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Geriatric Pharmacy (PHR 586) Lecture (4)

Cardiovascular Function and Disease in the Elderly


By: Dr. Maged Wasfy (Lecturer of Pharmacology, Faculty of Pharmacy, Pharos University in Alexandria) Intended learning outcomes (ILOs) By the end of this lecture, student will be able to: 1. Identify the major cardiovascular changes that associated with normal aging process and with major cardiovascular disease in elderly. 2. Discuss the epidemiology of hypertension. 3. Explain the classification system most commonly used to stage blood pressure disorders 4. List risk factors for hypertension 5. List medications that can cause or exacerbate hypertension. 6. Outline goals and therapeutic interventions appropriate for elderly patients with hypertension. 7. Describe the benefits of pharmacological treatment of hypertension and classes of agents most commonly used. 8. Describe indications, contraindications, dosing guidelines and side effects of common antihypertensive drugs.

Introduction The elderly represent the fastest-growing segment of the developed population. Cardiac function is altered in an age-related manner even in absence of any disease. Moreover, cardiovascular diseases increase with increasing age. Cardiovascular changes during aging could be classified into: 1. Cardiac changes associated with normal physiological aging (i.e., not disease), 2. Cardiac changes associated with major cardiovascular diseases in elderly, with subsequent modifications of therapy for elderly patients

1. Cardiovascular changes with Physiologic Aging A. Rhythm 1. Heart Rate Resting heart rate is not generally affected by aging.
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Heart rate in response to exercise, fever, hypovolemia, and postural stress (that are -adrenergically mediated) is decreased in healthy aging. The response to beta-adrenergic blockade (as well as stimulation) is also reduced with healthy aging. 2. Atrioventricular Conduction The time for conduction through the atrioventricular (AV) node is increased with healthy aging. 3. Arrhythmias Atrial premature contractions increase with age at rest and during exercise in the absence of detectable cardiac disease. Atrial fibrillation is usually associated with coronary, hypertensive, valvular, sinus node disease or thyrotoxicosis but may occur in elderly patients with no other detectable diseases. Isolated and even multiform ventricular ectopy has been reported in up to 80 % of elderly men and women. B. Cardiac Contractility/ Left Ventricular Function at Rest and During Exercise Left ventricular mass is preserved or increased with age (In contrast to the decline in skeletal muscle mass seen with aging in healthy populations) The nature of heart muscle relaxation is decreased (i.e, become stiffer) 1. Systolic Function Contractile responses (force) to beta-adrenergic responses are decreased with aging. Therefore, cardiac output may be reduced due to both the decrease in heart rate and cardiac contractility (stroke volume) in response to beta-adrenergic blockade in the elderly. 2. Diastolic Function The time for cardiac relaxation and for ventricular filling are prolonged with aging. The etiology of the prolonged time for relaxation may be multifactorial--increased ventricular mass, collagen infiltration, or altered myocardial calcium handling. C. Valvular Changes Degenerative calcification (leading to sclerosis) affects the aortic and mitral valves with aging.

D. The vascular system The walls of the arteries tend to lose their elasticity, even without internal blockage from fatty deposits (atherosclerosis). This may lead to a specific kind of high blood pressure among elderly people called isolated systolic hypertension. Slowing of reflex that maintains blood pressure upon standing up, that increase chances of orthostatic hypotension. 2. Cardiac changes associated with major cardiovascular diseases in elderly The cardiac changes associated with cardiovascular diseases in elderly are similar to those in young population Several unique modifications for treatment of cardiovascular diseases in elderly patients due to: 1. The whole changes in body physiological functions with aging 2. The presence of several concomitant diseases and medications usually present in old age.

