1. 1 Cecil Medicine Section VIII Chapter 66 Arterial Hypertension Prof. Shen-Jiang Hu

2. 2 Definition of Hypertension Hypertension is a clinical syndrome, defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Hypertension should be considered a major risk factor for an array of cardiovascular and related disease as well as diseases leading to a marked increase in cardiovascular risk.

3. Hypertension in China(1991) ≥15% ≥15% ≥10%~14.9% ≥10%~14.9% ＜ 10% ＜ 10% 河南 青海 云南 山东 安徽 湖南 四川 贵州 甘肃 海南 天津 黑龙江 北京 上海 河北 西藏 吉林 内蒙古 辽宁 湖北 江苏 新疆 山西 陕西 广东 宁夏 广西 浙江 江西 福建 台湾

4. Mortality % Circulatory system - Cerebral disease 38.5 - Heart disease16.8 Cancer 23.9 Respiratory system13.9 Trauma, toxicosis6.3 Digestive system3.0 Others 6.4 Mortality in China City in Mortality in China City in 1999

5. Mortality % 30.8 Circulatory system 30.8 - 18.4 - Cerebral disease 18.4 - 12.4 - Heart disease 12.4 22.0 Respiratory system 22.0 18.4 Cancer 18.4 11.0 Trauma, toxicosis 11.0 4.0 Digestive system 4.0 Others 5.1 Mortality in China Countryside in Mortality in China Countryside in 1999

6. HypertensionHypertension Atrial Fibrillation Aortic Dissection Dementia Chronic Renal failure Heart Failure LV Hypertrophy MI Hypertensive Encephalopathy CHD Intracerebral Hemorrhage Ischemic Cerebral Infarction Complications of Hypertension

7. Trends in Awareness, Treatment, and Control of Hypertension in China Awareness(%) Treatment(%) Control(%) 1991 26.6 12.2 2.9 1991 26.6 12.2 2.9 2002 30.2 24.7 6.1 2002 30.2 24.7 6.1

8. 8 Etiology of Hypertension Genetic factors play an important role. Children with one- or two-hypertensive parents have higher blood pressures. Environmental factors also are significant. Increased salt intake has long been incriminated as a pathogenic factor in essential hypertension. It alone is probably not sufficient to elevate blood pressure to abnormal levels; a combination of too much salt plus a genetic predisposition is required.

9. 9 Etiology

10. 10

11. 11 Pathogenesis The pathogenesis of essential hypertension is multifactorial. Sympathetic nervous system hyperactivity. It is most apparent in younger hypertensives, who may exhibit tachycardia and an elevated cardiac output. However, correlations between plasma catecholamines and blood pressure are poor.

12. 12 Pathogenesis Renin-angiotensin system (RAS). Renin acts on angiotensinogen to cleave of the ten-amino-acid peptide angiotensin I. This peptide is then acted upon by angiotensin-converting enzyme to create the eight-amino-acid peptide angiotensin II, a potent vasoconstrictor and a major stimulant of aldosterone release from the adrenal glands.

13. 13 Pathogenesis Defect of natriuresis. Hypertensive patients exhibit a diminished ability to excrete a sodium load. This defect may result in increased plasma volume and hypertension.

14. 14 Pathogenesis Intracellular sodium and calcium. An increase in intracellular Na + may lead to increased intracellular Ca 2 + concentrations as a result of facilitated exchange. This could explain the increase in vascular smooth muscle tone.

15. 15 Pathogenesis Exacerbating factors. The best-documented is obesity, which is associated with an increase in intravascular volume and an elevated cardiac output. Some hypertensives respond to high salt intake with substantial blood pressure increases. Excessive use of alcohol also raises blood pressure. Cigarette smoking acutely raises blood pressure.

16. 16 Pathology Heart. Left ventricular hypertrophy may cause or facilitate many cardiac complications of hypertension, including congestive heart failure, ventricular arrhythmias, myocardial ischemia, and sudden death.

17. 17 Pathology Brain. Hypertension is the major predisposing cause of stroke, especially intracerebral hemorrhage but also ischemic cerebral infarction.

18. 18 Pathology Kidney. Chronic hypertension leads to nephrosclerosis, a common cause of renal insufficiency.

19. 19 Clinical Findings Symptoms: Elevations in pressure are often intermittent early. Even in established case, the blood pressure fluctuates widely in response to emotional stress and physical activity.

20. 20 Clinical Findings Symptoms: Mild to moderated essential hypertension is usually associated with normal health and well-being for many years.

21. 21 Clinical Findings Symptoms: Suboccipital pulsating headaches, but any type of headache, may occur. Accelerated hypertension is associated with somnolence, confusion, palpitation.

