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ESSENTIAL HYPERTENSION. DEFINITION Essential, primary, or idiopathic hypertension is defined as high BP in which secondary causes or mendelian (monogenic)

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Presentation on theme: "ESSENTIAL HYPERTENSION. DEFINITION Essential, primary, or idiopathic hypertension is defined as high BP in which secondary causes or mendelian (monogenic)"— Presentation transcript:

1 ESSENTIAL HYPERTENSION

2 DEFINITION Essential, primary, or idiopathic hypertension is defined as high BP in which secondary causes or mendelian (monogenic) forms are not present High BP – repeatedly measured BP exceeding 140/90 mmHg, i.e. a systolic BP above 140 and/or diastolic BP above 90

3 Aetiology of Hypertension Primary – 90-95% of cases – also termed “essential” of “idiopathic ” Secondary – about 5% of cases –Renal or renovascular disease –Endocrine disease Phaeochomocytoma Cusings syndrome Conn’s syndrome Acromegaly and hypothyroidism –Coarctation of the aorta –Iatrogenic Hormonal / oral contraceptive NSAIDs

4 Definitions and classifications of BP levels 2003 ESH/ESC guidelines for the management of arterial hypertension

5 Definitions and classifications of BP levels JNC 7 th Report on Prevention, Detection, Evaluation and Treatment of High Blood Pressure

6 WHO Classification of Hypertension (1993) Stage I – no evident signs of target organ damage Stage II – presence of at least one of the following signs of target organ damage: Heart: LVH (diagnosed radiologically, on ECG or by Echocardiography) Retina: generalized or focal narrowing of retinal arteries Kidney: microalbuminurua, proteinuria, creatinine<2mg/dl (176 µmol/l) Vessels: increased IMT or plaques in carotid, iliac, or femoral arteries Stage III – signs of severe target organ damage: Heart: angina pectoris, myocardial infarction, heart failure Brain: stroke, TIA, vascular dementia Retina: haemorrhages, exudates, papilloedema Kidney: renal insufficiency (creatinine>2mg/ml) Vessels: dissecting aortic aneurysm, symptomatic occlusive peripheral arterial disease

7 Adapted from WHO/ISH Recommendations on Hypertension. Journal of Hypertension 2003, Vol 21 No 6 Blood pressure (mmHg) Other risk factors and disease history Normal SBP 120-129 or DBP 80-84 High normal SBP 130-139 or DBP 85-89 Grade 1 SBP 140-159 or DBP 90-99 Grade 2 SBP 160-179 or DBP 100- 109 Grade 3 SBP ≥180 or DBP ≥110 I. No other risk factors Average risk Low added risk Moderate added risk High added risk II. 1-2 risk factors Low added risk Moderate added risk Very high added risk III. ≥3 risk factors or target organ damage or diabetes Moderate added risk High added risk Very high added risk IV. Associated clinical conditions High added risk Very high added risk DEFINITION The “New Definition” of hypertension must include overall risk (ND Kaplan, MD, 2005 ASH meeting)

8 EPIDEMIOLOGY Treatment Approaches: Lifestyle Pharmacological Swales JD (ed.) Textbook of hypertension. Oxford: Blackwell Scientific Publishers. © 1994, 22–36

9 EPIDEMIOLOGY Burt et al., Hypertension 1995;25:305–13.

10 Trends in awareness, treatment, and control of high blood pressure in adults aged 18-74*

11 Multiple interactions in the pathogenesis of hypertension

12 MAJOR RISK FACTORS Age Genetics and family history Family and personal history of hyperlipidaemia Family and personal history of diabetes Cigarette smoking Environment (stress, sedentary lifestyle) Weight Dietary habits (high alcohol intake, high sodium intake, low potassium intake) Race Personality

13 Search for exogenous potentially modifiable factors that can induce/aggravate hypertension Salt Excessive Alcohol Recreational drugs (e.g. cocaine) Non-steroidal anti-inflammatory drugs Oral contraceptive pill Corticosteroids Anabolic steroids Erythropoietin Calcineurin inhibitors (cyclosporin, tacrolimus) Ephedrine /pseudo-ephedrine Licorice Sleep apnea