Common Cardiovascular Diseases and Management in Elderly Patients 1. Hypertension Hypertension is defined as systolic BP >= 140 mm Hg or diastolic BP >= 90 mm Hg. Hypertension in elderly people generally defined as blood pressure that ranging from 160/90 mm Hg and above. High blood pressure is more common with advancing age, and usually associated with several complications as stroke, kidney disease, heart attack, and heart failure. Etiology Primary hypertension (essential): 90% of people of all ages with hypertension of no identifiable cause. Secondary hypertension has a specific cause, these causes, such as: o Atherosclerotic renal artery stenosis, which may contribute to high BP in 5 to 10% of elderly patients. o Endocrine disorder (eg, Cushing's syndrome, hyperthyroidism, primary aldosteronism, pheochromocytoma), but this factor is not increased with aging. o Kidney disorder (eg, polycystic kidney disease, glomerulonephritis, chronic pyelonephritis), but this factor is not increased with aging. Common conditions among elderly patients may exacerbate primary hypertension or shift pre-hypertension into the hypertensive range. These conditions include: o Renal insufficiency and failure o Excessive use of OTC drugs (eg, pseudoephedrine), o Prescription of drugs (eg, NSAIDs, COX-2 inhibitors, corticosteroids, cyclosporine, tacrolimus, erythropoietin), or herbal remedies (eg, Liquorice) o Excess alcohol o Obesity; hyperthyroidism or hypothyroidism A special type of high blood pressure that is more common in elderly people is called isolated systolic hypertension. o In this condition, only the systolic reading is elevated (for example, 160/70 or 200/80). o The systolic reading represents a recording of the pressure exerted against the arterial walls when the heart contracts and pumps blood out.
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o Thus, isolated systolic hypertension is thought to be due to thickening of the arterial wall which makes it less distensible and less able to buffer the rise in pressure that occurs with cardiac ejection. These changes result in an elevated systolic blood pressure with a relatively unchanged diastolic blood pressure. o Treating isolated systolic hypertension can now be recommended to reduce the incidence of stroke, heart attack, and heart failure. Another condition resulting from high blood pressure, especially in old age, is left ventricular hypertrophy, or thickening of the hearts main pumping chamber, the left ventricle. o After many years of pumping against heightened resistance, the heart enlarges under strain and its walls begin to thicken. o This condition usually leads to heart failure.

Treatments of Hypertension: Treatment goals are now the same for elderly patients as they are for younger patients (to maintain systolic blood pressure < 140 mmHg and diastolic pressure < 90 mmHg). A. Non pharmacologic Regimen: o Diet (weight reduction if obese; low sodium for all, and < 1 oz of alcohol/day) o Exercise & Walking for 30 min/day. o Stop smoking. o Decrease fats intake B. Pharmacologic Therapy: Hypertension treatment design in elderly is similar to young adults, but the difference may be in the priority of class selection. Treatment design includes: o Mono-therapy with one class of antihypertensive drugs (usually diuretics). o If the initial dose of an antihypertensive drug does not control BP, the dose may be increased, or a 2nd drug may be added to reduce risk of dose-related adverse effects of the 1st drug. Most elderly patients ultimately require >= 2 antihypertensive drugs; one drug is usually a thiazide-type diuretic. Selection of Antihypertensive class depends on the whole circumstances of the elderly patient. 1. For the elderly patient with hypertension (and no other diseases),the first-line pharmacologic therapy a) Thiazide diuretics (chlorthalidone 12.5-25 mg/day, hydrochlorothiazide 25 mg/day) alone or in combination with beta-blockers (atenolol 50 mg/day, metoprolol 50 mg/day). Advantages: this regimen demonstrates longevity (long-term benefits) benefit and lower cost. N.B: 1. Elderly patients show enhanced responsiveness to diuretics and Ca channel blockers, particularly those with systolic hypertension, than ACE inhibitorswhy???? This is because, in most elderly patients, the arterial pressure is greatly affected by the increased total peripheral resistance (exerted by the rigid atherosclerotic arteries). While plasma-renin activity and angiotensin II levels are normal or even reduced, suggesting a minimal relationship between elevated blood pressure and the reninangiotensin system. Thus ACE inhibitors have less beneficial effect in elderly patients than diuretics & Ca-channel blockers.
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2. For the elderly patient with hypertension associated with other diseases, the first-line pharmacologic therapy
a) Calcium channel blockers, for coronary artery disease, cerebrovascular

b) c) d) e)

disease, diabetes, chronic obstructive pulmonary disease, diabetes with renal disease. Angiotensin converting enzyme (ACE) inhibitors, congestive heart failure, diabetic with renal failure, 1-blockers, for prostate disease Angiotensinogen II blockers -blockers have an advantage in the post-myocardial infarction patient.

Serious considerations of some antihypertensive classes: 1. In elderly patients with urinary incontinence, diuretics may worsen bladder control. 2. Men with benign prostatic hyperplasia may obtain dual benefit from 1-blockers, although these drugs should not be used as monotherapy because they may increase risk of hospitalization for heart failure. 3. Non-cardioselective -blockers are relatively contraindicated in patients with peripheral vascular disease or lung disorders. Adverse effects of antihypertensive drugs: 1. Loop diuretics may increase risk of orthostatic hypotension. 2. Centrally acting -agonists are more likely to have CNS effects (eg, depression, forgetfulness, vivid dreams, hallucinations, sleep problems). 3. Thiazides, centrally acting -agonists, and -blockers may cause erectile dysfunction in men. 4. -blockers should be used cautiously in patients with a heart rate < 60 beats/min. These effects are not a reason to withhold drug therapy in patients with hypertension, but if the diastolic BP falls to < 60 mm Hg, dose reduction should be considered.

(Important)

Thiazide is not used for patient with renal insufficiency, why????

The most used diuretics for mild to moderate hypertension ????

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