1. Hypertension - general overview (guidelines ) Hypertension - general overview (guidelines ) Andrzej Tomaszewski Ass. Prof. M.D. Ph. D. Dept. of Cardiology, Medical University Lublin, Poland CARDIONALE, 26. 11. 2010, Prague

2. History of BP measurement In 1896 Riva-Rocci described an inflatable cuff that allowed measurement of brachial systolic pressure. In 1896 Riva-Rocci described an inflatable cuff that allowed measurement of brachial systolic pressure. In 1904 Korotkov reported the auscultatory method that allowed measurement of systolic and diastolic pressure. In 1904 Korotkov reported the auscultatory method that allowed measurement of systolic and diastolic pressure.

3. Basis for the lecture: 2007 Guidelines for the management of arterial hypertension The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Authors/Task Force Members: Giuseppe Mancia, Co- Chairperson (Italy), Guy De Backer, Co-Chairperson (Belgium), Anna Dominiczak (UK), Renata Cifkova (Czech Republic), Robert Fagard (Belgium), Giuseppe Germano (Italy), Guido Grassi (Italy), Anthony M. Heagerty (UK), Sverre E. Kjeldsen (Norway), Stephane Laurent (France), Krzysztof Narkiewicz (Poland), Luis Ruilope (Spain), Andrzej Rynkiewicz (Poland), Roland E. Schmieder (Germany), Harry A.J. Struijker Boudier (Netherlands), Alberto Zanchetti (Italy) European Heart Journal 2007;28:1462-1536

4. Basis for the lecture: Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document 2009 Giuseppe Mancia, Stephane Laurent, Enrico Agabiti-Rosei, Ettore Ambrosioni, Michel Burnier, Mark J. Caulfield, Renata Cifkova,Denis Cle´ment, Antonio Coca, Anna Dominiczak, Serap Erdine,Robert Fagard, Csaba Farsang, Guido Grassi, Hermann Haller,Antony Heagerty, Sverre E. Kjeldsen, Wolfgang Kiowski, Jean Michel Mallion,Athanasios Manolis, Krzysztof Narkiewicz, Peter Nilsson, Michael H. Olsen,Karl Heinz Rahn, Josep Redony Jose´ Rodicio, Luis Ruilopea,Roland E. Schmiedera, Harry A.J. Struijker-Boudiera, Pieter A. van Zwietena,Margus Viigimaaa and Alberto Zanchettia Journal of Hypertension 2009, Vol 27,2121-58

5. Epidemiology of arterial hypertension Arterial hypertension is one of the most prevalent cardiovascular diseases. Arterial hypertension is one of the most prevalent cardiovascular diseases. Arterial hypertension affects 20-50 % of adults in developed countries. Arterial hypertension affects 20-50 % of adults in developed countries. Frequency of arterial hypertension suddenly increases after 50 years of life (>50% of this population). Frequency of arterial hypertension suddenly increases after 50 years of life (>50% of this population). Worldwide, hypertension affects over 970 milion persons. Worldwide, hypertension affects over 970 milion persons.

6. Definition and classification of blood pressure levels (mmHg) Category Systolic Diastolic Optimal <120 and <80 Normal 120–129 and/or 80–84 High normal 130–139 and/or 85–89 Grade 1 hypertension 140–159 and/or 90–99 Grade 2 hypertension 160–179 and/or 100–109 Grade 3 hypertension ≥180 and/or ≥110 Isolated syst. ≥140 and <90 hypertension

7. * Defined as death due to CV disease; recognized myocardial infarction (MI), stroke, or congestive heart failure (CHF). Adapted from Vasan RS. N Engl J Med. 2001;345:1291-1297. Cumulative Incidence (%) of Major CV Events 1616 1212 1010 8 6 4 2 0 1414 024681012 Time (y) Optimal BP (<120/80 mm Hg) Normal BP (120-129/80-84 mm Hg) High-normal BP (130-139/85-89 mm Hg) Impact of High-Normal BP on Risk of Major CV Events* in Men

