VENICE CHAIRIADI, MD FIHA

Hypertension
More Than Just High BP

A complex syndrome in which neurohumoral and

metabolic abnormalities influence development
and progression of vascular disease and clinical
events

A complex inherited syndrome of cardiovascular risk factors

Hypertension Syndrome
Giles,TD, JCI Suppl,2005
Proportion of deaths attributable to leading
risk factors worldwide (2000)

Systolic blood pressure

greater than 115 mmHg

0 1 2 3 4 5 6 7 8
Attributable Mortality

WHO 2000 Report. Lancet. 2002;360:1347-1360.

 Cardiovascular Mortality Risk Doubles with Each 20/10 mmHg
Increment in Systolic/Diastolic BP*

Cardiovascular mortality risk

8
8X
risk
6

4
4X
risk
2
2X
1X risk risk
0
115/75 135/85 155/95 175/105
Systolic BP/Diastolic BP (mmHg)

*Individuals aged 40–69 years Lewington et al. Lancet 2002;360:1903–13

RISKESDAS 2013

Sumber Data : Riskesdas 2013

CIRCADIAN RHYTHM
PATOGENESIS
Blood Pressure Reduction Is Critical:
the Lower, the Better

Meta-analysis of 61 prospective, observational studies

1 million adults
12.7 million person-years
7% reduction
in risk of
ischemic heart
2–mm Hg
disease
decrease in
mean SBP 10% reduction in
risk of stroke
mortality

*Epidemiologic studies, not clinical trials of hypertension agents.

Lewington S et al. Lancet. 2002;360:1903-1913.

 Integrated Perspective on CV Risk Factors and
Vascular Disease
Endothelial Dysfunction

Oxidative Stress & Inflammation

CV
Disease

Ross. N Engl J Med. 1999;340:115-126.

Ross. N Engl J Med. 1999;340:115-126.

 Hypertension-thrombosis via Ang II

 LDL  BP Diabetes Smoking

Oxidative Stress

Endothelial Dysfunction and Smooth Muscle

Activation
 NO • ∆ Local Mediators •  Tissue ACE, AII

PAI-1, Platelet Growth Factors

Endothelin VCAM/ICAM Proteolysis
Aggregation, Cytokines
Catecholamines Cytokines Inflammation
Tissue Factor Matrix

Vascular Lesion
Vasoconstriction Thrombosis Inflammation Plaque Rupture and Remodeling

Reprinted with permission from Dzau VJ. Hypertension. 2001;37:1047-1052.

 Progression From Hypertension
to Heart Failure

Obesity LVH
Diabetes Diastolic
Dysfunction
Hypertension CHF
Smoking
Systolic
Dyslipidemia
Diabetes MI Dysfunction

Normal LV LV Subclinical LV Overt Heart

Structure Remodeling Dysfunction Failure
and Function
LVH, left ventricular hypertrophy; MI, myocardial infarction; CHF, chronic heart failure.
Vasan RS and Levy D. Arch Intern Med. 1996;156:1789-1796.
Non-pharmacological/ lifestyle
Pharmacological
 Lifestyle Modifications

Modification Approximate SBP reduction

(range)

Weight reduction 5–20 mmHg/10 kg weight loss

Adopt DASH eating plan 8–14 mmHg

Dietary sodium reduction 2–8 mmHg

Physical activity 4–9 mmHg

Moderation of alcohol 2–4 mmHg

consumption
Non-pharmacological interventions
Measures that lower blood pressure:
 weight
 salt intake
 alcohol consumption
 physical exercise
 fruit & vegetable consumption
Measures to reduce cardiovascular risk:
Stop smoking
 saturated fat,  poly- & mono-unsaturates

 oily fish consumption

 total fat intake

BHS Guidelines 1999

 Drug treatment of hypertension
Diuretic ACE-inhibitor

Calcium-channel Angiotensin receptor

blocker blocker

Beta-blocker (Alpha-blocker)

