Impact of Blood Pressure - The Importance of Achieving and Maintaining Target Goals-2

8/4/2019 Impact of Blood Pressure - The Importance of Achieving and Maintaining Target Goals-2

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Impact of Blood Pressure Impact of Blood Pressure

The Importance of Achieving andThe Importance of Achieving andMaintaining Target GoalsMaintaining Target Goals

Dr Annuar RapaeeDr Annuar RapaeeMBBS(Malaya); MRCP(UK); AdvMCard(UKM); CCMR(GermanyMBBS(Malaya); MRCP(UK); AdvMCard(UKM); CCMR(Germany

AM; FNHAM; FAsCC;FACCAM; FNHAM; FAsCC;FACC

Consultant Cardiologist Serdang HospitalConsultant Cardiologist Serdang Hospital..

PMPL000701MYSG201004


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Lecture Outline:Lecture Outline:

Burden of HypertensionBurden of Hypertension

What guidelines tell us ?What guidelines tell us ?

Choosing the ideal blood pressureChoosing the ideal blood pressure

Impact of blood pressure treatmentImpact of blood pressure treatment


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Burden of Hypertension iBurden of Hypertension iMalaysiaMalaysia

PMPL000501MYSG201004


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The prevalence of hypertension in Malaysians aged 30 yearsThe prevalence of hypertension in Malaysians aged 30 years

and above was 42.6% in 2006and above was 42.6% in 2006

Hypertension is a silent disease; 4.8 million individuals withHypertension is a silent disease; 4.8 million individuals with

hypertension in Malaysia, the majority of cases (64%) inhypertension in Malaysia, the majority of cases (64%) in

the country remain undiagnosed.the country remain undiagnosed.

Prevalence of Hypertension in MalaysiaPrevalence of Hypertension in Malaysia


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2029 3039 4049 5059 6069 70

Prevalence of Hypertension by AgePrevalence of Hypertension by Age

and Genderand Gender

Age


6/93WHO World Health Report 2004

CV diseases

Cancer

Infectious andparasitic diseases

Other non-infectiousdiseases

Injuries

Respiratory diseases

Respiratory infections

Maternal and perinatal conditionsNutritional deficiencies

Cardiovascular Disease Leading Cause of GlobaCardiovascular Disease Leading Cause of Globa

MortalityMortality


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Global Mortality : Risk FactorsGlobal Mortality : Risk Factors

Ezzati et al. Lancet. 2002;360:1347-1360

Attributable Mortality x 1000

High mortality, developing region

Lower mortality, developing region

Developed region

0 80007000600050004000300020001000

High blood pressure

Tobacco

High cholesterol

Unsafe sex

High BMI

Physical inactivity

Alcohol

Indoor smoke from solid fuels

Iron deficiency

Underweight


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Cardiovascular Disease : AdmissionCardiovascular Disease : Admission

Government Hospital 1985 - 2000Government Hospital 1985 - 2000

Hypertensive Disease

Ischaemic Heart Disease

Disease of Pulmonary Circulation &other Forms of Heart Disease

Cerebrovascular Disease

Disease of Arteries, Veins, LymphaticVessels & Unspecified Disorders of theCirculatory System

Rheumatic Fever & Rheumatic Heart Disease

Data from MOH,

C di l Di D thCardiovascular Disease : Deaths


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Cardiovascular Disease : DeathsCardiovascular Disease : Deaths

Government Hospital 1985 - 2000Government Hospital 1985 - 2000

6205

6058

5959

6221

6336

6574

6475

6535

6352

67157071

7249

7496

7307

7559

781

Data from MOH

Th C di l C i


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Atherosclerosis

& LVH

Risk eg Hypertension

Remodelling VentricularDilation

CHF

End-stage

microvascular &heart disease

Death

MI

Adapted from Dzau et al.

The Cardiovascular ContinuumThe Cardiovascular Continuum


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Hypertension : Increased CV RiskHypertension : Increased CV Risk

Framingham Heart Study

Coronary Disease Stroke Peripheral Artery

Disease

Cardiac Failure

BiennialA

ge-AdjustedRate

per

100

0

Kannel et al JAMA 1996

3 - 4 times2 times 3 - 4 times


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20-74 75-84 85-94 95-104 105-160DBP, mm Hg

Risk of CV Events Increases with Diastolic BPRisk of CV Events Increases with Diastolic BP

Framingham study 38-year follow-upFramingham study 38-year follow-up

Kannel. Am J Cardiol 2000

0

10

20

30

40

50Age-adjusted annual rate Percent of events

0

10

20

30

40

50

Rate/1000 women Rate/1000 men

Events in women Events in men


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Risk of CV Events Increases with Systolic BPRisk of CV Events Increases with Systolic BP

