Healthcare in India

Healthcare in India

Geriatric Cardiology: An Overview

Last few decades evidences an accelerated demographic transition in India. Cardiovascular disease (CVD) is the most frequent diagnosis in elderly people and is the leading cause of death in both men and women older than 65 years of age. Cellular, enzymatic and molecular alterations in the vessels and heart are the proposed pathophysiological considerations for CVDs in geriatric population. Appropriate drug selection and dose regimen are critical for the management of CVD in elderly. While systolic hypertension is more prevalent with aging, diastolic BP remains relatively constant. Silent ischemias, acute MI, heart failure and stroke are widely reported in patients 65 years or older. While risk factor modification is a standard of care in management regimen for CAD, medical management plays a vital role. While thiazide diuretics are the drug of choice, beta blockers are generally not recommended in elderly hypertensive patients. While the use of thrombolytics and anti-thrombotics have pivotal role in management of acute coronary syndrome, the use of GP IIb/IIIa inhibitor administration is still controversial. Though aspirin and warfarin play an important role in the management of stroke, aspirin-clopidogrel combination is not generally recommended. A thorough risk benefit assessment is necessitated to select between PCI and CABG. Revascularization is not recommended for the management of stroke. For heart failure, pharmacological therapy is targeted at control of systolic and diastolic hypertension, use of diuretics to control pulmonary congestion, and pulmonary edema and control of ventricular response rate in patients with atrial fibrillation. Increasing emphasis is being placed on preventive strategies for CVD in older patients and improving the quality of care using current therapies.
Cardiovascular disease is the most frequent diagnosis in elderly people and is the leading cause of death in both men and women older than 65 years of age.1
Hypertension occurs in one half to two thirds of people older than 65 years of age, and heart failure (HF) is the most frequent hospital discharge diagnosis in the elderly specially women. Systolic, but not diastolic, blood pressure increases with aging, resulting in increased pulse pressure.2 Coronary artery disease (CAD) is more likely to involve multiple vessels and left main artery disease.3,4
The high morbidity and mortality from cardiovascular disease in the elderly warrant aggressive approaches to prevention and treatment that have been shown to be effective in older patients.2 The projected increase in numbers of older people from previously understudied and undertreated groups presents both medical and economic challenges for cardiovascular disease treatment.
The World Health Organization uses 60 years of age to define “elderly”, whereas most U.S. classification use the age of 65 years. Progressive increase in systolic blood pressure, pulse wave velocity, left ventricular (LV) mass, and increased incidence of CAD and atrial fibrillation are common presentations. Reproducible age-related decreases are also noticeable in rates of elderly LV diastolic filling, maximum heart rates, maximal cardiac output, maximum aerobic capacity or maximal oxygen consumption (VO2max), exercise-induced augmentation of ejection fraction, reflex responses of heart rate, heart rate variability, and vasodilation in response to beta-adrenergic stimuli or endothelial-mediated vasodilator compounds.
Cellular, enzymatic, and molecular alterations in the arterial vessel wall lead to arterial dilatation and increased intimal thickness resulting in increased vascular stiffness.
While extracellular changes in atria contribute to sinus node dysfunction and atrial fibrillation, altered myocardial calcium handling results from similar changes in ventricle.7 The result is prolongation of the membrane action potential and inward calcium current with prolongation of both contraction and relaxation.6,7 Other age related changes include altered platelet phospholipid content and increased platelet activity and impaired fibrinolysis.6,8 Consistent changes in the autonomic nervous system accompanying aging influence cardiovascular function.6,9 Some of the age-related cardiovascular changes can be partially, reversed by lifestyle modifications.10,11 Vascular responses to beta-adrenergic agonists and alpha-adrenergic blockade are also reduced with aging.5,6,12

Medical Therapy for Elderly Patients
The vast majority of therapeutic interventions for elderly are pharmacological. Hence, appropriate drug selection and modification regimens for older patients are important. Routine dosage/weight adjustments should be made in loading doses of medications, especially those with low therapeutic-to-toxicity ratios resulting in doses that are usually lower in older population.13
Medication Adherence is lower in geriatric patients andcan be associated with the cost of medications, difficulty with understanding directions because of small print of written directions, hearing impairment, impaired memory, inadequate instructions, complex dosing regimens, difficulties with packaging materials, or insufficient patient or family or caregiver education on medication use.14 These can be overcome by programs for low-income seniors, visual or memory aids, medication-dispensing tools, use of geriatric-friendly packaging, assessment of cognitive status and patient understanding, and inclusion of caregivers or family members in discussions regarding medications.15
Geriatric Handling of Cardiovascular Disease

