Heart Disease in the Elderly 39

705

From: Essential Cardiology: Principles and Practice, 2nd Ed.

Edited by: C. Rosendorff © Humana Press Inc., Totowa, NJ

39 Heart Disease in the Elderly

Michael W. Rich, ^MD

INTRODUCTION

The 20th century has seen a dramatic shift in the demographics of the US population, as average life expectancy at birth has increased from approx 49 yr in 1900 to almost 80 yr today. As a result, both the absolute number and the relative proportion of older individuals in the population has increased exponentially, and these trends are expected to continue well into the current century.

Of particular note is that the “oldest old,” defined as individuals aged 85 yr or older, is the most rapidly growing segment of the US population.

Cardiovascular disease is the leading cause of death and major disability in the US, and a dis- proportionate number of individuals with cardiovascular disease are over 65 yr of age. Indeed, it is estimated that 70% of individuals over age 70 have clinically manifest cardiovascular disease (including hypertension). In addition, 84% of all deaths attributable to cardiovascular disease occur in patients over age 65, and 64% are in patients over the age of 75. The elderly also account for 65% of all cardiovascular hospitalizations, as well as an increasing proportion of all cardiovascu- lar procedures (Table 1).

For these reasons, it is important for the practitioner to have an understanding of the effects of aging on the cardiovascular system, a working knowledge of cardiovascular therapeutics in the elderly, and an appreciation of the limitations of currently available data relevant to the treatment of older cardiac patients.

EFFECTS OF AGING ON THE CARDIOVASCULAR SYSTEM

Aging is associated with diffuse changes in cardiovascular structure and function (Table 2) (1).

From the clinical perspective, the principal effects of aging are as follows:

• Increased vascular stiffness, resulting in increased impedance to left ventricular ejection

• Impaired ventricular filling, due to altered relaxation and decreased ventricular compliance

• Diminished responsiveness to -adrenergic stimulation

• Reduced capacity to augment adenosine triphosphate (ATP) production in response to increased demands

• Impaired endothelial function

• Progressive decline in sinus node function

These changes affect disease expression, clinical manifestations, and response to therapy in older patients. Thus, increased vascular stiffness contributes to the progressive rise in systolic blood pres- sure with advancing age. In turn, systolic hypertension is a key risk factor for coronary heart dis- ease, heart failure, and stroke in the elderly.

Impaired diastolic filling, a hallmark of cardiovascular aging, is caused by increased interstitial

collagen deposition, compensatory myocyte hypertrophy, and altered calcium flux leading to im-

paired relaxation during early diastole. These changes result in decreased filling during early and

Table 1

Major Cardiovascular Procedures by Age: 2000

<45 Age, yr 45–64 65

No.^a % No.^a % No.^a %

Cardiac catheterization 122 (9.3) 550 (41.7) 646 (49.0)

Percutaneous coronary revascularization 62 (6.1) 437 (42.7) 524 (51.2)

Coronary bypass surgery 17 (3.3) 216 (41.6) 286 (55.1)

Permanent pacemaker — (NA) 20 (13.4) 129 (86.6)

Implanted cardioverter-defibrillator — (NA) 10 (31.2) 22 (68.8)

Carotid endarterectomy — (NA) 32 (26.0) 91 (74.0)

aIn thousands. (Adapted from ref. 111.)

Table 2

Effects of Aging on the Cardiovascular System Gross anatomy

Increased left ventricular wall thickness Decreased left ventricular cavity size Endocardial thickening and sclerosis Increased left atrial size

Valvular fibrosis and sclerosis Increased epicardial fat Histology

Increased lipid and amyloid deposition Increased collagen degeneration and fibrosis

Calcification of fibrous skeleton, valve rings, and coronary arteries Shrinkage of myocardial fibers with focal hypertrophy

Decreased mitochondria, altered mitochondrial membranes Decreased nucleus:myofibril size ratio

Biochemical changes Decreased protein elasticity

Numerous changes in enzyme content and activity affecting most metabolic pathways, but no change in myosin ATPase activity

Decreased catechol synthesis, esp. norepinephrine Decreased acetylcholine synthesis

Conduction system

Degeneration of sinus node pacemaker and transition cells

Decreased number of conducting cells in the AV-node and HIS–Purkinje system Increased connective tissue, fat, and amyloid

Increased calcification around conduction system Vasculature

Decreased distensibility of large and medium-sized arteries Aorta and muscular arteries become dilated, elongated, and tortuous Increased wall thickness

Increased connective tissue and calcification Autonomic nervous system

Decreased responsiveness to -adrenergic stimulation

Increased circulating catecholamines, decreased tissue catecholamines Decreased -adrenergic receptors in left ventricle

Decreased cholinergic responsiveness

Diminished response to Valsalva and baroreceptor stimulation Decreased heart rate variability

mid-diastole, and are accompanied by increased reliance on atrial contraction to optimize left ven- tricular end-diastolic volume. Clinical implications of these alterations include a progressive rise in the prevalence of atrial fibrillation and in the syndrome of heart failure with normal left ventric- ular systolic function, and a diminished capacity to augment stroke volume via the Frank-Starling mechanism (2).

The effects of reduced responsiveness to -adrenergic stimulation include a linear decline of approx 10 beats per decade in the maximum attainable heart rate, reduced ability to augment con- tractility, and impaired 

-mediated vasodilation. Taken together, these effects greatly reduce the capacity of the older heart to increase cardiac output in response to increased demands, and this capacity is further diminished by the inability of cardiac mitochondria to maximally upregulate ATP production in response to increased energy requirements.

Impaired endothelial function contributes to the development of atherosclerosis and limits coro- nary artery vasodilation, thereby reducing maximum coronary blood flow. These changes predis- pose older adults to the development of coronary heart disease and also lower the coronary ischemic threshold.

Finally, degenerative changes in the sinus node and atrial conducting tissues result in a ris- ing prevalence of “sick sinus syndrome” with advancing age, and predispose older individuals to the development of supraventricular tachyarrhythmias, especially atrial fibrillation. As shown in Table 1, more than 80% of permanent pacemakers are implanted in individuals over 65 yr of age, and sinus node dysfunction is by far the most common indication for pacemaker insertion.

In addition to age-related changes in the cardiovascular system, there are also important changes in renal, pulmonary, neurohumoral, and hemostatic function that have important implications for older patients with cardiovascular disease (Table 3). Older patients are also subject to numerous medical, behavioral, psychosocial, and financial influences that may have an impact on symptoma- tology, adherence to prescribed therapy, and overall prognosis. Finally, aging is associated with significant changes in the absorption, distribution, metabolism, and elimination of virtually all medications.