Framingham study 38-year follow-upFramingham study 38-year follow-up

74-119 120-139 140-159 160-179 180-300SBP, mm Hg

0

10

20

30

40

50Age-adjusted annual rate Percent of events

0

10

20

30

40

50

Kannel. Am J Cardiol 2000

Rate/1000 women Rate/1000 men

Events in women Events in men

f S CRi k f St k d C H t


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Stroke CHD7 prospective observational studies 9 prospective observational studies

MacMahon et al. Lancet 1990

Risks of Stroke and Coronary HeartRisks of Stroke and Coronary Heart

Disease Increases with Diastolic BPDisease Increases with Diastolic BP

Approximate mean DBP, mm Hg

76 84 91 98 105

Relative risk of stroke

76 84 91 98 105

4.00

2.00

1.00

0.50

0.25

Relative risk of CHD

4.00

2.00

1.00

0.50

0.25

CV risk Doubles with Each BP Rise ofCV risk Doubles with Each BP Rise of


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Lewington et al Lancet 2003

* Individuals aged 40-70 yrs, starting at BP 115/75

CV risk Doubles with Each BP Rise ofCV risk Doubles with Each BP Rise of

20/10 mmHg20/10 mmHg

C A t Di (CAD) i th M tCoronary Artery Disease (CAD) is the Most


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Coronary Artery Disease (CAD) is the MostCoronary Artery Disease (CAD) is the Most

Common Cause of Morbidity and Mortality inCommon Cause of Morbidity and Mortality in

Patients with HypertensionPatients with Hypertension

* Individuals aged 40-70 years, starting at BP 115/75 mm Hg

CV mortality risk

Blood pressure (mm Hg)

0

1

2

3

4

5

6

7

8

115/75 135/85 155/95 175/105

Lewington et al. Lancet 2003JNC VII. JAMA 2003


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Erdine. European Society of Hypertension Scientific Newsletter 2000

Hypertension Poorly Controlled WorldwideHypertension Poorly Controlled Worldwide

Percentage of Patients with Controlled BP (


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Blood Pressure Control in MalaysiaBlood Pressure Control in Malaysia

Proportion of patients (%)

NHMS;1996

by MOH 21,000 subjects > 30yr - 33% HPT, only 23% on Rx and only 6% < 140/90 mmHg Manjung Hosp,Perak Hypertension Survey 2003

397 subjects, 98% > 30yr 22.9% HPT, 45% on Rx, 55% not aware and only 22.6% < 140/90 mmHgGHKL Physician clinic 2005

N=222 patients, 22.1% one drug,33.3% 2 drugs,34.2% 3 drugs, 8.1% 4 drugs.

10.8% BP140/90mmHg.


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The Rule of HalvesThe Rule of Halves **********

Only 1/2 have been diagnosedOnly 1/2 have been diagnosed

Only 1/2 of those diagnosed have been treatedOnly 1/2 of those diagnosed have been treated

Only 1/2 of those treated are adequately controlledOnly 1/2 of those treated are adequately controlled

Thus, only 12.5% overall are adequately controlledThus, only 12.5% overall are adequately controlled

1999

HOImpact of HypertensionImpact of Hypertension


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HOImpact of HypertensionImpact of Hypertension

Untreated or sub-optimally controlled hypertension leads toincreased cardiovascular, cerebrovascular and renalmorbidity and mortality

In persons older than 50 years, SBP > 140 mmHg is a muchmore important CVD risk factor than DBP

Risk of CVD beginning at 115/75 mmHg doubles with eachincrement of 20/10 mmHg Individuals who are normotensive at age 55 have a 90%

lifetime risk of developing hypertension

Clinical Practice Guidelines Management off Hypertension (3rd Edition Feb 2008)

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (August 2004)


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Choosing the ideal blood pressureChoosing the ideal blood pressure

Impact of blood pressure treatmentImpact of blood pressure treatment

Blood Pressure has Multiple


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Sympathetic nervous system

Renin-angiotensin system

Total body sodium

Patient 1 Patient 2 Patient 3

B. Waeber, March 2007, with permiss

Blood Pressure has MultipleRegulatory Pathways


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Questions to be AnsweredQuestions to be Answered

What is high blood pressure?

Clinical evaluation - what should be done?

Which factors influence prognosis?

Do patients benefit from antihypertensive treatment?

CPG Management of HypertensionCPG Management of Hypertension


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JNC 7JNC 7


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JNC 7JNC 7

JNC 7JNC 7


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JNC 7JNC 7


JNC 7JNC 7


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JNC 7JNC 7


UK NICE Guidelines for treatment of HypertensiUK NICE Guidelines for treatment of Hypertensi


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The update of the NICE guideline on hypertension in

primary care was undertaken because recent large

clinical outcome trials had provided new information

about the pharmacological treatment of

hypertension.


