05min 1h30min

Jogging 3h30min 30min 40min

Running 2h 20min 25min

Gardening 4h40min 40min 1h

Dancing 9h20min 1h20min 1h50min

Shopping 8h 1h10min 1h35min

Swimming (slow crawl) 3h40min 30min 45min

Swimming (fast crawl) 3h 30min 35min

Cleaning carpet or rug 10h30min 1h30min 2h10min

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Hostility and anger: hostility is a trait of personality characterized by distrust, anger and tendency to engage in aggressive and maladaptive social relationships. A recent meta-analysis confirmed that hostility and anger are associated with increased risk of cardiovascular events in both healthy subjects and patients with CVDs. Patients with CVD who suppress anger have an increased risk of adverse cardiac events267.

Type D personality: type D personality (“distressed”) involves a permanent tendency to show negative emotions (negative affectivity) and social inhibition. The Type D personality is associated with worse prognosis in patients with CVD, regardless of depressive symptoms, stress and anger268.

Assessment of psychosocial risk factors269

As previously seen, psychosocial factors increase the vulnerability to diseases and thus, their evaluation is essential in planning prevention according to the individual’s risk profile270. Yet, there is scant evidence on the benefits of including this assessment into routine care. Standardized tools and questionnaires to assess anxiety, depression, hostility, socioeconomic status, social support, psychosocial stress and Type D personality that have been validated in our country are available. As a practical option, a simplified evaluation can be carried out by asking a few questions, as follows.

Low socioeconomic status

What is your educational level?

Are you a blue-collar worker?

Work and family stress

Can’t you accomplish your tasks at work?

Is the reward for your efforts inadequate?

Do you have serious problems with your spouse?

Social isolation

Do you live alone?

Do you miss having a close partner?

Depression

Do you feel down, depressed or hopeless?

Have you lost your interest and pleasure in life?

Anxiety

Do you frequently feel nervous, anxious or on edge?

Do you often feel unable to stop or control your worries?

Hostility

Do you often feel angry over small things?

Do you often feel uncomfortable with other people’s habits?

Type D personality

Do you often feel anxious, angry or depressed?

Do you avoid sharing your thoughts and feelings with others?

Significance of Interventions on the Psychosocial Risk

Factors269

Changing behaviors is a complex matter, as it involves individual, cultural and environmental aspects, among others. Thus, it is essential to adopt simple and effective strategies and, especially among them, the multimodal

behavioral interventions and appropriate, simple and understandable communication.

Cognitive-behavioral methods: are recommended as they are effective in providing support to people wishing to adopt a healthy life style. However, there is limited evidence to determine the most effective interventions for specific groups regarding age, gender and socioeconomic level, for instance.

Social support can help people adhere to healthy habits and medical advice, and are particularly important to explore each patient’s experiences, thoughts and concerns, prior knowledge and everyday life circumstances. Individualized counseling is the basis to obtain motivation and commitment on the part of the patient.

Decision-making should be shared with patients and caregivers. A crucial step is to help the individual set realistic goals that can be further expanded.

For individuals at high risk of CVD multimodal interventions are indicated, integrating education about a healthy life style and medical resources, physical activity, stress management and counseling about psychosocial risk factors. Individuals of low socioeconomic status, the elderly or females may need individualized programs to meet their specific needs for information and emotional support.

Whenever possible, the multimodal treatment must be carried out with doctors, nurses, psychologists and experts in nutrition, cardiac rehabilitation and sports Medicine.

Adequate communication: it must follow some principles such as:

• allow enough time to create a good relationship;

• acknowledge the individual’s view of the disease and contributing factors;

• encourage the expression about worries and anxiety, self-assessment and motivation for successful behavior change;

• use the patient’s language and be supportive of each improvement in life style;

• check whether the individual understood the guidelines and have all the support needed to follow them;

• recognize the difficulty to change lifelong habits and that sustainable gradual change can be more efficient than rapid changes;

• accept the need for long-term support and repeated efforts to encourage and maintain life changes;

• make sure that all health professionals involved provide consistent information.

The European guidelines recommend 10 practical strategic steps to increase the efficiency of counseling for behavioral changes, as follows.

“Ten strategic steps” to improve counseling for behavioral

change

1. Develop a therapeutic alliance.

2. Advise all individuals at risk or with CVD.

3. Help individuals understand the association between health and behavior.

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Guidelines



4. Help individuals assess the barriers to behavior change.

5. Obtain commitments from individuals to promote behavior change.

6. Get individuals involved in the identification and selection of risk factors to be modified.

7. Match strategies, including strengthening individual capacity for change.

8. Design a life style modification plan.

9. Involve the healthcare team whenever possible.

10. Monitor progress during follow-up.

Interventions on depression, anxiety and distress: the treatment of these conditions improves quality of life and should always be considered, as they are safe in cardiac patients. However, conclusive evidence is still lacking about their influence on cardiovascular outcomes, even for depression, which has been the most extensively studied271,272.

Stress management programs improve the well-being, risk factors and CVD outcomes. Interventions to control hostility in coronary patients may lead to decreased levels of behavioral hostility and depression, improves physiological parameters (autonomic response, reactivity to mental stress), strengthening the social support and life satisfaction273. Recently, a program of stress reduction for women prolonged life regardless of other prognostic factors274.

Programs in the workplace aimed to improving autonomy and increase control can reduce stress for workers of all hierarchical levels273.

Future Directions

Despite the lack of definitive evidence, everything suggests that psychological interventions to address psychosocial stress and promote healthy behaviors can contribute to the prevention and control of CVDs. Therefore, they should be implemented and properly assessed to produce data that allow the development of more effective treatment strategies.

Adherence to cardiovascular disease prevention strategies: life style and medication

Definition

Permanent adherence is defined as the measure the behavior of an individual in terms of taking the medication as the recommended by the health care provider and persistence

as the overall duration of treatment during which patients continue to take the prescribed medications274. Persistence is particularly important for the control of chronic (such as heart failure) and/or asymptomatic conditions (such as hypertension and dyslipidemia).

Impact

Several studies have shown that adherence to the medication by high-risk individuals with CVD is low, with worse outcomes and higher healthcare costs. For instance, months after the acute myocardial infarction (AMI), 25%-30% of patients stop taking at least one medication, with a progressive decline in adherence over time. After one year, only 50% of patients report the use of statins, beta-blockers (BBs) and antihypertensive drugs. The PURE study275 showed that the use of antiplatelet agents, BBs, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and statins in individuals with a history of coronary artery disease (CAD) or cerebrovascular accident (CVA) is low worldwide, especially in low-income and rural areas.

Causes

Adherence and persistence are dynamic and multifactorial processes that require continuous attention and long-term interventions. The World Health Organization (WHO) classifies them into five major groups of factors that influence poor adherence276.

• Health system - low quality of care; little knowledge about the medication and/or low acceptance of counseling; lack of appropriate communication (e.g., complex or confusing instructions), lack of access to health care and lack of care continuity.

• Patient’s condition - chronic asymptomatic disease, mental (such as depression or cognitive impairment) or physical comorbidities that cause dependence (such as problems with vision or mobility), psychological/behavioral factors (lack of awareness and motivation about treatment, impulsivity), younger age group.

• Treatment - complexity of the therapeutic regimen, adverse effects.

• Socioeconomic factors - low literacy level; costs of medication, lack of social support.

• The causes of poor adherence were also classified as predictable (low literacy level, lack of compliance with the first prescription, lack of response to treatment, irregular

Table 10.1 – Class of recommendation and level of evidence when addressing psychosocial factors in the primary prevention


Behavioral change with cognitive-behavioral strategy (motivational) I A

Integration of education and motivational strategies with multidisciplinary team whenever possible I A

Psychiatric or psychological consultation for cases of more signiicant disorder I C

Assessment of psychosocial risk factors IIa B

Pharmacological and psychotherapeutic treatment in patients with depression, anxiety, hostility of great impact aiming at better quality of life, despite the lack of evidence

IIb B

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acquisition of drugs, costs) and unpredictable (severe mental illness, severe adverse effects)276.

These factors tend to agglutinate and bring difficulties. For instance, complex medication regimens are often necessary in patients with asymptomatic chronic disease or multiple risk factors, unmotivated patients and those that lack proper perception about treatment reasons and regimens. Another complicating factor is the association between disease/cardiovascular risk factors and cognitive alterations277, as well as between depression and cognitive decline278.

Evaluation

The identification of patients with poor adherence is difficult. The measurement of adherence and/or persistence has obstacles. It is based on self-report, use of questionnaires or tools such as the Morisky scale (Chart 10.1)279, medical reports for the Monitoring System, “smart” packaging, pill counting records, pharmacy records and serum concentrations of drugs. In most studies adherence and/or persistence were measured by self-report, with obvious limitations.

It is known that adherence depends on the time of evaluation. It is higher in the period within five days before and after contact with the healthcare provider (“white coat adherence”), but it usually decreases significantly within 30 days. This knowledge influences intervention strategies to improve adherence.

The European Prevention Guidelines strongly recommend “that physicians assess adherence and identify the reasons for non-adherence, to adopt additional individualized interventions”.

Interventions

Many interventions have been developed and evaluated, but most have produced only modest results280,281.

A recent systematic review of interventions to improve adherence in CVDs and diabetes, focused on the mechanism of transferring information to patients, concluded that the highest success rates were obtained with the following: electronic interventions; personal intervention made by pharmacists in a place of drug distribution, and personal intervention directed at patients at the time of hospital discharge283.

Recently, a careful review of community interventions used in patients with hypertension, dyslipidemia, congestive heart failure or ischemic heart disease found that behavioral interventions show greater success in relation to educational strategies282. Behavioral strategies include motivational counselling, self-monitoring (using daily records, drug packages with calendars, electronic reminders and alerts), positive reinforcement (e.g., digital feedback mechanisms, trends, incentives and rewards) and partnerships with providers and support groups on the web. It is worth mentioning that this review mentioned only one study carried out in our country280.

