What Is Blood Pressure?

     Blood pressure measures the pressure of the blood in arteries. Arteries are groups of tubes which carry blood from your heart to the rest of your body. The arteries can automatically contract (get smaller) or expand (get bigger). When arteries contract, the pressure inside becomes higher. When arteries expand, the pressure inside becomes lower.

If arteries remain contracted or become clogged, the condition called hypertension or high blood pressure results.

How Is Blood Pressure Measured?

    A blood pressure reading consists of two numbers: systolic and diastolic. Systolic refers to systole, the phase when the heart pumps blood out into the aorta. Diastolic refers to diastole, the resting period when the heart refills with blood. At each heartbeat, blood pressure is raised to the systolic level, and, between beats, it drops to the diastolic level.

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 Congenital anomalies, pyelonephritis, renal artery obstruction, acute and chronic glomerulonephritis Reduced blood flow to kidney causes release of renin. Renin reacts with serum protein in liver Coarctation of aorta EndocrinePheochromocytoma Adrenal cortex tumors Cushing’s syndrome Hyperthyroidism Medications such as estrogens, sympathomimetics, antidepressants, NSAIDs, steroids, Amphetamines Neurogenic Miscellaneous

Identifiable Causes of Hypertension 1.

2.

3.

4.

5.

6.

7.

Sleep apnea Drug-induced Chronic kidney disease Primary aldosteronism Renovascular disease Chronic steroid therapy and Cushing’s syndrome Pheochromocytoma Coarctation of the aorta Thyroid or parathyroid disease

Hypertension: Predisposing factors

      Age > 60 years Sex (men and postmenopausal women) Family history of cardiovascular disease Smoking High cholesterol diet High intake of alcohol      Sedentary life style Too much salt in the diet Stress Chronic kidney disease Co-existing disorders such as diabetes, obesity and hyperlipidaemia Adrenal and thyroid disorders

Causes Hypertension

 The exact causes of hypertension are not known. Several factors and conditions may play a role in its development, including:

The old renin-angiotensin-aldosterone system...

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

Optimal Normal High-normal Grade 1 hypertension (mild) Borderline subgroup Grade 2 hypertension (moderate) Grade 3 hypertension (severe) ISH Borderline subgroup

SBP (mm Hg)

< 120 < 130 130-139 140-159 140-149 160-179 > 180 > 140 140-149

DBP (mm Hg)

< 80 < 85 85-89 90-99 90-94 100-109 > 110 < 90 < 90

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

JNC-VI, 1997



Optimal: <120 / and <80



Normal: <130 / and <85



High-Normal: 130-139 / or 85-89



Stage I: 140-159 / or 90-99



Stage II: 160-179 / or 100-109



Stage III: ≥180 / or ≥110

Definitions thankfully simplified

    

JNC-VII, 2003 NORMAL: <120/ and <80 Pre-Hypertension: 120-139/ or 80-89 Stage I: 140-159 / or 90-99 Stage II: >160 / or ≥100-109

1999 WHO-ISH Guidelines: Stratification of risk to Quantify Prognosis Risk factors and disease history

I No other risk factors II 1-2 risk factors III > 3 risk factors or target organ disease or diabetes IV Associated Clinical conditions

Grade 1-mild (SBP 140-159 or DBP 90-99)

Low risk

Degree of hypertension (mm Hg) Grade 2-moderate (SBP 160-179 or DBP 100-109)

Med risk

Grade3-severe (SBP > 180 or DBP > 110)

High risk Med risk High risk Med risk high risk Very high risk Very high risk Very high risk Very high risk Very high risk

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

CLINICAL MANIFESTATIONS

    There are usually no symptoms or signs of hypertension. In fact, nearly one-third of those who have it don't know it. The only way to know if you have hypertension definitely is to have your blood pressure checked May cause headache, dizziness, blurred vision when greatly elevated BP readings more than 140/90 mm of Hg

DIAGNOSTIC EVALUATION

       ECG Chest X-ray Proteinuria, elevated serum blood urea nitrogen (BUN), and creatinine levels Serum potassium Urine (24-hour) for catecholamines Renal scan Renal duplex imaging Outpatient ambulatory BP measurements

Diseases Attributable to Hypertension

Gangrene of the Lower Extremities Aortic Aneurym Heart Failure Left Ventricular Hypertrophy Myocardial Infarction Hypertensive Encephalopathy

HYPERTENSION

Blindness Coronary Heart Disease Chronic Kidney Failure Stroke Preeclampsia/ Eclampsia Cerebral Hemorrhage

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

Health Problems Are Associated With Hypertension 1.

