Cardiometabolic Syndrome (2)

Cardiometabolic Syndrome

Nabil SulaimanHOD Family and Community Medicine, Sharjah

University and University of Melbourne

&Dr Dhafir A. Mahmood

Consultant EndocrinologistAl- Qassimi & Al-Kuwait Hospital

Sharjah

Cardiometabolic Syndrome II

Aims

• Abdominal obesity prevalence

• Targeting Cardiometabolic Risk factors

• Multiple Risk Factor management

• A Critical Look at the Metabolic Syndrome

Clustering of ComponentsClustering of Components::

• Hypertension: BP. > 140/90

• Dyslipidemia: TG > 150 mg/ dL ( 1.7 mmol/L )

HDL- C < 35 mg/ dL (0.9 mmol/L)

• Obesity (central): BMI > 30 kg/M2

Waist girth > 94 cm (37 inch)

Waist/Hip ratio > 0.9

• Impaired Glucose Handling: IR , IGT or DM

FPG > 110 mg/dL (6.1mmol/L)

2hr.PG >200 mg/dL(11.1mmol/L)

• Microalbuninuria (WHO)

Global cardiometabolic risk*

Gelfand EV et al, 2006; Vasudevan AR et al, 2005* working definition

The new IDF definition focusses on abdominal obesity

rather than insulin resistance

International Diabetes Federation (IDF) Consensus Definition 2005

Why a New Definition of the MeS: IDF Objectives

Needs:

• To identify individuals at high risk of developing

cardiovascular disease (and diabetes)

• To be useful for clinicians

• To be useful for international comparisons

Fat Topography In Type 2 Diabetic Subjects

Intramuscular

Intrahepatic

Subcutaneous

Intra-abdominal

FFA*TNF-alpha*Leptin*IL-6 (CRP)*Tissue Factor*PAI-1*

Angiotensinogen*

Abdominal obesity and increased risk of cardiovascular events

Dagenais GR et al, 2005

Ad

just

ed r

elat

ive

risk

1 1 1

1.17 1.16 1.14

1.29 1.27

1.35

0.8

1

1.2

1.4

CVD death MI All-cause deaths

Tertile 1

Tertile 2Tertile 3

Men Women<95

95–103>103

<87

87–98>98

Waistcircumference (cm):

The HOPE study

Adjusted for BMI, age, smoking, sex, CVD disease, DM, HDL-cholesterol, total-C; CVD: cardiovascular disease; MI: myocardial infarction; BMI: body mass index; DM: diabetes mellitus; HDL: high-density lipoprotein cholesterol

Abdominal obesity increases the risk of developing type 2 diabetes

<71 71–75.9 76–81 81.1–86 86.1–91 91.1–96.3 >96.3

24

20

16

12

8

4

0

Rel

ativ

e ri

sk

Waist circumference (cm)

Carey VJ et al, 1997

Abdominal obesity is linked to an increased risk of coronary heart disease

Waist circumference has been shown to be independently associated with increased age-adjusted risk of CHD, even after

adjusting for BMI and other cardiovascular risk factors

0.0

0.5

1.0

1.5

2.0

2.5

3.0

<69.8 69.8<74.2 74.2<79.2 79.2<86.3 86.3<139.7

1.27

2.06 2.31

2.44p for trend = 0.007

Rel

ativ

e ri

sk

Quintiles of waist circumference (cm)

Rexrode KM et al, 1998

CHD: coronary heart disease; BMI: body mass index

Diabetes in the new millenniumInterdisciplinary problem

Diabetes


OBESITY


DIAB

ESITY

TargetingTargeting

Cardiometabolic RiskCardiometabolic Risk

Central obesity: a driving force for cardiovascular disease & diabetes

“Balzac” by RodinFront

Back

Insulin Resistance: Associated Conditions

Linked Metabolic AbnormalitiesLinked Metabolic Abnormalities::

• Impaired glucose handling/ insulin resistance

• Atherogenic dyslipidemia

• Endothelial dysfunction

• Prothrombotic state

• Hemodynamic changes

• Proinflammatory state

• Excess ovarian testosterone production

• Sleep-disordered breathing

Resulting Clinical ConditionsResulting Clinical Conditions::

• Type 2 diabetes

• Essential hypertension

• Polycystic ovary syndrome (PCOS)

