Penyakit Jantung Hipertensi (Hypertensive Heart Disease) Bagian Kardiologi & Kedokteran Vaskuler FKUSU

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Coronary Thrombosi s Myocard ial Ischemia Coronar y Artery Disease Atherosclerosi s Risk Factors Hypertension High Cholesterol Diabetes Mellitus Insulin Resistance Platelets Smoking
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Myocardia l Arrhythm Infarction ia and Loss of Muscle

Sudden Death

Remodelin g Ventricular Dilation

End stage Heart Disease

Congestiv e Heart Failure

Kuliah Penyakit Jantung Hipertensi

Hypertension and the risk of further disease

Disease Coronary artery disease Stroke Heart failure Peripheral vascular disease Relative risk
(hypertensives versus normotensives)

2- to 3-fold 7-fold 2- to 3-fold 2- to 3-fold

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Prevalence of CHD risk factors in hypertensive patients

Risk factor Elevated serum cholesterol (>5.2 mmol/L) Low exercise output Left ventricular hypertrophy Cigarette smoking Low HDL-cholesterol levels (<0.9 mmol/L) Glucose intolerance (including diabetes) Use of synthetic oestrogens (eg contraceptive pill) Prevalence (%) 85 >75 50 35 25 13 2

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Sever (1992) 4

National Heart, Lung, and Blood Institute National High Blood Pressure Education Program
Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) EXPRESS

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New Features and Key Messages

For persons over age 50, SBP is a more important than DBP as CVD risk factor. Starting at 115/75 mmHg, CVD risk doubles with each increment of 20/10 mmHg throughout the BP range. Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN. Those with SBP 120139 mmHg or DBP 8089 mmHg should be considered prehypertensive who require health05/22/12 Kuliah Penyakit Jantung 6 promoting lifestyle modificationsHipertensi to prevent CVD.

Blood Pressure Classification

BP Classification Normal Prehypertension Stage 1 Hypertension Stage 2 Hypertension SBP mmHg <120 120139 140159 >160 and or or or DBP mmHg <80 8089 9099 >100

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Types of hypertension
Essential hypertension

90% No underlying cause

Secondary hypertension

Underlying cause
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Causes of Secondary Hypertension Renal

Parenchymal Vascular Others

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Endocrine Neurogenic Miscellaneous Unknown

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Hypertension: Predisposing factors

Age > 60 years Sex (men and postmenopausal women) Family history of cardiovascular disease Smoking High cholesterol diet Co-existing disorders such as diabetes, obesity and hyperlipidaemia High intake of alcohol SedentaryKuliah Penyakit Jantung Hipertensi life style 05/22/12

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1999 WHO-ISH Guidelines : Definitions and Classifications of BP Levels

SBP (mm Hg) < 120 < 130 130-139 140-159 140-149 160-179 > 180 > 140 140-149 DBP (mm Hg) < 80 < 85 85-89 90-99 90-94 100-109 > 110 < 90 < 90

Category* Optimal Normal High-normal Grade 1 hypertension (mild) Borderline subgroup Grade 2 hypertension (moderate) Grade 3 hypertension (severe) ISH Borderline subgroup

WHO-ISH Guidelines Subcommittee J Hypertens 1999; 17:151

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1999 WHO-ISH Guidelines: Stratification of risk to Quantify Prognosis

Degree of hypertension (mm Hg) Grade 1-mild Grade 2-moderate Grade3-severe (SBP 140-159 (SBP 160-179 (SBP > 180 or DBP 90-99) or DBP 100-109) or DBP > 110) Low risk Med risk High risk Med risk High risk Med risk high risk Very high risk Very high risk

Risk factors and disease history I No other risk factors II 1-2 risk factors III > 3 risk factors or target organ disease or diabetes IV Associated Clinical conditions

Very high risk

Very high risk

Very high risk

WHO-ISH Guidelines Subcommittee J Hypertens 1999;17:151

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Diseases Attributable to Hypertension