CARDIOVASCULAR RISK FACTORS

In general, the major risk factors for cardiovascular disease are similar in older and younger patients, but the relative importance of some risk factors (e.g., smoking, total cholesterol) declines with age. However, since the prevalence of cardiovascular disease increases with age, the clinical significance of these risk factors is maintained or even increases with age.

Table 3

Effects of Aging on Other Organ Systems Kidneys

Gradual decline in glomerular filtration rate, ~8 cc/min/decade Impaired fluid and electrolyte homeostasis

Lungs

Reduced ventilatory capacity

Increased ventilation/perfusion mismatching Neurohumoral system

Reduced cerebral perfusion autoregulatory capacity Diminished reflex responsiveness

Impaired thirst mechanism Hemostatic system

Increased levels of coagulation factors Increased platelet activity and aggregability

Increased inflammatory cytokines and C-reactive protein Increased inhibitors of fibrinolysis and angiogenesis

Relative vs Attributable Risk

Relative risk refers to the likelihood that an individual with a given risk factor will develop a specific disease, as compared to an individual without that risk factor. Attributable risk refers to the actual number of cases of a disease that can be attributed to the presence of a specific risk factor.

As such, the attributable risk reflects both relative risk and disease prevalence, and it provides a more accurate estimate of the potential impact of risk factor modification (i.e., the number of cases prevented by the eradication of a given risk factor). Stated another way, since older individuals are at higher risk for developing cardiovascular disease, the potential benefit of treating a specific risk factor is often greater in older than in younger patients, even though the relative risk may be lower in the elderly.

Hypertension

As shown in Fig. 1, systolic blood pressure increases with age in both men and women, whereas diastolic blood pressure tends to peak and plateau in middle age, then declines slightly at older age.

Although systolic and diastolic blood pressure are each independent risk factors for cardiovascu- lar disease in the elderly, systolic hypertension is more common, and it is also a more powerful risk factor.

To date there have been at least 10 prospective, randomized, placebo-controlled clinical trials evaluating the effects of antihypertensive therapy in the elderly (Table 4) (3–13). Six of these studies focused on diastolic hypertension (3–9), three enrolled patients with isolated systolic hyperten- sion (10–12), and one included subjects with either systolic or diastolic hypertension (13). These studies provide compelling evidence that treatment of systolic and diastolic hypertension substan- tially reduces the incidence of stroke, coronary heart disease, and cardiac failure in older adults.

Moreover, the benefits of treating diastolic hypertension persist at least up to the age of 80, while the benefits of treating systolic hypertension are apparent at least up to the age of 90.

Fig. 1. Average systolic and diastolic blood pressure in the US population as a function of age, sex, and race:

NHANES III. (From ref. 112, reproduced with permission. Copyright 1995 Lippincott Williams & Wilkins.)

Treatment of hypertension is similar in older and younger patients (14). However, older patients are more susceptible to adverse drug reactions, so therapy should generally be initiated with lower drug dosages, and close follow-up is essential to assess efficacy and tolerability.

Hyperlipidemia

In men, total cholesterol levels tend to peak in late middle age, then decline modestly at older age (15). In the absence of estrogen replacement, cholesterol levels rise rapidly after menopause in women, surpassing those in men after the age of 60. In the Framingham Heart Study, the impor- tance of total cholesterol as a risk factor for coronary heart disease declined with age, but the ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C) remained a strong independent risk factor in both men and women at older age (16). Similar findings from other studies confirm the importance of hyperlipidemia as a cardiovascular risk factor in the elderly.

In the Heart Protection Study, 40 mg simvastatin daily was associated with significant reduc- tions in death, myocardial infarction, and stroke in patients 40 to 80 yr of age with vascular disease or diabetes, and the benefits were similar in older and younger patients (17). More recently, the PROSPER study (PROspective Study of Pravastatin in the Elderly at Risk) showed that 40 mg/d pravastatin reduced the risk of myocardial infarction, stroke, or coronary heart disease death by 15% in patients 70 to 82 yr of age with established vascular disease, diabetes, hypertension, or current smoking (18). Age-specific subgroup analyses from several earlier trials also provide strong evidence that treatment with an HMG-CoA reductase inhibitor (“statin”) reduces mortality and nonfatal coronary events in patients up to the age of 75 (Table 5) (19–22). Based on these trials, an HMG-CoA reductase inhibitor, in conjunction with an appropriate low-fat diet, is recommended for older individuals with manifest coronary heart disease, peripheral arterial disease, or prevalent risk factors in the absence of other major life-limiting illnesses.

Diabetes

The prevalence of diabetes increases with age, approaching 20% in persons over age 65. Dia- betes is somewhat more common in older men than in older women, and it is significantly more com- mon in African-Americans and Hispanics than in Caucasians. Diabetes remains a potent independent

Table 4

Trials of Antihypertensive Treatment in the Elderly

Risk reduction (%)

Trial (ref.) n Age CVA CAD CHF All CVD

Australian (3) 582 60–69 33% 18% NR 31%

EWPHE (4) 840 >60 36% 20% 22% 29%

Coope (5) 884 60–79 42% 3% 32% 24%

STOP-HTN (6) 1627 70–84 47% 13% 51% 40%

MRC (7) 4396 65–74 25% 19% NR 17%

HDFP (8,9) 2374 60–69 44% 15% NR 16%

SHEP (10) 4736 60 33% 27% 55% 32%

Syst-Eur (11) 4695 60 42% 26% 36% 31%

STONE (13) 1632 60–79 57% 6% 68% 60%

Syst-China (12) 2394 60 38% 33% 38% 37%

CAD, coronary artery disease; CHF, congestive heart failure; CVA, cerebrovascular accident;

CVD, cardiovascular disease; EWPHE, European Working Party on High Blood Pressure in the Elderly; HDFP, Hypertension Detection and Follow-up Program; MRC, Medical Research Council;

NR, not reported; SHEP, Systolic Hypertension in the Elderly Program; STONE, Shanghai Trial of Nifedipine in the Elderly; STOP-HTN, Swedish Trial in Old Patients with Hypertension; Syst- China, Systolic Hypertension in China; Syst-Eur, Systolic Hypertension in Europe.

risk factor for coronary heart disease and other cardiovascular diseases at older age. In the Fram- ingham Heart Study, the relative risk for coronary heart disease in diabetic men over age 65 was 1.4, while in women diabetes conferred a relative risk of 2.1. In both men and women, the excess risk for coronary heart disease in diabetics is greater in persons over 65 yr of age than in younger individuals.