• Nonalcoholic fatty liver disease

• Sleep apnea

• Cardiovascular Disease (MI, PVD, Stroke)

• Cancer (Breast, Prostate, Colorectal, Liver)

Multiple Risk Factor ManagementMultiple Risk Factor Management

• Obesity

• Glucose Intolerance

• Insulin Resistance

• Lipid Disorders

• Hypertension

• Goals: Goals: Minimize Risk of Type 2 Minimize Risk of Type 2 Diabetes and Cardiovascular DiseaseDiabetes and Cardiovascular Disease

Glucose AbnormalitiesGlucose Abnormalities::

• IDF:IDF:– FPG >100 mg/dL (5.6 mmol. L) or previously

diagnosed type 2 diabetes

– (ADA: FBS >100 mg/dL [ 5.6 mmol/L ])

HypertensionHypertension::

• IDF:IDF:– BP >130/85 or on Rx for previously

diagnosed hypertensionhypertension

DyslipidemiaDyslipidemia::

• IDF:IDF:– Triglycerides - >150mg/dL (1.7 mmol /L)– HDL - <40 mg/dL (men), <50 mg/dL

(women)

Public Health ApproachPublic Health Approach

Screening/Public Health ApproachScreening/Public Health Approach

• Public Education

• Screening for at risk individuals:– Blood Sugar/ HbA1c– Lipids– Blood pressure– Tobacco use– Body habitus– Family history

Life-Style Modification: Is it Important?Life-Style Modification: Is it Important?

• Exercise– Improves CV fitness, weight control, sensitivity

to insulin, reduces incidence of diabetes

• Weight loss– Improves lipids, insulin sensitivity, BP levels,

reduces incidence of diabetes

• Goals: Goals: Brisk walking - 30 min./dayBrisk walking - 30 min./day 10% reduction in body wt.10% reduction in body wt.

Smoking Cessation / AvoidanceSmoking Cessation / Avoidance::

• A risk factor for development in children and adults

• Both passive and active exposure harmful

• A major risk factor for:– insulin resistance and metabolic syndrome– macrovascular disease (PVD, MI, Stroke)– microvascular complications of diabetes– pulmonary disease, etc.

Diabetes Control - How ImportantDiabetes Control - How Important??

GoalsGoals:

• FBS - premeal <110, FBS - premeal <110,

• postmealpostmeal <180. <180.

• HbA1c <7%HbA1c <7%• For every 1% rise in Hb A1c there is an 18% rise in risk

of cardiovascular events & a 28% increase in peripheral arterial disease

• Evidence is accumulating to show that tight blood sugar control in both Type 1 and Type 2 diabetes reduces risk of CVD

Lifestyle modification

• Diet• Exercise• Weight loss• Smoking

cessation

If a 1% reduction in HbA1c is achieved, you could

expect a reduction in risk of:

• 21% for any diabetes-related endpoint

• 37% for microvascular complications

• 14% for myocardial infarction

However, compliance is poor and most patients will require oral pharmacotherapy within a few years of diagnosis

Stratton IM et al. BMJ 2000; 321: 405–412.

Overcome Insulin Resistance/ DiabetesOvercome Insulin Resistance/ Diabetes::

• Insulin Sensitizers:– Biguanides – metformin– Glitazones, Gltazars – Can be used in combination

• Insulin Secretagogues:– Sulfonylurea - glipizide, glyburide,

glimeparide, glibenclamide– Meglitinides - repaglanide, netiglamide

BP Control - How ImportantBP Control - How Important??

• Goal: BP.BP.<130/80<130/80• MRFIT and Framingham Heart Studies:

– Conclusively proved the increased risk of CVD with long-term sustained hypertension

– Demonstrated a 10 year risk of cardiovascular disease in treated patients vs non-treated patients to be 0.40.

– 40% reduction in stroke with control of HTN

• Precedes literature on Metabolic Syndrome

Lipid Control - How ImportantLipid Control - How Important??

• Goals:Goals: HDL >40 mg% (>1.1 mmol /l) HDL >40 mg% (>1.1 mmol /l)

LDL LDL <100 mg/dL (<3.0 mmol /l)<100 mg/dL (<3.0 mmol /l)

TG <150 mg% (<1.7 mmol /l)TG <150 mg% (<1.7 mmol /l)

• Multiple major studies show 24 - 37% reductions in cardiovascular disease risk with use of statins and fibrates in the control of hyperlipidemia.