In addition to the relative scarcity of available data, important differences should be considered between research and the real world (such as type of patient, physician profile, motivation, monitoring, and follow-up), which can promote, in clinical practice, inferior results than those obtained in researches.

The implementation of clinical strategies to improve adherence (Chart 10.2) should employ evidence-based strategies in an integrated manner and consider the peculiarities in each case. Their goal should be shared and involve all members of the healthcare team, the patient, family members, providers, community contacts and health policy makers. Local strategic actions, even if restricted, can bring results and knowledge276.

Low compliance/persistence requires a multifaceted solution. Many interventions could, if effectively implemented, have an impact on public health improvement. An initial step is to search for solutions to some of the key issues involving representatives of the government, industry (pharmaceutical,

Chart 10.1 – Morisky medication adherence scale279

1. Do you sometimes forget to take your medicine?

2. In the past 2 weeks, were there any days when you did not take your medicine?

3. Have you ever cut back or stopped taking your medicine without telling your doctor because you felt worse when you took it?

4. When you travel or leave home, do you sometimes forget to bring along your medicine?

5. Did you take all your medicines yesterday?

6. When you feel like your symptoms are under control, do you sometimes stop taking your medicine?

7. Do you ever feel hassled about sticking to your treatment plan?

8. Do you often have dificulty remembering to take all your medicine?

Chart 10.2 – Clinical strategy to improve adherence276

Estratégias para melhorar a adesão

• Simplify the dosage • Decrease the number of tablets and the daily doses

• Decrease costs • Lower-cost drugs • Generic Drugs• Government subsidies and low-cost

programs

• Adequate communication

• Provide clear information on treatment beneits, possible adverse effects and duration

• Evaluate, without judging or criticizing, the presence of poor adherence

• Actively check for possible side effects (e.g., sexual dysfunction, cough, bleeding)

• Avoid using technical terms and overwhelming the patient with too much information

• Behavioral strategies • Incorporate the use of medications to patients’ routines, adjusting the dosage to activities, mealtimes and time when patients usually go to sleep

• Use pill-boxes, daily alert electronic devices, packaging with calendars

• Internet support groups• Positive reinforcement (incentives,

rewards)• Give instructions on self-monitoring• Motivational counseling

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Table 10.2 – Classiication of recommendation and level of evidence of adherence to strategy in cardiovascular prevention, lifestyle and medication

Recommendation class level of evidence

Assess and identify the causes of lack of adherence to deine the proper orientation I A

Use behavioral and motivational strategies for patients with persistent lack of adherence IIa A

packaging), insurers, employers, service providers and patients. The main shortcoming has been the incapacity to measure and monitor adherence in routine care276.

The technology that allows continuous exchange of information between patients and providers can be an important tool. Incentives, including financial ones, to patients and providers should be considered.

11. Childhood and Adolescence

Dyslipidemia

Epidemiology in Brazil

Brazilian population studies have demonstrated, according to region and criteria, prevalence of 10% to 35% of dyslipidemia in children and adolescents283.

Screening

The measurement of serum lipid profile in children should occur after 2 years old, as until this age, a higher intake of fat is necessary for myelination. Before that, cases must be analyzed individually, according to concomitant diseases, therapeutic measures and family history284.

The lipid profile should be screened in children between 2 and 10 years when:

• they have male family members (parents or grandparents) with a history of ischemic heart disease before 55 years and females before 65 years;

• they have parents with total cholesterol levels higher than 240 mg/dL;

• they have other risk factors such as hypertension, obesity, smoking, diabetes mellitus (DM), were born small for gestational age;

• have diseases that course with dyslipidemia (human immunodeficiency syndrome, chronic cholestasis, hypothyroidism, nephrotic syndrome, obesity, chronic inflammatory diseases);

• use drugs that alter the lipid profile (valproic acid, beta-blockers, smoking, oral contraceptives, corticosteroids, parenteral nutrition, amiodarone);

• have clinical manifestations of dyslipidemia (xanthoma, xanthelasma, corneal arcus, recurrent abdominal pain, pancreatitis).

After 10 years of age, every child should have total cholesterol levels measured at least once, regardless of the presence of risk factors.

Reference values

The reference values for lipids and lipoproteins in children and adolescents are described in Table 11.1285.

Treatment

In most cases, dyslipidemia is caused by poor life habits: poor diet (high in saturated or trans-fats) and sedentary life style. Obesity also has an adverse metabolic effect, with increase in levels of triglycerides and low-density lipoprotein cholesterol (LDL-C) and decrease in high-density lipoprotein cholesterol (HDL-C), in addition to altering the lipid subfractions, increasing the concentration of the pro-atherogenic fractions286.

Changes in life style286

A healthy diet, of adequate quality and quantity for age, is the basis of dyslipidemia prevention in children, except in cases of familial hypercholesterolemia, which require specific approach. It consists in the most varied, balanced diet possible regarding amounts of proteins, carbohydrates and fats. One should give preference to natural vegetable fats, monounsaturated or polyunsaturated (vegetable oils and almonds) plant. It is recommended to avoid fried foods, processed foods rich in trans-fats and visible fat from meat and skin from poultry. It is also very important to prefer foods rich in insoluble (fruits, vegetables and whole grains) and soluble fibers (legumes, fruits rich in pectin and whole grains). To facilitate the nutritional advice given to the population, it is suggested to use, whenever possible, whole grains and five servings of fruits or vegetables a day.

In the treatment of dyslipidemia, there are two phases of the diet according to the concentration of lipids and lipoproteins in the blood.

• Type I Diet: up to 30% of calories from fat, up to 10% of saturated fat and 100 mg/1,000 cal of cholesterol (maximum 300 mg/d).

• Type II Diet: up to 20% of calories from fat, up to 7% saturated fat and 60 mg/1,000 cal of cholesterol (maximum 200 mg/d).

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Guidelines



When it is necessary to prescribe this diet, the child or adolescent should ideally be accompanied by a nutritionist, due to risk of impaired growth or development. Recent studies have shown benefits of a vegetarian diet at any age, as long as it is balanced, to foster proper growth and development and lower the risk of developing noncommunicable chronic diseases, including atherosclerosis287.

Physical activity should be encouraged, as an active daily routine, as well as with scheduled or supervised activities. Every child or adolescent must practice at least 30 minutes daily of moderate activity. At the population level, the practice of unstructured recreational activity should be recommended. The more varied and playful is this physical activity, the greater the chance that this practice will continue throughout adolescence and adulthood286.

Drug therapy

The lipid-lowering therapy may be initiated after 8 years of age, except in very severe cases, after individualized assessment. Figure 11.1 illustrates the ideal flow of conduct in the screening and treatment of dyslipidemia

in children and adolescents, and Figure 11.2 shows the algorithm of statin treatment in cases when drug therapy is necessary288,289.

The most commonly used medications are290:

• Statins: is the most frequently used drug, recommended for children aged > 8 years. There are not enough consensuses regarding when to start statins in childhood or what the target is in children290. The doses of statins commonly used in children and adolescents are described in Chart 11.1.

• Cholesterol absorption inhibitors (ezetimibe): its use is recommended as monotherapy starting at 5 years and in combination with statins, after 8 years old, reducing the side effects of these drugs.

• Bile acid sequestrants: they can be used at any age, associated with statins, at different times. Due to risk of malnutrition associated with fat-soluble vitamins, nutritional monitoring and supplementation are recommended according to objective criteria of deficiency.

• Supplements: Supplementation of 1.2 g to 1.5 g of phytosterols can lower total cholesterol and LDL-C290.

Table 11.1 – Reference values for lipids and lipoproteins in children and adolescents.

Parameter Acceptable Borderline High (p95) Low (p5)

TC < 170 170-199 > 200

LDL-C < 110 110-129 > 130

n-HDL-C 123 123-143 > 144

TG (0-9a) < 75 75-99 > 100

TG (10-19a) < 90 90-129 > 130

HDL-C > 45 35-45 < 35

Apo A1 > 120 110-120 < 110

Apo B < 90 90-109 > 110

TC: total cholesterol; LDL-C: low-density-lipoprotein cholesterol; n-HDL-C: non-high-density-lipoprotein cholesterol; TG: triglycerides; HDL-C: high-density-lipoprotein

cholesterol; Apo A1: apolipoprotein A1; Apo B: apolipoprotein B.

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Guidelines



Therapeutic target

Figure 11.1 – Algorithm for the diagnosis and management of dyslipidemia in children based on risk factors and lipid levels (mg/dL). Adapted from Giuliano I. and Caramelli B.290.

Legend: TC: total cholesterol; FH: family history; LDL-C: low-density-lipoprotein cholesterol; COI: coronary insuficiency; DLP: dyslipidemia; LS: lifestyle; RF: risk factor.Notes:

*In the presence of DM, HIV infection, Kawasaki disease, nephrotic syndrome and systemic lupus erythematosus, pharmacological treatment should be started if LDL-C

levels > 130 mg/dL, after lifestyle changes**Some authors consider the presence of emerging risk factors (high levels of lipoprotein(a), homocysteine and C-reactive protein) a determinant of the use of lipid-lowering drugs in children with LDL-C levels > 160 mg/dL. ***Type I diet: up to 30% of calories from fat, up to 10% of saturated fat, up to 100 mg/1000 Cal of cholesterol, maximum of 300 mg/dL.****Type II diet: up to 20% of calories from fat, up to 7% of saturated fat, up to 60 mg/1000 Cal of cholesterol, maximum of 200 mg/dL. *****For every child diagnosed with hypercholesterolemia, a secondary cause of dyslipidemia should be ruled out and/or their irst-degree relatives should undergo lipid screening.

