Hypertension is defined as systolic blood

pressure (SBP) of 140 mmHg or greater,

diastolic blood pressure (DBP) of

90 mmHg or greater, or taking

antihypertensive medication.VI JNC, 1997

Types of hypertension

Essential hypertension 90%

No underlying cause

Secondary hypertension Underlying cause

Causes of Secondary Hypertension

Renal Parenchymal Vascular Others

Endocrine Neurogenic Miscellaneous Unknown

Hypertension: Predisposing factors 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 High intake of alcohol Sedentary life style

1999 WHO-ISH Guidelines :Definitions and Classifications of BP Levels

SBP DBPCategory* (mm Hg) (mm Hg)Optimal < 120 < 80Normal < 130 < 85High-normal 130-139 85-89Grade 1 hypertension (mild) 140-159 90-99 Borderline subgroup 140-149 90-94Grade 2 hypertension (moderate) 160-179 100-109Grade 3 hypertension (severe) > 180 > 110ISH > 140 < 90 Borderline subgroup 140-149 < 90

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 Grade3-severedisease 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

factorsII 1-2 risk factors Med risk Med risk Very high riskIII > 3 risk factors or High risk high risk Very high risk

target organ diseaseor diabetes

IV Associated Very high risk Very high risk Very high riskClinical conditions

WHO-ISH Guidelines Subcommittee J Hypertens 1999;17:151

Diseases Attributable to Hypertension

HYPERTENSION

Gangrene of the Lower Extremities

Heart Failure

Left Ventricular Hypertrophy Myocardial

InfarctionHypertensive

EncephalopathyAortic

Aneurym

Blindness

Chronic Kidney Failure

Stroke Preeclampsia/Eclampsia

Cerebral Hemorrhage

Coronary Heart Disease

Adapted from Dustan HP et al. Arch Intern Med. 1996; 156: 1926-1935

1999 WHO-ISH Guidelines: Desirable BP Treatment Goals

Optimal or normal BP (< 130/85 mm Hg) for Young patientsMiddle-age patientsDiabetic patients

High-normal BP (< 140/90 mm Hg) desirable for elderly patients

Aggressive BP lowering may be necessary in patients with nephropathy, chronic renal failure, particularly if proteinuria is

< 1 g/d - 130/80 mm Hg> 1 g/d - 125/75 mm Hg

Significant benefits from intensive BP reductionin diabetic patients

24.4

18.6

11.9

0

5

10

15

20

25

30

< 90 mm Hg < 85 mm Hg < 80 mm Hg (targetDBP)

Major CV events / 100 patient-yr

Lancet 1998, 351, 1755

Relative risks of specific types of clinical complicationsrelated to tight and less tight BP Control

Patients with Absolute risk aggregate (events/1000 and points patients-yr)

Tight Less tight Less RR forcontrol control Tight tight tight control

Clinical end point (n=758) (n=390) control control p (95% Cl)Any diabetes-related 259 170 50.9 67.4 0.0046 0.76 (0.62-0.92)end pointDeaths related to 82 62 13.7 20.3 0.019 0.68 (0.49-0.94)diabetesAll cause mortality 134 83 22.4 27.2 0.17 0.82 (0.63-1.08)Myocardial infarction 107 69 18.6 23.5 0.13 0.79 (0.59-1.07)Stroke 38 34 6.5 11.6 0.013 0.56 (0.35-0.89)Peripheral vascular 8 8 1.4 2.7 0.17 0.51 (0.19-1.37)diseaseMicrovascular disease 68 54 12.0 19.2 0.0092 063 (0.44-0.89)

Ref : UK Prospective Diabetes Study Group BMJ 1998; 317:703

Life style modifications

Lose weight, if overweight Limit alcohol intake Increase physical activity Reduce salt intake Stop smoking Limit intake of foods rich in fats

and cholesterol

Factors affecting choice of antihypertensive drug

The cardiovascular risk profile of the patient

Coexisting disorders

Target organ damage

Interactions with other drugs used for concomitant conditions

Tolerability of the drug

Cost of the drug

Drug therapy for hypertension

Class of drug Example Initiating dose Usualmaintenance 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 Amlodipine 2.5-5 mg o.d. 5-10 mg o.d.channelblockers

-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 25-50 mg o.d. 50-100 mg o.d.receptor blockers

Diuretics

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

Beta blockers

Example: Atenolol Block 1 receptors on the heart Block 2 receptors on kidney and inhibit release of renin Decrease rate and force of contraction and thus reduce

cardiac output Drugs of choice in patients with co-existent coronary

heart diseaseDrawbacks Adverse effects: lethargy, impotency, bradycardia Not safe in patients with co-existing asthma and diabetes Have an adverse effect on the lipid profile