June 2007June 2007

National Institute of Health and Clinical Excellence (NICE) NICE Clinical Guidelines (Published August 2004)



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According to the new NICE guidelines for treatment ofhypertension of June 2006, calcium channel blockers or

thiazide-type diuretics are now recommended for initial

treatment in patients over 55 years of age and in black

patients of all ages.

ACE-inhibitors or Angiotensin-II Receptor Antagonists (if

ACE-inhibitors are not tolerated) are recommended for

younger patients.


June 2007June 2007




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Beta-blockers are no longer considered apreferred routine initial therapy in the generalpopulation, but are still to be considered as initialtherapy in younger patients, e.g. those withincreased sympathetic drive and those withintolerance or contraindications to ACE-inhibitorsand angiotensin-II antagonists.


June 2007June 2007




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UK NICE Guidelines for treatment of Hypertensiyp

June 2007June 2007


New (1999) WHO-ISH Definitions andNew (1999) WHO-ISH Definitions and


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New (1999) WHO ISH Definitions andNew (1999) WHO ISH Definitions andClassification of BP LevelsClassification of BP Levels

Category Systolic BP Diastolic BP(mm Hg) (mm Hg)

Optimal BP


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Clinical Evaluation - What Should Be Done?Clinical Evaluation - What Should Be Done?

Exclude secondary causes of hypertension

To ascertain the presence or absence of target organ damage

To assess lifestyle and identify other cardiovascular risk factors or concomdisorders that affect risk factors, prognosis and guide treatment

Such information is obtained from adequate history, physical

examination, laboratory investigations and other diagnostic

procedures




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Risk factors of CVD

I. Used for risk stratification

II.Other factors adversely influencing

prognosis

Target organ damage (TOD)

Associated clinical conditions (ACC)


1999 WHO-ISH Hypertension Practice Guidelines for Primary Care Physicians

Which Factors Influence Prognosis?Which Factors Influence Prognosis?


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Decisions should not be made on BP alone, but also opresence of other risk factors, target organ damage, an

concomitant diseases, as well as on other aspects

patients personal, medical, social, economic, ethnic, an

cultural characteristics


More Than 80% of Patients with


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40

30

20

10

0None

Hypertensiv

epatients(%)

1 2 3 4

Additional risk factors

Mancia et al. J Hypertens 2004;22:517Copyright 2004, with permission from Lippincott, Williams and Wilkins

o e a 80% o at e ts tHypertension Have Additional Risk Factors

14

40

32

12

2



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Risk Factors for CVD


Major Risk Factors

Hypertension Cigarette Smoking Central Obesity

Physical Inactivity Dyslipidaemia Diabetes Mellitus Microalbuminurea Estimated GFR < 60 mL/min) Age (>55 years for men, >65 years for women)

Family History of Premature Cardiovascular Disease (


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Risk Factors for CVD


Target Organ Damage

Heart Left Ventricular Hypertrophy Angina or Prior Myocardial Infarction

Prior Coronary Revascularization

Brain Stroke or Transient Ischaemic Attack

Chronic Kidney Disease

Peripheral Arterial DiseaseRetinopathy




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Associated Clinical Conditions (ACC)


Cerebrovascular Disease Ischaemic Stroke Cerebral Haemorrhage Transient Ischaemic Attack (TIA)

Heart Disease Myocardial Infarction Angina Pectoris Coronary Revascularization Congestive Heart Failure




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Associated Clinical Conditions (ACC)


Renal Disease Diabetic nephropathy Renal Failure, Plasma Creatinine Concentration > 177 mmol/L (>2.0 mg/dL)

Vascular Disease

Dissecting Aneurysm Symptomatic Arterial Disease

Advanced Hypertensive Retinopathy Haemorrhages or Exudates Papillpedema


Stratifying Risk Quantifying PrognosisStratifying Risk Quantifying Prognosis


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Stratifying Risk Quantifying PrognosisStratifying Risk Quantifying Prognosis




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Low risk =


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Example 1:

65-year old man with diabetes, TIAs, and BP of 145/90 mm Hg

will have annual risk of major CVD event 20 times greater than

40-year old man with same BP but without diabetes or history ofCVD

gg



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Example 2:

40-year old man with BP of 170/105 mm Hg will have risk of

major CV event 2-3 times greater than man of same age with

BP of 145/90 mm Hg and similar other risk factors

gg

L t O tliLecture Outline:


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Choosing the ideal blood pressureChoosing the ideal blood pressure Impact of blood pressure treatmentImpact of blood pressure treatment

HO


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The relationship between BP and risk of CVD

events is continuous, consistent and independent of

other risk factors.