22. 22 Signs ： High blood pressure. Physical findings depend upon the duration and severity, and the degree of effect on target organs. A loud aortic second sound and an early systolic ejection click may occur.

23. 23 Initial Evaluation for Hypertension Goal 1: Accurate Assessment of Blood Pressure

24. 24 Blood pressure (BP) measurement When measuring BP, care should be taken to: Allow the patients to sit for several minutes in a quiet room before beginning BP measurements Take at lease two measurements spaced by 1-2 minutes, and additional measurements if the first two are quite different

25. 25 Blood pressure (BP) measurement Use a standard bladder (12-13 cm long and 35 cm wide) but have a larger and a smaller bladder available for fat and thin arms, respectively. Use the smaller in children Have the cuff at the heart level, whatever the position of the patient

26. 26 Blood pressure (BP) measurement

27. 27 Blood pressure (BP) measurement

28. 28 Category JNC 7 （ USA ） European China Optimal <120 and <80 Normal <120 and <80120-129 and/or 80-84<120 and <80 High-normal 120-139 or 80-89130-139 and/or 85-89120-139 or 80-89 Hypertension ≥ 140 or ≥ 90 Grade I 140-159 or 90-99140-159 and/or 90-99140-159 or 90-99 Grade II ≥ 160 or 100 160-179 and/or 100-109160-179 or 100-109 Grade III ≥ 180 and/or ≥ 110 ≥ 180 or ≥ 110 Isolated Systolic Hypertension ≥ 140 and <90 Definition and Classification of Blood Pressure Levels in different Country

29. 29 Initial Evaluation for Hypertension Goal 2: Cardiovascular Risk Stratification

30. 30 Stratification of CV Risk Stratification of CV Risk in four categories. SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: Cardiovascular events; HT: hypertension. Low, moderate, high and very high risk refer to 10 year risk of a CV fatal or non-fatal event. The term “ added ” indicates that in all categories risk is greater than average. OD: subclinical organ damage; MS: metabolic syndrome. The dashed line indicates how definition of hypertension may be variable, depending on the level of total CV risk.

31. Estimate total cardiovascular risk  Framingham Study ： Risk for cardiovascular events over 10 years Very high High Moderate Low >30% 20-30% 15-20% <15%  SCORE charts ： the risk of dying from cardiovascular disease over 10 years Very high High Moderate Low >8% 5-8% 4-5% <4%

32. 32 Factors influencing prognosis Risk factors Systolic and diastolic BP levels Levels of pulse pressure (in the elderly) Age (M > 55 years; W > 65 years) Smoking Dyslipidaemia TC > 5.7 mmol/l (220 mg/dl) or: LDL-C > 3.3 mmol/l (130 mg/dl) or: HDL-C: < 1.0 mmol/l (40 mg/dl) Fasting plasma glucose 6.1-6.9 mmol/L Abnormal glucose tolerance test Abdominal obesity (Waist circumference > 90 cm (M), > 85 cm (W)) Family history of premature CV disease (M at age < 55 years; W at age < 65 years)

33. 33 Factors influencing prognosis Subclinical Organ Damage Electrocardiographic LVH or: Echocardiographic LVH Carotid wall thickening (IMT > 0.9 mm) or plaque Carotid-femoral pulse wave velocity > 12 m/s Ankle/brachial BP index < 0.9 Slight increase in plasma creatinine: M: 115-133 µ mol/l (1.3-1.5 mg/dl); W: 107-124 µ mol/l (1.2-1.4 mg/dl) Low estimated glomerular filtration rate (<60 ml/min/1.73 m2) Microalbuminuria 30-300 mg/24 h or albumin-creatinine ratio: ≥ 30 mg/g

34. 34 Factors influencing prognosis Established CV disease Cerebrovascular disease: ischaemic stroke; cerebral haemorrhage; transient ischaemic attack Heart disease: myocardial infarction; angina; coronary revascularization; heart failure Renal disease: diabetic nephropathy; renal impairment (serum creatinine: M>133, W>124 μmol/L; porteinuria ≥300 mg/24h) Peripheral artery disease Advanced retinopathy: haemorrhages or exudates, papilloedema Diabetes mellitus: fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dl); postload plasma glucose > 11.1 mmol/L (200 mg/dl); HbA1c ≥ 6.5%

35. 35 Initial Evaluation for Hypertension Goal 3: Identification and Treatment of Secondary (Identifiable) Causes of Hypertension

36. 36 two circumstances when there is a compelling finding on the initial evaluation when the hypertensive process is so severe that it either is refractory to intensive multiple-drug therapy or requires hospitalization

37. 37 Physical examination for secondary hypertension

38. 38 Secondary Hypertension Renal disease: any disease of the renal parenchyma can cause hypertension, and these conditions are the most common causes of secondary hypertension. Hypertension may result from glomerular diseases, tubular interstitial disease, and polycystic kidneys. Diabetic nephropathy is another cause of chronic hypertension.