Gangrene of the Lower Extremities Aortic Aneurym Heart Failure Left Ventricular Hypertrophy Myocardial Infarction Hypertensive Encephalopathy

HYPERTENSION
Coronary Heart Disease Chronic Kidney Failure Stroke Preeclampsia/ Eclampsia Cerebral Hemorrhage

Blindness

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Adapted from Dustan HP et Kuliah Penyakit Jantung Hipertensi al. Arch Intern Med. 1996; 156: 1926-1935 13

The Cardiovascular disease continuum

Myocardial infraction Coronary thrombosis Myocardial ischaemia Remodelling Coronary artery disease Ventricular dilation Atherosclerosis, left Ventricular hypertrophy Sudden death Arrhytmia & loss of muscle

Heart failure

Risk factors (hypertension, lowEndstage heart density lipoprotein, diabetes 05/22/12 Kuliah disease mellitus, etc) Penyakit Jantung Hipertensi

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Heart Failure:

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What is Heart Failure? Heart failure is a clinical syndrome, encompassing a wide range of pathophysiological states The main clinical manifestations of heart failure are breathlessness, fatigue and signs of fluid retention

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Development of heart failure in the hypertensive patient

Sustained pressure overload
Genetic factors Mechanical stretch neurohormonal signalling Co-morbidities

Diastolic dysfunction Altered expression of contractility regulating genes Systolic dysfunction Heart Failure

Compensated concentric or eccentric hypertrophy

Microvascular abnormalities Apoptosis necrosis

Ischaemia

Cell loss

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Decompensated concentric hypertrophy Decompensated Kuliah Penyakit Jantung Hipertensi eccentric hypertrophy

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BP A
Systolic dysfunction

B
Diastolic dysfunction

LVH

Ejection fraction End diastolic volume LV dilation

Ventricular arrhytmias

Ejection fraction or End diastolic volume or LV size normal

Low cardiac output syndrome

LV filling pressure

BP = arterial blood pressure

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Pulmonary venous Congestion Dyspnea

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A PREVALENT CONDITION
PREVALENCE OF HF (PER 1000 POPULATION)

Age (years) 50-59 80-89 All ages

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Men 8 66 7.4

Women 8 79 7.7
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Framingham Heart Study: Ho et al. 1993 J Am Coll Cardiol;22:6

A GROWING BURDEN
DEATHS FROM HF 1979-1997 (USA)
50000 40000 HF deaths 30000 20000 10000 0 1979
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1985

1991

1997
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Source: Vital Statistics of the United States, National Center for Health Stat

AN ECONOMIC BURDEN
ANNUAL COST OF HF ESTIMATED TO BE $22.5 BILLION (USA) Healthcare Drugs providers Indirect Costs 2.2 1.5 1.1 15.5 2.2

Home health/Other medical durables

Hospital/Nursing home
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Costs in billions of dollars

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American Heart Association, 2000 Heart and Stroke Statistical Upd

Hypertension Therapy Goals

New approach Standard approach

Vascular Dysfunction

Elevated BP

Morbidity/Mortality

Pepine CJ. Am J Cardiol 1998,82.21H-24H 05/22/12 Kuliah Penyakit Jantung Hipertensi

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USUAL TREATMENT TODAY

AIMS OF HEART FAILURE MANAGEMENT TO IMPROVE SYMPTOMS
DIURETICS DIGOXIN ACE INHIBITORS

TO IMPROVE SURVIVAL
ACE INHIBITORS BLOCKERS ORAL NITRATES PLUS HYDRALAZINE SPIRONOLACTONE
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Davies et al. BMJ 2000;320:428-431

HF: MORTALITY REMAINS HIGH

ACEI
RISK REDUCTION 35%
(MORTALITY AND HOSPITALIZATIONS)1

BLOCKERS

RISK REDUCTION 38%

(MORTALITY AND HOSPITALIZATIONS)2

ORAL NITRATES AND HYDRALAZINE

BENEFIT VS. PLACEBO; INFERIOR TO ENALAPRIL
(MORTALITY) HOWEVER: 4-YEAR MORTALITY REMAINS ~40%
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Davies et al. BMJ 2000;320:428-431 (metanalysis: 32 trials, n=7105)