8. Arterial Hypertension as a risk factor Hypertension is a highly prevalent risk factor for cardiovascular disease Hypertension is a highly prevalent risk factor for cardiovascular disease Hypertension plays a major etiologic role in the development of cerebrovascular disease, ischemic heart disease, cardiac and renal failure Hypertension plays a major etiologic role in the development of cerebrovascular disease, ischemic heart disease, cardiac and renal failure

9. Assessment of global cardiovascular risk in arterial hypertension grades of hypertension grades of hypertension total cardiovascular risk (coexistence different risk factors, organ damage, concomitant diseases) total cardiovascular risk (coexistence different risk factors, organ damage, concomitant diseases)

10. Stratification of total CV risk Four categories : Four categories : - Low - Low - Moderate - Moderate - High - High - Very high - Very high refer to 10 year risk of fatal or non-fatal CV event refer to 10 year risk of fatal or non-fatal CV event

11. Diagnostic evaluation in arterial hypertension Establishing BP values Establishing BP values Identyfying secondary causes of AH Identyfying secondary causes of AH Searching for : Searching for : -other risk factors -other risk factors -subclinical organ damage -subclinical organ damage -concomitant diseases -concomitant diseases -accompanying CV and renal complications -accompanying CV and renal complications

12. Diagnostic procedures in arterial hypertension repeated BP measurements repeated BP measurements family and clinical history family and clinical history physical examination physical examination laboratory and instrumental investigation laboratory and instrumental investigation

13. Laboratory and instrumental investigation- routine tests Fasting plasma glucose Serum total cholesterol, LDL-cholesterol, HDL-cholesterol Fasting serum triglycerides Serum potassium Serum uric acid Serum creatinine Estimated creatinine clearance Haemoglobin and haematocrit Urinalysis Electrocardiogram

14. Laboratory and instrumental investigation Echocardiogram Carotid ultrasound Quantitative proteinuria Fundoscopy Glucose tolerance test (if fasting plasma glucose >5.6 mmol/L (100 mg/dL) Home and 24 h ambulatory BP monitoring

15. Left ventricular hypertrophy, parasternal long axis view

16. Left ventricular hypertrophy, parasternal short axis view

17. Left ventricular hypertrophy, four-chamber view

18. Left ventricular hypertrophy, subcostal view

19. Extended laboratory and instrumental investigation Search for cerebral, cardiac, renal, vascular damage, for secondary hypertension: Search for cerebral, cardiac, renal, vascular damage, for secondary hypertension: measurement of renin, aldosteron,corticosteroids,catecholamines in plasma and/or urine measurement of renin, aldosteron,corticosteroids,catecholamines in plasma and/or urine arteriographies, CT, MRI arteriographies, CT, MRI

20. Secondary causes of AH : Renal parenchymal disease (most common cause) Renal parenchymal disease (most common cause) Renovascular hypertension (2nd most common cause) Renovascular hypertension (2nd most common cause) Pheochromocytoma Pheochromocytoma Primary hyperaldosteronism Primary hyperaldosteronism Cushing’s syndrome Cushing’s syndrome Obstructive sleep apnea Obstructive sleep apnea Coarctation of aorta Coarctation of aorta Drug-induced hypertension Drug-induced hypertension

21. Evidence on the benefit of antihypertensive treatment Placebo controlled trials provided evidence that BP lowering reduces fatal and non-fatal CV events Placebo controlled trials provided evidence that BP lowering reduces fatal and non-fatal CV events Trials comparing different antihypertensive drugs emphasise role of BP lowering of all CV events (stroke, myocardial infarction, heart failure) Trials comparing different antihypertensive drugs emphasise role of BP lowering of all CV events (stroke, myocardial infarction, heart failure) BP-independent effects (protection against subclinical organ damage, prevention of high risk condition such as diabetes, renal failure, atrial fibrillation) BP-independent effects (protection against subclinical organ damage, prevention of high risk condition such as diabetes, renal failure, atrial fibrillation)