39. 39 Secondary Hypertension Renal vascular hypertension: it is due to artery stenosis, fibromuscular hyperplasia, and atherosclerotic stenoses. It should be suspected in the following circumstances: (1) if the documented onset is below age 20 or after age 50; (2) if there are epigastric or renal artery bruits; (3) if there is atherosclerotic disease of aorta or peripheral arteries; or (4) if there is abrupt deterioration in renal function after administration of angiotensin- converting enzyme inhibitors.

40. 40 Secondary Hypertension Primary hyperaldosteronism and Cushing ’ s syndrome: the diagnosis should be suspected when patients present with hypokalemia prior to diuretic therapy associated with excessive urinary potassium excretion, increased serum sodium, and suppressed levels of plasma renin activity. Aldosterone concentrations in urine and blood are elevated. The lesion can be demonstrated by CT scanning or MRI.

41. 41 Secondary Hypertension Pheochromocytoma: although hypertension due to pheochromocytoma may be episodic, most patients have sustained elevations. The majority of patients have orthostatic falls in blood pressure, the converse of essential hypertension; some develop glucose intolerance.

42. 42 Secondary Hypertension Other causes of secondary hypertension: hypertension has also been associated with acromegaly, hyperthyroidism, hypothyroidism, and a variety of neurologic disorders causing increased intracranial pressure.

43. 43 Management

44. 44 Goals of treatment

45. 45 Goals of treatment

46. 46 Stratification of CV Risk Stratification of CV Risk in four categories. SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: Cardiovascular events; HT: hypertension. Low, moderate, high and very high risk refer to 10 year risk of a CV fatal or non-fatal event. The term “ added ” indicates that in all categories risk is greater than average. OD: subclinical organ damage; MS: metabolic syndrome. The dashed line indicates how definition of hypertension may be variable, depending on the level of total CV risk.

47. Relationship between BP reduction with CV events and Mortality Lancet 2003;362:1527-45 0 -5 -10 -15 -20 -25 -30 Stroke CHD HF Mortality 23% 15% 16% 14% － 4/3 mmHgN ＝ 20 888 Major CV 15%

48. 48 Management Lifestyle Modification Weight Loss Sodium Restriction Potassium Supplementation High-Fiber, Low-Fat Diet Alcohol Moderation Smoking cessation Exercise

49. 49 When to initiate antihypertensive treatment Based on two criteria: -The level of systolic and diastolic blood pressure -The level of total cardiovascular risk

50. 50 Initiation of antihypertensive treatment

51. 51 Choice of antihypertensive drugs Five major classes of antihypertensive agents – thiazide diuretics, calcium antagonists, ACE inhibitors, angiotensin receptor antagonists and β-blockers – are suitable for the initiation and maintenance of antihypertensive treatment, alone or in combination.

52. 52 Monotherapy versus combination therapy Monotherapy could be the initial treatment for a mild BP elevation with a low or moderate total cardiovascular risk.

53. 53 Monotherapy versus combination therapy A combination of two drugs at low doses should be preferred as first step treatment when initial BP is in the grade 2 or 3 range or total cardiovascular risk is high or very high.

54. 54 Monotherapy versus combination therapy In several patients BP control is not achieved by two drugs, and a combination of three of more drugs is required.

55. 55 Choice of antihypertensive drugs

56. 56 Choice of antihypertensive drugs

57. 57 Antihypertensive treatment: Preferred drugs

58. 58 Antihypertensive treatment: Preferred drugs

59. 59 Antihypertensive treatment: Preferred drugs

60. 60 Choice of antihypertensive drugs

61. 61 Compelling and possible contraindications to use of antihypertensive drugs

62. 62 Choice of antihypertensive drugs

63. 63 Choice of antihypertensive drugs

64. 64 Choice of antihypertensive drugs

65. 65 Monotherapy versus combination therapy strategies

66. 66 Possible combinations between some classes of antihypertensive drugs

67. 67 References 1. http://www.escardio.org/guidelines- surveys/Pages/welcome.aspx http://www.escardio.org/guidelines- surveys/Pages/welcome.aspx 2. http://www.acc.org/login/index.taf http://www.acc.org/login/index.taf

68. 68 Thanks for your attention!