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

2 made by a Cambridge Reverend, Stephen Hales, in He measured blood pressure by inserting the end of a long glass tube into the carotid artery of a horse and noting that the blood came up the tube to a height of nine feet eight inches, which was the blood pressure of the horse.

3 It took Riva-Rocci, together with a Prussian general called Korotkoff, to develop the modern sphygmomanometer which was introduced into clinical practice in about The device that probably many of us still use today to measure blood pressure has changed very little from this early device.

4 Blood Pressure has a unimodal distribution in the Population

5 Question: Is it important if the person’s blood pressure is higher?

6 “ Hypertension may be an important compensatory mechanism which should not be tampered with, even were it certain that we could control it. ” White PD, 1931 “ The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try to reduce it. ” Hay J, 1931

7 Franklin D. Roosevelt （ FDR ） was referred to Dr. Howard Bruenn, a cardiologist at Bethesda Naval Hospital who, on March 27, 1944 found him cyanotic, breathless, with an enlarged left ventricle and a blood pressure of 186/108. Bruenn diagnosed hypertensive heart disease and wanted to give digitalis, but was prohibited by Dr. Ross McIntire, the president's personal physician and then surgeon-general of the U.S. Navy.Dr. “ Franklin D. Roosevelt ’ s health was excellent ” ！？－ 1944

8 The next day, FDR developed moist rales at the base of the right lung. By March 30, Bruenn diagnosed congestive heart failure. On the next day, digitalis was begun. By April 3, FDR was better. His color was better, he could lie flat without dyspnea, and the crackles disappeared from both lungs. His blood pressure, however, was 210/110. “ Franklin D. Roosevelt ’ s health was excellent ” ！？－ 1944

9 The nation was stunned when FDR died unexpectedly on April 12, less than six months after being elected to a fourth term in office. The death was unexpected because the president's personal physician, VADM Ross McIntire, whenever asked, had proclaimed that FDR's health was excellent. “ Franklin D. Roosevelt ’ s health was excellent ” ！？－ 1944

10 Question: How do we know the hypertension is responsible for the total risk of CV events?

11 Knowledge about risk and treatment of hypertension Framingham Heart Study: Hypertension and CHD 1961 Hypertension and Stroke 1970 World Health Organization (WHO): Treatment of Hypertension, firstly 1978 JNC II: DBP for diagnosis and treatment of hypertension 1980 JNC V: SBP and DBP is same important for hypertension 1992 JNC VII ： HBP to target BP is central for reduction of the total risk of CV events China guideline for hypertension: HBP should be reduced to target BP 2005 WHO: HBP should be reduced to target BP. 2006

12 The Relationship between DBP and Cardiovascular Events

13

14 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

15 Question: What is hypertension?

16 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.

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

Mortality % Circulatory system - Cerebral disease 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

Mortality % 30.8 Circulatory system Cerebral disease Heart disease Respiratory system Cancer Trauma, toxicosis Digestive system 4.0 Others 5.1 Mortality in China Countryside in Mortality in China Countryside in 1999

Trends in Awareness, Treatment, and Control of Hypertension in China Awareness(%) Treatment(%) Control(%)

22 Question: What is etiology of hypertension?

23 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.

24 Etiology

25

26 Question: How about the pathogenesis in hypertension is ?

27 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.

28 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.

29 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.

30 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.

31 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.

32 Question: Which pathologic changes will be happen in hypertension ?

33 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.

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

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

36 Question: How to know the patient with hypertension?

37 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.

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

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

40 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.

41 Question: What should we do if the patient may be with hypertension?

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

43 How to measure blood pressure

44 Category JNC 7 （ USA ） European China Optimal <120 and <80 Normal <120 and < and/or 80-84<120 and <80 High-normal or and/or or Hypertension ≥ 140 or ≥ 90 Grade I or and/or or Grade II ≥ 160 or and/or or 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

45 Initial Evaluation for Hypertension Goal 2: Cardiovascular Risk Stratification

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.

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%

48 Factors influencing prognosis

49 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 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)

50 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: µ mol/l ( mg/dl); W: µ mol/l ( mg/dl) Low estimated glomerular filtration rate (<60 ml/min/1.73 m2) Microalbuminuria mg/24 h or albumin-creatinine ratio: ≥ 30 mg/g

51 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%

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

53 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

54 Physical examination for secondary hypertension

55 Management

56 Goals of treatment

57 Goals of treatment

58 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.

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

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

61 Initiation of antihypertensive treatment

62 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.

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

64 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.

65 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.

66 Goals of treatment

67 Choice of antihypertensive drugs

68 Choice of antihypertensive drugs

69 Antihypertensive treatment: Preferred drugs

70 Antihypertensive treatment: Preferred drugs

71 Antihypertensive treatment: Preferred drugs

72 Choice of antihypertensive drugs

73 Compelling and possible contraindications to use of antihypertensive drugs

74 Choice of antihypertensive drugs

75 Choice of antihypertensive drugs

76 Choice of antihypertensive drugs

77 Monotherapy versus combination therapy strategies

78 Possible combinations between some classes of antihypertensive drugs β-blockers Calcium antagonists Diuretics Angiotesin II antagonists ACE inhibitors Journal of Hypertension 2007, 25:1105–1187. α-blockers

79 References 1. surveys/Pages/welcome.aspx surveys/Pages/welcome.aspx 中国高血压防治指南（ 2010 年修订版 )

80 Thanks for your attention!