Elderly and Heart Disease
Madhan Shanmugasundaram
Toshinobu Kazui
INTRODUCTION
Heart disease is common in the elderly, and health care providers are often met with unique therapeutic challenges in this group. The elderly are often excluded from trials; hence, generalizing various treatment strategies becomes difficult. Health care providers should understand the physiology of cardiovascular changes that occurs with aging. Age should not be the only factor used in making therapeutic decisions. It is critical to individualize treatment to elderly patients. Although prolonging survival is a goal of many cardiovascular therapies, older adults may prioritize quality of life over reduction in mortality.
EPIDEMIOLOGY
Older adults or the elderly (>65 years of age) are a rapidly growing population. In the United States, 12% of the population in 2000 was older than 65 years, and it is estimated that this will increase to 20% by 2030 with the very elderly (>85 years of age) constituting almost one-third of this population.
Coronary artery disease (CAD), congestive heart failure (CHF), and atrial fibrillation (AF) are the most common cardiac diseases seen in the elderly, and cardiovascular disease is the most common cause of death in the elderly. Heart disease in the elderly is different from that in younger patients because of physiologic changes that occur with aging and an increased prevalence of comorbidities. Even though the elderly appear to have high morbidity and mortality from heart disease, therapies have shown to be more beneficial in this group than that in younger patients. Unfortunately, a treatment risk paradox exists in that even though the elderly are considered to be a high-risk population in whom treatments would have more benefit, they do not receive guideline-directed therapies. This chapter presents an overview of various heart diseases pertaining to the elderly and available evidence supporting various therapeutic strategies.
AGING AND THE HEART
Various physiologic changes occur in the cardiovascular system with age. Understanding these physiologic changes and differentiating them from various pathologic conditions is critical. These physiologic changes also form the basis of some of the pathologic changes in the elderly. Increased arterial stiffness and decreased compliance, especially in the central arteries, is one of the most important changes seen in the elderly. A combination of increased collagen and elastase—that, in turn, results in decreased elastin in the arteries—results in stiff noncompliant arteries with poor distensibility. There are other biologic changes such as increase in levels of matrix metalloproteinase, angiotensin II, and transforming growth factor that lead to endothelial dysfunction, with decreased nitric oxide production and impaired vasodilatation. These changes result in isolated systolic hypertension in the elderly, which is characterized by increased systolic pressure, decreased diastolic pressure, and widened pulse pressure.
In the heart, there is loss of myocytes, but the remaining myocytes hypertrophy resulting in concentric left ventricular (LV) hypertrophy. Excess fibroblast activity has been demonstrated in the aging heart, which causes fibrosis and ventricular noncompliance (stiffness). This results in diastolic dysfunction that, when advanced, can result in heart failure (HF) symptoms. Even though the LV ejection fraction remains normal with age, there are other structural changes such as “sigmoid” septum (ie, isolated hypertrophy [>15 mm] of the basal LV septum without hypertrophy elsewhere) that may cause LV outflow tract obstruction in the setting of hypovolemia or tachycardia. A decrease in sinoatrial nodal cells and fibrosis in the conduction system may result in bradyarrhythmia. Aortic and mitral valve (MV) thickening (sclerosis) are noted in the aging heart. Although this is not linearly associated with development of stenotic valve disease,1 it is considered to be a marker of increased cardiovascular outcomes.
TREATMENT GOALS IN ELDERLY WITH HEART DISEASE
Most therapeutic strategies in cardiology are associated with a reduction in mortality and improved survival. Although these are very important objectives, elderly patients may prefer a better quality of life over extended survival. Some treatment strategies that improve survival in the elderly may adversely impact the quality of life. Elderly patients being treated for chronic diseases report that independence in activities of daily living is their primary goal.2 Other equally important goals in elderly include decreased hospitalization and symptom-free living.3 The elderly patients also consider psychosocial and financial burden of the disease and its treatments before making therapeutic decisions. In addition to estimating the potential gain in life expectancy achievable in elderly patients with various treatment options, health care providers should thus account for all these variables before offering treatments in elderly patients.