Management of diabetes is similar in younger and older patients. In addition to maintaining effective glucose control, hypertension should be treated to a target blood pressure of <130/80 mmHg (14), the LDL-cholesterol fraction should be reduced to <100 mg/dL (23), weight should be maintained in a desirable range (body mass index <25 kg/m

), regular exercise should be encour- aged, and tobacco use should be strongly discouraged. As noted above, the Heart Protection Study provides strong evidence that statin therapy reduces mortality and nonfatal vascular events in older diabetics (17,24). In addition, data from the Heart Outcomes Prevention Evaluation (HOPE) indicate that an angiotensin-converting enzyme inhibitor is effective in reducing cardiovascular morbidity and mortality in diabetic patients over age 55 (25,26).

Smoking

Smoking prevalence declines with age due to smoking-related mortality and successful smok- ing cessation. Nonetheless, continued smoking remains an important risk factor for myocardial infarction and stroke in older individuals. Moreover, there is strong evidence that smoking cessa- tion is beneficial at all ages. In the Coronary Artery Surgery Study (CASS) Registry, for example, coronary patients over 70 yr of age who continued to smoke had a 3.3-fold higher risk of death and a 2.9-fold higher risk of death or myocardial infarction during a 6-yr follow-up period com- pared with those who stopped smoking (27).

The efficacy of smoking cessation programs, nicotine replacement therapy, and other medica- tions (e.g., bupropion) in elderly smokers is unknown, but older smokers tend to be more receptive to counseling interventions than younger individuals. In addition, the motivation to quit smoking often peaks following an index cardiovascular event, and the importance of smoking cessation should be strongly emphasized in individuals of all ages who suffer such an event.

Table 5

Impact of HMG-CoA Reductase Inhibitors on Coronary Events

Risk reduction (%) n Coronary events Death 4S (19)

<65 yr 3423 34% 28%

65–70 yr 1021 34% 34%

CARE (20)

<65 yr 2876 19% 11%

65–75 yr 1283 32% 45%

LIPID (21)

<65 yr 5500 23% NR

65–75 yr 3514 21% NR

AFCAPS/TexCAPS (22)

median age^a 3425 46% NR

>median age 3180 30% NR

a57 Years in men, 62 yr in women.

4S, Scandinavian Simvastatin Survival Study; CARE, Cholesterol and Recurrent Events; LIPID, Long-Term Intervention with Pravastatin in Ische- mic Disease; AFCAPS/TexCAPS, Air Force/Texas Coronary Atheroscler- osis Prevention Study; NR, not reported.

Other Risk Factors

Left ventricular hypertrophy, physical inactivity, obesity, and elevated levels of C-reactive pro- tein, fibrinogen, and homocysteine are all associated with increased risk for cardiovascular dis- ease in older men and women. In addition, data from the Cardiovascular Health Study indicate that increased carotid artery intima-medial thickness and an ankle-arm blood pressure index less than 0.9 are predictive of an increased risk for incident cardiovascular events in older adults (28). The impact of treating these risk factors in elderly patients is presently unknown.

CORONARY ARTERY DISEASE Acute Myocardial Infarction

The incidence of acute myocardial infarction (MI) increases with age in both men and women.

In 1999, 61.4% of patients hospitalized with acute MI in the US were over 65 yr of age, and 36.8%

were over the age of 75. Case fatality rates increase with age, and 84% of deaths due to acute MI occur in patients over age 65, while 60% occur in patients over age 75. In addition, women comprise nearly half of all patients with acute MI over age 65, and MI is the leading cause of death in both men and women in this age group.

C

M

After age 75, patients with acute MI are less likely to present with typical ischemic chest dis- comfort, and shortness of breath is the most common initial symptom in patients over the age of 80 (29). Diaphoresis occurs less frequently at older age, whereas nonspecific neurological symp- toms, such as lightheadedness, confusion, or syncope, are more common in the elderly, and may be the presenting manifestation in up to 20% of MI patients over the age of 85.

Older MI patients often present with nondiagnostic electrocardiograms (ECGs), due to the presence of preexisting ECG abnormalities (e.g., paced rhythm, left bundle branch block, or left ventricular hypertrophy) and a high prevalence of non-ST elevation MI (NSTEMI). The combi- nation of atypical symptomatology and a nondiagnostic ECG may obfuscate the diagnosis unless a high index of suspicion is maintained. Lack of diagnostic certainty is also an important factor contributing to reduced utilization of reperfusion therapy and other interventions in older patients.

In addition to increased mortality, older patients with acute MI are more likely to develop heart failure, hypotension, atrial fibrillation, conduction abnormalities, myocardial rupture, and cardio- genic shock. Although ventricular arrhythmias are also more common in the elderly, older patients are less likely to develop primary ventricular fibrillation.

R

T

A series of prospective randomized placebo-controlled trials completed in the 1980s estab- lished the efficacy of fibrinolytic therapy for reducing mortality in patients up to 75 yr of age with acute MI, but the value of fibrinolysis in patients over age 75 has been somewhat controversial (30,31). However, a recent reanalysis of data from the large Fibrinolytic Therapy Trialists’ over- view confirmed that fibrinolytic treatment is associated with lower mortality in patients over age 75 with ST elevation or left bundle branch block MI who present within 12 h of symptom onset (Table 6) (32). Note that the absolute mortality benefit, as defined by the number of lives saved per 1000 patients treated, was twofold greater in patients over age 75 than in patients under age 55, and similar to that seen in patients 55 to 74 yr of age (32).

Intracranial hemorrhage occurs in 0.3 to 0.5% of patients receiving fibrinolytic therapy for acute MI, but the risk increases with advancing age. Other major bleeding complications occur slightly more frequently in patients receiving fibrinolysis, but the risk is not age-dependent (33).

The choice of fibrinolytic agent in patients over the age of 75 remains controversial. In the

Global Utilization of Streptokinase and rt-PA for Occluded Arteries (GUSTO-I) trial, recombi-

nant tissue plasminogen activator (rt-PA) was associated with a somewhat lower mortality rate

than streptokinase in patients over age 75 (19.3% vs 20.6%), but the difference was not statistically

significant (34). In addition, rt-PA was associated with more intracranial hemorrhages in this age group (2.1% vs 1.2% with streptokinase, p < .05).

Percutaneous transluminal coronary angioplasty (PTCA) is an effective alternative to thromboly- tic therapy in patients with acute MI, and it is associated with improved patency rates and fewer intra- cranial hemorrhages than thrombolysis. Among 300 patients over age 70 enrolled in the GUSTO- IIb trial, which compared PTCA with rt-PA in patients with acute MI, the composite endpoint of death, reinfarction, or disabling stroke tended to occur less frequently in patients randomized to PTCA (35). More recently, de Boer and colleagues found that PTCA was associated with improved outcomes relative to streptokinase in a small randomized trial involving 87 patients 75 yr of age or older with acute MI (36). These findings suggest that primary PTCA may be the preferred reper- fusion strategy in appropriately selected elderly patients. However, to date very few patients over the age of 80 have been studied, and the value of PTCA in this age group remains undefined.