22. Benefits of Lowering BP Average r eduction Stroke incidence 35–40% Myocardial infarction 20–25% Heart failure50%

23. Aim of antihypertensive therapy The primary goal of treatment is to achieve maximum reduction in the long-term total risk of CV disease The primary goal of treatment is to achieve maximum reduction in the long-term total risk of CV disease For this reason lowering BP therapy (at least For this reason lowering BP therapy (at least < 140/90 mm Hg) and treatment of all reversible risk factors are indicated < 140/90 mm Hg) and treatment of all reversible risk factors are indicated In diabetes and in high and very high risk patients BP target should be at least < 130/80 mmHg In diabetes and in high and very high risk patients BP target should be at least < 130/80 mmHg

24. Treatment guidelines (ESH/ESC 2007) Average riskLow added riskModerate added riskHigh added riskVery high added risk ESH – ESC Guidelines Committee. J Hypertens 2007; 25: 1105–1187

25. Lifestyle changes smoking cessation smoking cessation weight reduction weight reduction reduction of excessive alkohol intake reduction of excessive alkohol intake physical exercise physical exercise reduction of salt intake reduction of salt intake increase in fruit and vegetables intake increase in fruit and vegetables intake decrease in saturated and total fat intake decrease in saturated and total fat intake

26. Choice of the antihypertensive drugs Five major classes of these drugs are suitable for initiation and maintenance of treatment, alone or in combination : Five major classes of these drugs are suitable for initiation and maintenance of treatment, alone or in combination : thiazide diuretics thiazide diuretics calcium antagonists (CA) calcium antagonists (CA) ACE-inhibitors (ACEI) ACE-inhibitors (ACEI) angiotensin receptor blockers (ARB) angiotensin receptor blockers (ARB) beta-blockers (BB) beta-blockers (BB)

27. Conditions favouring the use of some antihypertensive drugs versus other Subclinical organ damage: Subclinical organ damage: LVH ACEI, CA, ARB LVH ACEI, CA, ARB Asymptomatic Atherosclerosis CA, ACEI Asymptomatic Atherosclerosis CA, ACEI Microalbuminuria ACEI, ARB Microalbuminuria ACEI, ARB Renal dysfunction ACEI, ARB Renal dysfunction ACEI, ARB

28. Conditions favouring the use of some antihypertensive drugs versus other Clinical event: Clinical event: Previous stroke any BP lowering agent Previous stroke any BP lowering agent Previous MI BB, ACEI, ARB Previous MI BB, ACEI, ARB Heart failure diuretics, BB, ACEI, Heart failure diuretics, BB, ACEI, ARB, anti-aldosterone agents ARB, anti-aldosterone agents Tachyarrhythmias BB Tachyarrhythmias BB Periph.art.disease CA Periph.art.disease CA LV dysfunction ACEI LV dysfunction ACEI

29. Conditions favouring the use of some antihypertensive drugs versus other Condition : Condition : ISH (elderly) diuretics,CA ISH (elderly) diuretics,CA Metabolic syndrome ACEI,ARB,CA Metabolic syndrome ACEI,ARB,CA Diabetes mellitus ACEI, ARB Diabetes mellitus ACEI, ARB Pregnancy CA,methyldopa,BB Pregnancy CA,methyldopa,BB Glaucoma BB Glaucoma BB

30. Monotherapy versus combination therapy Monotherapy allows to achieve BP target only in a limited number of patients Monotherapy allows to achieve BP target only in a limited number of patients Use of more than one agent is necessary to achieve target BP Use of more than one agent is necessary to achieve target BP Initial therapy: monotherapy or combination of two drugs in low doses with subsequent increase in drug doses or number Initial therapy: monotherapy or combination of two drugs in low doses with subsequent increase in drug doses or number