The higher the BP, the greater is the chance of

heart attack, heart failure, stroke and kidney disease


HO


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What physicians do in regards to

cardiovascular diseases is important

S Julius 1998

HO


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Treatment adaptation of hypertensive patients not on target

Unchanged repeat84%

Dose increaseAddition

Switch

Based on 7 246 treated hypertensive patients whose diastolic bloodpressure was not on target in France, Germany, Italy, Spain and UK

Copyright 1992 CardioMonitor

, Taylor Nelson HealtS Julius 1998

HOBenefits of Lowering Blood PressureBenefits of Lowering Blood Pressure


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Antihypertensive therapy reduces the incidence of

Stroke by 35 40%

Myocardial Infarction by 20 25%

Heart Failure by >50%


HOBenefits of Lowering Blood PressureBenefits of Lowering Blood Pressure


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Antihypertensive therapy

In patients with Stage 1 hypertension and additional CV risk

factors, achieving 12mmHg reduction in SBP over 10 years

Prevents 1 death for 11 patients treated

In presence of CVD or target organ damage

Only 9 patients would require BP reduction to prevent 1 death


HOGoals of TherapyGoals of Therapy


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JNC 7

The ultimate public health goal of Antihypertensive

therapy is the reduction of cardiovascular and renalmorbidity and mortality


HOIntensive BP Control Reduces CV RiskIntensive BP Control Reduces CV Risk


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Relative Risk (95% CIs)Relative Risk (95% CIs)

1.01.0 1.251.25

More Intensive BPControl Better

Less Intensive BControl Better

0.50.5

StrokeStroke

Coronary Heart DiseaseCoronary Heart Disease

Heart FailureHeart Failure

BPLTTC Lancet 2003

Major CV EventsMajor CV Events

CV DeathCV Death

Total MortalityTotal Mortality

HO


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Hypertension Optimal Treatment

A Landmark Study

A 3.8-Year International Study Of18,790 Patients

Malaysia was one of the

investigation centres

HOT Study, Hansson & Zanchetti, 1998)

HOPrimary Analysis of the HOT StudyPrimary Analysis of the HOT Study


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to assess the relationship between major cardiovascularevents and three target diastolic blood pressures (< 90, 27 kg/m2

Treatment Flow Chart


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Study Endpoints


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Primary Endpoint

Time to first stroke

Prespecified Secondary Endpoints

All cardiovascular events

All cardiac events Death from any cause

Recruitment


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Baseline Patient Characteristics


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Difference in Blood Pressure


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Difference in Blood Pressure

Reduction of 4.2/2.1 mmHg in the felodipine group

Primary Outcome27% RR in All Strokes


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Lower incidences of CV events among felodipine

patients


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patients

Secondary Outcomes

27% RR in total cardiovascular events


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27% RR in total cardiovascular events

Secondary Outcomes31% RR in all cause death


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Other Observations32% RR in coronary events


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Other Observations

33% RR in cardiovascular death


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33% RR in cardiovascular death

Felodipine ER was Well-Tolerated


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Adverse events reported during treatment

Discussion


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The FEVER study shows that in Chinese hypertensive patient

receiving a small dose of the diuretic hydrochlorothiazide (12.5 mgonce a day) the addition of a small dose of the calcium antagonistfelodipine (5 mg once a day), instead of placebo, is accompanied bya further SBP/DBP decrease of 4/2 mmHg (despite a more frequentadd-on therapy in the placebo group

Discussion


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Marked reductions in

fatal and non-fatal stroke (27%, P = 0.001), total cardiovascular events (27%, P < 0.001),

total cardiac events (34%, P 0.012),

coronary events (32%, = 0.024), c

cardiac failure (30%, NS),

death by any cause(31%, = 0.006), cardiovascular death (17%, P = 0.019), and

cancer (36%, P = 0.017).

Relevant Clinical Conclusions FEVER


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Even a small difference in SBP/DBP, amounting to

approximately 4/2 mmHg, can be associated withsubstantial reductions in the incidence of most types ofcardiovascular events in Chinese hypertensive patients

Relevant clinical conclusions FEVER


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It substantiates and supports guidelines recommendations, andindicates that even small differences in the control of SBP just belowand just above the 140 mmHg goal (and DBP just below and above85 mmHg) are accompanied by substantial differences in outcomes.

SBP and DBP values achieved in the felodipine group of FEVERclosely correspond to the SBP/DBP values of 138.5/82.6 mmHg(138.1/82.3 mmHg) indicated as optimal blood pressures in the HOTstudy

Relevant Clinical Conclusions FEVER


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FEVER shows the benefits of treating hypertension with a low-

dose combination of antihypertensive agents The results of FEVER directly show that adding a low

dihydropyridine dose to a low-dose thiazide diuretic furtherreduces blood pressure and cardiovascular outcomes

HO


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THANK YOU

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Impact of Blood Pressure - The Importance of Achieving and Maintaining Target Goals-2