A

Among 3411 patients over 70 yr of age enrolled in the ISIS-2 trial, the administration of 162.5 mg aspirin daily to patients with acute myocardial infarction was associated with a 21% mortality reduction at 35 d (37). Moreover, the absolute benefit of aspirin increased with advancing age, from 1.0% in patients under age 60 to 4.7% in those age 70 or older. Long-term aspirin use following MI also reduces the incidence of death, reinfarction, or stroke by approx 25% in patients of all ages.

C

The addition of clopidogrel to aspirin reduces the risk of cardiovascular death, MI, or stroke by about 20% compared to aspirin alone during the 12-mo period following hospitalization for unstable angina or NSTEMI, with similar absolute benefits in patients younger or older than age 65 (38). The value of clopidogrel in patients over age 75 and in those with STEMI is unknown, and the cost-effectiveness of routine clopidogrel therapy is uncertain (39).

H

Although older patients with acute MI often receive intravenous heparin, the value of this treat- ment is unproven. In a study involving 6935 Medicare patients hospitalized with acute MI, hepa- rin use was associated with more bleeding complications and an increased length of hospital stay, but there was no evidence of a beneficial effect on mortality or reinfarction (40).

Low-molecular-weight heparins (LMWHs) such as enoxaparin and dalteparin offer several advantages over conventional unfractionated heparin (UFH), and recent studies indicate that these agents are associated with improved clinical outcomes in patients with unstable coronary syndromes, including the elderly (41–43). Based on these findings, subcutaneous LMWH is now preferred over intravenous UFH in the management of patients with acute MI or unstable angina.

G

II

/III

I

Glycoprotein IIb/IIIa inhibitors improve clinical outcomes in selected patients up to the age of 75 (44–48), but the value of these agents in older patients is less clear. For example, in a trial involv-

Table 6

Effect of Fibrinolytic Treatment on 35-d Mortality in Patients With ST-Elevation or Left Bundle Branch Block Myocardial Infarction Presenting Within 12 h of Symptom Onset: Reanalysis of Data From the Fibrinolytic Therapy Trialists’ Overview

Mortality, Mortality, Relative risk Lives saved/

Age (yr) n control fibrinolysis reduction 1000 patients

<55 10,047 5.4% 3.8% 29.6% 16

55–64 12,252 10.7% 8.1% 24.3% 26

65–74 10,053 19.0% 15.0% 21.1% 40

75 3322 29.4% 26.0% 11.6% 34

ing more than 10,000 patients, eptifibatide reduced the risk of death or nonfatal MI in patients up to the age of 80, but there was an increase in event rates among patients over 80 yr of age receiving eptifibatide (48). In another study involving 1915 patients, tirofiban was associated with improved outcomes in patients younger or older than age 65, but outcomes for patients over age 75 were not reported (47). Based on currently available evidence, the addition of a glycoprotein IIb/IIIa inhibi- tor to aspirin and heparin is recommended for patients with acute MI who are likely to undergo percutaneous coronary intervention. Treatment with either eptifibatide or tirofiban is also recom- mended for high-risk patients, including those over age 75, who are not expected to undergo early cardiac catheterization. It should be noted, however, that the risk of bleeding complications in- creases with age, and this may attenuate the benefit of glycoprotein IIb/IIIa inhibitors in the very elderly.

W

Long-term warfarin following acute MI reduces the risk of death, reinfarction, and stroke in elderly patients (49), and two recent studies found that the combination of aspirin and full-dose warfarin was superior to aspirin alone in reducing recurrent events after MI (50,51). However, combination therapy was associated with an increased risk of bleeding, and very few patients over age 75 were included in these trials. For these reasons, warfarin use in the very elderly is generally restricted to patients who are intolerant of aspirin, and to those who have clear indications for long- term anticoagulation (e.g., chronic atrial fibrillation).









-B

Table 7 summarizes data from three large randomized trials evaluating the use of intravenous

-blockers in patients with acute MI (52). Intravenous -blockade reduced mortality by 23% in older patients, but there was no significant effect in younger patients. In these trials, -blockers also reduced the incidence of both supraventricular and ventricular arrhythmias, as well as recur- rent ischemic events. Although these studies were conducted prior to the advent of reperfusion ther- apy, the results of these trials remain applicable today, since the majority of older patients with acute MI do not receive thrombolytic therapy or undergo primary PTCA.

Long-term -blocker therapy is also associated with greater benefits in older than in younger patients (6.0 vs 2.1 lives saved per 100 treated patients) (52). In addition, since event rates are higher in the elderly, -blockade is more cost-effective in older than in younger individuals.

N

Nitrates can be administered safely to most elderly patients with acute MI, and data from the GISSI-3 trial indicate that early treatment with transdermal nitroglycerin is associated with favor- able trends in mortality and in the combined endpoint of death, heart failure, or severe left ventric- ular dysfunction in patients over 70 yr of age (53). The value of long-term nitroglycerin therapy following MI is unknown.

Table 7

Mortality in 3 Large Trials of Intravenous -Blockers:

Pooled Results by Age (Total N = 23,200)

Younger Older

(n = 14,687) (n = 8513) Mortality

Control group 2.6% 8.9%

-blocker group 2.5% 6.9%

Mortality reduction 5.0% 23.2%

Lives saved/100 patients 0.1 2.1

p-value NS 0.0005

NS, not significant.

A

-C

E

(ACE) I

In the GISSI-3 trial, treatment with lisinopril within 24 h of symptom onset reduced the com- bined endpoint of death, heart failure, or severe left ventricular dysfunction by 17% in patients over 70 yr of age (53). Similarly, in patients with anterior MI not receiving a thrombolytic agent, early treatment with zofenopril reduced the incidence of death or severe heart failure by 34%, and the absolute benefit was threefold greater in patients over 65 yr of age than in younger patients (54).

In patients with acute MI complicated by heart failure or left ventricular dysfunction (ejection fraction 40%), long-term ACE inhibitor therapy reduces mortality, hospitalizations, and heart failure progression, and the benefits of treatment are at least as great in older as in younger patients (55,56). Indeed, in the Acute Infarction Ramipril Efficacy (AIRE) trial, the mortality benefit of ramipril was limited to older patients (56). Since older patients are at greater risk for drug-induced hypotension and renal dysfunction, the use of these agents must be carefully monitored.