Child at risk aged < 10 years or child aged > 10 years regardless of risk

TC < 170 170 - 199 > 199

Repeat TC

TC < 170 170 - 199

Child with FH+ for early cardiovascular disease

Healthy lifestyleOnaverage, 2 lipidprofiles

LDL-C < 100 LDL-C 100-129 LDL-C ≥ 130*

LDL-C > 160 and

early COI or + 1 RF**

LDL-C > 190

Healthy LS – measure in 5 years

Type I diet*** measure in 1 year

Type II diet****

Secondary DLP*****?Type II diet and lipid-lowering drugs

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Guidelines



Figure 11.2 – Algorithm to monitor the use of statins in children and adolescents. Adapted from Giuliano I. and Caramelli B.290.

Legend: RF: risk factor; CK: creatine kinase; AST: aspartate transaminase; ALT: alanine transaminase; *CK: symptomatic + 3 to 10x; asymptomatic: > 10x

Statin use criteria

Age of start depends on the number and magnitude of

other RF or xanthomasIdeally, over 8 years

Observe interaction with cyclosporine, fibrates, niacin,

erythromycin, antifungal drugs, protease inhibitors

Begin with < dose, 1x/day; measure CK, AST and ALT

Instructions on risk for teratogenesis

Myalgia?CK?

Stop using Resume use after solution

Risk CK > 10x/baseline

AST/ALT >3x/baselineLipids, AST, ALT, CK

Minimum LDL-C < 130 Ideal LDL-C < 100

Enzyme alteration* Goal met Goal not met

Reduce dose orchangestatin; reassess in 2 weeks

Monitor 8 weeksand 3/3 months

Double the dose and tests in 4 weeks

4 weeks

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Guidelines



Obesity

Definition and Epidemiology

The change of life style habits, such as inadequate eating patterns associated with sedentary habits, has contributed to the increased prevalence of obesity in recent decades, leading the World Health Organization (WHO) to declare obesity a global epidemic291. A review of 450 prevalence studies in 144 countries showed that 43 million children were overweight in the world in 2010, with 35 million in developing countries. In 2020, it is estimated that approximately 9% of children worldwide will be obese, i.e., a total of 60 million children292. In Brazil, approximately a third (33.5%) of the children aged 5-9 years are overweight293.

Prognosis

Children and adolescents who are overweight have an increased risk for obesity in adulthood, a phenomenon known as “tracking phenomenon”. The proportion of overweight adolescents who become overweight adults can vary from 22% to 58%294.

Furthermore, several studies have shown that children/adolescents who are overweight or obese have a greater risk of having DM, cerebrovascular accident (CVA), dyslipidemia, coronary artery disease and hypertension and early mortality in adulthood295.

Diagnosis

The diagnosis of obesity or overweight in children is a clinical one, established by history and physical examination, followed by the comparison of anthropometric data with population parameters through curves of body mass index (BMI) for age. The curves used earlier, by the National Center for Health Statistics (NCHS/1977)296 and the Centers for Disease Control and Prevention (CDC/2000) were based on populations of North-American children who received artificial feeding and, therefore, they tended to underestimate the prevalence of obesity and overestimate malnutrition, significantly changing clinical management. The WHO developed a multicenter study and in 2006 published the new curves for assessing nutritional status of children aged zero to five years (WHO Multicentre Growth Reference Study

Group. WHO Child Growth Standards based on length/height, weight and age)297. These curves are based on data from six countries, including Brazil, and they are prescriptive, i.e., they are based on children who were breastfed and received proper nutrition in infancy298. In 2007, the WHO published the reference curves for children older than 5 years299. The use of this standard was recommended by the Brazilian Ministry of Health in 2007 and the growth curves were included in the Child Health Handbook.

After weight and height measurement, BMI is calculated (weight (kg)/height (m2). Overweight is considered when values are > the 85th percentile or z score +2, and severe obesity when values are > the 97th percentile or z score +3 of BMI. For calculations it is also possible to use the free software available on the WHO page300 or on the telehealth page301.

Additional examinations may be used for more detailed evaluation of body composition, to investigate secondary causes and to identify consequences of obesity, such as changes in metabolic and inflammatory profiles, orthopedic and sleep disorders.

Prevention and Treatment

From a lifetime perspective, prevention begins before birth, which is called primordial prevention, i.e., preventing the child from developing a risk profile. Thus, prevention includes proper nutrition during pregnancy, breastfeeding promotion302 and identification of family risk factors, in addition to monitoring the growth and development of the child303.

Similarly, treatment of obesity in children and adolescents (primary prevention) is mainly based on changing habits, especially adopting a healthy diet and increasing physical activity overall. It is important to involve the children’s entire family, parents, teachers and health professionals, as well as a multidisciplinary team303-307.

Systemic Arterial Hypertension

The prevalence of systemic arterial hypertension (SAH) in children and adolescents ranges from 0.8 % to 8.2 %308-312. Some studies indicate a mean prevalence of 3.5% when the diagnosis is attained through repeated measures, both for the diagnosis of hypertension and for the pre-hypertension, but others report a prehypertension prevalence of 12% to 17% through isolated measures, particularly in overweight and obese adolescents308-313.

Although secondary hypertension with defined etiology is the most common type in children, primary hypertension is being increasingly diagnosed, especially in older children and adolescents, when other risk factors are associated, with overweight and obesity being the most common.

The consequences of hypertension are usually evident after the fifth decade of life, but there is evidence that primary hypertension originates in childhood and that high blood pressure levels in this phase of life are strong predictors of hypertension in adult life. It is also known that left ventricular hypertrophy detected by echocardiography, considered the greatest marker of target-organ injury from hypertension in children and adolescents, is present in 34 % to 38% of

Chart 11.1 – Doses of hypolipidemic used in children and adolescents

Drug Doses (mg/d)

Lovastatin 10-40

Pravastatin 10-40

Simvastatin 10-40

Rosuvastatin 5-40

Atorvastatin 10-40

Cholestyramine 4-16

Ezetimibe 10-

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Guidelines



individuals in this age group that have moderate hypertension and are not receiving treatment. In addition, primary hypertension in children and adolescents is often associated with excess weight and both are present in metabolic syndrome (MS), which also includes elevated triglycerides, low HDL - C, central obesity and hyperinsulinemia, known risk factors for the development of atherosclerosis. Autopsy studies in children, adolescents and young adults have shown that as the number of risk factors for atherosclerosis increases, the number and extent of fatty streaks and fibrous plaques also increase in the aorta and coronary arteries of these individuals313-315.

Blood pressure (BP) measurement is considered mandatory after 3 years of age, annually or before that age when children have neonatal history of morbidities, kidney disease or family risk factors 316-318. Arterial hypertension is defined as the percentile of BP in relation to age, gender and height. Tables with age and height percentiles can be obtained from the CDC growth charts available at http://www.cdc.gov/growthcharts/2000growthchart-us.pdf. Once defined the height percentile for age and sex, it should be correlated with the 90th, 95th or 99th percentile regarding the obtained BP level318-319. Table 11.2 shows the levels of BP in normal and hypertensive children and adolescents. The diagnosis of SAH should be attained after three measurements on different occasions.

Studies suggest that there is a progression rate of approximately 7% per year from pre-hypertension to hypertension and that this persists in approximately one third of boys and a quarter of girls in a longitudinal follow-up of two years318-319.

For all children and adolescents with BP persistently at or above the 95th percentile, the initial evaluation should attempt to identify the etiology, if any, through data on sleep habits, family history, risk factors, diet, smoking and alcohol intake. The initial complementary study should include complete blood count, serum urea, creatinine, sodium, potassium, calcium, uric acid, urinalysis, urine culture and kidney ultrasound. Levels of fasting glucose, total cholesterol, LDL-C, HDL-C and triglycerides should be measured in all children with hypertension and also in those with borderline BP that are overweight, have chronic kidney disease or a family history of cardiovascular disease (CVD).

Ches t r ad iog raphy, e l ec t roca rd iog raphy and echocardiography: Echocardiography should be requested to assess left ventricular hypertrophy or other cardiac abnormalities in all children and adolescents with hypertension and those with borderline BP that have comorbidities

(including DM and kidney disease). Other tests that investigate in target-organs damage from SAH, such as the assessment of intima-media carotid thickness and microalbuminuria measurement, still have no recommendation for routine use.

Ambulatory blood pressure monitoring (ABPM) is indicated in children and adolescents to investigate white coat hypertension, to assess therapeutic efficacy in hypertensive individuals or hypotension-related symptoms during the use of antihypertensive drugs, to investigate episodic BP elevations and to assess BP patterns throughout the day in individuals with diabetes, chronic kidney disease or autonomic dysfunction. Additional examinations are necessary when a disease that courses with elevated BP is suspected and include: polysomnography, measurement of renin or plasma renin activity, renal scintigraphy with captopril administration, measurement of plasma and urinary catecholamines, serum steroids in plasma and urine, nuclear magnetic resonance, digital angiography and renal arteriography318-319.

Obesity is probably the most important associated condition for primary hypertension in children and adolescents, accounting for more than 50% of the risk of developing SAH320,321,322. Thus, dieting, exercise and weight loss are mentioned as important factors in changing the life style317. Observational and intervention studies have shown beneficial effects of weight reduction in pediatric patients321,322 and weight loss improves not only BP but also other cardiovascular risk factors associated with obesity, such as insulin resistance and dyslipidemia. Some recommendations can be mentioned in relation to changes in life style317: moderate aerobic physical activity (see separate chapter); avoid excessive intake of sugar, soft drinks, saturated fat and salt and eat more fruits, vegetables and grains; implement changes in behavior (physical activity and diet) adapted to the individual and family characteristics; get relatives and family to be part of the process and provide educational support material; set realistic goals; develop a reward system for health promotion; the competitive sports should be limited in the presence of uncontrolled stage 2 hypertension. The goals are appropriate to BMI, and when BMI is below the 85th percentile, the weight should be maintained; when between percentiles 85th and 89th, it is indicated for children to maintain weight or gradual weight loss in adolescents to reduce BMI to a percentile < 85th. When the BMI is above the 95th percentile, gradual weight loss is indicated (1-2 kg/month) until values below the 85th percentile are attained316,317 .