Hypertension
Hypertension has been well established as an important risk factor for cardiovascular disease in the elderly. Initially thought to be a physiologic response to aging because of increased arterial stiffness, it is now known to be associated with stroke, myocardial infarction (MI), peripheral artery disease, and cognitive impairment that increases the risk of dementia. The Joint National Committee 8 (JNC 8) guidelines for management of hypertension defines hypertension in the elderly (60 years or older) as blood pressure (BP) greater than or equal to 150 mm Hg systolic and/or greater than or equal to 90 mm Hg diastolic. The treatment goal in the elderly is BP less than 150/90 mm Hg; however, if the patient is on well-tolerated medications with a BP less than 140/80 mm Hg, then the guidelines recommend no changes to therapy or treatment goal.4 However, based on more recent results from the Systolic Blood Pressure Intervention Trial (SPRINT, see later), for most adults 65 years or older, a more aggressive systolic BP target less than 130 mm Hg is recommended (see Table 20.1).5
The Systolic Hypertension in the Elderly Program (SHEP) study that randomized elderly patients (average age 72 years) with isolated systolic hypertension to pharmacotherapy versus placebo, demonstrated a significant reduction in hemorrhagic and ischemic strokes in patients in the treatment arm. A significant reduction in the nonfatal MI, coronary deaths, and all-cause mortality was also reported.6 In the HYpertension in the Very Elderly Trial (HYVET) that randomized over 3000 patients older than 80 years (mean age 84 years) to treatment or placebo, a significant reduction in fatal and nonfatal stroke, all-cause mortality and cardiovascular death occurred with treatment, thus confirming the benefits of antihypertensive therapy even in the very elderly patients.7 SPRINT randomized over 9000 patients with hypertension (≥130 mm Hg systolic BP) to intensive treatment (<120 mm Hg) or standard therapy (<140 mm Hg) and demonstrated a significant reduction in the composite outcome of MI, stroke, HF, and cardiovascular death in the intensive treatment arm, with the benefits of intensive BP lowering seen in the elderly patient (≥75 years) subgroup as well (Table 20.2).
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Dyslipidemia
Dyslipidemia is common in elderly patients, but is undertreated because of the perceived lack of “benefit” and theoretical increased risk of adverse effects from statin therapy. The PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) study randomized approximately 6000 patients older than 70 years of age at risk for vascular disease to pravastatin or placebo and demonstrated a significant reduction in the composite end point of death, nonfatal MI, and fatal or nonfatal stroke in the pravastatin arm.9 The Heart Protection Study (HPS) randomized more than 20,000 patients with known history of vascular disease or diabetes to either simvastatin or placebo, and demonstrated a significant reduction in all-cause mortality and fatal and nonfatal vascular events in the simvastatin arm. A subgroup analysis of this study showed that the benefit was preserved in the elderly patients.10 A post hoc analysis of the TNT (Treatment to New Targets) trial that included over 3000 patients older than 65 years of age, showed a significant reduction in first major cardiovascular event (death from CAD, nonfatal non-procedure-related MI, resuscitated cardiac arrest, or fatal or nonfatal stroke) in patients treated with high-dose (80 mg/day) versus low-dose (10 mg/day) atorvastatin. A large primary prevention trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin, JUPITER) randomized approximately 17,000 patients with no prior cardiovascular disease and low-density lipoprotein cholesterol (<130 mg/dL, high-sensitive C-reactive protein > 2 mg/L) to either rosuvastatin or placebo and showed a significant reduction in the combined primary end point of MI, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes with rosuvastatin.11 A secondary analysis of this study showed that in elderly patients (70 years or older), there was a greater benefit with rosuvastatin than with that in younger patients, thus confirming the benefits of statin therapy for primary prevention in the elderly patients.
A population-based study in France showed that statin cessation in elderly patients (older than 75 years of age) for primary prevention was associated with a 33% increased risk of admission for cardiovascular event. Consequently, the
American Heart Association/American College of Cardiology (AHA/ACC) lipid guidelines assign a Class II level A recommendation for statin therapy in elderly patients for secondary prevention of cardiovascular disease and a Class II level B recommendation for primary prevention.
American Heart Association/American College of Cardiology (AHA/ACC) lipid guidelines assign a Class II level A recommendation for statin therapy in elderly patients for secondary prevention of cardiovascular disease and a Class II level B recommendation for primary prevention.
TABLE 20.2 Cardiovascular Conditions and Therapies in Elderly With Strength of Evidence | |||||||||||||||
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Coronary Artery Disease
The prevalence of CAD increases with age, and the elderly with CAD have high morbidity and mortality. About 20% of men and 13% of women aged 60 to 79 years in the United States have CAD. In those older than 80 years, over 30% of men and 25% of women have established CAD, with the majority of them presenting with acute MI. In 2014, about 50% of percutaneous coronary intervention (PCI) procedures were performed in the elderly (65 years or older). The financial burden of this disease is significant as well. CAD in the elderly is more advanced than it is in younger patients, with multivessel involvement, a higher incidence of left main coronary stenosis, more calcified lesions, diffuse critical disease, and impaired LV function. The elderly with stable CAD also have a different presentation compared to that in the younger patients, with only a minority reporting angina. Most elderly patients present with atypical symptoms such as fatigue, exertional dyspnea, and lack of energy.
