New (1999) WHO-ISH Definitionsand Classification of BP Levels

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

Optimal BP <120 <80Normal BP <130 <85High-Normal 130-139 85-89

Grade 1 Hypertension (mild) 140-159 90-99 Subgroup: Borderline 140-149 90-94Grade 2 Hypertension (moderate) 160-179 100-109Grade 3 Hypertension (severe) >180 >110

Isolated Systolic Hypertension >140 <90 Subgroup: Borderline 140-149 <90

What is the Goalof the Practice Guidelines?

To lower blood pressure (BP) and other risk factors in order to reduce the risk of cardiovascular disease (CVD)

Why is Hypertension Management Needed? (1)

• 600 million hypertensives in the world

• 3 million die annually as a direct result of hypertension

Why is Hypertension Management Needed? (2)

The Rule of Halves• Only 1/2 have been diagnosed

• Only 1/2 of those diagnosed have been treated

• Only 1/2 of those treated are adequately controlled

• Thus, only 12.5% overall are adequately controlled

Why BP <130/85 mm Hgand Not <140/90 mm Hg? (1)

• The relationship between CV risk and BP is continuous

• Today, more than 50% of all hypertensives have BP >160/90 mm Hg and 75% have BP >140/90

• The major determinant of the risk reduction conferred by antihypertensive therapy is the BP level attained

Why BP <130/85 mm Hgand Not <140/90 mm Hg? (2)

• In diabetics, there is a clear benefit of lowering BP <85 mm Hg

• The HOT Study showed that lowering BP < 85 mm Hg did not increase CV risk

• The goal should be to attain normal BP (<130/85 mm Hg)

What is High Blood Pressure?

• BP levels are continuously related to the risk of CVD

• Definition of hypertension or raised BP is arbitrary

• Even within the normotensive range, people with the lowest BP levels have the lowest rates of CVD

Relative Risk of CHD and Stroke in Relation to Patient’s Usual Diastolic BP

Clinical Evaluation - What Should Be Done?

• Confirm elevation of BP

• Exclude or identify secondary causes of hypertension

• Determine presence of target organ damage and quantify extent

• Search for other CV risk factors and clinical conditions that may influence prognosis and treatment

Multiple BP Measurements Recommended

Because BP is characterized by large spontaneous variations, diagnosis should be based on multiple BP measurements taken on several separate occasions

Minimum RoutineInvestigations

Clinical and family history

Full physical examination as described in medical textbooks

Laboratory investigations, including:– urinalyses for blood, protein, and glucose– microscopic examination of the urine– blood chemistry for potassium, creatinine, fasting glucose,

and total cholesterol

Electrocardiography (ECG)

“Isolated” Office Hypertension

In some patients office BP is persistently elevated whereas daytime BP outside clinic environment is not. Continuing debate whether “isolated” office hypertension (“white coat hypertension”) is an innocent phenomenon or carries an increased risk of CVD

Ambulatory BP Monitoring

BP values obtained by home measurement or ambulatory monitoring are several mm Hg lower than office measurement

Average 24 hour or home BP values around 125/80 mm Hg = office BP 140/90 mm Hg

Which Factors Influence Prognosis? (1)

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

concomitant diseases, as well as on other aspects of patients’ personal, medical, social, economic, ethnic, and

cultural characteristics

• Risk factors of CVD

I. Used for risk stratificationII. Other factors adversely influencing

prognosis

• Target organ damage (TOD)

• Associated clinical conditions (ACC)

Which Factors Influence Prognosis? (2)

Which Factors Influence Prognosis? (3)

I. Used for risk stratification• Levels of systolic and diastolic blood

pressure (Grades 1-3)• Men >55 years• Women >65 years• Smoking• Total cholesterol >6.5 mmol/L (250 mg/dl)• Diabetes• Family history of premature

cardiovascular disease

Risk factors for CVD

Which Factors Influence Prognosis? (4)

II.Other factors adversely influencing prognosis• Reduced HDL cholesterol• Raised LDL cholesterol• Microalbuminuria in diabetes• Impared glucose tolerance• Obesity• Sedentary lifestyle• Raised fibrinogen• High risk socioeconomic group• High risk ethnic group• High risk geographic region