14 Diagnosis Diagnostic procedures are aimed at: 1.Establishing BP levels 2.Identifying secondary causes of hypertension 3.Evaluating the overall CV risk by searching for other risk factors, target organ damage, concomitant diseases or accompanying clinical conditions. The diagnostic procedures comprise: 1.Repeated BP measurements 2.Medical history 3.Physical examination 4.Laboratory and instrumental investigations

15 Procedures for Blood Pressure Measurement

16 Blood Pressure Assessment

17 Medical History 1.Duration and previous level of high BP 2.Indications of secondary hypertension Family history of renal disease (polycystic kidney) Renal disease, UTI, haematuria, analgesic abuse (parenchymal renal disease) Drug/substance intake: oral contraceptives, liquorice, nasal drops, cocaine, steroids, NSAID’s, erythropoietin, cyclosporin Episodes of sweating, headache, anxiety, palpitation (phaeochromocytoma) Episodes of muscle weakness (aldosteronism) 3.Risk factors 4.Symptoms of organ damage 5.Previous antihypertensive therapy (drugs used, efficacy, adverse effects) 6.Personal, family, environmental factors

18 Symptoms of organ damage Heart: palpitations, chest pain, shortness of breath, swollen ankles Brain and eyes: headaches, vertigo, impaired vision, TIA’s, sensory or motor deficit Kidney: thirst, polyuria, nocturia, haematuria Peripheral arteries: cold extremities, intermittent claudication

19 Signs of organ damage Brain: murmurs over neck arteries, motor or sensory deficits Eyes: funduscopic abnormalities Heart: location and characteristics of apical impulse, abnormal cardiac rhythms, ventricular gallop, pulmonary rales, peripheral oedema Peripheral arteries: absence, reduction, or asymmetry of pulses, cold extremities, ischaemic skin lesions

20 Physical examination for secondary hypertension and organ damage Signs suggesting secondary hypertension Features of Cushing syndrome Skin stigmata of neurofibromatosis (phaeochromocytoma) Palpation of enlarged kidneys ( polycystic kidney) Auscultation of abdominal murmurs (renovascular hypertension) Auscultation of precordial chest murmurs (aortic coarctation or aortic disease) Diminished and delayed femoral pulse and reduced femoral BP (aortic coarctation or aortic disease)

21 White coat effect (Office-induced blood pressure elevation) Further assess using 24-h ambulatory blood pressure monitoring If office BP measurement is elevated and Home BP is normal Daytime average BP over 135/85 mm Hg should be considered elevated A drop in nocturnal BP of <10% is associated with increased risk of CV events

22 WHO Classification of Hypertension (1993) Stage I – no evident signs of target organ damage Stage II – presence of at least one of the following signs of target organ damage: Heart: LVH (diagnosed radiologically, on ECG or by Echocardiography) Retina: generalized or focal narrowing of retinal arteries Kidney: microalbuminurua, proteinuria, creatinine<2mg/dl (176 µmol/l) Vessels: increased IMT or plaques in carotid, iliac, or femoral arteries Stage III – signs of severe target organ damage: Heart: angina pectoris, myocardial infarction, heart failure Brain: stroke, TIA, vascular dementia Retina: haemorrhages, exudates, papilloedema Kidney: renal insufficiency (creatinine>2mg/ml) Vessels: dissecting aortic aneurysm, symptomatic occlusive peripheral arterial disease

23 Search for target organ damage: LVH

24 Sokolow-Lyons >35 mm (S V1 +R V5-6 ) Cornell (R avL +S V3 ): F: >20mm, M: >24-28 mm

25 Search for target organ damage: LVH

26 WHO Classification of Hypertension (1993) Stage I – no evident signs of target organ damage Stage II – presence of at least one of the following signs of target organ damage: Heart: LVH (diagnosed radiologically, on ECG or by Echocardiography) Retina: generalized or focal narrowing of retinal arteries Kidney: microalbuminurua, proteinuria, creatinine<2mg/dl (176 µmol/l) Vessels: increased IMT or plaques in carotid, iliac, or femoral arteries Stage III – signs of severe target organ damage: Heart: angina pectoris, myocardial infarction, heart failure Brain: stroke, TIA, vascular dementia Retina: haemorrhages, exudates, papilloedema Kidney: renal insufficiency (creatinine>2mg/ml) Vessels: dissecting aortic aneurysm, symptomatic occlusive peripheral arterial disease