Gibbs et al. BMJ 2000;320:495-498 (metanalysis: 18 trials,

BLOCKADE OF RAS
LOCAL ANG II SYNTHESIS IS INDEPENDENT OF ACE ANGIOTENSINOGEN
(LIVER)

RENIN INHIBIT OR BRADYKININ ACE PEPTIDES INHIBIT OR

CHYMASE ANGIOTENSIN I

ANGIOTENSIN II

VALSARTAN
AT1 RECEPTOR BLOCKER 05/22/12

AT1

AT2
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ROLE OF AT1 AND AT2 RECEPTORS

ANGIOTENSIN II
AT1
VASOCONSTRICTION VASCULAR PROLIFERATION ALDOSTERONE SECRETION CARDIAC MYOCYTE PROLIFERATION INCREASED SYMPATHETIC TONE

AT2
VASODILATION ANTIPROLIFER ATION APOPTOSIS

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1999 WHO-ISH Guidelines: Desirable BP Treatment Goals

Optimal or normal BP (< 130/85 mm Hg) for Young patients Middle-age patients Diabetic patients High-normal BP (< 140/90 mm Hg) desirable for elderly patients Aggressive BP lowering may be necessary in patients with nephropathy, chronic renal failure, particularly if proteinuria is < 1 g/d - 130/80 mm Hg > 1 g/d - 125/75 mm Hg 05/22/12 Kuliah Penyakit Jantung Hipertensi 31

Life style modifications

Lose weight, if overweight Limit alcohol intake Increase physical activity Reduce salt intake Stop smoking Limit intake of foods rich in fats and cholesterol
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Factors affecting choice of antihypertensive drug

The cardiovascular risk profile of the patient Coexisting disorders Target organ damage Interactions with other drugs used for concomitant conditions Tolerability of the drug
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Cost of the drug

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Drug therapy for hypertension

Class of drug Diuretics -blockers Calcium channel blockers -blockers ACE- inhibitors Angiotensin-II receptor blockers Example Hydrochlorothiazide Atenolol Amlodipine Initiating dose 12.5 mg o.d. 25-50 mg o.d. 2.5-5 mg o.d. Usual maintenance dose 12.5-25 mg o.d. 50-100 mg o.d. 5-10 mg o.d.

Doxazosin Lisinopril Losartan

1 mg o.d. 2.5-5 mg o.d. 25-50 mg o.d.

1-8 mg o.d. 5-20 mg o.d. 50-100 mg o.d.

Diuretics
Example: Hydrochlorothiazide Act by decreasing blood volume and cardiac output Decrease peripheral resistance during chronic therapy Drugs of choice in elderly hypertensives Drawbacks Hypokalaemia Hyponatraemia Hyperlipidaemia Hyperuricaemia (hence contraindicated in gout) Hyperglycaemia (hence not safe in diabetes) Not safe in renal and hepatic insufficiency
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Beta blockers
Example: Atenolol Block 1 receptors on the heart Block 2 receptors on kidney and inhibit release of renin Decrease rate and force of contraction and thus reduce cardiac output Drugs of choice in patients with co-existent coronary heart disease Drawbacks Adverse effects: lethargy, impotency, bradycardia Not safe in patients with co-existing asthma and diabetes Have an adverse effect on the lipid profile
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Calcium channel blockers Example: Amlodipine Block entry of calcium through calcium channels Cause vasodilation and reduce peripheral resistance Drugs of choice in elderly hypertensives and those with co-existing asthma Neutral effect on glucose and lipid levels Drawbacks Adverse effects: Flushing, headache, Pedal edema 05/22/12 Kuliah Penyakit Jantung Hipertensi

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ACE inhibitors Example: Lisinopril, Enalapril Inhibit ACE and formation of angiotensin II and block its effects Drugs of choice in co-existent diabetes mellitus Drawbacks Adverse effect: dry cough, hypotension, angioedema
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Angiotensin II receptor blockers