  • Hypertension

Diastolic (>90 mm Hg) and/or systolic (>140 mm Hg) hypertension occurs in half to two-thirds of people older than 65 years and in 75 percent people older than 80 years. Systolic hypertension becomes more prevalent with aging, whereas diastolic blood pressure is relatively constant from 50 to 80 years of age, with average diastolic pressures higher in men than women from ages 50 to 80 years.16
Following recommendations are cited in most of the guidelines proposed for management of hypertension in elderly patients:

  • Treatment thresholds and targets should be based on the patient’s global atherosclerotic risk, target organ damage and comorbid conditions.
  • Blood pressure should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those with diabetes mellitus and chronic kidney disease.
  • Most patients will require more than one agent to achieve these target blood pressures. For all adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Special care should be taken to avoid hypokalemia in patients treated with thiazide diuretic monotherapy.
  • Note that beta blockers are not recommended as first line therapy in patients 60 years of age or older.
  • A combination of two first line agents may also be considered for initial treatment of hypertension if systolic blood pressure is 20 mmHg above or if diastolic blood pressure is 10 mmHg above target. However, caution must be exercised. 
  • Individuals with isolated systolic hypertension are recommended an initial monotherapy with a thiazide diuretic, a long acting dihydropyridine CCB or an ARB.
  • Statin therapy is recommended in hypertensive patients with three or more cardiovascular risk factors like left ventricular hypertrophy, peripheral arterial disease, previous stroke or transient ischemic attack, microalbuminaria or proteinuria, diabetes mellitus, smoking, family history of premature cardiovascular disease, total cholesterol to high-density lipoprotein cholesterol ratio ? 6, or other ECG abnormalities: left bundle branch block, left ventricular strain pattern, abnormal Q wave or ST-T changes compatible with ischemic heart disease.
  • Addition of low dose acetylsalicylic acid therapy should be strongly considered in hypertensive patients.

Non Pharmacological Treatment
Non pharmacological control of blood pressure is as important as pharmacological therapy. The following is recommended-

  • Restrict dietary sodium intake to less than 100 mmol/day (65 mmol/day to 100 mmol/day in hypertensive patients)
  • 30–60 minutes of aerobic exercise 4–7 days per week
  • Maintainance of body weight (BMI: 18.5–24.9 Kg/m2; waist circumference smaller than       102 cm for men and smaller than 88 cm for women)
  • Limit alcohol consumption to no more than 14 units per week in men or 9 units per week in women
  • Follow a diet that is reduced in saturated fat and cholesterol
  • Emphasize on including fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources in the routine diet
  • Consider stress management

Emphasis should be on diagnosis and treatment of hypertension that requires combination regimens in older patients rather than the choice of initial individual therapeutic agents.

  • Coronary Artery Disease

More than 50% people of age 60 years or older have CAD with increasing prevalence of left main or triple-vessel CAD with older age.17 The life-time risk of development symptomatic CAD is estimated as 1 in 3 for men and 1 in 4 for women with onset of symptoms about 10 years earlier in men compared with women, and with hypertension, diabetes, and lipid abnormalities influencing individual risk.18 
Predictive models that incorporate traditional risk factors (e.g., Smoking, blood pressure, selected lipid levels, diabetes) and age-specific markers such as pulse pressure or arterial stiffness with further adjustment for sex may provide the best current estimates of cardiovascular risk in people without known CAD.19
The cardiovascular Health Study, a large population based prospective study of community-dwelling adults older than age 65, has found the strongest predictors of death caused by an acute cardiac event to be a history of cardiac disease, myocardial infarction, or HF.20
History and Presentation
Anginal symptoms are more likely to be absent and ischemia is more likely to be silent in older patients compared with young patients. Lack of symptoms during evidence of MI on ECG (silent ischemia) has been reported in 20 to 50 percent of patients 65 years or older. Symptoms are “atypical”, described primarily as dyspnea, shoulder or back pain, weakness, fatigue (in women), or epigastric discomfort and may be precipitated by concurrent illness. Moreover, these symptoms may occur at rest or during mental stress.