27 Search for target organ damage: funduscopy Example of moderate hypertensive retinopathy: Arteriovenous nicking (black arrows) and cotton- wool spots (white arrows) Example of mild hypertensive retinopathy: Arteriovenous nicking (black arrow) and focal narrowing (white arrow) Example of malignant hypertensive retinopathy: Multiple cotton-wool spots (white arrows), retinal haemorrhages (black arrows), and swelling of the optic disc are visible

28 WHO Classification of Hypertension (1993) Stage I – no evident signs of target organ damage Stage II – presence of at least one of the following signs of target organ damage: Heart: LVH (diagnosed radiologically, on ECG or by Echocardiography) Retina: generalized or focal narrowing of retinal arteries Kidney: microalbuminurua, proteinuria, creatinine<2mg/dl (176 µmol/l) Vessels: increased IMT or plaques in carotid, iliac, or femoral arteries Stage III – signs of severe target organ damage: Heart: angina pectoris, myocardial infarction, heart failure Brain: stroke, TIA, vascular dementia Retina: haemorrhages, exudates, papilloedema Kidney: renal insufficiency (creatinine>2mg/ml) Vessels: dissecting aortic aneurysm, symptomatic occlusive peripheral arterial disease

29 Search for target organ damage: kidney The diagnosis of hypertension-induced renal damage is based on the finding of an elevated value of serum creatinine (>/=133 µmol/l (1.5 mg/dl) in men and 124 µmol/l (1.4 mg/dl) in women, or by the finding of estimated creatinine clearance values below 60-70 ml/min

30 WHO Classification of Hypertension (1993) Stage I – no evident signs of target organ damage Stage II – presence of at least one of the following signs of target organ damage: Heart: LVH (diagnosed radiologically, on ECG or by Echocardiography) Retina: generalized or focal narrowing of retinal arteries Kidney: microalbuminurua, proteinuria, creatinine<2mg/dl (176 µmol/l) Vessels: increased IMT or plaques in carotid, iliac, or femoral arteries Stage III – signs of severe target organ damage: Heart: angina pectoris, myocardial infarction, heart failure Brain: stroke, TIA, vascular dementia Retina: haemorrhages, exudates, papilloedema Kidney: renal insufficiency (creatinine>2mg/ml) Vessels: dissecting aortic aneurysm, symptomatic occlusive peripheral arterial disease

31 Search for target organ damage: vessels IMT>/=0.9 mm Plaques

32 Routine Laboratory Tests 1. Urinalysis 2. Complete blood count 3. Blood chemistry (potassium, sodium and creatinine) 4. Fasting glucose 5. Fasting total cholesterol and high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), triglycerides 6. Standard 12-leads ECG Investigation of all patients with hypertension

33 Recommended Tests Echocardiogram Carotid (femoral) ultrasound C-reactive protein Microalbuminuria (essential test in diabetics) Quantitative proteinuria (if dipstick test is positive) Funduscopy (in severe hypertension)

34 Screening for Hyperaldosteronism Spontaneous hypokalemia (<3.5 mmol/L) Profound diuretic-induced hypokalemia (<3.0 mmol/L) Hypertension refractory to treatment with 3 or more drugs Incidental adrenal adenomas. Should be considered for patients with the following characteristics:

35 Screening for Hyperaldosteronism Screening for hyperaldosteronism should include plasma aldosterone and plasma renin activity - measured in morning samples - taken from patients in a sitting position after resting at least 15 minutes. Aldosterone antagonists, ARBs, beta-blockers and clonidine should be discontinued prior to testing. A positive screening test should lead to referral or further testing.