DIAGNOSIS
Owing to the high prevalence of baseline electrocardiogram abnormalities, exercise treadmill testing (ETT) alone is often not sufficient to evaluate the presence of CAD. Also, many elderly have orthopedic issues or limited functional status that precludes them from performing adequate levels of exercise needed for traditional ETT. That said, there are several modified ETT protocols that provide valuable information with good diagnostic accuracy. The rationale for stress testing in the elderly is very similar to that in the younger population, which is to diagnose CAD, but these tests should only be used in patients with intermediate pretest probability for CAD; these tests do not add prognostic value in patients with either low or high pretest probability. Adding an imaging modality—either nuclear perfusion or echocardiography—increases the sensitivity and specificity of stress testing. A meta-analysis of different stress test modalities in elderly patients (65 years of age or older) concluded that imaging-based stress testing improved the diagnostic yield compared to ETT alone.12 For elderly patients with poor exercise capacity, pharmacologic stress testing could be considered. Owing to the high prevalence of calcific CAD in the elderly, coronary calcium score and coronary computed tomography angiography are not usually recommended. Invasive angiography is typically reserved for elderly patients with markedly abnormal noninvasive stress tests or medically refractory symptoms.
MANAGEMENT OF THE OLDER PATIENT WITH CORONARY ARTERY DISEASE
Medical Management
Antianginal medications work in a similar manner and are as effective in the elderly as in the non-elderly patients, although one should be cognizant of their side effects such as hypotension and bradycardia, which may be more pronounced in the elderly. The goals of medical therapy in stable CAD include improvement of symptoms, decreased risk of future cardiovascular events, and reduction in mortality.
Aspirin (low dose, 81 mg) in combination with beta-blocker (sotalol) was shown to reduce the risk of death and MI in patients with stable angina compared to sotalol alone.13 A meta-analysis of over 140 trials confirms the benefit of aspirin therapy in both primary and secondary prevention of cardiovascular events.14
Beta-blockers decrease heart rate, thereby lowering the myocardial oxygen demand in patients with angina, and they are currently indicated as first-line therapy for these patients because of their negative inotropic and chronotropic properties. However, beta-blockers need to be carefully administered in the elderly because of their potential to cause bradyarrhythmias and heart block.
Angiotensin-converting enzyme inhibitors (ACEIs) are indicated in patients with stable CAD to reduce major adverse cardiovascular events. This was studied in three major trials: (1) Heart Outcomes Prevention Evaluation (HOPE)15; (2) EUropean trial on Reduction Of cardiac events with Perindopril in patients with stable coronary Artery disease (EUROPA)16; and (3) Prevention of Events with Angiotensin-Converting Enzyme inhibition trial (PEACE).17 A meta-analysis of these trials concluded that ACEI use in patients with stable CAD is associated with significant reduction in all-cause mortality, cardiovascular mortality, nonfatal MI, and stroke.
Nitrates and calcium channel blockers are also indicated for treatment of angina in patients with stable CAD, but
these drugs do not reduce cardiovascular events. Ranolazine is another antianginal medication that has been shown in a subgroup analysis to provide anginal relief in elderly patients without causing hemodynamic compromise.
these drugs do not reduce cardiovascular events. Ranolazine is another antianginal medication that has been shown in a subgroup analysis to provide anginal relief in elderly patients without causing hemodynamic compromise.
PCI is a well-established treatment strategy for angina relief in patients with stable CAD; however, PCI is associated with a greater risk of complications in the elderly than in younger patients, including acute kidney injury, bleeding, stroke, death, and periprocedural MI. In recent years, the role of PCI in patients with stable CAD has been debated since the publication of Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation (COURAGE) trial that showed no significant difference in outcomes among patients with stable CAD treated with optimal medical therapy (OMT) versus those treated with PCI and OMT.18 Analysis of the elderly (older than 65 years) subgroup in this study showed no difference in major cardiac events or angina-free rates between the OMT and PCI plus OMT-treated patients.19 The randomized Trial of Invasive versus Medical therapy in Elderly patients (TIME) study reported an early benefit for PCI with OMT compared to OMT alone in elderly patients with stable CAD; however, after 1 year of follow-up, there was no difference in the symptoms, quality of life, and death or nonfatal MI with PCI between the groups.20 Hence, PCI should be reserved for patients who have refractory symptoms despite maximal tolerated medical therapy in patients with stable CAD.
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