A

-R

B

In the recently completed OPTIMAAL study (Optimal Trial in Myocardial Infarction with Angio- tensin II Antagonist Losartan), which included 5477 patients 50 yr of age or older with acute MI complicated by heart failure or left ventricular dysfunction, mortality was higher (without reaching statistical significance) with the angiotensin-receptor blocker losartan than with the ACE inhibi- tor captopril, and these findings were consistent across age groups (57). Therefore, ACE inhibitors remain the preferred agents in post-MI patients. However, losartan was better tolerated than cap- topril, and angiotensin-receptor blockers are an acceptable alternative in patients who are unable to take an ACE inhibitor.

A

A

Eplerenone is a selective aldosterone antagonist that has been shown to reduce mortality and cardiovascular hospitalizations following acute MI in patients with left ventricular dysfunction and heart failure (58). Although the efficacy of eplerenone was similar in younger and older patients, the role of this agent and other aldosterone antagonists in the routine management of older post- MI patients remains to be established.

A

A

Antiarrhythmic agents have not been shown to reduce mortality or improve clinical outcomes in elderly MI patients, and the routine use of these agents is not recommended.

Non-ST Elevation MI

Non-ST elevation MI (NSTEMI) increases in frequency with advancing age, and accounts for more than 50% of all MIs in patients over the age of 70. Although the short-term prognosis fol- lowing NSTEMI is more favorable than that following ST elevation MI, NSTEMI patients are at increased risk for reinfarction and death during follow-up.

In general, the treatment of NSTEMI is similar in younger and older patients (see Chapter 26), and recent studies indicate that early coronary angiography followed by percutaneous or surgical revascularization is associated with improved outcomes relative to conservative management in high-risk patients, including the elderly (59–61).

Chronic Coronary Artery Disease

Coronary artery disease (CAD) is highly prevalent in the elderly, and older patients account

for more than half of hospital admissions for angina pectoris. Older CAD patients usually have

more diffuse disease than younger patients, and they are more likely to have multivessel and left

main coronary disease. Because older patients tend to be more sedentary than their younger coun-

terparts, they are more likely to be asymptomatic or minimally symptomatic despite having more

severe CAD. Older patients also have a higher prevalence of silent ischemia and infarction than

younger patients.

The treatment of chronic CAD is similar in older and younger patients (see Chapter 25) and will not be reviewed here. However, a brief discussion of revascularization procedures is in order.

P

T

C

A

As shown in Table 1, more than 50% of PTCAs in the US are performed in patients over 65 yr of age. Compared with younger patients, older patients referred for PTCA are more likely to be female and have more severe symptoms, more comorbidity, and more complex “target” lesions (62). These factors, in conjunction with age-related reductions in cardiovascular reserve, result in increased procedure-related morbidity and mortality in older patients, particularly those over the age of 80, and hospital mortality following elective PTCA in octogenarians ranges from 1 to 7% (62). In addition, although late survival following successful PTCA in older patients is good, there is a higher incidence of recurrent angina than in younger patients, primarily due to incom- plete revascularization.

C

B

S

Over 50% of all coronary artery bypass graft (CABG) operations in the US are performed in patients over age 65. As with PTCA, older patients referred for CABG are more likely to be female, have more advanced coronary disease, are more symptomatic, and have more comorbidity than younger patients. Perioperative mortality rates range from 5 to 10% in patients over age 75 under- going isolated CABG, as compared to 1 to 2% in patients under age 65 (63). Older patients also have a higher incidence of perioperative complications, including atrial fibrillation, heart failure, stroke, bleeding, cognitive dysfunction, respiratory disorders, and renal insufficiency. As a result, postoperative length of stay is substantially longer in older patients. Despite these difficulties, the long-term results following CABG in older patients are excellent, with up to 90% of patients experi- encing sustained symptomatic improvement, and the majority reporting improved functional capac- ity and quality of life. In addition, a recent randomized trial comparing CABG to medical therapy in elderly patients with symptomatic angina found that CABG had a more favorable effect on symp- toms and quality of life than medical therapy (64).

VALVULAR HEART DISEASE Aortic Valve

Aortic stenosis severe enough to warrant surgical consideration occurs in 2 to 3% of individuals over the age of 75, and aortic valve replacement is the second most common major cardiac opera- tion in this age group (after CABG) (65,66). Age-related degenerative changes occurring on a normal trileaflet aortic valve account for the majority of cases. Other causes include a congenitally bicuspid valve and rheumatic disease.

Aortic stenosis in the elderly is often occult because sedentary older individuals may experi- ence few symptoms, or they may attribute their symptoms to “old age.” Similarly, the physician may ascribe the symptoms of aortic stenosis to other causes. In addition, the murmur of aortic ste- nosis in older patients may be less prominent due to changes in chest wall geometry (increased anteroposterior diameter) and reduced stroke volume. An S

gallop is a nonspecific finding in older individuals, but the absence of an S

during sinus rhythm makes the diagnosis of severe aortic stenosis unlikely. The A

component of the second heart sound is frequently diminished in older patients with severe aortic stenosis, but this may be difficult to appreciate on routine examination.

As a result of decreased vascular compliance, the carotid upstrokes may be well-preserved in older

patients with severe aortic stenosis. In addition, although the electrocardiogram usually shows left

ventricular hypertrophy with ST-segment and T-wave changes, these findings may be attributed

to long-standing hypertension or other causes. For these reasons, echocardiography should be

performed in all elderly patients with unexplained symptoms that could potentially be due to aortic

stenosis. Cardiac catheterization should also be performed in patients with severe aortic stenosis

who are suitable candidates for valve replacement.

Aortic valve replacement is the treatment of choice for severe aortic stenosis in adults of all ages.

However, some elderly patients, such as those with dementia, advanced frailty, or major comor- bidity, may not be suitable candidates for the procedure. The results of aortic valve replacement in the elderly are excellent, even in octogenarians, with several series reporting perioperative mor- tality rates of 4 to 7% for isolated valve replacement (66). Mortality rates are somewhat higher when valve replacement is combined with CABG. The majority of patients experience marked improve- ment in symptoms and functional capacity following the procedure (67,68), and long-term survi- val is comparable to the general population at similar age.

The prevalence of aortic regurgitation increases with age, but most cases are of insufficient sever- ity to require surgery. Causes of acute aortic regurgitation in the elderly include type A aortic dis- section, infective endocarditis, prosthetic valve dysfunction, and sinus of Valsalva rupture. Causes of chronic aortic regurgitation include rheumatic or calcific aortic valve disease, healed endo- carditis, and aneurysms of the aortic root due to atherosclerosis, syphilis, or other disorders. Treat- ment of aortic regurgitation is similar in older and younger adults.