Risk factors for CVD

Which Factors Influence Prognosis? (5)

Target organ damage (TOD)• Left ventricular hypertrophy (electrocardiogram,

echocardiogram, or radiogram)

• Proteinuria and/or slight elevation of plasma creatinine concentration 106-177 mmol/L (1.2-2.0 mg/dl)

• Ultrasound or radiological evidence of atherosclerotic plaque (carotid, iliac, and femoral arteries, aorta)

• Generalised or focal narrowing of the retinal arteries

Which Factors Influence Prognosis? (6)

Associated clinical conditions (ACC)

Cerebrovascular disease• Ischaemic stroke• Cerebral haemorrhage• Transient ischaemic attack (TIA)

Heart disease• Myocardial infarction• Angina pectoris• Coronary revascularisation• Congestive heart failure

Which Factors Influence Prognosis? (7)

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• Papilloedema

Stratifying Risk - Quantifying Prognosis

Effects of Antihypertensive Treatment in Randomised Controlled Trials

Initiate lifestyle measures wherever appropriate in all patients, including those

who require drug treatment

• Smoking cessation

• Weight reduction

• Moderation of alcohol consumption

• Reduction of salt intake

• Increased physical activity

Management Strategy

Principles of Drug Treatment (1)

• Use a low dose of one drug to initiate therapy

• If good response and tolerability but inadequate control increase the dose of the first drug

• If little response or poor tolerability change to another drug class

Principles of Drug Treatment (2)

• It is often preferrable to add a small dose of a second drug rather than increase the dose of the first drug

• Use long-acting drugs providing 24-hour efficacy on a once daily basis. Improves adherence to therapy and minimizes BP variability.

Principles of Drug Treatment (3)

There are six maindrug classes used worldwide - diuretics, beta-blockers, ACE

inhibitors, calcium antagonists, alpha blockers, and angiotensin

II antagonists.

Principles of Drug Treatment (4)

All 6 classes are suitable for the initiation and maintenance of BP lowering therapy, but the choice

of drugs will be influenced by cost and by many factors for special groups

of patients. In some parts of the world, reserpine and methyldopa are

also used frequently.

Indications

Compelling PossibleHeart failure Diabetes

Elderly patients

Systolic hypertension

Diu

reti

cs

Contraindications

Compelling PossibleGout Dyslipidaemia

Sexually active

males

IndicationsCompelling Possible

Angina Heart failure

After myocardial infarct Pregnancy

Tachyarrhythmias DiabetesContraindications

Compelling Possible

Asthma and Dyslipidaemia

Chronic obstructive Athletes and

Pulmonary disease Physically active

Heart block (AV 2,3) Patients

Peripheral

vascular disease

Beta

-Blo

ckers

IndicationsCompelling PossibleAngina Peripheral

Elderly patients Vascular disease

Systolic hypertension

Calc

ium

Anta

gonis

ts

Contraindications

Compelling PossibleHeart block (AV 2,3) Heart failure** verapamil or diltiazem

IndicationsCompelling Possible

Heart failure

Left ventricular dysfunct

After myocardial infarct

Diabetic nephropathy

ContraindicationsCompelling Possible

Pregnancy

Bilateral renal

artery stenosis

Hyperkalaemia

AC

E Inhib

itors

ACE inhibitors:Mech. of eff.: inhibition of the conversion of AT I onto AT II, degradation of bradykine,

decrease of PVR and slight venodilatation vasokonstriction ATII, secretion of aldosterone -natriuresis regression of hypertrophia of left ventricle and vessel’s wall

heart insufficiency - mortality rate 20-30 %

glom. pressure - proteinuria during DM nephropatia

- cardioprotective, vasoprotective and renoprotective eff.

