HHD

04/07/23 Kuliah Penyakit Jantung Hipertensi 1

Penyakit Jantung Hipertensi(Hypertensive Heart Disease)

Bagian Kardiologi &

Kedokteran Vaskuler

FKUSU


End stage Heart Disease

Risk FactorsHypertension High CholesterolDiabetes Mellitus Insulin ResistancePlateletsSmoking

Atherosclerosis

Coronary Artery Disease

Congestive Heart Failure

Ventricular Dilation

Remodeling

Arrhythmia and Loss of Muscle Sudden

Death

Myocardial InfarctionCoronary

Thrombosis

Myocardial Ischemia


Hypertension and the risk of further disease

DiseaseDisease Relative riskRelative risk(hypertensives versus normotensives)(hypertensives versus normotensives)

Coronary artery diseaseCoronary artery disease 2- to 3-fold2- to 3-fold

StrokeStroke 7-fold7-fold

Heart failureHeart failure 2- to 3-fold2- to 3-fold

Peripheral vascular diseasePeripheral vascular disease 2- to 3-fold2- to 3-fold


Risk factor Prevalence (%)

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

Prevalence of CHD risk factors in hypertensive patients

Sever (1992)Sever (1992)


Seventh Report of the Joint National Committee onPrevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) EXPRESS

National Heart, Lung, andBlood Institute

National High Blood PressureEducation Program


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 120–139 mmHg or DBP 80–89 mmHg should be considered prehypertensive who require health-promoting lifestyle modifications to prevent CVD.

New Features and Key Messages


Blood Pressure Classification

Normal <120 and <80

Prehypertension 120–139 or 80–89

Stage 1 Hypertension

140–159 or 90–99

Stage 2 Hypertension

>160 or >100

BP Classification SBP mmHg DBP mmHg


Types of hypertension

Essential hypertension

90%

No underlying cause

Secondary hypertension

Underlying cause


Causes of Secondary Hypertension

Renal Parenchymal Vascular Others

Endocrine Neurogenic Miscellaneous Unknown


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 Sedentary life style


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

SBP DBP

Category* (mm Hg) (mm Hg)

Optimal < 120 < 80

Normal < 130 < 85

High-normal 130-139 85-89

Grade 1 hypertension (mild) 140-159 90-99

Borderline subgroup 140-149 90-94

Grade 2 hypertension (moderate) 160-179 100-109

Grade 3 hypertension (severe) > 180 > 110ISH > 140 < 90 Borderline subgroup 140-149 < 90

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


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

Degree of hypertension (mm Hg)

Risk factors and Grade 1-mild Grade 2-moderate Grade3-severe

disease history (SBP 140-159 (SBP 160-179 (SBP > 180

or DBP 90-99) or DBP 100-109) or DBP > 110)

I No other risk Low risk Med risk High risk

factors

II 1-2 risk factors Med risk Med risk Very high risk

III > 3 risk factors or High risk high risk Very high risk

target organ disease

or diabetes

IV Associated Very high risk Very high risk Very high risk

Clinical conditions

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


Diseases Attributable to Hypertension

HYPERTENSION

Gangrene of the Lower Extremities

Heart Failure

Left Ventricular Hypertrophy Myocardial

Infarction

Hypertensive Encephalopathy

Aortic Aneurym

Blindness

Chronic Kidney Failure

Stroke Preeclampsia/Eclampsia

Cerebral Hemorrhage

Coronary Heart Disease

Adapted from Dustan HP et al. Arch Intern Med. 1996; 156: 1926-1935


Myocardial infraction

Endstage heart disease

Heart failure

Remodelling

Arrhytmia & loss of muscle

Sudden death

Myocardial ischaemia

Atherosclerosis, left Ventricular hypertrophy

Coronary artery disease

Risk factors (hypertension, low-density lipoprotein, diabetes

mellitus, etc)

Ventricular dilation

The Cardiovascular disease continuum

Coronary thrombosis


Heart Failure:Heart Failure:


