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New (1999) WHO-ISH Definitions and Classification of BP Levels Category Systolic BP (mm Hg) Diastolic BP (mm Hg) Optimal BP Normal BP High-Normal <120 <130 130-139 <80 <85 85-89 Grade 1 Hypertension (mild) Subgroup: Borderline Grade 2 Hypertension (moderate) Grade 3 Hypertension (severe) 140-159 140-149 160-179 >180 90-99 90-94 100-109 >110 Isolated Systolic Hypertension Subgroup: Borderline >140 140-149 <90 <90 What is the Goal of 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 Hg and 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 Hg and 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 Routine Investigations 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 Which Factors Influence Prognosis? (2) • Risk factors of CVD I. Used for risk stratification II.Other factors adversely influencing prognosis • Target organ damage (TOD) • Associated clinical conditions (ACC) Which Factors Influence Prognosis? (3) Risk factors for CVD 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 Which Factors Influence Prognosis? (4) Risk factors for CVD 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 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 Management Strategy 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 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 main drug 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. Diuretics Indications Compelling Possible Heart failure Elderly patients Systolic hypertension Diabetes Contraindications Compelling Possible Gout Dyslipidaemia Sexually active males Beta-Blockers Indications Compelling Angina Possible Heart failure After myocardial infarct Tachyarrhythmias Pregnancy Diabetes Compelling Asthma and Chronic obstructive Pulmonary disease Heart block (AV 2,3) Possible Dyslipidaemia Athletes and Physically active Patients Peripheral vascular disease Contraindications Calcium Antagonists Indications Compelling Possible Angina Elderly patients Systolic hypertension Peripheral Vascular disease Contraindications Compelling Heart block (AV 2,3) * verapamil or diltiazem Possible Heart failure* ACE Inhibitors Indications Compelling Heart failure Possible Left ventricular dysfunct After myocardial infarct Diabetic nephropathy Contraindications Compelling Pregnancy Bilateral renal artery stenosis Hyperkalaemia Possible 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 Alpha-Blockers Indications Compelling Prostatic Hypertrophy Possible Glucose intolerance Dyslipidaemia Contraindications Compelling Possible Orthostatic hypotension - blockers Central 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 Angiotensin II Antagonists Indications Compelling ACE-I cough Possible Heart failure Contraindications Compelling Pregnancy Bilateral renal Artery stenosis Hyperkalaemia Possible 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 “highnormal” BP in elderly patients (below 140/90 mm Hg) How should hypertension during 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 drugs most widely used acutely during pregnancy • Nifedipine • Labetalol • Hydralazine Antihypertensive drugs most widely used chronically during pregnancy • 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 Drugs most widely avoided 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 Hypertension in 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 Hypertension in Type-2 Diabetics (2) • Progressive decline in glomerular function can be slowed with antihypertensive treatment • Similar lifestyle measures are recommended for hypertension and diabetes Hypertension in Type-2 Diabetics (3) Good evidence for reduction in CVD events in diabetic patients treated with antihypertensive drugs, including diuretics, and more recently, beta-blockers and ACE inhibitors Hypertension in 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)