36 Screening for Pheochromocytoma Paroxysmal and/or severe sustained hypertension refractory to usual antihypertensive therapy; Hypertension and symptoms suggestive of catecholamine excess (two or more of headaches, palpitations, sweating, etc); Hypertension triggered by beta-blockers, monoamine oxidase inhibitors, micturition, or changes in abdominal pressure; Incidentally discovered adrenal mass; Multiple endocrine neoplasia (MEN) 2A or 2B; von Recklinghausen’s neurofibromatosis, or von Hippel-Lindau disease. Should be considered for patients with the following characteristics:

37 Screening for Pheochromocytoma Screening for pheochromocytoma should include a 24 hour urine for metanephrines and creatinine Assessment of urinary VMA is inadequate

38 Blood Pressure Threshold Values for Initiation of Pharmacological Treatment of Hypertension ConditionInitiation SBP / DBP mmHg Diastolic ± systolic hypertension 140/90 Isolated systolic hypertension 160 Diabetes 130/80 Renal disease (130/80) Proteinuria >1 g/day (125/75)

39 Lifestyle Recommendations for the Treatment of Hypertension 1.Healthy diet; High in fresh fruits, vegetables and low fat dairy products, low in saturated fat and salt in accordance with the DASH diet 2. Regular physical activity: optimum 30-60 minutes of moderate cardiorespiratory activity 4/week or more 3.Reduction in alcohol consumption in those who drink excessively 4.Weight loss ( ≥ 5 Kg) in those who are over weight (BMI>25) 5.Waist Circumference < 102 cm for men < 88 cm for women 6. In individuals considered salt-sensitive, such as: Canadians of African descent, age over 45, individuals with impaired renal function or with diabetes. Restrict salt intake to less than 100 mmol/day 7.Smoke free environment

40 Lifestyle Recommendations for Hypertension: Dietary Fresh Fruits Vegetables Low Fat dairy products Low fat diet in accordance with the DASH diet http://www.hc-sc.gc.ca/hpfb-dgpsa/onpp-bppn/food_guide_rainbow_e.html Dietary Sodium Restrict to target range of 65-100 mmol/day ( Most of the salt in food is hidden and comes from processed food) Dietary Potassium If required, daily dietary intake >80 mmol Calcium supplementation No conclusive studies for hypertension Magnesium supplementation No conclusive studies for hypertension

41 Lifestyle Recommendations for Hypertension: Physical Activity For patients who are prescribed pharmacological therapy: Exercise should be prescribed as adjunctive therapy Should be prescribed to reduce blood pressure TypeDynamic exercise - Walking, jogging - Cycling - Non-competitive swimming Time- 30-60 minutes Intensity- Moderate Frequency- Four or more days per week F I T T

42 Lifestyle Recommendations for Hypertension: Alcohol Low risk alcohol consumption Women: maximum of 9 drinks/week Men: maximum of 14 drinks/week 0-2 drinks/day 1 drink = one beer, or 1 glass of wine or 1 ounce of 40% spirit

43 Lifestyle Recommendations for Hypertension: Stress Management Hypertensive patients in whom stress appears to be an important issue Individualized cognitive behavioral interventions are more likely to be effective when relaxation techniques are employed Stress management Behaviour Modification

44 Lifestyle Recommendations for Hypertension: Weight Loss Hypertensive and all patients BMI over 25 for hypertension - Encourage weight reduction - Healthy BMI: 18.5-24.9 kg/m 2 Waist Circumference < 102 cm for men < 88 cm for women For patients prescribed pharmacological therapy: weight loss has additional antihypertensive effects. Weight loss strategies should employ a multidisciplinary approach and include dietary education, increased physical activity and behavioural modification.

45 Impact of Lifestyle Therapies on Blood Pressure in Hypertensive Adults InterventionChangeSBP/DBP Sodium intake- 100 mmol/day-5.8 / -2.5 Weight- 4.5 kg-7.2 / -5.9 Alcohol intake- 2.7 drinks/day-4.6 / -2.3 Exercise*3 times/week-7.4 / -5.8 Dietary patternsDASH diet-11.4 / -5.5 * 1- Exercise and Hypertension. Medicine & Science in Sports & Exercise. 36(3):533-553, March 2004. 2- Result of aggregate and metaanalyses of short term trials. Miller ER et al. J Clin Hyper 1999: Nov/Dec:191-8.