Most hypertensives will need  2 drugs to control BP

Drug combinations may be synergistic
CCB + ACE I/ARB :
The Synergies of Counter-Regulation (1)

CCB
 Arteriodilation
 Peripheral oedema
 Effective in low-renin patients
 Reduces cardiac ischaemia
BP

CCB
Synergistic  RAS activation
BP reduction  No renal or CHF
Complementary benefits
clinical benefits

Mistry et al. Expert Opin Pharmacother. 2006;7:575–581;

Sica. Drugs. 2002;62:443–462; Quan et al. Am J Cardiovasc Drugs. 2006;6:103113.
CCB +ACE I/ ARB :
The Synergies of Counter-Regulation (2)

CCB
 Arteriodilation ACEi/ARB
 Peripheral oedema  RAS blockade
 Effective in low-renin patients  CHF and renal
 Reduces cardiac ischaemia benefits
BP

ACEi/ARB CCB
 Venodilation Synergistic  RAS activation
 Attenuates peripheral oedema BP reduction  No renal or CHF
 Effective in high-renin patients benefits
Complementary
 No effect on cardiac ischaemia
clinical benefits

Mistry et al. Expert Opin Pharmacother. 2006;7:575–581; Sica. Drugs. 2002;62:443–462;

Quan et al. Am J Cardiovasc Drugs. 2006;6:103113.
 Venous Fluid Leakage Induced by CCBs …

Opie et al. In: Opie LH, editor. Drugs for the Heart. 3rd ed. 1991:42–73; White et al. Clin Pharmacol Ther.
1986;39:43–48; Gustaffson. J Cardiovasc Pharmacol. 1987;10:S121–S131.
 … Gets Reduced by Co-administration of ACEI/ARBs

Opie et al. In: Opie LH, editor. Drugs for the Heart. 3rd ed. 1991:42–73; White et al. Clin Pharmacol Ther. 1986;39:43–48; Gustaffson. J
Cardiovasc Pharmacol. 1987;10:S121–S131; Messerli et al. Am J Cardiol. 2000;86:11821187.
 Recommended
Drugs
Compelling

Aldo Ant
Diuretic
Clinical trial basis
Indication*

ACEI

CCB
ARB
BB
Heart Failure ACC/AHA Heart Failure Guideline, MERITHF,
COPERNICUS, CIBIS, SOLVD, AIRE, TRACE,
ValHEFT, RALES, CHARM

Postmyocardial ACC/AHA Post-MI Guideline, BHAT, SAVE,

Infarction Capricorn, EPHESUS

High Coronary Disease ALLHAT, HOPE, ANBP2, LIFE, CONVINCE,

Risk EUROPA, INVEST

Diabetes NKF-ADA Guideline, UKPDS, ALLHAT

Chronic Kidney Disease NKF Guideline, Captopril Trial, RENAAL, IDNT,

REIN, AASK

Recurrent Stroke PROGRESS

Prevention
ISH Spring Meeting. 2010
 Obat HL Onset Durasi PPT Bioav (%)

Lisinopril 12 jam 1-6 jam 24 jam 6-8 jam 25

Ramipril 13-17 jam 4 jam 24 jam 2-4 jam 50-60%

Perindopril 3-10 jam 1,5 jam 24 jam 1 jam 75 %

Trandolapril 6-10 jam 4 jam 24 jam 1 jam 80 %

Enalapril 1,3 jam 1-4 jam 12-24 jam 1 jam 60 %

Losartan 1,5-2 jam 6 jam 24 jam 1-1,5jam 25%

Valsartan 6-9 jam 2 jam 6-8 jam 2-4 jam 25 %

Medscape, drugs, conditions, procedures, 2011

PENUTUP
- Modifikasi gaya hidup sangat penting untuk
mencegah terjadinya hipertensi
- Tujuan pengobatan hipertensi mencegah
terjadinya komplikasi kardiovaskular
- Untuk kasus hipertensi tidak terkontrol
memerlukan terapi farmakologik seumur
hidup