The decrease in body weight may make the drug treatment unnecessary, but it should not delay its start when indicated316,

Table 11.2 – Blood pressure classiication in children and adolescents318-319

Class Percentile of systolic or diastolic blood pressure

Normal < 90

Pre-hypertension Normal high

90 to < 95 or BP ≥ 120 x 80 mmHg

Stage 1 SAH 95 to 99 plus 5 mmHg

Stage 2 SAH > 99 plus 5 mmHg

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Guidelines



as well as the reduction of sodium intake to 1.2 g/day for children aged 4-8 years and 1.5 g/day for those older than 8 years and adolescents seems to be an effective measure312,316.

Changes in life style are the initial therapeutic recommendation of primary SAH in children and adolescents. Drug treatment is indicated for individuals with symptomatic hypertension, secondary hypertension, target-organ injury from SAH, diabetes types 1 and 2 and persistent SAH despite the adoption of non-drug measures, situations in which these measures are complementary to the drug treatment317,322.

Physical activity

The current strategy for the reduction in cardiovascular mortality in developed and developing countries is the prevention of its most important risk factors, by adopting healthy habits (especially those related to physical activity and diet), beginning as early as possible in the lives of individuals323,324. As the performance of physical activity (PA) by young individuals is the greatest predictor of its maintenance in adult life, this is a strong argument to encourage its continuous performance in children and adolescents324.

Children and adolescents are more physically active than adults325; however, it is believed that currently, a progressive and significant reduction in daily PA is occurring in individuals of all ages as a result of several changes occurring in society, among which stands out the abundant means of transportation to different places (cars, buses, subways), eliminating the need to walk or ride bikes, for instance. The reduction of PA in leisure is favored by urban violence, lack of safe play areas in large cities and the working hours of both parents, who end up confining children at home, in addition to greater propensity to habits that do not require energy expenditure (watch TV/video, computer and phone use). There have been reports that physical inactivity in Brazilian cities can reach 93.5 % of its young population310.

This growing inactivity among individuals at a stage of life that is naturally and biologically of great activity can generate immediate and negative consequences for children’s health (such as overweight and its comorbidities)326-329 and lead them (tracking) to a habit (non-propensity toward PA) that can extend to the rest of the individual’s life330,331, thus contributing in the long-term, to the occurrence of chronic- degenerative diseases in adults, including cardiovascular atherosclerotic disease 332.

Thus, PA should be encouraged in children and adolescents so that they acquire an active habit that will remain throughout life and for PA to acts as an agent:

a) to assist growth (strengthening muscles, bones and joints); b) therapeutic (in those who have other cardiovascular risk factors such as obesity, hypertension, diabetes mellitus, dyslipidemia, metabolic syndrome (MS), anxiety and depression); c) prevention, including CVDs in adults332-335. A systematic review of 18 studies involving 12,742 participants aged 0-4 years has shown that high levels of physical activity are associated with better parameters of adiposity, bone and muscle health, motor and cognitive development and cardiovascular health, even at this range early age range336.

Therefore, children and adolescents should be encouraged to engage in physical activities that are pleasurable to them at home, at school and at play, through physical education classes, sports, games, play, actively commuting to school (walking, cycling) among others337-340. For that, a joint action is required: a) by the family (that must be active together and not just encourage the children to practice PA); b) by the health professionals (investigating the level of PA carried out by the children and their parents; by encouraging an active life style; by investigating morbid conditions that limit the practice of PA or require special care); c) school (by offering regular physical education classes, sports, health education promotion; inclusion of parents in PA programs, opening the school for the community; d) community (requesting PA programs in schools and recreational areas in the cities, as well as a health promotion policy that includes PA in education, sports and health care)332-335.

In general, it is recommended that children and adolescents participate in moderate to severe PA (“that will make them sweat, become breathless or with tired legs”), lasting at least 60 minutes, preferably on every day of the week332-335. This recommendation includes intense activity at least three days a week and activities that promote muscle and bone strength at least three days a week337. A higher level of daily physical activity promotes more health benefits337.

When structuring an active life style for children and adolescents, it is also extremely important to reduce the number of daily hours spent in sedentary activities (TV, video games, computer, phone)332-335. A study carried out in a Brazilian capital showed that children aged 7 to 17 years spent around three hours (median) in front of the TV343. There is evidence that the time spent watching television during childhood and adolescence is greater than the time spent at school and that the prevalence of obesity increases by 2% for each additional hour watching TV; that 4 or more hours watching TV is associated to higher frequency of smoking, hostile behavior, depression and alcohol consumption and that a high number of hours watching TV in childhood and adolescence is associated with obesity, low physical fitness, smoking, and hypercholesterolemia in adulthood332-335. Thus, it is suggested that the daily time spent in sedentary activities is limited to a maximum of 2 hours.

A systematic review of studies on the effectiveness of interventions to promote PA in pediatric patients (particularly adolescents) showed better results when associated with actions at school involving the family or the community and educational activities involving environmental and health policies338.

Therefore it is recommended that when planning PA for children and adolescents, it should be based on the identification of cognitive-behavioral mediators (self-awareness, self-esteem, knowledge, intention to become active, pleasurable activities, favorite activities) and social support (family, friends)338 that may be used to evaluate the effectiveness of the chosen strategies, so that the best can continue to be used in future programs aimed at this population337-339.

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Guidelines



Table 11.3 – Classiication of recommendation and level of evidence for the presence of cardiovascular diseases (CVD) in children and adolescents.

Recommendation class level of evidence

Obesity screening

• Obesity screening by use of BMI in children ≥ 6 years, providing or indicating intensive behavioral interventions directed to achieving a healthy weight

• Ask about early CAD family history to identify children at risk

• In the presence of positive family history, assess all family members, especially the parents

I B

• In children aged > 2 years with BMI ≥ 85th percentile:• Reinforce preventive instructions (see below)

• Identify complications and RF: SBP, gallbladder disease symptoms, diabetes, sleep apnea, hypothyroidism, orthopedic disorders, lipid proileI C

In children aged > 2 years with BMI ≥ 85th– 94th percentile,• all measures above plus:

• control of weight gain and fat ingestion, focusing on nutrition and development

• treatment of RF and complications

• multidisciplinary approach of moderate to high intensity

• measure aspartate transaminase (AST), alanine transaminase (ALT) and blood sugar in children ≥ 10 years of age

I C

In children aged > 2 years with BMI ≥ 95th percentile, • all measures above plus:

• Long-term objective: maintain BMI < 85

I B

• Consider more aggressive approaches if conservative strategies fail

• Check urea and creatinine every 2 yearsI A

Nutrition – Milk/other beverages

Exclusive maternal breastfeeding for the irst 6 months I B

From the 12th to the 24th month, transition to non-aromatic low-fat milk (2% or skim) I B

From 2 to 21 years of age, non-aromatic skim milk should be the major beverage I A

Avoid sugar beverages, encourage water ingestion I B

Dietary fat

Fat ingestion by infants should not be restricted without medical indication I C

From the 12th to the 24th month, transition to family meals with fat corresponding to 30% of the total caloric ingestion, 8%-10% of which of saturated fat

I B

From 2 to 21 years of age, fat should correspond to 25%-30% of the total caloric ingestion, 8%-10% of which of saturated fat I A

Avoid trans fat I B

Cholesterol < 300 mg/dL I A

Others

From 2 to 21 years of age, encourage iber ingestion, limit sodium ingestion and encourage healthy life habits: family meals, breakfast, limit fast snacks

I B

Physical activity

Parents should create an environment that promotes physical activity and limit sedentary activities, and be role models I C

Limit sedentary activities, especially TV/video I B

Moderate to vigorous physical activity every day I A

BMI: body mass index; CAD: coronary artery disease; RF: risk factors; SBP: systolic blood pressure

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Guidelines



12. Legislation and prevention of risk

factors for cardiovascular disease

Introduction

Some considerations should be made regarding the association between legislation and prevention of risk factors (RFs) for cardiovascular disease (CVD), starting with simple matters such as: can specific health laws fulfill an effective role in health promotion and CVD prevention?

In principle, the answer is yes. Knowledge of the RFs for the development of CVDs is the first step to change the lifestyle of the population, supporting their prevention. Encouraging CVD prevention and control, promoting and creating healthy environments requires that both the population and the health managers be well informed about the importance of surveillance, prevention, care, rehabilitation and health promotion.

For that purpose, the creation of public policies that have the support of the population, consolidating the actions of the community and redirecting health services is essential. Thus, it is necessary to develop actions for health promotion and disease prevention that integrate individual actions and assistance to population actions of collective comprehensiveness, positively intervening with RFs for CVDs through legislation and regulatory actions, as well as educational, information and community mobilization ones.

The last two decades have shown evidence of legal restrictions concerning:

1. Cigarette advertising in the media;

2. The content of nicotine and substances that potentiate its action;

3. Smoking in enclosed public places;

4. The sale of cigarettes to minors, among others - and of utmost importance - in association with educational measures.

These restrictions resulted in a significant reduction (of approximately 50%) in the population of smokers in the country340.

As smoking is one of the biggest RFs for the group of CVDs, morbimortality statistics were expected to stabilize or decrease during this period, in the group of smoking-related diseases. This was indeed observed, according to several scientific studies published in recent years and the data released by the mortality information system of the country341,342.

Therefore, one can infer that legislative and regulatory actions can play an effective role in the prevention of tobacco-related diseases, such as coronary artery disease (CAD) and cerebrovascular accident (CVA) and in the group of CVDs and respiratory diseases, such as emphysema, chronic obstructive pulmonary disease (COPD) and lung cancer343,344.

