Hypertension is defined as systolic blood pressure SBP

Hypertension is defined as systolic blood pressure (SBP) of 140 mm. Hg or greater, diastolic blood pressure (DBP) of 90 mm. Hg or greater, or taking antihypertensive medication. VI JNC, 1997

Types of hypertension n Essential hypertension u 90% u No underlying cause n Secondary hypertension u Underlying cause

Causes of Secondary Hypertension n Renal u u u n n Parenchymal Vascular Others Endocrine Neurogenic Miscellaneous Unknown

Hypertension: Predisposing factors n n n Age > 60 years Sex (men and postmenopausal women) Family history of cardiovascular disease Smoking High cholesterol diet Co-existing disorders such as diabetes, obesity and hyperlipidaemia n High intake of alcohol n Sedentary life style

1999 WHO-ISH Guidelines : Definitions and Classifications of BP Levels SBP DBP Category* (mm Hg) Optimal < 120 < 80 Normal < 130 < 85 High-normal 130 -139 85 -89 Grade 1 hypertension (mild) 140 -159 90 -99 Borderline subgroup 140 -149 90 -94 Grade 2 hypertension (moderate) 160 -179 109 Grade 3 hypertension (severe) > 180 > 110 ISH > 140 < 90 Borderline subgroup 140 -149 < 90 100 - WHO-ISH Guidelines Subcommittee J Hypertens 1999; 17: 151

1999 WHO-ISH Guidelines: Stratification of risk to Quantify Prognosis Degree of hypertension (mm Hg) Risk factors and Grade 1 -mild Grade 2 -moderate Grade 3 -severe disease history (SBP 140 -159 (SBP 160 -179 (SBP > 180 or DBP 90 -99) or DBP 100 -109) or DBP > 110) I No other risk Low risk Med risk High risk factors II 1 -2 risk factors Med risk Very high risk III > 3 risk factors or High risk high risk Very high risk target organ disease or diabetes IV Associated Very high risk Clinical conditions WHO-ISH Guidelines Subcommittee J Hypertens 1999; 17: 151

Diseases Attributable to Hypertension Gangrene of the Lower Extremities Heart Failure Left Ventricular Hypertrophy Myocardial Infarction Hypertensive Encephalopathy Aortic Aneurym HYPERTENSION Coronary Heart Disease Blindness Chronic Kidney Failure Stroke Cerebral Preeclampsia/ Hemorrhage Eclampsia Adapted from Dustan HP et al. Arch Intern Med. 1996; 156: 1926 -1935

1999 WHO-ISH Guidelines: Desirable BP Treatment Goals n Optimal or normal BP (< 130/85 mm Hg) for u Young patients u Middle-age patients u Diabetic patients n High-normal BP (< 140/90 mm Hg) desirable for elderly patients n Aggressive BP lowering may be necessary in patients with nephropathy, chronic renal failure, particularly if proteinuria is u < 1 g/d - 130/80 mm Hg u > 1 g/d - 125/75 mm Hg

Significant benefits from intensive BP reduction in diabetic patients Major CV events / 100 patient-yr Lancet 1998, 351, 1755

Relative risks of specific types of clinical complications related to tight and less tight BP Control Patients with aggregate and points Tight Less tight control Tight Clinical end point (n=758) (n=390) Any diabetes-related 259 end point Deaths related to 82 62 diabetes All cause mortality 134 83 Myocardial infarction 107 Stroke 38 34 6. 5 Peripheral vascular 8 8 disease Microvascular disease 68 tight control 170 Absolute risk (events/1000 patients-yr) Less RR for tight control p (95% Cl) 50. 9 67. 4 0. 0046 0. 76 (0. 62 -0. 92) 13. 7 20. 3 0. 019 22. 4 69 11. 6 1. 4 27. 2 18. 6 0. 013 2. 7 0. 17 0. 82 (0. 63 -1. 08) 23. 5 0. 13 0. 79 (0. 59 -1. 07) 0. 56 (0. 35 -0. 89) 0. 17 0. 51 (0. 19 -1. 37) 54 12. 0 19. 2 0. 68 (0. 49 -0. 94) 0. 0092 063 (0. 44 -0. 89) Ref : UK Prospective Diabetes Study Group BMJ 1998; 317: 703

Life style modifications n Lose weight, if overweight n Limit alcohol intake n Increase physical activity n Reduce salt intake n Stop smoking n Limit intake of foods rich in fats and cholesterol