AE: hypotension after initial dose, renal impairment (acute renal insufficiency, hyperkalaemia, dry cough, angioedema

short acting: captoprile - three times a day

medium term: enalaprile - twice a day

long acting: perindoprile, lisinoprile, quinaprile, ramiprile, spiraprile, trandolaprile

Indications

Compelling Possible

Prostatic Hypertrophy Glucose intolerance

Dyslipidaemia

Contraindications

Compelling Possible

Orthostatic

hypotension

Alp

ha-B

lock

ers

- blockersCentral acting - 2, I1 rec. - decrease of sympatic influence

clonidine - 2,I1-agonist - renal hypertension, !sedation, dyssomnia

methyldopa, guanfacine - 2-rec.

moxonidine, rilmenidine - imidazolin I1 rec. reserpine -depletion of catecholamines - only in combination - NÚ!!!

Combined - urapidile - block of postsyn. 1-rec., activation of 5-HT1Arec. in CNS

Peripheral -blockers 1 - prazosine, doxazosine, metazosine, terazosine

1+2 - phentolamine - th. of feochromocytoma + - labetalol, carvedilol

Indications

Compelling Possible

ACE-I cough Heart failure

ContraindicationsCompelling Possible

Pregnancy

Bilateral renal

Artery stenosis

Hyperkalaemia

Ang

iote

nsi

n II

Anta

gonis

ts

Antagonists of AT II:

Antagonists of AT II block of AT1 rec., regression of hypertr. LV, renoprotective eff. In AE of ACEI losartan, valsartan, irbesartan, telmisartan,……

Direct vasodilat. eff.: hydralazines (endralazine, dihydralazine), minoxidil, sodium nitroprusside reflex. tachycardia - in combination with -blockers and diuretics

Combination Therapy (1)

In most patients, appropriate combination therapy produces BP

reductions that are twice as great as those obtained with monotherapy.

Combination Therapy (2)Effective drug combinations to treat hypertension are:

• diuretic and beta-blocker• diuretic and ACE inhibitor (or Angiotensin II

antagonist)• calcium antagonist (dihydropyridine) and

beta-blocker• calcium antagonist and ACE inhibitor• alpha-blocker and beta-blocker

Other Drugs to Consider in Hypertension

• Aspirin

• Cholesterol lowering therapy

Treatment Goal

The goal of antihypertensive treatment should be to achieve “optimal” or “normal” BP in young, middle-aged, or diabetic subjects (below 130/85 mm Hg), and at least “high-

normal” BP in elderly patients (below 140/90 mm Hg)

How should hypertensionduring pregnancy be defined?

Hypertension in pregnancy usually defined as:

pre-existing chronic hypertension de novo diagnosed, gestational hypertension or

pre-eclampsia pre-eclampsia superimposed on chronic

hypertension

Antihypertensive drugsmost widely used acutely

during pregnancy

• Nifedipine

• Labetalol

• Hydralazine

• Beta-blockers:oxprenolol, pindolol, labetalol

atenolol, however, is associated with fetal growth retardation when used long-term throughout pregnancy

• Methyldopa

• Prazosin, hydralazine, nifedipine, and isradipine

Antihypertensive drugsmost widely used chronically

during pregnancy

Drugs most widelyavoided during pregnancy

• ACE inhibitors (associated with possible adverse fetal effects)

• Angiotensin ll antagonists (effects may be similar to ACE inhibitors)

• Diuretics used infrequently because of concerns of reducing already compromised plasma volume

Hypertensionin Type-2 Diabetics (1)

• Diabetes and hypertension are multiplicative risk factors for CVD

• Absence of hypertension in diabetes is associated with a better long-term survival

Hypertensionin Type-2 Diabetics (2)

• Progressive decline in glomerular function can be slowed with antihypertensive treatment

• Similar lifestyle measures are recommended for hypertension and diabetes

Hypertensionin Type-2 Diabetics (3)

Good evidence for reductionin CVD events in diabetic patients treated

with antihypertensivedrugs, including diuretics,

and more recently, beta-blockersand ACE inhibitors

Hypertensionin Type-2 Diabetics (4)

The goal of antihypertensive treatment in Type-2 diabetics should be to achieve

“optimal” or “normal” BP (that is below 130/85 mm Hg)