  • Risk Factor Modifications
  • Advice smoking cessation. Pharmacological agents may be used.
  • Adequate blood pressure control is beneficial. For patients with CAD, especially those with decreased left ventricular function (ejection fraction < 40%), diabetes and chronic kidney disease, the use of ACE-inhibitors is recommended.
  • Current Adult Treatment Panel (ATP) III guidelines recommend a target LDL-C of < 100 mg/dl. Patients with a value > 100 mg/dl should be started on LDL-lowering therapy.
  • Current recommendations target non-high-density lipoprotein (HDL)-C, especially in patients with triglyceride levels > 200 mg/dl. The target goal is a reduction of non-HDL-C level to < 130 mg/dl by a more intensive reduction of LDL-C or medical therapy using niacin or fibric acid derivatives. [A combination of a statin and niacin has shown to decrease LDL-C and increase HDL-C levels].
  • Diabetes has been closely linked to the development and progression of atherosclerosis, especially CAD. The American Diabetic Association has recommended that patients with diabetes achieve the goal of a hemoglobin A1C level < 7% through initiation of aggressive lifestyle modification, appropriate pharmacology therapy and control of other cardiovascular risk factors.
  • Large clinical trials have shown, the use of antiplatelet therapy including either aspirin or clopidogrel results in a significant reduction in cardiovascular events. This therapy consists of aspirin (75–325 mg daily), or in cases of aspirin allergy, clopidogrel 75 mg daily. Dual-antiplatelet therapy is routinely used in patients with CAD who have undergone percutaneous revascularization or a recent ACS episode.
  • Cilastozol, at a dose of 100 mg twice daily, has been effectively used in patients with claudication. However, the use of cilastozol is not recommended in patients with heart failure.
  • Medical Treatment
  • Therapeutic and management goals that have been established for chronic stable angina targeted at symptom relief with nitrates, beta blockers, calcium antagonists, and partial free fatty acid inhibitors or risk reduction and slowing the progression of disease with lifestyle modifications, lipid lowering agents, and aspirin.21
  • Those with immediate benefits such as lifestyle changes of smoking cessation, increased activity, and weight control have a strong likelihood of benefits.22-24 Moreover, increased use of cholesterol-lowering agents has been suggested as an area for quality of care improvement efforts.
  • Recent studies demonstrate that higher doses of statins for 6 years have been shown to decrease the number of CHD events in white male CAD patients (mean age of 61 years at study entry). However, risk of death from all causes was not reduced.25 Moreover it is recommended that the smallest effective dose should be used in geriatric patients.

Additional Consideration

  • Marked vasodilatation caused by rapid absorption or higher peak effects of isosorbide dinitrates can exacerbate postural hypotension, so agents with smooth concentration versus time profiles such as mononitrates or transdermal formulations may be preferred for daily administration (although cost may be prohibitive).
  • Calcium channel blockers, especially the dihydropyridines, can produce pedal edema more frequently in the older patients. Short acting formulations can produce or exacerbate postural hypotension and should be avoided. Verapamil can exacerbate constipation, especially in the inactive elderly.
  • Both beta blockers and nondihydropyridine calcium channel blockers should be avoided in the presence of sick sinus node disease.
  • In older women, hormone replacement therapy is not indicated for either primary prevention of CHD or treatment of CHD.
  • Adverse effects of dizziness, constipation, nausea, asthenia, headache dyspepsia and abdominal pain with the newer piperazine derivative ranolazine are more common in elderly patients, and women may have less exercise benefit with ranolazine compared with men.
  • Revascularization

