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 Secondary 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 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 SBP DBP Category* (mm Hg) (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) 160-179 100-109 Grade 3 hypertension (severe) > 180 > 110 ISH > 140 < 90 Borderline subgroup 140-149 < 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 Degree of hypertension (mm Hg) Risk factors and Grade 1-mild Grade 2-moderate Grade3-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 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 Very high risk Very high risk Clinical conditions 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 Left Ventricular Hypertrophy Heart Failure Gangrene of the Lower Extremities Myocardial Infarction Hypertensive Encephalopathy Aortic Aneurym HYPERTENSION Coronary Heart Disease Blindness Cerebral Hemorrhage Chronic Kidney Failure Stroke Preeclampsia/Eclampsia Adapted from Dustan HP et al. Arch Intern Med. 1996; 156: 1926-1935

Health Problems Are Associated With Hypertension 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.

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

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 Absolute risk aggregate (events/1000 and points patients-yr) Tight Less tight Less RR for control 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 point Deaths related to 82 62 13.7 20.3 0.019 0.68 (0.49-0.94) diabetes All 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) disease Microvascular 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 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 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 Amlodipine 2.5-5 mg o.d. 5-10 mg o.d. channel blockers -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 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 b1 receptors on the heart Block b2 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 a-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 b-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 a-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

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

Limitations on use of antihypertensives in patients with coexisting disorders Coexisting Diuretic b-blocker ACE All CCB a1-blocker Disorder inhibitor antagonist Diabetes Caution/x Caution/x     Dyslipidaemia x x     CHD       Heart failure  3/Caution   Caution  Asthma/COPD  x  /Caution    Peripheral  Caution Caution Caution   vascular disease Renal artery   x x   stenosis

Effect of various antihypertensives on coexisting disorders Total LDL- HDL- Serum Glucose Insulin cholesterol cholesterol cholesterol triglycerides tolerance sensitivity Diuretic ­ ­ ¯ ­­ ¯ ¯ b-blockers - ­ ¯¯ ­­­ - - ACE inhibitors - - - - ­ ­ All antagonists - - - - ­ ­ CCBs - - - - - - a-blockers ¯ ¯ ­ ¯ ­ ­

(Combination therapy) 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 b-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) b-blocker and Diuretic (e.g. Atenolol and Hydrochlorothiazide)

Reduces BP effectively Efficacy and Tolerability of a fixed-dose combination of amlodipine and atenolol (Amlopres-AT) in Indian Hypertensives (n=369) Reduces BP effectively 80.5% 175.4+19.4 143.8 + 13.2 Blood Pressure (mm Hg) 106.8 + 10.5 % responders 88.2 + 7.6 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.

Reduces BP effectively Efficacy and Tolerability of combined amlodipine and lisinopril (Amlopres-L) in Indian hypertensives (n=330) Reduces BP effectively 77.65 175.4+19.4 143.8 + 13.2 Blood Pressure (mm Hg) 106.8 + 10.5 % responders 88.2 + 7.6 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 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

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 MALIGNANT: papilledema ACCELERATED: retinal hemorrhages and exudates No clinical difference so all “Accelerated-Malignant”

“Severe elevation of blood pressure” Hypertensive Urgency “Severe elevation of blood pressure” Generally DBP >115-130 No progressive end organ damage RISK OF IMMINENT TARGET ORGAN DAMAGE ALTHOUGH INJURY HAS NOT YET OCCURRED NO EVIDENCE BASED DATA EXISTS TO GUIDE PRACTITIONER IN MANY CASES CLINICIANS MAY BE FORCED TO INITIATE ANTI-HTN TREATMENT WITHOUT BEING CERTAIN OF DIAGNOSTIC CLASSIFICATION

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 Occurs in 1% of HTNsives Rare unless DBP > 130 NOT DEFINED BY ABSOLUTE PRESSURE MEASUREMENTS BUT INSTEAD CONTINGENT ON PRESENCE OF RELATIVE BP INCREASES COMBINED WITH EVIDENCE OF END ORGAN DAMAGE. Evidence suggests it is the rate of rise, not how high BP gets… Like temp spikes in febrile seizures.

Urgency vs. Emergency Urgency Emergency 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 MAIN CAUSE IS OF HYPERTENSIVE URGENCY IS MEDICATION NON-COMPLIANCE SO GENERALLY FIND OUT WHY NOT TAKING AND RESTART OR CHOOSE NEW AGENTS.