Arterial Hypertension Dr. Xiao-Sheng Hu 1st Affiliated hospital, Zhejiang University 1

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. 2

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. 3

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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. 5

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. 6

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. 7

Pathogenesis Intracellular sodium and calcium. An increase in intracellular Na+ may lead to increased intracellular Ca2 + concentrations as a result of facilitated exchange. This could explain the increase in vascular smooth muscle tone. 8

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. 9

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. 10

Pathology Brain. Hypertension is the major predisposing cause of stroke, especially intracerebral hemorrhage but also ischemic cerebral infarction. 11

Pathology Kidney. Chronic hypertension leads to nephrosclerosis, a common cause of renal insufficiency. 12

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. 13

Clinical Findings Symptoms: Mild to moderated essential hypertension is usually associated with normal health and well-being for many years. 14

Clinical Findings Symptoms: Suboccipital pulsating headaches, but any type of headache, may occur. Accelerated hypertension is associated with somnolence, confusion, palpitation. 15

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. 16

Initial Evaluation for Hypertension Goal 1: Accurate Assessment of Blood Pressure 17

How to measure blood pressure 18

Blood pressure (BP) measurement When measuring BP, care should be taken to: Allow the patients to sit for 3-5 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. 19

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 large (arm circumference >32 cm) and thin arms, respectively. Have the cuff at the heart level, whatever the position of the patient 20

Blood pressure (BP) measurement Use phase I and V (disappearance) Korotkoff sounds to identify systolic and diastolic BP, respectively. Measure BP in both arms at first visit to detect possible differences. In this instance, take the arm with the higher value as the reference. 21

Blood pressure (BP) measurement Measure at first visit BP 1 and 3 min after assumption of the standing position in elderly subjects, diabetic patients, and in other conditions in which orthostatic hypotension may be frequent or suspected. 22

Definition and Classification of Blood Pressure Levels in different Country Category JNC 7（USA） European China Optimal <120 and <80 Normal 120-129 and/or 80-84 High-normal 120-139 or 80-89 130-139 and/or 85-89 Hypertension ≥ 140 or ≥ 90 Grade I 140-159 or 90-99 140-159 and/or 90-99 Grade II ≥ 160 or 100 160-179 and/or 100-109 160-179 or 100-109 Grade III ≥ 180 and/or ≥ 110 ≥ 180 or ≥ 110 Isolated Systolic Hypertension ≥ 140 and <90 23

Definition of hypertension by office and out-of-office blood pressure levels Category SBP (mmHg) DBP (mmHg) Office BP ≥140 and/or ≥90 Ambulatory BP Daytime (or awake) ≥135 ≥ 85 Nighttime (or asleep) ≥120 ≥ 70 24-h ≥ 130 ≥80 Home BP ≥ 135 ≥85 24

Stratification of total CV risk in hypertension 25

Factors--other than office BP--influencing prognosis; used for stratification of total CV risk Risk factors Male sex Age (M > 55 years; W > 65 years) Smoking Dyslipidaemia TC > 5.72 mmol/L (220 mg/dL) and/or: LDL-C > 3.3 mmol/L (130 mg/dL) and/or: HDL-C < 1.0 mmol/L (40 mg/dL Abdominal obesity (waist circumference > 85cm (M), > 80 cm (W)) Family history of premature CV disease (< 50 years) 26

Factors--other than office BP--influencing prognosis; used for stratification of total CV risk Asymptomatic Organ Damage Pulse pressure (in the elderly) ≥60 mmHg Electrocardiographic LVH or: Echocardiographic LVH Carotid wall thickening (IMT > 0.9 mm) or plaque CKD with eGFR 30-60 ml/min/1.73 m2 (BSA) Microalbuminuria (30-300 mg/24h), or albumin- creatinine ratio(male > 22mg/g ;female > 31mg/g) 27

Factors--other than office BP--influencing prognosis; used for stratification of total CV risk Diabetes mellitus Fasting plasma glucose ≥7.0 mmol/L (126 mg/dL) on two repeated measurements, and/or: HbA1C >7%, and/or Post-load plasma glucose >11.0 mmol/L (198 mg/dL) 28