Factors affecting choice of antihypertensive drug n The cardiovascular risk profile of the patient n Coexisting disorders n Target organ damage n Interactions with other drugs used for concomitant conditions n Tolerability of the drug n Cost of the drug

Drug therapy for hypertension Class of drug Example Initiating dose Usual maintenance dose Diuretics Hydrochlorothiazide 12. 5 mg o. d. 12. 5 -25 mg o. d. -blockers Atenolol 25 -50 mg o. d. 50 -100 mg o. d. Calcium channel blockers Amlodipine 2. 5 -5 mg o. d. 5 -10 mg o. d. -blockers Doxazosin 1 mg o. d. 1 -8 mg o. d. ACE- inhibitors Lisinopril 2. 5 -5 mg o. d. 5 -20 mg o. d. Angiotensin-II Losartan receptor blockers 25 -50 mg o. d. 50 -100 mg o. d.

Diuretics Example: Hydrochlorothiazide n Act by decreasing blood volume and cardiac output n Decrease peripheral resistance during chronic therapy n Drugs of choice in elderly hypertensives Drawbacks n Hypokalaemia n Hyponatraemia n Hyperlipidaemia n Hyperuricaemia (hence contraindicated in gout) n Hyperglycaemia (hence not safe in diabetes) n Not safe in renal and hepatic insufficiency

Beta blockers Example: Atenolol n Block 1 receptors on the heart n Block 2 receptors on kidney and inhibit release of renin n Decrease rate and force of contraction and thus reduce cardiac output n Drugs of choice in patients with co-existent coronary heart disease Drawbacks n Adverse effects: lethargy, impotency, bradycardia n Not safe in patients with co-existing asthma and diabetes n Have an adverse effect on the lipid profile

Calcium channel blockers Example: Amlodipine n Block entry of calcium through calcium channels n Cause vasodilation and reduce peripheral resistance n Drugs of choice in elderly hypertensives and those with co-existing asthma n Neutral effect on glucose and lipid levels Drawbacks n Adverse effects: Flushing, headache, Pedal edema

ACE inhibitors Example: Lisinopril, Enalapril n Inhibit ACE and formation of angiotensin II and block its effects n Drugs of choice in co-existent diabetes mellitus Drawbacks n Adverse effect: dry cough, hypotension, angioedema

Angiotensin II receptor blockers Example: Losartan n Block the angiotensin II receptor and inhibit effects of angiotensin II n Drugs of choice in patients with co -existing diabetes mellitus Drawbacks n Adverse effect: dry cough, hypotension, angioedema

Alpha blockers Example: Doxazosin n Block -1 receptors and cause vasodilation n Reduce peripheral resistance and venous return n Exert beneficial effects on lipids and insulin sensitivity n Drugs of choice in patients with co-existing hyperlipidaemia, diabetes mellitus and BPH Drawbacks n Adverse effects: Postural hypotension

Antihypertensive therapy: Side-effects and Contraindications Class of drugs Main side-effects Special Precautions Contraindications/ Diuretics Electrolyte imbalance, Hypersensitivity, Anuria (e. g. Hydrochloro total and LDL cholesterol thiazide) levels, ¯ HDL cholesterol levels, glucose levels, uric acid levels -blockers Impotence, Bradycardia, Hypersensitivity, (e. g. Atenolol)Fatigue Bradycardia, Conduction disturbances, Diabetes, Asthma, Severe cardiac failure

Antihypertensive therapy: Side-effects and Contraindications (Contd. ) Class of drug Main side-effects Contraindications/ Special Precautions Calcium channel blockers Pedal edema, Headache Non-dihydropyridine (e. g. Amlodipine, CCBs (e. g diltiazem)– Diltiazem) Hypersensitivity, Bradycardia, Conduction disturbances, Congestive heart failure, Left ventricular dysfunction. Dihydropyridine CCBs– Hypersensitivity -blockers Postural hypotension (e. g. Doxazosin) Hypersensitivity ACE-inhibitors (e. g. Lisinopril) Hypersensitivity, Pregnancy, Bilateral renal artery stenosis Cough, Hypertension, Angioneurotic edema Angiotensin-II receptor blockers (e. g. Losartan) Headache, Dizziness Hypersensitivity, Pregnancy, Bilateral renal artery stenosis