31. Monotherapy versus combination therapy Monotherapy in mild BP elevation with low or moderate total CV risk Monotherapy in mild BP elevation with low or moderate total CV risk Two drugs at low doses should be preferred as the first step when BP is in grade 2 or 3 or total CV risk is high or very high with mild hypertension Two drugs at low doses should be preferred as the first step when BP is in grade 2 or 3 or total CV risk is high or very high with mild hypertension Fixed combination of two drugs simplify the treatment Fixed combination of two drugs simplify the treatment If BP control is not achieved by two drugs, combination of three or more drugs is required If BP control is not achieved by two drugs, combination of three or more drugs is required

32. Possible combinations of different classes of antihypertensive agents The preferred combinations in general hypertensive population are represented as thick lines. The frames indicate classes of agents proven to be beneficial in controlled interventional trials Diuretics AT 1 -receptor blockers β-blockers α-blockers CCBs ACE inhibitors ACE, angiotensin-converting enzyme AT, angiotensin CCB, calcium-channel blocker ESH – ESC Guidelines Committee. J Hypertens 2007; 25: 1105–1187

33. Antihypertensive therapy in special groups Elderly patients Elderly patients Diabetic patients Diabetic patients Patients with renal dysfunction Patients with renal dysfunction Patients with cerebrovascular disease Patients with cerebrovascular disease Patients with coronary heart disease and heart failure Patients with coronary heart disease and heart failure Patients with atrial fibrillation Patients with atrial fibrillation

34. Hypertension in women Response to antihypertensive drugs, beneficial effect of BP lowering is similar in men and women Response to antihypertensive drugs, beneficial effect of BP lowering is similar in men and women Oral contraceptives Oral contraceptives Hormone replacement therapy Hormone replacement therapy Hypertension in pregnancy Hypertension in pregnancy

35. Resistant hypertension Poor adherence to therapeutic plan Failure to modify lifestyle including: weight gain, heavy alcohol intake Intake of drugs that raise blood pressure Obstructive sleep apnoea Unsuspected secondary cause Irreversible or scarcely reversible organ damage Volume overload due to:inadequate diuretic therapy, progressive renal insufficiency, high sodium intake, hyperaldosteronism

36. Unsuspected secondary cause

38. Coarctation of aorta Unsuspected secondary cause Coarctation of aorta

40. Malignant hypertension Clear overlap between resistant and malignant hypertension Clear overlap between resistant and malignant hypertension Severe BP elevation (DBP usually >140 mmHG) with vascular damage (retinal haemorrhage, papilloedema, hypertensive encephalopathy,deterioration in renal function, DIC) Severe BP elevation (DBP usually >140 mmHG) with vascular damage (retinal haemorrhage, papilloedema, hypertensive encephalopathy,deterioration in renal function, DIC)

41. Hypertensive emergiences Hypertensive encephalopathy Hypertensive left ventricular failure Hypertension with myocardial infarction Hypertension with unstable angina Hypertension and dissection of the aorta Severe hypertension associated with subarachnoid haemorrhage or cerebrovascular accident Crisis associated with phaeochromocytoma Use of recreational drugs such as amphetamines, LSD, cocaine or ecstasy Hypertension perioperatively Severe pre-eclampsia or eclampsia

42. Echocardiography Echocardiography Examples of two hypertensive emergencies: Examples of two hypertensive emergencies: - aortic dissection - aortic dissection - fatal myocardial infarction - fatal myocardial infarction