Studies evidence that patient aged 65 to 80 years had higher early morbidity and mortality after CABG compared with PCI but greater angina relief and fewer repeat procedures after CABG. Also, stroke was more common after CABG than after PCI, and HF and pulmonary edema were more common after PCI, suggesting a thorough risk benefit assessment prior to the selection of procedure.
In immediate post operative period, longer durations of ventilator support, greater need for inotropic support and intraaortic balloon placement, and greater incidence of atrial fibrillation, bleeding, delirium, renal failure, perioperative infarction, and infection are seen in older patients compared with younger patients. N-acetylcysteine has been reported to prevent contrast-induced nephropathy from PCI. Smaller randomized trials have reported both improved cognitive outcomes and no difference in outcomes with use of off-pump versus on-pump CABG.27 Moreover postoperative considerations should also include evaluation for depression.
Study comparing invasive (PCI or CABG) versus optimized medical therapy in CAD patients older than 75 years with angina refractory to standard therapy (TIME) demonstrated that though the initial analysis at 6 months reported an advantage for revascularization, the advantage was no longer present at 1 year. Revascularization presented an early risk of death and complications whereas optimized medical therapy carried a chance of latter events (hospitalization and revascularization) without a clear advantage of either strategy.
In a single site series of CABG patients with ejection fractions less than 35 percent, early operative mortality was higher in older patients and 5-year survival was less than 30 percent for patients 75 years of age and older.26 Studies also suggest that for those surviving past 6 months, survival was better for patients who underwent CABG.  While PCI data were from bare metal stent implants, and CABG data were from on-pump procedures in more than 85 percent.
Special Consideration
ACC/AHA Coronary Artery Bypass Surgery and PCI Guidelines conclude that age alone should not be used as the sole criterion when considering revascularization procedures.
Individualized prognostic information, patient preference and disability or prolonged hospitalization should also be considered. Death, recurrent angina, or MI may not be viewed as carrying the same negative impact as a disabling stroke to many older patients.

  • Acute Coronary Syndrome

About 60 percent of hospitalized admissions for acute myocardial infarction (AMI) are in people older than 65 years, and approximately 85 percent of deaths caused by AMI occur in this group. Mortality rates are usually higher in older women than in older men with AMI, as are adverse outcomes with thrombolytics, fibrinolytics, and glycoprotein (GP) IIb/IIIa inhibitors. As age increases past 65 years, there are more patients with functional limitation, HF, prior coronary disease, and renal insufficiency; more women; and lower proportions of diabetics, smokers, or patients with prior revascularization. Fewer older patients present with chest pain or ST elevation on ECG within 6 hours of symptom onset. Angiographic evidence of collateral circulation to infarct-related arteries also decreases markedly after age 70 years. Mortality is at least threefold higher in the patients older than 85 years compared with the patient younger than 65 years. Thus older patients with AMI differ from both middle-aged and younger elderly patients.
Thrombolysis: For patients up to the age of 75 years, fibrinolytic, antiplatelet and antithrombin therapy is associated with a survival advantage28 but with higher complication rates of minor and major bleeding and transfusion.
Antithrombotic Agents: Trial data demonstrate that aspirin reduces mortality in patients older than 70 years and is recommended for routine administration to older patients with AMI.29 Also, the addition of clopidogrel to aspirin after non-ST-elevation MI reduces major events rates by 20 percent.30 Moreover, newer GP IIb/IIIa inhibitors appear efficacious in older patients. However clinical trials show that bleeding risk including intracranial hemorrhage is increased about twofold with GP IIb/IIIa inhibitors.31
Invasive Strategies: Results from several studies and database reviews have suggested that primary angioplasty in experienced centers is associated with improved outcomes compared with thrombolytic strategies in elderly patients with ST-elevation acute MI.29
In an analysis of community practice outcomes as part of the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE), the use of five therapies, including early use of aspirin, beta blockers, heparin, GP IIb/IIIa inhibitors and cardiac catheterization, were recommended.32
Additional Pharmacological agents

  • Beta blocker administration is recommended for all patients with AMI regardless of age in the absence of contraindications.
  • In presence of LV systolic dysfunction or anterior wall MI, ACE inhibitors are recommended within the first 24 hours of onset of AMI.
  • ACE inhibitors are recommended after 24 hours for all other MI patients, especially those with reduced LV ejection and prior MI.
  • As with other agents in the elderly, small initial doses and slower titration are indicated, as is close monitoring of renal function.
  • Carotid Artery Disease/ Stroke

Modifiable risk factors for noncardioembolic ischemic stroke or TIA in the elderly are hypertension, smoking and passive smoking, hyperlipidemia, lack of physical activity, inadequate treatment of atrial fibrillation, carotid artery disease and HF. Diabetes confers additional risk. Sleep apnea has recently been identified as a potential modifiable risk factor, as has estrogen administration to postmenopausal women.