2.

3.

4.

Atherosclerosis: Blood vessel damage occurs through arteriosclerosis in which smooth muscle cell proliferation, lipid infiltration, and calcium accumulation occur in the vascular epithelium Damage to heart, brain, eyes, and kidneys is termed target organ disease Heart Disease: heart failure (the heart can't adequately pump blood), ischemic heart disease (the heart tissue doesn't get enough blood), and hypertensive hypertrophic cardiomyopathy (enlarged heart) are all associated with high blood pressure.

1.

2.

3.

Kidney Disease: Hypertension can damage the blood vessels and filters in the kidneys, so that the kidneys cannot excrete waste properly Stroke: Hypertension can lead to stroke, either by contributing to the process of atherosclerosis (which can lead to blockages and/or clots), or by weakening the blood vessel wall and causing it to rupture. Eye Disease: Hypertension can damage the very small blood vessels in the retina.

1999 WHO-ISH Guidelines: Desirable BP Treatment Goals

   Optimal or normal BP (< 130/85 mm Hg) for  Young patients  Middle-age patients  Diabetic 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

15 10 5 0 30 Significant benefits from intensive BP reduction in diabetic patients Major CV events / 100 patient-yr 24.4

25 20 18.6

11.9

< 90 mm Hg < 85 mm Hg < 80 mm Hg (target DBP)

Lancet 1998, 351, 1755

Relative risks of specific types of clinical complications related to tight and less tight BP Control Clinical end point

Any diabetes-related end point Deaths related to diabetes All cause mortality Myocardial infarction Stroke Peripheral vascular disease Microvascular disease

Patients with aggregate and points Tight Less tight control (n=758)

259

control (n=390)

170

Absolute risk (events/1000 patients-yr) Less Tight control

50.9

tight control

67.4

82 62 13.7

20.3

134 107 38 8 83 69 34 8 22.4

18.6

6.5

1.4

27.2

23.5

11.6

2.7

68

p

0.0046

RR for tight control (95% Cl)

0.76 (0.62-0.92) 0.019

0.68 (0.49-0.94) 0.17

0.13

0.013

0.17

0.82 (0.63-1.08) 0.79 (0.59-1.07) 0.56 (0.35-0.89) 0.51 (0.19-1.37) 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 Discourage excessive consumption of coffee and other caffeine-rich products .

Diet

 A healthy diet, such as the DASH (Dietary Approaches to Stop Hypertension) diet, is very effective at lowering high blood pressure. The DASH diet calls for a certain number of daily servings from various food groups, including fruits, vegetables, and whole grains. The following steps can also help: Eating more fruits, vegetables, and low-fat dairy foods  Eating less of foods that are high in saturated fat and cholesterol, such as fried foods Eating more whole grain products, fish, poultry, and nuts Eating less red meat and sweets Eating foods that are high in magnesium, potassium, and calcium

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

Diuretics  -blockers Calcium channel blockers  -blockers ACE- inhibitors Angiotensin-II receptor blockers

Example

Hydrochlorothiazide Atenolol Amlodipine Doxazosin Lisinopril Losartan

Initiating dose

12.5 mg o.d.

25-50 mg o.d.

2.5-5 mg o.d.

1 mg o.d.

2.5-5 mg o.d.

25-50 mg o.d.

Usual maintenance dose

12.5-25 mg o.d.

50-100 mg o.d.

5-10 mg o.d.

1-8 mg o.d.

5-20 mg o.d.

50-100 mg o.d.

Diuretics

Example:

Hydrochlorothiazide

   Act by decreasing blood volume and cardiac output Decrease peripheral resistance during chronic therapy Drugs of choice in elderly hypertensives

Drawbacks

  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 Block  2 receptors on the heart 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 disease

Drawbacks

 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

Diuretics (e.g. Hydrochloro thiazide) Electrolyte imbalance, total and LDL cholesterol levels,  HDL cholesterol levels, glucose levels, uric acid levels  -blockers (e.g. Atenolol) Impotence, Bradycardia, Fatigue

Contraindications/ Special Precautions

Hypersensitivity, Anuria Hypersensitivity, Bradycardia, Conduction disturbances, Diabetes, Asthma, Severe cardiac failure

Antihypertensive therapy: Side-effects and Contraindications

(Contd.)