43. Aortic dissection Aortic dissection

45. Chronic aortic dissection Chronic aortic dissection

47. Fatal myocardial infarction Fatal myocardial infarction

51. Fatal myocardial infarction,cardiac tamponade

52. Hypertension – treatment of associated risk factors Lipid lowering agents: Lipid lowering agents: - all hypertensive pts with CV disease or diabetes should be considered for statin therapy aiming total cholesterol < 175 mg/dl and LDL < 100mg/dl - all hypertensive pts with CV disease or diabetes should be considered for statin therapy aiming total cholesterol < 175 mg/dl and LDL < 100mg/dl - pts with high CV risk should be considered for statin therapy, even if total and LDL cholesterol are not elevated - pts with high CV risk should be considered for statin therapy, even if total and LDL cholesterol are not elevated

53. Hypertension – treatment of associated risk factors Antiplatelet therapy (low dose aspirin): Antiplatelet therapy (low dose aspirin): -for pts with previous CV events -for pts with previous CV events -for pts without history of CV disease if older than 50 y., with moderate increase in serum creatinine or with high CV risk -for pts without history of CV disease if older than 50 y., with moderate increase in serum creatinine or with high CV risk Glycemic control : Glycemic control : - lowering fasting plasma glucose to 108 mg/dl, glycated hemoglobin of <6,5% - lowering fasting plasma glucose to 108 mg/dl, glycated hemoglobin of <6,5%

54. Reappraisal of European guidelines on hypertension management: a ESH Task Force document, 2009 What is new today after reappraisal 2009 ? 1/Some of new studies have reinforced the evidence on which the recommendations of the 2007 ESH/ESC guidelines were based 2/Other studies have widened the information available in 2007 3/Modifying some of the previous concepts 4/New evidence-based recommendations could be appropriate.

55. New evicence-based recommendations: - blood pressure goals of treatment - blood pressure goals of treatment - indications for starting antihypertensive pharmacotherapy - indications for starting antihypertensive pharmacotherapy Reappraisal of European guidelines on hypertension management: a ESH Task Force document, 2009

56. Blood pressure goals of treatment: Blood pressure goals of treatment: there is sufficient evidence to recommend that SBP be lowered below 140mmHg (and DBP below 90mmHg) in all hypertensive patients, both those at low moderate risk and those at high risk. The recommendation of previous guidelines to aim at a lower goal SBP (<130mmHg) in diabetic patients and in patients at very high cardiovascular risk (previous cardiovascular events) may be wise, but it is not consistently supported by trial evidence.

57. Reappraisal of European guidelines on hypertension management: a ESH Task Force document, 2009 Blood pressure goals of treatment: Blood pressure goals of treatment: on the basis of current data, it may be prudent to recommend lowering SBP/DBP to values within the range 130–139/80–85mmHg, and possibly close to lower values in this range, in all hypertensive patients.

58. Reappraisal of European guidelines on hypertension management: a ESH Task Force document, 2009 Indications for starting antihypertensive pharmacotherapy Indications for starting antihypertensive pharmacotherapy In the vast majority of hypertensive patients, effective BP control can only be achieved by combination of at least two antihypertensive drugs.

59. Reappraisal of European guidelines on hypertension management: a ESH Task Force document, 2009 Recommended combinations for priority use: Diuretic + ACEI Diuretic + ARB Diuretic + CA ACEI + CA ARB +CA

60. Reappraisal of European guidelines on hypertension management: a ESH Task Force document, 2009 Not recommended combinations: Not recommended combinations: Beta-blocker + diuretic combination favors the development of diabetes Beta-blocker + diuretic combination favors the development of diabetes ACE inhibitor + angiotensin receptor antagonist combination presents dubious potentiation of benefits with a serious side efects ACE inhibitor + angiotensin receptor antagonist combination presents dubious potentiation of benefits with a serious side efects

61. Reappraisal of European guidelines on hypertension management: a ESH Task Force document, 2009 In no less than 15–20% of patients, BP control cannot be achieved by a two-drug combination. The most rational combination of three drugs appears to be a blocker of the renin–angiotensin system, a calcium antagonist, and a diuretic at effective doses. β-blocker or an α-blocker, may be included in a multiple approach, depending on the clinical circumstances.

62. Thank you for your attention