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


Compensatedconcentric or eccentric hypertrophy

Sustained pressureoverload

Mechanical stretchneurohormonal signalling

Geneticfactors Co-morbidities

Microvascularabnormalities

Apoptosisnecrosis

Ischaemia Cell loss

Diastolicdysfunction

Heart Failure

Alteredexpression ofcontractilityregulatinggenes

Systolicdysfunction

Decompensated concentric hypertrophy

Decompensated eccentric hypertrophy

Development of heart failure in the hypertensive patient


BP

Systolic dysfunction

Diastolic dysfunction

A B

LVH

Ejection fraction End diastolic volume LV dilation

Low cardiac output syndrome

Ventricular arrhytmias

LV filling pressure

Pulmonary venous Congestion Dyspnea

BP = arterial blood pressure

LVH = left ventricular hypertrophy

Ejection fraction or End diastolic volume or LV size normal


A PREVALENT CONDITION

PREVALENCE OF HF (PER 1000 POPULATION)

Age (years)

50-59

80-89

All ages

Men

8

66

7.4

Women

8

79

7.7

Framingham Heart Study: Ho et al. 1993 J Am Coll Cardiol;22:6-13


A GROWING BURDEN

0

10000

20000

30000

40000

50000

1979 1985 1991 1997

HF

dea

ths

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

DEATHS FROM HF 1979-1997 (USA)


AN ECONOMIC BURDEN

American Heart Association, 2000 Heart and Stroke Statistical Update

Hospital/Nursing home

HealthcareprovidersIndirect Costs Home health/Other

medical durables

Drugs

15.5

2.2 1.5 1.1 2.2

ANNUAL COST OF HF ESTIMATED TO BE $22.5 BILLION (USA)

Costs in billions of dollars


Hypertension Therapy GoalsHypertension Therapy GoalsNew approach Standard approach

Vascular Dysfunction

Elevated

BPMorbidity/Mortality

Pepine CJ. Am J Cardiol 1998,82.21H-24H


USUAL TREATMENT TODAY

TO IMPROVE SYMPTOMS DIURETICS DIGOXIN ACE INHIBITORS

TO IMPROVE SURVIVAL ACE INHIBITORS BLOCKERS ORAL NITRATES PLUS HYDRALAZINE SPIRONOLACTONE

AIMS OF HEART FAILURE MANAGEMENT

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 HYDRALAZINEBENEFIT VS. PLACEBO; INFERIOR TO ENALAPRIL (MORTALITY)

HOWEVER: 4-YEAR MORTALITY REMAINS ~40%

1 Davies et al. BMJ 2000;320:428-431 (metanalysis: 32 trials, n=7105) 2 Gibbs et al. BMJ 2000;320:495-498 (metanalysis: 18 trials, n=3023)


ANGIOTENSIN I

ANGIOTENSINOGEN(LIVER)

AT1 AT2

ANGIOTENSIN II

ACE INHIBIT

OR

VALSARTANAT1 RECEPTOR

BLOCKER

RENIN INHIBIT

ORBRADYKININ

PEPTIDES

CHYMASE

LOCAL ANG II SYNTHESIS IS INDEPENDENT OF ACE

BLOCKADE OF RAS


ROLE OF AT1 AND AT2 RECEPTORS

VASOCONSTRICTIONVASCULAR PROLIFERATION ALDOSTERONE SECRETIONCARDIAC MYOCYTE PROLIFERATION

INCREASED SYMPATHETIC TONE

VASODILATIONANTIPROLIFERATION

APOPTOSIS

AT1 AT2

ANGIOTENSIN II


1999 WHO-ISH Guidelines: Desirable BP Treatment Goals

Optimal or normal BP (< 130/85 mm Hg) for Young patientsMiddle-age patientsDiabetic 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


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


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

Cost of the drug

Drug therapy for hypertension

Class of drug Example Initiating dose Usualmaintenance dose

Diuretics Hydrochlorothiazide 12.5 mg o.d. 12.5-25 mg o.d.

-blockers Atenolol 25-50 mg o.d. 50-100 mg o.d.