Substantial residual cardiovascular Substantial residual cardiovascular risk in statin-treated patientsrisk in statin-treated patients

Placebo Statin

Year of follow-up

% p

atie

nts

0 1 2 3 4 5 6

10

20

30

0

Risk reduction=24%(p<0.0001)

The MRC/BHF Heart Protection Study

Heart Protection Study Collaborative Group, 2002

19.8% of statin-treatedpatients had a majorcardiovascular event by 5 years

MedicationsMedications::

• Hypertension:– ACE inhibitors, ARBs– Others - thiazides, calcium channel

blockers, beta blockers, alpha blockers– Central acting Alfa agonist : Moxolidin

• Dylipidemia:– Statins, Fibrates, Niacin

• Platelet inhibitors:– ASA, clopidogrel

Individual metabolic abnormalities among Qatari population according to gender (Musallam et al 08)

Men (n = 405) Women (n=412)

Variable n(%) n(%) p-ValueATP III

Abdominal obesity 227(56.0) 308(74.8) <0.001

Hypertension 143(35.3) 156(37.9) 0.448

Diabetes 77(19.0) 107(26.0) 0.017

Hypertriglyceridemia 113(27.9) 83(20.1) 0.009

Low HDL 95(23.5) 121(29.4) 0.055

Individual metabolic abnormalities among Qatari population according to gender

Men (n = 405) Women (n=412)Variable n(%) n(%) p-Value

None 88(21.7) 74(18.0) –

One 103(25.4) 100(24.3) 0.033

Two 125(30.9) 111(26.9) –

Three or more 89(22.0) 127(30.8) –

No of components of ATP III

Prevalence of MeS in different Countries

CountryYear SamplePrevalence (%)

Arab Americans200354223

Oman2001141921

Jordan2002112136

Saudi Arabia2004225020.8

Palestine199817*

Qatar200781727.6

Turkey2004163733.4*

Iran?1036833.7

* Crude rates Mussallam et al. Int J Food Safety and PH 2008

A Critical Look at the Metabolic SyndromeA Critical Look at the Metabolic Syndrome

Is it a Syndrome?*Is it a Syndrome?*• “…too much clinically important information

is missing to warrant its designations as a syndrome.”

• Unclear pathogenesis, Insulin resistance is not a consistent finding in some definitions.

• CVD risks has not shown to be greater than the sum of it’s individual components.

*ADA


Research

• “Until much needed research is

completed, clinicians should evaluate and

treat all CVD risk factors without regard to

whether a patient meets the criteria for

diagnosis of the ‘metabolic syndrome’.”


Lifestyle

• The advice remains to treat individual risk

factors when present & to prescribe

therapeutic lifestyle changes & weight

management for obese patients with

multiple risk factors.


Determinants and dynamics of the CVD Epidemic in the developing

Countries Data from South Asian Immigrant studies

• Excess, early, and extensive CHD in persons of South Asian origin

• The excess mortality has not been fully explained by the major conventional risk factors.

• Diabetes mellitus and impaired glucose tolerance highly prevalent. (Reddy KS, circ 1998).

• Central obesity, ↑triglycerides, ↓HDL with or without glucose intolerance, characterize a phenotype.

• genetic factors predispose to ↑lipoprotein(a) levels, the central obesity/glucose intolerance/dyslipidemia complex collectively labeled as the “metabolic syndrome”

Determinants and dynamics of the CVD epidemic in the developing

countries

Other Possible factors

• Relationship between early life characteristics and susceptibility to NCD in adult hood ( Barker’s hypothesis) (Baker DJP,BMJ,1993)

– Low birth weight associated with increased CVD

– Poor infant growth and CVD relation

•Genetic–environment interactions(Enas EA, Clin. Cardiol. 1995; 18: 131–5)

- Amplification of expression of risk to some environmental changes esp. South Asian population)

- Thrifty gene (e.g. in South Asians)

CVD epidemic in developing &developed countries. Are they

same?• Urban populations have higher levels of CVD risk

factors related to diet and physical activity (overweight, hypertension, dyslipidaemia and diabetes)

• Tobacco consumption is more widely prevalent in rural population

• The social gradient will reverse as the epidemics mature.