  • Modification of the above mentioned risk factors is of substantial advantage in the management of stroke. However, blood pressure management in the setting of acute stroke remains controversial with aggressive reduction in pressure not generally recommended. When hypertension is treated, intravenous agents are recommended for initial therapy (labetalol or nicardipidine for systolic or mixed hypertension with diastolic pressures <140 mmHg; nitroprusside for diastolic pressures >140 mmHg). Blood pressure control should precede thrombolytic therapy. Pharmacological thrombolysis with recombinant tissue plasminogen activator (rt-PA) is recommended for selected patients with ischemic stroke with a measurable neurological deficit in whom it can be administered within 3 hours of stroke onset. However, no age-specific recommendations for rtPA have been made, but delays in diagnosis are more likely in elderly.
  • Data further supports the administration of aspirin within 48 hours of acute stroke for most patients. However early anticoagulation with unfractionated or low-molecular-weight heparin or use of other antiplatelet agents is not generally recommended.

Few clinical trials demonstrated that LDL cholesterol reduction with statins reduces the risk of stroke in patients with cardiovascular disease (CVD) or major CVD risk factors. 33
Antiplatelet Drugs
Aspirin reduces the long-term risk of stroke, as well as cardiovascular events, after stroke or TIA and is considered standard therapy after a stroke regardless of patient age. Combined aspirin and clopidogrel have failed to show additive benefit, in fact the combination is not recommended.34,35
In most reports, bleeding complications with antiplatelet drugs are more frequent in older compared with younger patients. Although the minimally effective dose for aspirin has not been determined, lower doses are recommended for the geriatric patients, in particular.
Anticoagulant Drugs
For older patients at moderate and higher risk for stroke, anticoagulation with warfarin is appropriate, unless contraindicated. The target INR is 2-3. Both initial and maintenance warfarin doses are usually lower in older adults compared with middle-aged patients (usually 2-5 mg daily in elderly).
Surgical and endovascular approaches
Several clinical trials have demonstrated that carotid endarterectomy (CEA) in symptomatic patients with 70 to 99 percent internal carotid artery (ICA) stenosis who have had a stroke and TIA attributable to the stenosis is safe and effective in reducing the risk of ipsilateral carotid ischemia.36
Moreover, revascularization is not recommended for patient with lesions of less than 50 percent. Preliminary results from ongoing trials suggest an overall disadvantage of stenting compared with CEA and that older patients, especially those older than 70-80 years of age, have the highest peri-procedural rates of stroke and death, even with distal protection devices.