Class of drug

Calcium channel blockers (e.g. Amlodipine, Diltiazem)

Main side-effects

Pedal edema, Headache Postural hypotension

Contraindications/ Special Precautions

Non-dihydropyridine CCBs (e.g diltiazem) – Hypersensitivity, Bradycardia, Conduction disturbances, Congestive heart failure, Left ventricular dysfunction.

Dihydropyridine CCBs – Hypersensitivity Hypersensitivity  -blockers (e.g. Doxazosin) ACE-inhibitors (e.g. Lisinopril) Angiotensin-II receptor blockers (e.g. Losartan) Cough, Hypertension, Angioneurotic edema Headache, Dizziness Hypersensitivity, Pregnancy, Bilateral renal artery stenosis Hypersensitivity, Pregnancy, Bilateral renal artery stenosis

Choosing the right antihypertensive Condition

Asthma Diabetes mellitus High cholesterol levels

Preferred drugs

Calcium channel blockers  -blockers/ACE inhibitors/ Angiotensin-II receptor blockers  -blockers Elderly patients (above 60 years) Calcium channel blockers/Diuretics BPH  -blockers

Other drugs that can be used

 -blockers/Angiotensin-II receptor blockers/Diuretics/ ACE-inhibitors Calcium channel blockers

Drugs to be avoided

  -blockers Diuretics/ -blockers ACE inhibitors/ Angiotensin-II receptor blockers/ Calcium channel blockers  -blockers/ACE inhibitors/Angiotensin-II receptor blockers/  - blockers  -blockers/ ACE inhibitors/ Angiotensin-II receptor blockers/ Diuretics/ Calcium channel blockers  -blockers/ Diuretics

Limitations on use of antihypertensives in patients with coexisting disorders Coexisting Disorder

Diabetes Dyslipidaemia CHD Heart failure Asthma/COPD Peripheral vascular disease Renal artery stenosis

Diuretic

Caution/x x      

-blocker

Caution/x x  3 /Caution x Caution 

ACE All inhibitor antagonist

      /Caution     Caution Caution

CCB

   Caution    1

-blocker

      x x  

Effect of various antihypertensives on coexisting disorders

Diuretic  -blockers ACE inhibitors All antagonists

Total LDL HDL Serum Glucose Insulin cholesterol cholesterol cholesterol triglycerides tolerance sensitivity

    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 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



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 by JNC-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)

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

Reduces BP effectively

200 150 100 50 0

175.4+ 19.4

143.8

+ 13.2

Systolic

106.8

+ 10.5

88.2

+ 7.6

Diastolic 90 80 70 60 50 40 30 20 10 0

80.5%

Basal Week 4

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)

Reduces BP effectively

200 150 100 50 0

175.4+ 19.4

143.8

+ 13.2

Systolic

106.8

+ 10.5

88.2

+ 7.6

Diastolic 90 80 70 60 50 40 30 20 10 0

77.65

Basal Week 4

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

Pregnancy  Coronary heart disease

Preferred Drugs

 Nifedipine, labetalol, hydralazine, beta-blockers, methyldopa, prazosin  Beta-blockers, ACE inhibitors, Calcium channel blockers  Congestive heart failure  ACE inhibitors, beta-blockers

1999 WHO-ISH guidelines

BEST MANAGEMENT OF HYPERTENSION    To use the fewest drugs at the lowest doses while encouraging the patient to maintain lifestyle changes. After BP has been under control for at least 1 year, a slow, progressive decline in drug therapy can be attempted.

However, most patients need to resume medication within 1 year.

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

ISOLATED SYSTOLIC HYPERTENSION  Systolic BP elevation in the absence of elevated diastolic BP is termed isolated systolic hypertension

Definitions

 Hypertensive

Crisis

 Urgency or Emergency

Hypertensive Urgency

 “Severe elevation of blood pressure”  Generally DBP >115-130  No

progressive

end organ damage

Hypertensive Emergency

 “Severe elevation of blood pressure”  Generally occurs with DBP >130  WITH

significant or progressive

end organ damage • Hypertensive Encephalopathy • CVA – Ischemic versus hemorrhagic • Acute Aortic Dissection • Acute LVF with Pulmonary Edema • Acute MI / Unstable Angina • Acute Renal Failure • Eclampsia

Urgency vs. Emergency



Urgency

 No need to acutely lower blood pressure  May be harmful to rapidly lower blood pressure  Death

not

imminent 

Emergency



Immediate control of BP essential



Irreversible end organ damage or death within hours