Mitral Valve

Mitral stenosis in the elderly is usually rheumatic in origin, but severe mitral valve annulus calcification can occasionally cause mitral stenosis in patients with small left ventricular cavities (65). As in younger patients, the symptoms of mitral stenosis are often insidious, and it is not unusual for the diagnosis to be clinically unsuspected until echocardiography is performed. In most elderly patients with mitral stenosis, the valve apparatus is heavily calcified or there is significant mitral regurgitation, thus precluding percutaneous valvuloplasty or open commissurotomy. However, in elderly patients who are suitable candidates for valvuloplasty, the procedure can be performed safely, and it produces significant hemodynamic and clinical improvement in the majority of cases. In other patients with severe symptoms, mitral valve replacement offers the only viable ther- apeutic option (66). As with aortic valve replacement, mitral valve surgery in elderly patients is associated with increased morbidity and mortality. The perioperative mortality rate for elective mitral valve surgery in elderly patients is 10 to 20%, although some centers are now reporting mor- tality rates of less than 10%.

Mitral regurgitation is the most common valvular lesion in elderly patients, but in most cases it is not severe enough to require surgical intervention. Common causes of mitral regurgitation in the elderly include ischemic mitral valve dysfunction, ischemic or nonischemic dilated cardiomy- opathy, mitral valve prolapse, rheumatic heart disease, and mitral valve annulus calcification (65).

Less commonly, mitral regurgitation may be due to infective or noninfective endocarditis, pros- thetic valve dysfunction, or hypertrophic cardiomyopathy. In patients with mild to moderate mitral regurgitation, medical management with afterload reduction (e.g., ACE inhibitors, hydralazine) is appropriate. In patients with severe symptomatic mitral regurgitation and satisfactory left ventric- ular function, surgical treatment should be considered. As in younger patients, mitral valve repair, when feasible, is associated with more favorable outcomes. Long-term results following success- ful mitral valve repair or replacement in elderly patients are generally favorable, with significant symptomatic improvement occurring in the majority of cases.

Infective Endocarditis

The incidence of infective endocarditis increases progressively with age, reflecting age-related changes in valve structure, the increasing prevalence of specific valvular pathologies in the elderly, and the increased prevalence of potential sources of bacteremia (e.g., poor dentition, respiratory and urinary tract infections, and procedures such as cystoscopy) (69). The diagnosis of endocardi- tis in the elderly is often difficult, as the clinical manifestations are usually nonspecific and pro- tean. The classical peripheral manifestations of endocarditis, such as Roth spots, Osler nodes, and Janeway lesions, are also uncommon in elderly patients.

In general, the causative organisms of endocarditis are similar in older and younger patients, with

streptococci, staphylococci, and enterococci being the most common agents, followed by Gram-

negative bacilli and other less common pathogens. In addition, up to 10% of cases may be culture- negative, usually due to the initiation of antibiotic therapy prior to obtaining an adequate number of blood cultures. As in younger patients, vegetations are visualized with transthoracic echocar- diography in less than 50% of cases, but the yield is substantially higher with the transesophageal approach. The treatment and complications of endocarditis are similar in older and younger patients, although mortality is higher in the elderly.

HEART FAILURE

The effects of aging on the cardiovascular system serve to markedly reduce cardiovascular reserve and predispose the older patient to the development of heart failure (HF). The prevalence of cardiovascular disease, particularly hypertension and CAD, also increases with age, and these factors combine to produce an exponential rise in HF with increasing age (70). Indeed, HF is rela- tively uncommon in younger adults, but the prevalence doubles with each decade after age 45, and HF affects 1 in 10 individuals over the age of 80. As a result, HF is the most common indication for hospitalization in persons over age 65, and it is the most costly diagnosis-related group (DRG) by a factor of almost 2. HF is also a major cause of chronic disability in the elderly, and mortality rates from HF increase progressively with age (Fig. 2).

Hypertension is the most common antecedent illness in elderly patients with HF, and 70 to 80%

of cases can be attributed to either hypertension or CAD. Valvular disease is the third most com- mon cause of HF in the elderly, followed by nonischemic cardiomyopathy. Importantly, the prev- alence of HF with preserved systolic function (so-called “diastolic HF”) increases with age, and accounts for over 50% of cases after the age of 80.

HF in the elderly is both overdiagnosed and underdiagnosed. The cardinal symptoms of HF—

shortness of breath, edema, fatigue, and exercise intolerance—are common in the elderly, and these symptoms are often attributed to HF even when caused by other disorders. Conversely, sedentary elderly individuals may not report exertional symptoms, and neurological symptoms, such as altered sensorium or irritability, or gastrointestinal disturbances, such as anorexia or bloating, may be the only overt manifestations of HF. Similarly, the physical findings are often nonspecific, and the chest radiograph may be difficult to interpret in patients with mild HF.

Recently, plasma B-type natriuretic peptide (BNP) levels have been shown to be a valuable aid in distinguishing dyspnea due to HF from that related to other causes, such as pulmonary disorders (71). BNP levels tend to be elevated in both systolic and diastolic HF, and they also correlate with

Fig. 2. Mortality rates for heart failure per 100,000 persons in the US by age, sex, and race: 1990. BF, black female; BM, black male; WF, white female; WM, white male. (Adapted from ref. 113. Copyright 1993 with permission from Elsevier.)

response to therapy and prognosis. However, BNP levels also increase with age in healthy indivi- duals without HF, particularly women, and, as a result, the specificity and predictive accuracy of BNP levels decline with age (72). Nonetheless, in cases of diagnostic uncertainty, a low or normal BNP level effectively excludes HF, whereas a markedly elevated level provides strong evidence in support of the diagnosis.

Management

The principal goals of HF management in elderly patients are to maximize quality of life, reduce medical resource utilization, and extend functional survival. In the past 25 yr, there have been major advances in the treatment of HF, but older patients are much less likely to receive aggressive therapy. In addition, management of older HF patients is often confounded by a variety of behav- ioral and psychosocial factors, particularly noncompliance, which contribute to the high rate of repetitive hospitalizations (73). For these reasons, many centers are now utilizing a multidiscipli- nary disease management strategy for optimizing medication prescribing practices, enhancing compliance with medications and diet, and providing appropriate followup for older HF patients.

Several studies have documented the efficacy of this approach in reducing hospitalizations and cost of care, while improving quality of life and overall compliance (74,75).

Medical Therapy

In general, the pharmacologic treatment of patients with systolic HF is similar in older and younger patients (see Chapter 20). Considerations specific to the elderly are discussed briefly in the following paragraphs.