Calcium Amlodipine 2.5-5 mg o.d. 5-10 mg o.d.channelblockers

-blockers Doxazosin 1 mg o.d. 1-8 mg o.d.

ACE- inhibitors Lisinopril 2.5-5 mg o.d. 5-20 mg o.d.

Angiotensin-II Losartan 25-50 mg o.d. 50-100 mg o.d.receptor blockers


Diuretics

Example: Hydrochlorothiazide

Act by decreasing blood volume and cardiac output Decrease peripheral resistance during chronic therapy Drugs of choice in elderly hypertensivesDrawbacks Hypokalaemia Hyponatraemia Hyperlipidaemia Hyperuricaemia (hence contraindicated in gout) Hyperglycaemia (hence not safe in diabetes) Not safe in renal and hepatic insufficiency


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


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


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


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


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

Antihypertensive therapy:Side-effects and Contraindications

Class of drugs Main side-effects Contraindications/Special Precautions

Diuretics Electrolyte imbalance, Hypersensitivity, Anuria(e.g. Hydrochloro- total and LDL cholesterol thiazide) levels, HDL cholesterol

levels, glucose levels, uric acid levels

-blockers Impotence, Bradycardia, Hypersensitivity, (e.g. Atenolol) Fatigue Bradycardia, Conduction

disturbances, Diabetes,Asthma, Severe cardiacfailure

Class of drug Main side-effects Contraindications/ Special

Precautions

Calcium channel blockers Pedal edema, Headache Non-dihydropyridine(e.g. Amlodipine, CCBs (e.g diltiazem)– Diltiazem) Hypersensitivity,

Bradycardia, Conductiondisturbances, Congestive heartfailure, Left ventriculardysfunction.Dihydropyridine CCBs–

Hypersensitivity

-blockers Postural hypotension Hypersensitivity(e.g. Doxazosin)

ACE-inhibitors Cough, Hypertension, Hypersensitivity, Pregnancy,(e.g. Lisinopril) Angioneurotic edema Bilateral renal artery stenosis

Angiotensin-II receptor Headache, Dizziness Hypersensitivity, Pregnancy,blockers (e.g. Losartan) Bilateral renal artery stenosis

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

Choosing the right antihypertensive

Condition Preferred drugs Other drugs Drugs to be that can be used avoided

Asthma Calcium channel -blockers/Angiotensin-II -blockersblockers receptor blockers/Diuretics/

ACE-inhibitors

Diabetes -blockers/ACE Calcium channel blockers Diuretics/mellitus inhibitors/ -blockers

Angiotensin-IIreceptor blockers

High cholesterol -blockers ACE inhibitors/ Angiotensin-II -blockers/levels receptor blockers/ Calcium Diuretics

channel blockers

Elderly patients Calcium channel -blockers/ACE- (above 60 years)blockers/Diuretics inhibitors/Angiotensin-II

receptor blockers/- blockers

BPH -blockers -blockers/ ACE inhibitors/

Angiotensin-II receptor

blockers/ Diuretics/

Calcium channel blockers


Limitations on use of antihypertensives in patientswith coexisting disorders

Coexisting Diuretic -blocker ACE All CCB -blockerDisorder inhibitor antagonist

Diabetes Caution/x Caution/x

Dyslipidaemia x x

CHD

Heart failure /Caution Caution

Asthma/COPD x /Caution

Peripheral Caution Caution Caution vasculardisease

Renal artery x x stenosis


Effect of various antihypertensives on coexisting disorders

Total LDL- HDL- Serum Glucose Insulincholesterol cholesterol cholesterol triglycerides tolerance sensitivity

Diuretic

-blockers - - -

ACEinhibitors - - - -

Allantagonists - - - -

CCBs - - - - - -

-blockers


Drugs in special conditions

Condition

Pregnancy

Coronary heart disease

Congestive heart failure

Preferred Drugs

Nifedipine, labetalol, hydralazine, beta-blockers, methyldopa, prazosin

Beta-blockers, ACE inhibitors, Calcium channel blockers

ACE inhibitors,beta-blockers

1999 WHO-ISH guidelines


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.

HHD

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