Choosing the right antihypertensive Condition Preferred drugs Other drugs Drugs to be that can be used avoided Asthma Calcium channel -blockers/Angiotensin-II -blockers receptor blockers/Diuretics/ ACE-inhibitors Diabetes -blockers/ACE Calcium channel blockers Diuretics/ mellitus inhibitors/ -blockers Angiotensin-II receptor blockers High cholesterol -blockers ACE inhibitors/ Angiotensin-II levels receptor blockers/ Calcium Diuretics channel blockers Elderly patients Calcium channel -blockers/ACEblockers/Diuretics inhibitors/Angiotensin-II receptor blockers/ - blockers BPH -blockers/ ACE inhibitors/ Angiotensin-II receptor blockers/ Diuretics/ Calcium channel blockers -blockers/ (above 60 years)

Limitations on use of antihypertensives in patients with coexisting disorders Coexisting Disorder Diureticb-blocker ACE inhibitor All CCB antagonist a 1 -blocker Diabetes Caution/x Dyslipidaemia x x Heart failure 3/Caution Asthma/COPD x /Caution Peripheral vascular disease Caution Renal artery stenosis CHD x x

Effect of various antihypertensives on coexisting disorders Total LDLcholesterol tolerance HDLSerum Glucose. Insulin cholesterol triglycerides sensitivity Diuretic ¯ ¯ ¯ -blockers - ¯¯ - - ACE inhibitors - - All antagonists - - CCBs - - - ¯ ¯ ¯ - a-blockers

Combination therapy for hypertension – Recommended by JNC-VI guidelines and 1999 WHO-ISH guidelines With any single drug, not more than 25– 50% of hypertensives achieve adequate blood pressure control J Hum. Hypertens 1995; 9: S 33–S 36 For patients not responding adequately to low doses of monotherapy Increase the dose of drug. This, however, may lead to increased side effects Substitute with another drug from a different class Add a second drug from a different class (Combination therapy) If inadequate response obtained Add second drug from different class (Combination therapy)

Advantages of fixed-dose combination therapy n Better blood pressure control n Lesser incidence of individual drug’s side-effects n Neutralisation of side-effects n Increased patient compliance n Lesser cost of therapy

Fixed-dose combinations as recommended by JNC-VI (1997) guidelines and 1999 WHO-ISH guidelines n Calcium channel blocker and -blocker (e. g. Amlodipine and Atenolol) n Calcium channel blocker and ACE-inhibitor (e. g. Amlodipine and Lisinopril) n ACE-inhibitor and Diuretic (e. g. Lisinopril and Hydrochlorothiazide) n -blocker and Diuretic (e. g. Atenolol and Hydrochlorothiazide)

Efficacy and Tolerability of a fixed-dose combination of amlodipine and atenolol (Amlopres-AT) in Indian Hypertensives (n=369) 80. 5% 175. 4+ 19. 4 143. 8 + 13. 2 106. 8 + 10. 5 88. 2 + 7. 6 % responders Blood Pressure (mm Hg) Reduces BP effectively Safe and well tolerated | Adverse events were reported in 7. 9% of patients | Common side effects included edema, fatigue and headache Indian Practitioner 1997; 50: 683 -688.

Efficacy and Tolerability of combined amlodipine and lisinopril (Amlopres-L) in Indian hypertensives (n=330) 175. 4+ 19. 4 77. 65 143. 8 + 13. 2 106. 8 + 10. 5 88. 2 + 7. 6 % responders Blood Pressure (mm Hg) Reduces BP effectively Safe and well tolerated | Adverse events were reported in 9. 7% of patients | Side effects commonly reported included cough and edema | Only 1. 76% of patients withdrew from the study. Indian Practitioner 1998; 51: 441 -447.

Drugs in special conditions Condition Preferred Drugs n Pregnancy n Nifedipine, labetalol, hydralazine, beta-blockers, methyldopa, prazosin n Coronary heart disease n Beta-blockers, ACE inhibitors, Calcium channel blockers n Congestive heart failure n ACE inhibitors, beta-blockers 1999 WHO-ISH guidelines

Summary n Hypertension is a major cause of morbidity and mortality, and needs to be treated n It is an extremely common condition; however it is still underdiagnosed and undertreated n Hypertension is not controlled with monotherapy in at least 50% of patients; in these patients combination therapy is required