Developing a system of health communication using local resources (radio, local and broad-circulation newspapers, television programs, the web), developing and maintaining educational campaigns with clear and accessible information to help individuals in changing habits, formulating strategies for drug treatment adherence, building the individuals’ empowerment to promote self-management of their diseases

and risks are relevant strategies that contribute to reducing the impact of CVDs. The appropriation of knowledge about the RFs, scientifically recognized as those involved in the genesis of CVDs, has provided new and more effective measures related to their prevention.

Epidemiological researches carried out in the American town of Framingham (Framingham Heart Study) at the end of the 1940s constitute the starting point and one of the most important scientific advances that established the base of knowledge capable of unequivocally correlating RFs and CVDs. Moreover, very importantly, allowed the capacity to strategically intervene effectively on the FRs and reduce the prevalence of CVD morbidity and mortality344.345.

Two important aspects must be considered from the strategic point of view, regarding the RFs related to CVDs and the expected response to control actions - rules, regulations and legislation - issued by authorities in the area of health: potential of response to interventions and possibility that the regulatory measures and legislation will induce effective changes in the epidemiological profile of the population.

Regarding the potential response to interventions, there is an accumulation of knowledge indicating that preventive actions are effective in reducing the prevalence of CVDs, as it was observed with smoking reduction, for instance. After the first decade of changes in habits of the population, it was already possible to see the effects of the phenomenon on morbimortality statistics340.

With the development of knowledge in the medical area in recent years, mainly through Evidence-based Medicine (EBM), it is now possible to quantify or categorize responses to interventions according to the degree of evidence observed.

Based on the concepts of EBM, four hierarchical categories of response to interventions were established:

a) those that prove a decrease in the risk of CVD;

b) those that clearly reduce the risk;

c) those that can reduce the risk;

d) those that are associated with increase in CVDs, but are not modifiable.

The first group - which have proven to reduce – include the following risk factors: smoking, LDL - C, diets high in fat/cholesterol, high blood pressure (hypertension), left ventricular hypertrophy, thrombogenic factors.

In the second – which obviously reduce - are: diabetes, sedentary lifestyle, HDL - C, triglycerides, LDL, obesity, postmenopausal period.

In the third group – which can reduce - are: psychosocial factors, lipoprotein (a), homocysteine, oxidative stress, non-alcohol consumption.

In the four – non-modifiable – are age, male gender, low socioeconomic status, history of early CVD345.

The World Health Organization (WHO) released in 2011, the most cost-effective interventions, some of which are still considered the “best buy” (actions that must be performed immediately to produce accelerated results in terms of lives saved, diseases prevented and avoided high costs). The WHO also disclosed cost-effective interventions at the

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Guidelines



population level (health promotion) and in relation to primary and secondary prevention and treatment. There are other promising measures, because the studies are still in progress. Chart 12.1 details the measures proposed by the WHO that may be effective for reducing CVDs346.

Regarding the “possibilities of normative actions and legislation on reduction and control of CVDs” one can expect the effectiveness of these interventions provided that they preceded/accompanied by educational measures and that laws and health standards originate from broad discussions with the community. After all, it is a difficult task, that of interfering with the freedom of individual citizens in relation to their habits of life: poor diet x healthy eating; sedentary life x correct practice exercises; free and exaggerated use of alcohol x moderate use.

Going back to the example of smoking, it is worth remembering that the antismoking campaign of the Ministry of Health at the end of the 1980s was planned and executed with the effective participation of social sectors, including universities, representatives of health professional - mainly in the areas of oncology, cardiology and pulmonology - community representatives and leaders, representatives of the political class, all with the collaboration of the individuals that have historically been at the front of the anti-tobacco fight.

Starting with educational actions, with appeals and messages that were quite different from previous campaigns, it was possible to gradually initiate the legal actions and restrictive rules, which were well assimilated by the general population and smokers, with positive results.

Finally, one needs to analyze what the state of the art is on the topic “legislation and control of CVDs”, by assessing:

• What place regulatory measures and legislation occupy in CVD control strategies and in health agencies at the three levels of the government.

• How this regulatory apparatus interacts with educational activities and society.

• What are the laws and regulations at the federal level, general and specific ones, aimed at the control of CVDs.

• What is still missing regarding the regulatory apparatus that could constitute into a gap to be filled by new laws, rules and regulations.

• Which measures seem more appropriate to make strategic use of the available Legislation and which need to be created, eventually, to obtain effective control of RFs involved in CVDs.

• What RFs are the priority and need to be addressed, of which reduction and / or control will result in effective impact on morbidity and mortality from CVD.

Let us consider, collectively, the questions listed in the previous item.

• It can be argued that, in general, there is a great positive expectation on the part of the population and health officials in relation to the coercive/normative strength of laws and regulations. If these laws and regulations are being effectively obeyed is a detail which, in most cases, is not taken into account. What is important is the mere existence of legislation.

Chart 12.1 – Evidence of interventions in CVD

1. Population interventions considered the “best buy” by the WHO:• Increase taxes and prices on tobacco products.• Protect individuals from tobacco smoke, prohibit smoking in public places

and warn about the dangers of tobacco consumption.• Enforce the prohibition of advertisement, sponsorship and promotion of

tobacco.• Restrict alcohol sales at retail.• Reduce salt intake and salt content in foods.• Replace trans-fats in foods by polyunsaturated fats.• Promote public understanding of nutrition and physical activity, including the

mass media.2. Other population-based cost-effective and low-cost interventions:• Promotion of breastfeeding and appropriate complementary feeding.• Apply laws against drinking and driving.• Restrict the advertising of foods and beverages high in salt, fats and sugars,

especially for children.• Taxes on foods and subsidies for healthy foods.3. Interventions with promising evidence and studies still in progress:• Healthy nutrition environments in schools.• Nutrition information and counseling in health care.• National guidelines for physical activity.• School-based physical activity programs for children.• Programs of physical activity and healthy eating in the workplace.• Community programs of physical activity and healthy eating.• Construction of environments that promote physical activity.4. Interventions for the health care of speciic groups:• Therapy with acetylsalicylic acid (ASA), statins and antihypertensive drugs

for prevention of acute myocardial infarction and other cardiovascular diseases.

• Counselling and multidrug therapy, including glycemic control for diabetes, for individuals older than 30 years, preventing fatal or nonfatal cardiovascular event.

• Treatment of nicotine dependence.• Financing and strengthening health systems to provide cost-effective

individual interventions through primary care approach.

• Hence the problem of effective significance of the legislation as a strategic element or component of preventive health actions. Using examples to clarify this argument, let us take the content of salt (sodium chloride) in processed foods for human consumption. The importance of salt intake control in primary and secondary prevention of hypertension is well-known. It is, therefore, essential to monitor, through the official organs, the sodium content of foods and if there is real consistency between this content and what is stated on the labels of these foods. This is a preventive health action.

• If the legal apparatus does not interact with society through continuous educational activities, the trend is that there is a gradual loosening of its standards, putting the population under its responsibility at unnecessary risk. It should be taken into account that the users/consumers are also agents responsible for verifying compliance with the laws, as long as they are warned and fully educated to pursue that task.

• There is a whole set of federal laws and regulations aimed at the control of CVDs. They originate from food and nutrition security surveillance organs aimed at children, adults and senior citizens, and, theoretically, can fulfill an important role in the prevention and control of non-transmissible chronic diseases. Other standards

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originate from specific government organs, which focus on detection and control of CVDs. The most significant part of this normative framework is listed in the Annexes of this Guideline.

Regarding RFs that, at first, should be considered as priority, the ones that will be considered strategic will be chosen. As such, those which interventions have - unarguably - demonstrated decreases in cardiovascular risks will be listed. Intervention is proposed for three RFs with high potential of response to interventions through educational measures - change of lifestyle - and drug interventions: smoking, hypertension and dyslipidemia. These factors will be addressed in a specific way, demonstrating that this strategic indication of priority is not done at the expense of other RFs, also important for the control of CVDs.

After establishing a close correlation between lifestyle x CVD, arterial hypertension x CVD and diabetes mellitus (DM) x CVD, it is essential to identify the common point of interaction between these factors. The evidence points to obesity and overweight as factors clearly associated with hypertension, dyslipidemia, diabetes and atherosclerosis.

Based on the changes observed in some important social determinants of health, obesity has become epidemic in many countries and is independent from the degree of economic and technological development achieved by them. Obesity and overweight currently constitute a severe public health problem. It affects millions of people, has severe repercussions on the health care services and impacts the quality of life and productive capacity of men and women, usually at the top of their functional capacity.

Changes in life style, such as using motor vehicles as a way of getting from home to work and vice versa, leading to a sedentary lifestyle; abuse of fast food and processed foods; introduction of sugar and carbohydrates in the diet; excessive stress of the urban life and abusive consumption of alcohol have combined to produce overweight individuals with risk aggregation, whose metabolism allows the development of the so-called diseases of modern life. And all this was caused by the rapid urbanization process.

From the physiopathological point of view, obesity is definitely related with diabetes and insulin resistance, with dyslipidemia and arterial hypertension, resulting, as the final outcome of this pathological cycle, in atherosclerosis.

It is known that in the obese individual: to insulin resistance develops by blocking the receptors of this hormone in tissues; there is an increase in total cholesterol and LDL-C due to increased production of fatty acids; due to insulin resistance, there is a gradual increase in these hormone levels, resulting in chronic activation of the sympathetic system and SAH.

It can be concluded, therefore, that the control of obesity / overweight, through laws, rules and regulations, conceptually becomes a measure capable of producing a significant epidemiological impact on CVD morbimortality statistics.

However there are two variables that hinder the full implementation of this measure.