Example: Losartan Block the angiotensin II receptor and inhibit effects of angiotensin II Drugs of choice in patients with co-existing diabetes mellitus Drawbacks Adverse effect: dry cough, hypotension, angioedema
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Alpha blockers
Example: Doxazosin Block -1 receptors and cause vasodilation Reduce peripheral resistance and venous return Exert beneficial effects on lipids and insulin sensitivity Drugs of choice in patients with co-existing hyperlipidaemia, diabetes mellitus and BPH Drawbacks Adverse effects: Postural hypotension
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Antihypertensive therapy: Side-effects and Contraindications

Class of drugs Diuretics (e.g. Hydrochlorothiazide) Main side-effects Electrolyte imbalance, total and LDL cholesterol levels, HDL cholesterol levels, glucose levels, uric acid levels Impotence, Bradycardia, Fatigue Contraindications/ Special Precautions Hypersensitivity, Anuria

-blockers (e.g. Atenolol)

Hypersensitivity, Bradycardia, Conduction disturbances, Diabetes, Asthma, Severe cardiac failure

Antihypertensive therapy: Side-effects and Contraindications (Contd.)

Class of drug Calcium channel blockers (e.g. Amlodipine, Diltiazem) Main side-effects Pedal edema, Headache Contraindications/ Special Precautions Non-dihydropyridine CCBs (e.g diltiazem) Hypersensitivity, Bradycardia, Conduction disturbances, Congestive heart failure, Left ventricular dysfunction. Dihydropyridine CCBs Hypersensitivity Hypersensitivity Hypersensitivity, Pregnancy, Bilateral renal artery stenosis Hypersensitivity, Pregnancy, Bilateral renal artery stenosis

-blockers (e.g. Doxazosin) ACE-inhibitors (e.g. Lisinopril) Angiotensin-II receptor blockers (e.g. Losartan)

Postural hypotension Cough, Hypertension, Angioneurotic edema Headache, Dizziness

Choosing the right antihypertensive

Condition Asthma Preferred drugs Calcium channel blockers -blockers/ACE inhibitors/ Angiotensin-II receptor blockers -blockers Calcium channel blockers/Diuretics -blockers Other drugs that can be used -blockers/Angiotensin-II receptor blockers/Diuretics/ ACE-inhibitors Calcium channel blockers Drugs to be avoided -blockers Diuretics/ -blockers -blockers/ Diuretics

Diabetes mellitus

High cholesterol levels Elderly patients (above 60 years) BPH

ACE inhibitors/ Angiotensin-II receptor blockers/ Calcium channel blockers -blockers/ACEinhibitors/Angiotensin-II receptor blockers/- blockers -blockers/ ACE inhibitors/ Angiotensin-II receptor blockers/ Diuretics/ Calcium channel blockers

Limitations on use of antihypertensives in patients with coexisting disorders

Coexisting Disorder Diabetes Dyslipidaemia CHD Heart failure Asthma/COPD Peripheral vascular disease Renal artery stenosis
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Diuretic Caution/x x

-blocker Caution/x x /Caution x Caution

ACE All inhibitor antagonist /Caution Caution Caution

CCB Caution

1 -blocker

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Effect of various antihypertensives on coexisting disorders

Total LDLHDLSerum Glucose Insulin cholesterol cholesterol cholesterol triglycerides tolerance sensitivity Diuretic -blockers ACE inhibitors All antagonists CCBs -blockers
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Drugs in special conditions

Condition Pregnancy Preferred Drugs Nifedipine, labetalol, hydralazine, beta-blockers, methyldopa, prazosin Beta-blockers, ACE inhibitors, Calcium channel blockers ACE inhibitors, beta-blockers
1999 WHO-ISH guidelines 46

Coronary heart disease

Congestive heart failure

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Summary

Hypertension is a major cause of morbidity and mortality, and needs to be treated It is an extremely common condition; however it is still underdiagnosed and undertreated Hypertension can cause heart failure.

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