ACE I

Although none of the ACE inhibitor trials have specifically targeted older patients, the average age of patients in CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study) was 71 yr (76), and the beneficial effects of enalapril were also similar in older and younger patients enrolled in the SOLVD (Studies of Left Ventricular Dysfunction) trials (77,78). Moreover, in the post-MI ACE inhibitor trials, the benefits of ACE inhibitors were, if anything, greater in older patients (55,56), and meta-analyses of all the ACE inhibitor studies have concluded that there is substantial benefit in all age groups, including the elderly (79,80). Thus, ACE inhibitors are indi- cated in all elderly individuals with significant left ventricular systolic dysfunction (ejection frac- tion <40–45%), whether or not overt HF symptoms are present. As in younger patients, the ACE inhibitor dosage should be gradually titrated to achieve a target daily dose of 150 mg captopril, 20 mg enalapril, or the equivalent. ACE inhibitors are usually well-tolerated in older patients, but hyperkalemia and renal dysfunction occur more frequently than in younger patients.

A

-R

B

Angiotensin II receptor blockers (ARBs) have a more favorable side-effect profile than ACE inhibitors, and both valsartan and candesartan have been shown to improve clinical outcomes in patients with symptomatic HF and reduced left ventricular systolic function who are intolerant to ACE inhibitors (81,82). Similarly, these agents have been shown to reduce mortality and hospital- izations when added to an ACE inhibitor (83,84). In all these studies, the beneficial effects were similar in older and younger patients (83,85). On the other hand, the effect of ARBs on mortality has not been shown to be equivalent to that of ACE inhibitors (57,86), so that ACE inhibitors remain the preferred agents for patients with HF and impaired left ventricular systolic function.

O

V

The combination of hydralazine and isosorbide dinitrate increased survival relative to placebo

in V-HeFT-I (Veterans Administration Heart Failure Trial) (87), but was less effective than enala-

pril in V-HeFT-II (88). Although few elderly patients were enrolled in these trials, this combination

is an acceptable alternative to ACE inhibitors or ARBs in appropriately selected patients.



 

 -B

Data from four large trials indicate that -blockers improve ventricular function and reduce mortality and hospitalizations in patients with symptomatic systolic HF, including those with New York Heart Association class IV symptoms and persons up to 80 yr of age (89–92). Use of -blockers in older patients may be limited by a higher prevalence of bradyarrhythmias and severe chronic lung disease, and older patients may also be more susceptible to the development of fatigue and impaired exercise tolerance during long-term -blocker administration. Nonetheless, -blockers should be considered standard therapy in older patients with stable HF and no contraindications, especially those with underlying coronary heart disease or an elevated resting heart rate.

D

Digoxin improves symptoms and reduces hospitalizations in patients with symptomatic systo- lic HF treated with ACE inhibitors and diuretics, but has no effect on total or cardiovascular mor- tality (93). Although these effects are similar in younger and older patients, including octogenarians (94), a recent retrospective analysis has questioned the value of digoxin in women (95).

The volume of distribution and renal clearance of digoxin decline with age. In addition, recent data indicate that the optimal therapeutic concentration for digoxin is 0.5 to 0.8 ng/mL (96). For most older patients with preserved renal function (est. creatinine clearance 50 cc/min), 0.125 mg digoxin daily provides a therapeutic effect. Lower dosages should be used in patients with renal insufficiency. Although older patients are often thought to be at increased risk for digitalis toxicity, this was not confirmed in an analysis from the Digitalis Investigation Group (DIG) (94).

D

Although conventional diuretics such as furosemide may not improve long-term outcomes in HF patients, diuretics remain a cornerstone of therapy due to their efficacy in relieving congestive symptoms and edema. Older patients are more susceptible to dehydration and to diuretic-induced electrolyte disturbances, so older patients receiving chronic diuretic therapy should be monitored closely with daily weights and periodic electrolyte assessments.

A

A

Spironolactone 12.5–50 mg daily added to standard therapy has been shown to reduce mortality by 30% in patients with class III–IV systolic HF, with similar benefits in older and younger patients (97). Eplerenone, a selective aldosterone antagonist, has also been shown to reduce mortality and sudden cardiac death in patients with left ventricular dysfunction following acute myocardial infarc- tion (58). Spironolactone is contraindicated in patients with severe renal insufficiency or hyperkal- emia, and up to 10% of patients develop painful gynecomastia. In addition, older patients receiving spironolactone in combination with an ACE inhibitor may be at increased risk for hyperkalemia, particularly in the presence of preexisting renal insufficiency or diabetes, and at doses in excess of 25 mg/d (98).

Diastolic Heart Failure

As noted previously, up to 50% of older HF patients have preserved left ventricular systolic func- tion; this represents a major clinical problem because few large-scale clinical trials have focused on treatment of this disorder.

Diuretics are effective in relieving congestion and edema, but they must be used cautiously because patients with diastolic dysfunction are dependent on a sufficient preload to maintain ade- quate stroke volume. Such patients are often “volume sensitive,” and are prone to developing pul- monary edema with modest volume overload, while volume contraction and prerenal azotemia may occur in response to overdiuresis.

The only major trial reported to date that was specifically designed to address the treatment of

patients with HF and preserved left ventricular systolic function is CHARM-Preserved (Candesartan

in Heart Failure Assessment of Reduction in Mortality and Morbidity) (99). In this study, cande- sartan reduced HF hospitalizations but had no effect on mortality in patients with class II–IV HF and an ejection fraction >40%. Pending results from several ongoing studies, candesartan should be considered first-line therapy for the treatment of older patients with HF and preserved left ventricular systolic function. Additionally, data from the DIG ancillary study indicate that digoxin may reduce HF hospitalizations in patients with class II–III HF and an ejection fraction of 45%

or greater (93,94). Thus, digoxin may play a role in the management of patients with diastolic HF unresponsive to other agents.

Prevention

Given the high rates of morbidity and mortality in older patients with established HF, preven- tion of this disorder is clearly desirable. At the present time, the best preventive measures include aggressive treatment of hypertension and other known coronary risk factors. Indeed, based on data from the Systolic Hypertension in the Elderly Program (SHEP), treatment of hypertension may reduce the risk of incident HF by as much as 50% during a 5-yr followup period, and the benefit is most pronounced in patients 80 yr of age or older (Fig. 3) (100).

Fig. 3. Effect of antihypertensive drug therapy on the incidence of heart failure in the Systolic Hypertension in the Elderly Program (SHEP). (A) 60–69 yr; (B) 70–79 yr; (C) 80 yr and older. In each panel, line 1 rep- resents placebo and line 2 represents active treatment. (From ref. 100, reproduced with permission. Copyright 1997 American Medical Association.)

ARRHYTHMIAS AND CONDUCTION DISORDERS

Supraventricular, ventricular, and bradyarrhythmias all increase in frequency with advancing age, as do supranodal, nodal, and infranodal conduction abnormalities. Each of these disorders is discussed briefly in the following paragraphs.

Supraventricular Arrhythmias

Atrial fibrillation is the most common and clinically important sustained supraventricular arrhyth- mia in older adults. The prevalence of atrial fibrillation increases from less than 1% in individuals under age 40 to more than 10% in those over the age of 80, and the median age of patients with atrial fibrillation is 75 yr. Atrial fibrillation is more common in men than in women at all ages, but the proportion of women increases with age.