The first is related to difficulties in attaining adherence of the several population age groups to changes in their

eating habits and cultural/behavioral patterns. Permanent educational campaigns are needed, with a priority strategic focus on the school environment, aiming at raising adults capable of keeping healthy life habits. As for children and adolescents, educational measures must be shared at the home level, aimed primarily at the parents. The content of salt, fats and trans-fats and the consumption of healthy foods in school cafeterias deserve special attention from educators and health authorities. Legal and regulatory measures are perfectly reasonable in this context.

The second variable, perhaps more complex and one that brings many difficulties and challenges to governmental authorities in the area of health, consists in the attitude of the food producing industry, which is repeating what cigarette manufacturers did in the past, when they decided to put into their products additive substances that were strongly inducers of tobacco addiction: they are adding substances capable of creating addiction in the consumer of foods that are harmful to their health, making them cheaper and more attractive. Studies on the behavior of consumers, including children and young adults, show how to alienate them from healthy foods, making them prefer food products with high sugar content and low in nutrients347.

In this context we show in Chart 12.2, the main regulatory actions and legislation related to strategies of health surveillance, prevention, care, rehabilitation and promotion in Brazil.

It is noteworthy that Brazil has been committed to the prevention and care of the NCDs and launched the Strategic Action Plan for the Fight against Noncommunicable Chronic Diseases (NCDs), 2011-2022, which defines and prioritizes actions and investments required to prepare the country to face and stop NCDs and their risk factors in the next 10 years. The plan addresses the four main groups of diseases (cardiovascular, cancer, diabetes and chronic respiratory diseases) and the modifiable risk factors they have in common (smoking, alcohol, physical inactivity, poor nutrition and obesity) and defines three strategic directions: a) surveillance, information, assessment and monitoring; b) health promotion; c) full care. The plan establishes goals and commitments made by Brazil in relation to NCDs340,348,349.

CVD is a multifaceted disease in relation to its RFs and its control demands articulated promotional and preventive actions that have an impact, such as the fight against sedentary life style and obesity and tobacco control, and integrated health services for the diagnosis and monitoring of detected and treated cases. The laws and decrees currently being enforced in the country are subsidies for managing NCDs, particularly CVD, requiring articulated efforts from the health area together with the other governmental, non-governmental and private sectors, both in the design, development and implementation of specific policies that coordinate and integrate health surveillance, prevention, care, rehabilitation and promotion, producing quality of life and citizenship.

Thus, the approach to public policymakers will imply in the adoption and development of integrated and comprehensive public health actions and policies, supported by intersectorial actions, taking into account the several cycles of life, local conditions and needs.

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Table 12.2 – Main legislation and regulatory actions related to strategies for health surveillance, prevention, care, rehabilitation and

promotion in Brazil

Decree/Law Content

• Decree n 687/GM/MS, March 30, 2006 • Health Promotion Policy

• Decree n 971/GM/MS, May 3, 2006 • National Policy on Integrative and Complementary Practices (PNPIC) in the Uniied Health System (SUS)

• Law N. 11.347, Sept. 27, 2006• Provides for the distribution of free medications and materials needed to implement and monitor

capillary blood glucose for patients with diabetes enrolled in education programs for diabetics

• Decree n 2.583, Oct. 10,2007• Deines list of medications and supplies available through SUS, pursuant to Law No. 11,347, 2006, for

users with diabetes mellitus

• Decree n. 1.559/GM/MS, Aug. 1, 2008 • National Policy for SUS Regulation

• Decree n. 992/GM/MS, May 13, 2009 • National Policy for Integrated Health of the Black Population;

• Decree n. 4.279/GM/MS, Dec. 30,2010 • Establishes guidelines for the organization of the health Care Network in SUS

• Decree n. 4.217, Dec. 28, 2010 • Basic component in Pharmaceutical Assistance

• Decree n. 1.600/GM/MS, July 7, 2011• Reformulates the National Policy for Emergency Health Care and establishes the Emergency Care

Network in SUS

• August 2011• Strategic Action Plan for the Fight against Noncommunicable Chronic Diseases (NCDs) in Brazil from

2011 to 2022

• Decree n. 2.029 Aug. 24, 2011 • Institutes Home Care in SUS

• Decree n. 2.488, Oct. 21, 2011• Approves the National Primary Care Policy, setting the review of guidelines and standards for the

organization of Primary Care for the Family Health Strategy (FHS) and Community Agent Program (PACS)

• Decree n. 2.715/GM/MS, Nov. 17,2011 • Updates the National Food and Nutrition Policy (PNAN)

• Decree nº 971, May 15, 2012 • Popular Pharmacy Program in Brazil

• Decree nº 252, Feb. 19, 2013 • Institutes the Health Care Network for Patients with Chronic Diseases in SUS

• Decree nº XX, March 19, 2013 • Creates a Priority Care Line of Treatment for Overweight and Obesity in SUS

13. Topics in Prevention

Autoimmune diseases and cardiovascular disease

Several autoimmune diseases can affect the heart through several manifestations including arrhythmias, pericardial diseases, cardiomyopathies and coronary diseases. Regarding the latter, advances and research in the field of atherosclerosis have increasingly supported the participation of the immune system in its physiopathology. The presence of lymphocytes and macrophages inside the atherosclerotic plaques suggests that inflammation is an important factor in the cascade of disease evolution. In patients with rheumatic autoimmune diseases, this inflammatory process is exacerbated and the result may be the occurrence of accelerated atherosclerosis350. The use of certain immunosuppressive drugs such as corticosteroids, may also contribute to this worsening of the cardiovascular risk profile. Accelerated atherosclerosis

may be the main explanation for the high percentages of cardiovascular morbidity and mortality of these patients350,352. Among the diseases that can occur together with this physiopathological characteristic, the following are worth mentioning: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis and certain primary vasculitis such as Wegener’s granulomatosis166,350,352.

RA is associated with a reduction of up to three-fold in survival, with ischemic heart disease as the primary cause of death353. Furthermore, the risk of acute myocardial infarction (AMI) is about two-fold higher than in the general population, and the prognosis after the event tends to be worse166. This profile starts its development early in the course of the disease and independently from other factors classically associated with atherosclerosis354. The use of methotrexate may also contribute to this scenario, perhaps by concomitant elevation of homocysteine during its use. In such cases, folate supplementation seems to reduce this risk, including evidence of cardiovascular mortality reduction355. Still, the functional limitation and consequent inactivity imposed by the disease can also increase the likelihood of developing other risk factors such as obesity, hypertension and diabetes. Dyslipidemia is another condition often found in these patients, with a prevalence of up to 65%356.

Just like RA, SLE also behaves as an independent risk factor for cardiovascular disease (CVD), with a prevalence of coronary disease of up to 10% and a risk up to eight times that found in the general population351,357. Some studies suggest that AMI may be the cause of death in up to 25% of

Table 13.1 – Recommended approach for autoimmune diseases in

the prevention of cardiovascular diseases

Recommendations ClassLevel of

Evidence

In the context of the prevention of cardiovascular events, the beneit of using more stringent therapeutic targets, speciically due to the presence of autoimmune diseases, is uncertain.

IIb C

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cases, mainly in patients with a longer time of the disease358. The risk of this complication can be 52-fold higher than that of the population without the disease, when the time of evolution exceeds five years351. At the same time, the prevalence of major cardiovascular risk factors such as SAH, diabetes, obesity, physical inactivity and dyslipidemia is also higher in individuals with SLE352. The frequent use of corticosteroids for disease management is another condition that helps worsen the metabolic profile, although lower daily doses of 10 mg of prednisone appear to be safe in this respect, as well as antimalarial drugs352,359. Nevertheless, the fact that coronary artery disease associated with SLE is most often associated with atherosclerosis than to vasculitis further reinforces the importance of these factors in this context. On the other hand, the association between anti-phospholipid antibody syndrome, often associated with SLE and accelerated atherosclerosis is less clear, although it is known to increase the risk of thrombotic events350.

Accelerated atherosclerosis associated with psoriasis also gives this disease a definitively higher risk of AMI. However, unlike with LES, this complication tends to occur more often in younger individuals and in those with more severe disease. This characteristic could be a consequence of a more exuberant inflammatory condition, which would be associated with greater activation of the immune system166.

The primary vasculites are another group of diseases that are relevant in this context, occurring together with systemic inflammation of autoimmune etiology that affects the vascular bed in different ways. The inflammatory process inherent to these diseases makes up an important aspect of the physiopathology, mainly when vessels of medium and large sizes are affected, thus increasing the risk of cardiovascular events. However, what has been increasingly recognized is the association of this group of diseases with atherosclerosis, although still less evident than in rheumatologic diseases 350. Vascular remodeling with endothelial dysfunction, increased formation of oxidized low-density lipoprotein cholesterol (LDL-C) and prolonged treatment with corticosteroids are important factors involved in this process352. However, clinical studies are scarce in this area, with only a few studies evaluating intermediate outcomes, such as the increase in carotid medial-intimal thickness in Wegener’s granulomatosis350. Still, it must be remembered that other diseases of this group, such as Takayasu arteritis, polyarteritis nodosa and Kawasaki disease can potentially affect coronary circulation, even though most of the time it occurs independently of atherosclerosis.

Most autoimmune diseases are more common among women, of which prevalence can be nine-fold higher, as in LES352. This is particularly relevant to the detailed cardiovascular risk stratification in the female gender in the presence of these diseases, even at an age group in which coronary disease is usually rarer (< 65 years). Nevertheless, the key issue is the lack of clinical studies demonstrating the benefits of aggressively treating this group of patients. To date, there is no evidence that the therapeutic targets for blood pressure, blood glucose, LDL-C, or any other risk factor should be modified due to the presence of an autoimmune disease.