46 Lifestyle Therapies in Hypertensive Adults: Summary InterventionTarget Sodium restriction65-100 mmol/day Weight loss Waist Circumference BMI <25 kg/m 2 < 102 cm for men < 88 cm for women Alcohol restrictionLess or equal to 2 drinks/day Exercise at least 4 times/week Dietary patternsDASH diet Smoking cessationSmoke free environment

47 Indications for Pharmacotherapy Strongly consider prescription if: Average DBP equal or over 90 mmHg and: Hypertensive Target-organ damage (or CVD) or Independent cardiovascular risk factors Elevated systolic BP Cigarette smoking Abnormal lipid profile Strong family history of premature CV disease Truncal obesity Sedentary Lifestyle Average DBP equal or over 80 mmHg in a patient with diabetes

48 Treatment of Adults with Systolic-Diastolic Hypertension without Other Compelling Indications INITIAL TREATMENT AND MONOTHERAPY * Not indicated as first line therapy over 60 Beta- blocker* Long- acting CCB Thiazide ACE-I ARB Lifestyle modification therapy TARGET <140 mm Hg systolic and < 90 mmHg diastolic

49 Considerations Regarding the Choice of First-Line Therapy Diuretic-induced hypokalemia should be avoided through the use of potassium sparing agent ACE-I are not recommended (as monotherapy) for black patients without another compelling indication Beta adrenergic blockers are not recommended for patients over 60 years without another compelling indication

50 Combination Therapy for Systolic-Diastolic Hypertension without Other Compelling Indications CONSIDER Nonadherence? Secondary HTN? Interfering drugs or lifestyle? White coat effect? Resistant Hypertension? If blood pressure is still not controlled, or there are adverse effects, other classes of antihypertensive drugs may be combined (such as alpha blockers, centrally acting agents, or nondihydropyridine calcium channel blocker). 2. Triple or Quadruple Therapy 1. Dual Combination Therapy If partial response to monotherapy

51 Summary: Treatment of Hypertension without Other Compelling Indications * Not indicated as first line therapy over 60 CONSIDER Nonadherence? Secondary HTN? Interfering drugs or lifestyle? White coat effect? Dual Combination Triple or Quadruple Therapy Lifestyle modification therapy Thiazide diuretic ACE-I Long-acting CCB Beta- blocker* ARB TARGET <140 mm Hg systolic and < 90 mmHg diastolic

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53 Useful Combinations

54 INDICATIONS FOR INDIVIDUAL DRUG CLASSES

55 Treatment of Hypertension in Patients with Ischemic Heart Disease Caution should be exercised when combining a non DHP-CCB and a beta-blocker If abnormal systolic left ventricular function: avoid non DHP-CCB (Verapamil or Diltiazem) 1. Beta-blocker 2. Long-acting CCB Stable angina ACE-I are recommended in ALL patients with established CAD Short-acting nifedipine

56 Treatment of Hypertension in Patients with Recent ST Segment Elevation-MI or non-ST Segment Elevation-MI Long-acting DHP CCB (Amlodipine, Felodipine) Beta-blocker and ACE-I Recent myocardial infarction Heart Failure ? NO YES Long-acting CCB If beta-blocker contraindicate d or not effective

57 Treatment of Hypertension with Left Ventricular Systolic Dysfunction Beta-blockers used in clinical were bisoprolol, carvedilol and metoprolol. Physicians who are not yet experienced in the use of beta-blockers should consider initiation of treatment in conjunction with a physician experienced in heart failure management particularly for NYHA Class III-IV patients If additional therapy is needed: Diuretic* for CHF class III-IV: Aldosterone Antagonist Systolic cardiac Dysfunction ACE-I if ACE-I intolerant: ARB If ACE-I and ARB are contraindicated: Hydralazine and Isosorbide dinitrate in combination If additional antihypertensive therapy is needed: ACE-I / ARB Combination Long-acting DHP-CCB (Amlodipine or Felodipine) Non dihydropyridine CCB and Beta-Blocker

58 Treatment of Hypertension for Patients with Cerebrovascular Disease Strongly consider blood pressure reduction in all patients after the acute phase of non disabling stroke or TIA. An ACE-I / diuretic combination is preferred Stroke TIA

59 Treatment of Hypertension in Patients with Left Ventricular Hypertrophy Vasodilators: Hydralazine, Minoxidil Can Increase LVH Left ventricular hypertrophy Hypertensive patients with left ventricular hypertrophy should be treated with antihypertensive therapy to lower the rate of subsequent cardiovascular events. - ACE-I - ARB, - CCB - Diuretic - BB (below age 60)*