Factors--other than office BP--influencing prognosis; used for stratification of total CV risk Established CV or renal disease Cerebrovascular disease: ischaemic stroke; cerebral haemorrhage; transient ischaemic attack CHD; myocardial infarction; angina; myocardial revascularization with PCI or CABG Heart failure, including heart failure with preserved EF Symptomatic lower extremities peripheral artery disease CKD with eGFR <30 mL/min/1.73m2 (BSA); proteinuria (>300 mg/24h) Advanced retinopathy; haemorrhages or exudates, papilloedema 29

Initial Evaluation for Hypertension Goal 3: Identification and Treatment of Secondary (Identifiable) Causes of Hypertension 30

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 31

Physical examination for secondary hypertension Features of Cushing syndrome Skin stigmata of neurofibromatosis (pheochromocytoma) Palpation of enlarged kidneys (polycystic kidney) Auscultation of precordial or chest murmurs (aortic coarctation; aortic disease; upper extremity artery disease) Diminished and delayed femoral pulses and reduced femoral blood pressure compared to simultaneous arm BP (aortic coarctation; aortic disease; lower extremity artery disease) Left-right arm BP difference (aortic coarctation; subclavian artery stenosis) 32

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. 33

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. 34

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. 35

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. 36

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. 37

Clinical indications and diagnostics of secondary hypertension CT, computed tomography; GFR, glomerular filtration rate; MRI, magnetic resonance imaging; RAA, renin-andiotensin-aldosterone 38

Clinical indications and diagnostics of secondary hypertension CT, computed tomography; GFR, glomerular filtration rate; MRI, magnetic resonance imaging; RAA, renin-andiotensin-aldosterone 39

Management 40

Goals of treatment In hypertensive patients, the primary goal of treatment is to achieve maximum reduction in the long-term total risk of cardiovascular disease. This requires treatment of the raised BP per se as well as of all associated reversible risk factors. 41

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

When to initiate antihypertensive treatment Based on two criteria: -The level of systolic and diastolic blood pressure -The level of total cardiovascular risk 43

Initiation of lifestyle changes and antihypertensive drug treatment 44

Blood pressure goals in hypertensive patients 45

Lifestyle Changes Weight Reduction Salt Restriction: 5-6g of salt/day Calcium and Potassium Supplementation High-Fiber, Low-Fat Diet Alcohol Moderation: 20-30g(M), 10-20g(F) of ethanol/day. Smoking cessation Regular Physical Exercise:30 min of moderate dynamic exercise on 5-7 days/week 46

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. 47

Monotherapy versus combination therapy Monotherapy could be the initial treatment for a mild BP elevation with a low or moderate total cardiovascular risk. 48

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. 49

Monotherapy versus combination therapy In several patients BP control is not achieved by two drugs, and a combination of three or more drugs is required. 50

Choice of antihypertensive drugs The choice of a specific drug or a drug combination, and the avoidance of others, should take into account the following: The previous favourable or unfavourable experience of the individual patient with a given class of compounds. 51

Choice of antihypertensive drugs The effect of drugs on cardiovascular risk factors in relation to the cardiovascular risk profile of the individual patient. The presence of asymptomatic organ damage, clinical cardiovascular disease, renal disease or diabetes which may be more favourably treated by some drugs than others. 52

Drugs to be preferred in specific conditions 53

Possible combination of classes of antihypertensive drugs 54

Monotherapy vs. drug combination strategies to achieve target BP 55

Compelling and possible contra-indications to the use of antihypertensive drugs 56

Choice of antihypertensive drugs The cost of drugs, either to the individual patient or to the health provider, but cost considerations should never predominate over efficacy, tolerability, and protection of the individual patient. Continuing attention should be given to side effects of drugs, because they are the most important cause of non-compliance. Drugs are not equal in terms of adverse effects, particularly in individual patients. 57

Choice of antihypertensive drugs The BP lowering effect should last 24 hours. This can be checked by office or home BP measurements at through or by ambulatory BP monitoring. Drugs which exert their anti hypertensive effect over 24 hours with a once-a-day administration should be preferred because a simple treatment schedule favours compliance. 58

Thanks for your attention! 59