The studies performed in this area focused mostly on surrogate outcomes such as the reduction of carotid medial-intimal thickness in SLE patients treated with atorvastatin. But it is noteworthy that the same study showed an increase in the occurrence of liver and muscle adverse effects in patients treated with the drug360. This suggests that this approach should be taken with caution, as it exposes the patient to a higher risk of adverse effects without necessarily providing a clinical benefit. Moreover, this risk does not appear to be restricted to SLE, as approximately 80% of patients with rheumatoid arthritis have at least one risk factor for myopathy associated with statins 361. The use of anti-inflammatory drugs or corticosteroids could also increase the risk of bleeding when associated with aspirin, often used in the setting of primary and secondary prevention of cardiovascular events362. However, the relatively low prevalence of these diseases in the population is the main factor limiting the performance of good quality studies to answer these questions. Possibly, the treatment itself directed to the underlying disease could reduce cardiovascular risk by controlling the inflammatory process, although this hypothesis also needs to be studied. The complexity becomes even greater when the medication used in the disease management is known to worsen the metabolic profile, as in the case of corticosteroids. Therefore, it is essential that each case be individualized, with constant reassessment throughout disease evolution, of potential risks and benefits of treatment.

The recommendations of this guideline for autoimmune diseases and cardiovascular diseases can be seen in Table 13.1.

Inluenza and cardiovascular disease

The possible association between the influenza virus and disease cardiovascular was first suggested in the early twentieth century, especially after the Spanish flu pandemic of 1918363. Since then, several observational studies have reinforced this association, with increasingly strong evidence that this is not a chance finding. In this context, it was observed over the last 100 years, the influenza epidemics tend to be accompanied by a significant increase in cardiovascular deaths and events364,365. Even during the 2009 pandemic of the H1N1 virus, it was observed in Brazil that chronic cardiovascular disease was the most prevalent comorbidity (23.8%) among patients who died366. Furthermore, it is currently acknowledged that most cardiovascular events affecting these patients occur in winter months, following the virus seasonal trend365.

The mechanisms involved in this association are not yet completely understood, but it is speculated that the virus may act directly on the destabilization of vulnerable atherosclerotic plaques, which makes its infection particularly relevant in individuals known to have coronary and/or cerebrovascular disease. This characteristic differentiates it from other infectious agents that have also been associated to increased cardiovascular risk, such as Chlamydia pneumonia and Mycoplasma pneumonia, which promote a more systemic inflammatory process. The loss of anti-inflammatory properties of high-density lipoprotein cholesterol (HDL-C) and endothelial dysfunction are also factors possibly involved in the physiopathology367,368. Nonetheless, regardless of the

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mechanism, the risk of AMI seems to be higher in the first 10 days of respiratory infection evolution369. The benefits of vaccination against influenza were investigated by several observational studies and, although the results have not been unanimous, a protective effect was observed in most of them, especially in relation to cardiac outcomes364. The largest cohort ever studied in this context followed more than 102,000 people older than 65 years, with or without CVD, for 10 months. The more than 35,000 participants that were vaccinated showed lower and statistically significant percentage of total death, cardiac death and stroke (CVA), when compared with the group that was not vaccinated370. Although this result is significant, one must consider the biases that accompany the interpretation of any observational study. Case-control studies on this subject have also been published, mostly with similar results and the same limitations364.

Three clinical trials have been performed to evaluate the effect of influenza vaccination on cardiovascular event prevention. However, all of them included only patients with established coronary disease, using the vaccine as a secondary prevention strategy367,371-373. Patients with or without a past history of myocardial infarction were studied, as well as those submitted or not to coronary interventions. Although the number of participants varied between 200 and 658 in the different studies, all showed similar results, with a reduction in the combined cardiovascular outcomes (death, AMI, need for hospitalization for ischemia or revascularization) in the vaccinated group throughout the 12 months of follow-up371-373. However, only the study “Flu vaccination in acute coronary syndromes and planned percutaneous coronary interventions (FLUVACS) showed a significant reduction in cardiovascular death, particularly among patients with a history of AMI373. A systematic review published in 2009 also suggested this same benefit by jointly analyzing data from the studies FLUVACS and “Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease” (FLUCAD), although the result was clearly influenced by the findings of the first one364.

These studies also showed limitations that should be considered when analyzing the results. Among them, we can highlight the small number of patients and outcomes, the lack of blinding and single-center characteristic. Moreover, the results may not be generalizable to individuals without established atherosclerotic disease as a primary prevention strategy for cardiovascular events, although the protective

effect of the vaccine on respiratory infection remains. Similarly, the impact of vaccination on the decrease of cerebrovascular events has not been established, although a positive result has been suggested by several observational studies373. Still, despite the relevance of these limitations, this evidence was vital to at least rule out the previously raised hypothesis that the period immediately after the vaccination could increase cardiovascular risk.

The recommendations of this guideline for influenza and cardiovascular disease can be seen in Table 13.2.

Chronic kidney disease

The relationship between CKD and CVD is well established and multiple interactions between them have been described. Apart from the fact that both have risk factors in common, CKD is an independent risk factor for coronary disease development374,375.

In general, patients with CKD have variable increases in the risk of developing cardiovascular events, being lower (43%) in patients with glomerular filtration rate (GFR) between 45-59 mL/min and higher (343%) in those with GFR < 15 mL/min376.

Moreover, the presence of proteinuria, regardless of age, gender, renal function and diabetes, increases the risk of coronary heart disease and perpetuates chronic kidney injury377.

However, the discussion on considering CKD an equivalent of coronary heart disease is extensive and controversial. In 2003, the recommendation of the National Kidney Foundation (USA) in fact considered CKD an equivalent of coronary disease378. However, factors such as the degree of reduction in GFR, presence of comorbidities, such as albuminuria, and especially the dynamic behavior of the disease, make that even patients with similar GFRs may present with different cardiovascular risk. Thus, more recent studies consider CKD an important risk factor for CVD, but not an equivalent of this disease379.

Thus, CKD should be considered in the overall context of the cardiovascular risk of each individual and should not be generalized as the equivalent of CVD for all patients. The guidelines of the Brazilian Society of Cardiology (SBC) have been considering CKD as such, either as target-organ injury in the VII Systemic Arterial Hypertension Guideline119, or as an aggravating cardiovascular risk factor in the Dyslipidemia Guideline22. Due to the significant association between the risk factors

Table 13.2 – Recommendation for inluenza approach in cardiovascular disease prevention


Evidence

– Indicate vaccination against inluenza annually for patients with established coronary heart disease or cerebrovascular disease, regardless of age

I B

– Indicate the inluenza vaccination annually for patients at high risk for coronary events, but without established cardiovascular disease, regardless of age

IIa C

Table 13.3 – Recommended approach for chronic kidney disease

(CKD) in the cardiovascular disease prevention


Evidence

Patients with chronic kidney disease should be considered very high risk for the approach of cardiovascular risk factors, being necessary to evaluate factors such as level of reduced glomerular iltration rate (GFR) and presence of comorbidities

I C

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Guidelines



for both diseases, measures of cardiovascular prevention in these patients resemble the therapeutic measures for each of them separately.

Thus, smoking cessation380, aerobic physical activity381 and weight reduction382 are part of the initial approach of these patients and should always be encouraged.

In addition to hypertension control for levels lower than 130/80 mmHg119 , diabetes control targeting a glycated hemoglobin (HbA1c) level < 7% and anemia correction, when indicated, should be considered targets to be achieved.

The use of statins for primary prevention in this population has been evaluated in several studies383,384 and showed reduction in mortality from all causes, from cardiovascular mortality383 and number of events mediated by atherosclerotic disease 384. Nevertheless, there is no consensus on the dose or the targets of lipid profile to be achieved379,384 and, therefore, an overall risk assessment of the patient is recommended according to the SBC guideline on the treatment of dyslipidemias22, taking into account that the presence of GFR < 60 mL/min, serum creatinine > 1.5 mg/dL and/or the presence of microalbuminuria are considered aggravating cardiovascular risk factors.

When choosing to initiate statin therapy, any of the drugs can be used, always starting with the lowest possible dose and gradually increasing it up to the therapeutic target, with frequent monitoring of liver enzymes and creatine phosphokinase (CPK).

Regarding antiplatelet therapy for primary prevention in patients with CKD, the evidence does not show a significant reduction in overall mortality or CVA, with significant increase in bleeding rates384,386. In a recent meta-analysis of more than 27,000 patients, the use of these drugs reduced the incidence of fatal or nonfatal myocardial infarction (reduction of three events per 1,000 treated patients), but at the cost of significant increase in the incidence of major bleeding (15 events for 1,000 treated patients), with no reduction in the frequency of CVA or mortality387.

Therefore, we recommend the evaluation of the patient’s overall cardiovascular risk, not just the consideration of CKD as enough to start treatment with these medications. Low-dose aspirin is the drug of choice due to the possible reduction in the effectiveness of clopidogrel in patients with CKD388-390.

The recommendations of this guideline for chronic kidney disease approach in cardiovascular disease prevention can be seen in Table 13.3.

Obstructive Artery Disease

As atherosclerosis is a systemic disease, the involvement of an arterial bed is often associated with the involvement of other beds, such as the carotid and coronary territories391 and thus, the presence of established peripheral artery disease (PAD), even in the absence of diabetes mellitus (DM), is considered an equivalent of coronary artery disease22, thus sharing aspects of secondary prevention of the latter392,393.

Therefore, as in KCD, the PAD shares risk factors with CVD, so that the approach to primary prevention in these patients is connected with the recommendations for the treatment of CVDs.

Changes in lifestyle, such as weight control (maintaining body mass index [BMI] ≤ 25 kg/m2), proper diet, diabetes control (target HbA1c < 7%), smoking cessation and control of hypertension aiming at BP levels ≤ 130/80 mmHg, are measures that are part of the approach to these patients.

Serum lipid control should be strict, preferably with drugs that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA-R), as several studies have shown a reduction in cardiovascular events when used in patients with PAD393-395. In the Heart Protection Study (HPS)396, for instance, the use of statins induced a reduction of 19% (relative risk) in the incidence of major cardiovascular events at five years in patients with PAD, even without proven CVD.