60 Treatment of Hypertension in Patients with with Non Diabetic chronic kidney disease Renal disease ACE-I/ARB: Bilateral renal artery stenosis 1. ACE-I 2. Alternate if ACE-I not tolerated: ARB Combination with other agents Additive therapy: Thiazide diuretic. Alternate: If volume overload: loop diuretic Target BP: Nondiabetic:< 130 mmHg systolic and < 80 mmHg diastolic Proteinuria: > 1 g/day: < 125 / 75 mmHg

61 Treatment of Hypertension in association with Renovascular Disease Close follow-up and early intervention (angioplasty and stenting or surgery) should be considered for patients with: uncontrolled hypertension despite therapy with three or more drugs, or deteriorating renal function, or bilateral atherosclerotic renal artery lesions (or tight atherosclerotic stenosis in a single kidney), or recurrent episodes of flash pulmonary edema. Does not imply specific treatment choice Renovascular disease Caution in the use of ACE-I/ARB in Bilateral renal artery stenosis or unilateral disease with solitary kidney

62 Treatment of Hypertension for Patients with Diabetes Mellitus

63 Threshold ≥ 130/80 mmHg and TARGET < 130 mmHg systolic and < 80 mmHg diastolic with Nephropathy Urinary albumin excretion rate equal or over 30 mg/day Diabetes without Nephropathy Isolated Systolic Hypertension Systolic- diastolic Hypertension Urinary albumin excretion rate less than 30 mg/day

64 Treatment of Systolic-Diastolic Hypertension without Diabetic Nephropathy ACE-Inhibitor or ARB or Thiazide diuretic IF ACE-I and ARB and Thiazide are contraindicated or not tolerated, SUBSTITUTE Cardioselective BB* or Long-acting CCB More than 3 drugs may be needed to reach target values for diabetic patients Urinary albumin excretion rate less than 30 mg/day * Cardioselective BB: Acebutolol, Atenolol, Bisoprolol, Metoprolol Combination of first line agents Addition of one or more of: Cardioselective BB or Long-acting CCB Diabetes without Nephropath y With Systolic diastolic Hypertensio n Threshold ≥ 130/80 mmHg and TARGET < 130 mmHg systolic and < 80 mmHg diastolic

65 Treatment of Hypertension in Association with Diabetic Nephropathy Urinary albumin excretion rate over 30 mg/day TARGET 1g/day is present If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control of volume is desired DIABETES with Nephropathy ACE Inhibitor or ARB IF ACE-I and ARB are contraindicated or not tolerated, SUBSTITUTE Cardioselective BB or Long-acting CCB or Thiazide diuretic Addition of one or more of Thiazide diuretic or Long-acting CCB 3 - 4 drugs combination may be needed Threshold ≥ 130/80 mmHg and TARGET < 130 mmHg systolic and < 80 mmHg diastolic

66 Treatment of Hypertension for Patients with Diabetes Mellitus: Summary More than 3 drugs may be needed to reach target values for diabetic patients If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control of volume is desired Threshold equal or over 130/80 mmHg and TARGET below 130/80 mmHg COMBINATION : ADD Cardioselective BB or Long-acting CCB or Thiazide diuretic, or an ACE-I with an ARB (or vice versa) Diabetes with Nephropathy Combination Effective 2-drug combination ACE Inhibitor or ARB ACE-Inhibitor or ARB or Thiazide diuretic without Nephropathy

67 Treatment of Hypertension for Patients Who Use Tobacco The benefits of treating smokers with beta- blockers remain uncertain in the absence of a specific indications like angina or post-MI SmokingBeta-blocker

68 Global Vascular Protection for Patients with Hypertension

69 Vascular Protection for Hypertensive Patients: Statins Statins are recommended in high-risk hypertensive patients with established atherosclerotic disease or with at least 3 cardiovascular risks such as : Male 55 y or older Smoking Type 2 Diabetes Total-C/HDL-C ratio of 6 or higher Premature Family History of CV disease Previous Stroke or TIA LVH ECG abnormalities Microalbuminuria or Proteinuria Peripheral Vascular Disease ASCOT-LLA Lancet 2003;361:1149-58

70 Vascular Protection for Hypertensive Patients : ASA Consider low dose ASA Caution should be exercised if BP is not controlled.

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