  • Heart Failure

Prevalence and Incidence
HF has become preliminary a disorder of the elderly. HF contributes to at least 20 percent of hospital admissions of patients older than 65 years of age with approximately three quarters of HF hospitalization occurring in patient older than 65 years and more than 85 percent of HF deaths occurring in patients older than 65 years of age. Asymptomatic LV systolic dysfunction is estimated to occur in another 3 to 5 percent of the community with higher prevalence at older ages. While the incidence and prevalence of HF is higher in men than women at all ages, HF is more likely to result from CAD.
Age Related Changes in Ventricular Function
Signs and symptoms of HF in older patients often occur in the presence of preserved LV function evaluated as ejection fraction. The pathophysiology is primary attributed to LV diastolic dysfunction (a leftward and upward shifted enddiastolic pressure-volume relationship), in which LV diastolic chamber size is normal or reduced despite elevated fillings pressures resulting in decreased stroke volume and cardiac output.
Although HF with preserved systolic function has a slightly better short-term prognosis than HF with abnormal function, there is a fourfold higher mortality risk compared with subjects free of HF.
Exercise intolerance is the primary symptoms in chronic HF of either systolic or diastolic cause. Dyspnea and fatigue are prominent symptoms in patient with HF, but fatigue also accompanies many chronic illnesses such as pulmonary disease, thyroid abnormality, anemia, or depression. Complaints of shortness of breath, orthopnea or development of nocturnal cough, or paroxysmal nocturnal dyspnea suggest the presence of HF.
Pharmacological therapy is targeted at control of systolic and diastolic hypertension, use of diuretics to control pulmonary congestion and pulmonary edema and control of ventricular response rate in patients with atrial fibrillation. Most systolic HF trials have tested therapies on a background of digitalis and diuretic administration.
Efficacy with the addition of ACE inhibitors and ARBs has been demonstrated in trials that have included elderly patients, and additional efficacy has been shown for diabetes, which is present in at least 10 percent of the older population. Moreover, beta blockers are usually considered next and can be instituted at low doses during periods of clinical stability. However, direct vasodilators may have less of a role in older patients with increased likelihood of orthostatic hypotension.
Benefit may be seen with these drugs used at lower doses in patients with severe HF, but age-related decreases in renal function increase the risk for hyperkalemia.
Dietary sodium restriction is advised, and moderate physical activity should be encouraged if feasible. Cardiac resynchronization therapy can decease hospitalizations and reduce mortality in selected patients with symptomatic systolic HF and prolonged cardiac repolarization or QRS intervals on the ECG.
In Heart Failure with Preserved Left Ventricular Ejection Fraction (Diastolic Heart Failure), management is based on control of physiological factors (blood pressure, heart rate, blood volume, and myocardial ischemia) that are known to exert important effects on ventricular relaxation and the treatment of diseases known to cause diastolic HF. Diuretics are advised for therapy of diastolic HF in the ACC/AHA Guidelines for evaluation and Management of Heart Failure Society Guidelines.
Digoxin was reported to yield symptomatic improvement and decreased hospitalization (without mortality benefit). Also, a vasodilating beta blocker has been shown to improve morbidity in older patients with diastolic and systolic HF.
Additional considerations for the older patient with heart failure
Elderly patients with HF have the highest rehospitalization rate. Education and involvement of the patient, family members, and/or caregivers is key to the management of older patient with HF.

  • Valvular Disease

Pathophysiology and Age-Related Changes
Age related changes in the fibromuscular skeleton of the heart include myxomatous degeneration and collagen infiltration termed sclerosis.
In older patients, fibrosis and valve calcification is the most common cause of valvular stenosis, especially at the aortic position. Ischemic or hypertensive disease has become the most common cause of valvular regurgitation, especially at the mitral valve. Similarly, pulmonary and tricuspid reguergitation in the elderly are usually secondary to pulmonary hypertension and dilation of the right ventricle resulting from LV ischemia, HF, or pulmonary disease. Less common etiologies of mild to moderate mitral or aortic regurgitation are ruptured chordate, endocarditis, trauma, aortic dissection, or rheumatic heart disease.
Treatment for symptomatic valvular disease relies on surgical approaches. Surgery in older patients between 70 and 80 years of age is increasingly common, but experience with those older than 90 years of age is limited and carries a high surgical mortality rate.
Management of the older patients with aortic stenosis is similar to that of younger patients with recognition of the increased likelihood of concomitant coronary disease and diseases of other organs. Antibiotic prophylaxis should be used to prevent bacterial endocarditis.
Surgical morbidity and mortality relate to the severity and duration of stenosis, degree of LV hypertrophy, presence or absence of HF or CAD, concomitant diseases (especially renal), and urgency and complexity of the procedure. Combined valve replacement and CABG are associated with higher perioperative morbidity and mortality than isolated valve replacements. Estimates of average operative mortality for older patients who have undergone valve replacement with or without CABG as part of clinical care have been reported as 6 percent for high-volume surgery centers and 13 percent in low-volume surgery centers.
Moreover, postoperative hospitalization and rehabilitation times are usually longer in older patient.
Additional consideration in the elderly
Drug induced valve disease is uncommon, but there are case reports of fibroproliferative lesions producing valvular insufficiency or regurgitation in older patients on chronic treatment with the anti-Parkinson disease dopamine receptor agonist pergolide.

Future Directions
Increasing emphasis is being placed on Preventive strategies for CVD in older patients and improving the quality of care using current therapies that were not designed for the elderly. A major limitation is the lack of understanding of the mechanism underlying many age related cardiovascular changes or disease. In this era of personalized medicine, studies emphasizing the health care requirements of geriatric population and the strategies to meet the same will be of substantial advantage.