Calcium channel blockers

Example: Amlodipine Block entry of calcium through calcium channels Cause vasodilation and reduce peripheral

resistance Drugs of choice in elderly hypertensives and

those with co-existing asthma Neutral effect on glucose and lipid levels

Drawbacks Adverse effects: Flushing, headache, Pedal

edema

ACE inhibitors

Example: Lisinopril, Enalapril Inhibit ACE and formation of

angiotensin II and block its effects Drugs of choice in co-existent diabetes

mellitus

Drawbacks Adverse effect: dry cough, hypotension,

angioedema

Angiotensin II receptor blockers

Example: Losartan Block the angiotensin II receptor

and inhibit effects of angiotensin II Drugs of choice in patients with

co-existing diabetes mellitus

Drawbacks Adverse effect: dry cough,

hypotension, angioedema

Alpha blockers

Example: Doxazosin Block -1 receptors and cause vasodilation Reduce peripheral resistance and venous

return Exert beneficial effects on lipids and insulin

sensitivity Drugs of choice in patients with co-existing

hyperlipidaemia, diabetes mellitus and BPH

Drawbacks Adverse effects: Postural hypotension

Antihypertensive therapy:Side-effects and Contraindications

Class of drugs Main side-effects Contraindications/Special Precautions

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 cardiacfailure

Class of drug Main side-effects Contraindications/ SpecialPrecautions

Calcium channel blockers Pedal edema, Headache Non-dihydropyridine(e.g. Amlodipine, CCBs (e.g diltiazem)– Diltiazem) Hypersensitivity,

Bradycardia, Conductiondisturbances, Congestive heartfailure, Left ventriculardysfunction.Dihydropyridine CCBs– Hypersensitivity

-blockers Postural hypotension Hypersensitivity(e.g. Doxazosin)

ACE-inhibitors Cough, Hypertension, Hypersensitivity, Pregnancy,(e.g. Lisinopril) Angioneurotic edema Bilateral renal artery stenosis

Angiotensin-II receptor Headache, Dizziness Hypersensitivity, Pregnancy,blockers (e.g. Losartan) Bilateral renal artery stenosis

Antihypertensive therapy: Side-effects and Contraindications (Contd.)

Choosing the right antihypertensive

Condition Preferred drugs Other drugs Drugs to be that can be used avoidedAsthma Calcium channel -blockers/Angiotensin-II -blockers

blockers receptor blockers/Diuretics/ACE-inhibitors

Diabetes -blockers/ACE Calcium channel blockers Diuretics/mellitus inhibitors/ -blockers

Angiotensin-IIreceptor blockers

High cholesterol -blockers ACE inhibitors/ Angiotensin-II -blockers/levels receptor blockers/ Calcium Diuretics

channel blockersElderly patients Calcium channel -blockers/ACE- (above 60 years)blockers/Diuretics inhibitors/Angiotensin-II

receptor blockers/- blockersBPH -blockers -blockers/ ACE inhibitors/

Angiotensin-II receptorblockers/ Diuretics/Calcium channel blockers

Limitations on use of antihypertensives in patientswith coexisting disorders

Coexisting Diuretic -blocker ACE All CCB -blockerDisorder inhibitorantagonist

Diabetes Caution/x Caution/x

Dyslipidaemia x x

CHD

Heart failure /Caution Caution

Asthma/COPD x /Caution

Peripheral Caution Caution Caution vasculardisease

Renal artery x x stenosis

Effect of various antihypertensives on coexisting disorders

Total LDL- HDL- Serum Glucose Insulincholesterol cholesterol cholesterol triglycerides tolerance sensitivity

Diuretic

-blockers - - -

ACEinhibitors - - - -

Allantagonists - - - -

CCBs - - - - - -

-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:S33–S36

For patients not responding adequatelyto 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)

Add second drug from different class (Combination therapy)

If inadequate response obtained

Advantages of fixed-dosecombination therapy

Better blood pressure control

Lesser incidence of individual

drug’s side-effects

Neutralisation of side-effects

Increased patient compliance

Lesser cost of therapy

Fixed-dose combinations as recommended byJNC-VI (1997) guidelines and 1999 WHO-ISH guidelines

Calcium channel blocker and -blocker(e.g. Amlodipine and Atenolol)

Calcium channel blocker and ACE-inhibitor (e.g. Amlodipine and Lisinopril)

ACE-inhibitor and Diuretic (e.g. Lisinopril and Hydrochlorothiazide)

-blocker and Diuretic (e.g. Atenolol and Hydrochlorothiazide)

0

50

100

150

200

Systolic Diastolic

Basal Week 4

Blo

od P

ress

ure

(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.

0

10

20

30

40

50

60

70

80

90

% re

spon

ders

175.4+19.4 143.8

+ 13.2106.8+ 10.5 88.2

+ 7.6

80.5%

Efficacy and Tolerability of a fixed-dose combination of amlodipine andatenolol (Amlopres-AT) in Indian Hypertensives (n=369)

Efficacy and Tolerability of combined amlodipine andlisinopril (Amlopres-L) in Indian hypertensives (n=330)

0

50

100

150

200

Systolic Diastolic

Basal Week 4

Blo

od P

ress

ure

(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.

0

10

20

30

40

50

60

70

80

90

% re

spon

ders

175.4+19.4

143.8+ 13.2 106.8

+ 10.5 88.2+ 7.6

77.65

Drugs in special conditionsCondition

Pregnancy

Coronary heart disease

Congestive heart failure

Preferred Drugs

Nifedipine, labetalol, hydralazine, beta-blockers, methyldopa, prazosin

Beta-blockers, ACE inhibitors, Calcium channel blockers

ACE inhibitors,beta-blockers

1999 WHO-ISH guidelines

Summary Hypertension is a major cause of morbidity

and mortality, and needs to be treated

It is an extremely common condition; however it is still underdiagnosed and undertreated

Hypertension is not controlled with monotherapy in at least 50% of patients; in these patients combination therapy is required