Thus, the recommendation is that the target should be the same for patients with manifest coronary artery disease, aiming at maintaining LDL - C levels < 100 mg/dL or, in selected cases, such as in patients with diffuse atherosclerosis or recurring events, < 70 mg/dL20,22,391.

Regarding the use of antiplatelet agents, low-dose aspirin is recommended (75-100 mg/day) for PAD patients, even without evidence of manifest coronary disease. Although the benefits are more evident in patients with symptomatic PAD (except in cases of carotid artery disease), its use is prescribed even in asymptomatic patients, because clinical presentation differences can be a confounding factor392,397-399. Clopidogrel is an alternative to aspirin in this population400.

The recommendations of this guideline for the approach of obstructive arterial disease in cardiovascular disease prevention can be seen in Table 13.4.

Socioeconomic factors

The association between high rates of mortality and low socioeconomic status has been demonstrated in Brazil and even in developed countries. An association between

Table 13.4 – Recommendation for approaching obstructive arterial

disease in cardiovascular disease prevention

Recommendation classlevel of

evidence

Patients with obstructive arterial disease should be considered at very high risk, similarly to that of manifest coronary artery disease, for approaching cardiovascular risk factors.

I C

Table 13.5 – Recommendation for the approach of socioeconomic

factors in cardiovascular disease prevention


Evedence

Socioeconomic indicators should be investigated in the clinical assessment and considered in patient management to improve quality of life and prognosis of circulatory diseases.

IIa B

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reduction in mortality from circulatory diseases (CAD) and improvement in socioeconomic indicators for each region are evident401,402. Several prospective studies have shown that low socioeconomic status, defined as low education, low income, low employment status, or live in poorer residential areas, has contributed to the increase in death from all causes, as well as the risk of mortality from CAD402-405.

Between 1930 and 1980, there was great economic development in Brazil, which despite the concentration of income, allowed educational, health, economic and infrastructure improvement, with a reduction in infectious diseases and consequently, of inflammatory processes. In developed countries, the decline in mortality from CAD started approximately 15 years after the end of World War II, which came after the Great Depression that occurred in the early 1930s and the 1918 influenza pandemic. In Brazil, this same decline began just over 40 years after the start of the economic growth period. Exposure to infectious agents and other unsanitary conditions in early life can make individuals more susceptible to the development of vascular atherothrombosis. The decline in infant mortality preceded that of mortality from CAD. It is also possible that a reduction in exposure to infectious diseases in the early stages of life is related to the observed decline in cardiovascular mortality in adults406-409.

Strong correlations have been demonstrated between the decrease in infant mortality, increase in the gross domestic product (GDP) per capita and increased schooling with the reduction in mortality from cardiovascular diseases in adults, since 1980, in the states of Rio de Janeiro, São Paulo and Rio Grande do Sul, showing that improvements in socioeconomic indicators preceded the reduction in cardiovascular deaths. The significant increase in educational levels over the past decades, which has nearly doubled in the three states, had a major impact on mortality and is associated with a reduction of more than 100 CAD deaths, with a one-year increase in the mean years of schooling in adults410.

Comprehensive improvement measures of socioeconomic indicators should be part of the paradigm for cardiovascular disease control. Socioeconomic development programs should be included in policies aiming at this control. Reductions in mortality from ischemic heart disease and cerebrovascular diseases depend not only on the health sector, but also on social policies including access to education, employment, reducing environmental risks and protection against evolutive impoverishment. These associations indicate the importance of improving life conditions of the population in order to reduce cardiovascular mortality411,412.

The evaluation of social factors in patients and individuals with cardiovascular risk factors is essential as a means to stratify future preventive efforts with the risk profile of individuals413.

The recommendations of this guideline for the approach of socioeconomic factors in the cardiovascular disease prevention can be seen in Table 13.5.

Obstructive Sleep Apnea

Obstructive sleep apnea is characterized by recurrent partial or total upper airway obstruction, with oxygen desaturation and sleep fragmentation. The adult prevalence is increasing due to increase in obesity and life expectancy of the world’s population. The estimated prevalence of moderate to important sleep disordered breathing (apnea-hypopnea index measured by events / time ≥ 15) in adult males is 10% (95% confidence interval [95% CI] = 7.12) in those aged 30-49 and 17% (95% CI = 15.21) at 50-70 years. In women it is relatively lower, being 3% (95% CI = 2.4) between 30-49 years and 9% (CI = 7.11) between 50-70 years. The estimated prevalence increased relatively from 14% to 50% over the past two decades depending on the age group considered414.

It is represented by a variety of symptoms, of which snoring and tiredness during the day are emphasized and was associated, in observational studies, to increased cardiovascular risk, cognitive alterations and mental problems. The gold standard for diagnosis is the polysomnography performed in the laboratory during the night. Obesity, hypertension, depression and diabetes have been frequently found in patients with obstructive sleep apnea. The change of lifestyle and the use of continuous positive airway pressure (CPAP) is the initial treatment of choice415.

The increase in sympathetic activity, with effects on blood pressure, and oxidative stress results in episodes of hypoxemia and is described as an intermediary mechanism associated with increased inflammatory mediators and onset of endothelial dysfunction and atherosclerosis416.

Obstructive sleep apnea is associated with 70% increase in the relative risk of cardiovascular morbidity and mortality and seems to have a complex bidirectional association, being both a cause and consequence of heart failure, arterial hypertension, arrhythmia and coronary heart disease and may worsen the course of these pathologies. Although the treatment of obstructive sleep apnea reduces the aggravation of chronic cardiovascular diseases, the reversal of treatment-related risks is not well established and randomized-controlled multicenter studies are required to elucidate this question417.

All patients with obstructive sleep apnea should be considered potential candidates for primary prevention, be submitted to cardiovascular risk stratification and be treated according to the observed risk estimates166.

Table 13.6 – Recommendation for the approach of obstructive sleep

apnea in cardiovascular disease prevention


Evidence

All patients with obstructive sleep apnea should be considered potential candidates for primary prevention; undergo cardiovascular risk stratiication and treated according to the observed risk estimates

IIa A

49

Guidelines



The recommendations of this guideline for obstructive sleep apnea approach in cardiovascular disease prevention can be seen in Table 13.6.

Erectile dysfunction

Erectile dysfunction (ED) is defined as the incapacity to achieve and maintain an erection satisfactory for sexual activity. It affects 52% of adult men aged 40-70 years and increases with advancing age. In the U.S., it is estimated to affect 18 million men aged 20 years or older and the projection for 2025 is to affect approximately 300 million men worldwide. Currently, it is believed that it could represent a sentinel marker for CVD418.

ED can result from psychological, neurological, hormonal, arterial or local disorders in the corpus cavernosum, or even the combination of these factors. Erectile dysfunction is associated with established atherosclerotic disease and increased cardiovascular risk, but the systematic research of this condition did not improve the prediction of the risk of developing CVDs, beyond that attributed to traditional risk factors166.

A meta-analysis of 20 prospective cohort studies involving 36,744 participants suggested that erectile dysfunction significantly increases the risk of ischemic heart disease, stroke and all-cause mortality and concluded that it could have an additive role in the quantification of cardiovascular risk based on traditional risk factors419.

A recent population-based Australian study420 carried out with 95,038 men aged ≥ 45 years showed that the risk of cardiovascular disease is related to the severity of erectile dysfunction in men without and with established CVD. In the first group, there was an increased risk of 1.60 (95% CI = 1.31 to 1.95) for ischemic heart disease, 8 (95% CI = 2.64 to 24.2) for heart failure and 1.92 (95% CI = 1.12 to 3.29) for peripheral vascular disease, among others. In the group with established disease, the corresponding relative risk was 1.70 (95% CI = 1.46 to 1.98), 4.40 (95% CI = 2.64 to 7.33) and 2.46 (1.63 to 3.70)420.

Changes in life style and drugs used for the treatment of traditional risk factors are effective for improving sexual dysfunction in men. All men with ED should be considered

potential candidates for primary prevention, be submitted to cardiovascular risk stratification and be treated according to the observed risk estimates166.

The recommendations of this guideline for erectile dysfunction approach in cardiovascular disease prevention can be seen in Table 13.7.

Periodontitis

The inflammatory process plays an important role in the pathogenesis of atherosclerosis, and systemic and chronic inflammatory diseases, such as periodontitis, have been associated with adverse cardiovascular outcomes.

Periodontitis is characterized by a chronic infection of the tissue that surrounds the teeth and is associated with an increase in biomarkers such as C-reactive protein, inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1β), interferon gamma (IFN-γ) and prostaglandin E2 (PGE2) as well as other inflammation mediators. Cohort and case-control studies have demonstrated the association between periodontitis and endothelial dysfunction, atherosclerosis and increased risk of AMI and CVA, although it is not possible to rule out confounding factors such as socioeconomic factors and smoking status, among others421.

A randomized, controlled, single-blind study with 120 patients with periodontitis showed significant improvement in endothelial dysfunction after six months of intensive periodontal treatment421.

More recently, the association of CKD with periodontitis has been demonstrated and its diagnosis and treatment is indicated to prevent kidney disease progression due to the concomitant presence of endothelial dysfunction and atherosclerosis385. The same was observed in association with DM423.

Periodontitis may be considered an indicator for cardiovascular health status, with local intensive treatment being indicated, as well as of associated risk factors166.

The recommendations of this guideline for the periodontitis approach in cardiovascular disease prevention can be seen in Table 13.8.

Table 13.7 – Recommended approach for erectile dysfunction in

cardiovascular disease prevention


Evidence

All men with ED should be considered potential candidates for primary prevention and should undergo cardiovascular risk stratiication and treated according to the observed risk estimate

IIa B

Table 13.8 – Recommendation for periodontitis approach in

cardiovascular disease prevention


Evidence

Patients with periodontitis should be considered for cardiovascular risk stratiication and local intensive treatment IIa B

50

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