• The poor will become progressively vulnerable to the ravages of these diseases and will have little access to the expensive and technology-curative care.

• The scarce societal resources to the treatment of these disorders dangerously depletes the resources available for the ‘unfinished agenda’ of infectious and nutritional disorders that almost exclusively afflict the poor

Burden of CVD in Pakistan

Coronary heart disease

Mortality statistics • Specific mortality data ideal for making

comparisons with other countries are not available

• Inadequate and inappropriate death certification, and multiple concurrent causes of death

Central obesity: a driving force for cardiovascular disease & diabetes

“Balzac” by RodinFront

Back

Why people physically inactive?

• Lack of awareness regarding the of physical activity for health fitness and prevention of diseases

• Social values and traditions regarding physical

exercise (women, restriction).

• Non-availability public places suitable for physical activity (walking and cycling path, gymnasium).

• Modernization of life that reduce physical activity (sedentary life, TV, Computers, tel, cars).


Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994

Pre

vale

nc

e (

%)

P

reva

len

ce

(%

)

05

10

15

2025

3035

40

45

20-29 30-39 40-49 50-59 60-69 > 70

MenMenWomenWomen

Age (years)Age (years)Ford E et al. JAMA. 2002(287):356.Ford E et al. JAMA. 2002(287):356.

1999-2002 Prevalence by IDF vs. NCEP Definitions (Ford ES, Diabetes Care 2005; 28: 2745-9) (unadjusted, age 20+)NCEP : 33.7% in men and 35.4% in women IDF: 39.9% in men and 38.1% in women

Prevention of CVD

• There is an urgent need to establish appropriate research studies, increase awareness of the CVD burden, and develop preventive strategies.

• Prevention and treatment strategies that have been proven to be effective in developed countries should be adapted for developing countries.

• Prevention is the best option as an approach to reduce CVD burden.

• Do we know enough to prevent this CVD Epidemic in the first place.

The new IDF definition focusses on

abdominal obesity rather than insulin

resistance



Central Obesity

Waist circumference – ethnicity specific*

– for Europids: Male > 94 cm

Female > 80 cm

plus any two of the following:

Raised triglycerides> 150 mg/dL (1.7 mmol/L)

or specific treatment for this lipid abnormality

Reduced HDL cholesterol< 40 mg/dL (1.03 mmol/L) in males

< 50 mg/dL (1.29 mmol/L) in females

or specific treatment for this lipid abnormality

Raised blood pressureSystolic : > 130 mmHg or

Diastolic: > 85 mmHg or

Treatment of previously diagnosed hypertension

Raised fasting plasma glucose

Fasting plasma glucose > 100 mg/dL (5.6 mmol/L) or

Previously diagnosed type 2 diabetes

If above 5.6 mmol/L or 100 mg/dL, OGTT is strongly recommended but is not necessary to define presence of the syndrome.

Treatment of Metabolic Syndrome: 2005

AspirinDiet,

Exercise, Lifestyle

change

Stop smoking

CB1 Receptor Blocker

Oral hypoglycaemics

Antihypertensives

Statins & Fibrates

Insulin

ACEI &/or A2 receptor blockers

Primary management for the Metabolic Syndrome is healthy lifestyle promotion. This includes:

• moderate calorie restriction (to achieve a 5-10% loss of body weight in the first year)

• moderate increases in physical activity

• change dietary composition to reduce saturated fat and total intake, increase fibre and, if appropriate, reduce salt intake.

Recommendations for treatment

• Appropriate & aggressive therapy is essentialfor reducing patient risk of cardiovascular disease

• Lifestyle measures should be the first action

• Pharmacotherapy should have beneficial effects on– Glucose intolerance/diabetes– Obesity– Hypertension– Dyslipidaemia

• Ideally, treatment should address all of the components of the syndrome and not the individual components

Management of the Metabolic Syndrome

Summary: new IDF definition for the Metabolic Syndrome

The new IDF definition addresses both clinical and research needs :

•provides a simple entry point for primary care physicians to diagnose the Metabolic Syndrome

•providing an accessible, diagnostic tool suitable for worldwide use, taking into account

ethnic differences

•establishing a comprehensive ‘platinum standard’ list of additional criteria that should

be included in epidemiological studies and other research into the Metabolic Syndrome

Health & Medicine

Cardiometabolic Syndrome (2)