Atrial fibrillation in the elderly is almost always associated with significant underlying cardiac disease, with hypertension, CAD, valvular heart disease, and sick-sinus syndrome being the most common precursors. Hyperthyroidism, alcoholism, nonischemic cardiomyopathies, chronic lung disease, and electrolyte disturbances (especially hypokalemia) are also important causes of atrial fibrillation in the elderly. In addition, atrial fibrillation frequently complicates major cardiac and noncardiac surgery in older patients.

The symptomatology of atrial fibrillation in the elderly is highly variable. Many patients are asymptomatic or experience only mild palpitations. Other patients describe fatigue, shortness of breath, or poor exercise tolerance, while still others present with acute pulmonary edema or stroke.

In the Framingham Heart Study, the proportion of strokes attributable to atrial fibrillation increased from 1.5% in patients 50 to 59 yr of age to 23.5% in patients over the age of 80 (101), thus demon- strating the importance of atrial fibrillation as a cause of stroke at older age.

Although it is clear that the risk of stroke in patients with atrial fibrillation increases with age, particularly after age 75, the management of atrial fibrillation in the very elderly remains some- what controversial. The greatest effect of warfarin in reducing the absolute risk of thromboembolic stroke occurs in patients over age 75, but the risk of major bleeding complications, including intra- cranial hemorrhage, is also highest in this age group. However, despite concerns about bleeding risk, most experts recommend that patients over age 75 with chronic atrial fibrillation and no major contraindications be treated with warfarin to maintain an international normalized ratio (INR) in the range of 2.0 to 3.0. Aspirin is a less-effective alternative in patients who are ineligible for warfarin.

In patients with recent-onset atrial fibrillation, i.e., within 6 to 12 mo, many clinicians attempt cardioversion at least once, and prescribe antiarrhythmic drug therapy to maintain sinus rhythm following successful cardioversion. However, data from the AFFIRM (Atrial Fibrillation Follow- up Investigation of Rhythm Management) trial and other studies indicate that a strategy of anti- coagulation and rate control is associated with superior outcomes in patients with atrial fibrillation who are minimally symptomatic (102,103).

The treatment of other supraventricular arrhythmias, including atrial flutter, is generally similar in older and younger patients, but the risk of antiarrhythmic drug toxicity is greater in the elderly.

Ventricular Arrhythmias

The prevalence and complexity of ventricular ectopic activity increase with age, with men being

affected more often than women (104). As in younger patients, the prognostic significance of ven-

tricular arrhythmias is primarily related to the underlying cardiac disease. Therefore, therapy

should be directed at the primary disorder (e.g., CAD, hypertension), and the arrhythmias should

be treated only if they are highly symptomatic or life-threatening. When indicated, treatment is

similar in older and younger patients. In particular, age is not a contraindication to an implanted

cardioverter-defibrillator (ICD). Indeed, the majority of ICD recipients are over age 65 (Table 1),

and long-term survival is similar in older and younger patients.

Bradyarrhythmias and Conduction Disturbances

Aging is associated with degenerative changes throughout the conduction system, and the prev- alence of virtually all bradyarrhythmias and conduction abnormalities increases with age. From the clinical perspective, “sick sinus syndrome” is the most important disorder of the conduction system in older adults (105). Increasing age is associated with a decline in the number of function- ing pacemaker cells in the sinus node, and by age 75 only about 10% of the cells remain capable of initiating an impulse. In addition, conduction of the impulse from the sinus node to the atrial tis- sues may be impaired (sinus exit block), and conduction within the atria and through the AV node may also be delayed. Sick sinus syndrome thus represents a generalized disorder of sinoatrial func- tion that is often manifested by both bradyarrhythmias and supraventricular tachyarrhythmias (tachy- brady syndrome). Importantly, most medications used to treat the tachyarrhythmias, including - blockers, diltiazem, verapamil, and antiarrhythmic agents, may exacerbate the bradyarrhythmias.

Bradyarrhythmias commonly associated with sick sinus syndrome include marked sinus brady- cardia, sinus pauses and sinus arrest, sinus exit block, advanced AV-nodal block, and atrial fibrilla- tion with slow ventricular response. These arrhythmias can produce a spectrum of symptoms ranging from fatigue, shortness of breath, angina, or reduced exercise tolerance to dizziness, impaired cognition, or syncope. In patients with major symptoms directly attributable to bradycardia, per- manent pacemaker implantation is indicated. In the US, more than 80% of all pacemakers are inserted in older individuals (Table 1), and sick sinus syndrome is the most common underlying disorder. For patients in sinus rhythm, dual-chamber pacing is associated with a lower risk for devel- oping atrial fibrillation, fewer hospitalizations for HF, and an improved quality of life compared to single-chamber ventricular pacing (106).

Cardiopulmonary Resuscitation

The value of cardiopulmonary resuscitation (CPR) in elderly patients remains a matter of debate.

Fewer than 10% of older patients who suffer cardiac arrest and receive CPR survive beyond 30 d with favorable neurological outcomes (107). In addition, there is little difference in outcome whether the arrest occurs in a hospital, nursing home, or community setting. Despite these grim statistics, a subgroup of older patients with substantially better outcomes can be identified. For example, previously healthy individuals who receive prompt CPR for a witnessed cardiac arrest and who are subsequently found to be in ventricular fibrillation have a 25 to 40% likelihood of surviving with a good neurological outcome. Thus, although the decision to initiate CPR must be based on both clin- ical and psychosocial considerations, the results of CPR can be quite gratifying in selected patients, even at an elderly age.

EXERCISE AND CARDIAC REHABILITATION

As in younger patients, physical inactivity is a risk factor for cardiovascular events in older adults, and regular physical exercise is associated with improved health status and sense of well- being in the elderly. In addition, the benefits of cardiac rehabilitation following myocardial infarc- tion or cardiac surgery are comparable in older and younger patients (108,109). Despite these con- siderations, physicians are less likely to recommend regular exercise or cardiac rehabilitation for older patients with or without cardiovascular disease. Nonetheless, the dictum “use it or lose it”

is most applicable in the elderly, and maintaining a physically, intellectually, and emotionally active lifestyle is perhaps the best approach for preserving independence and ensuring a high quality of life in older individuals.

ETHICAL ISSUES AND END-OF-LIFE CARE

As discussed throughout this chapter, older patients with cardiovascular disease are at increased

risk for a multitude of complications, including death. Elderly individuals maintain widely diver-

gent views about the use of life-sustaining interventions and other invasive medical procedures, as well as what constitutes an acceptable quality of life in the face of chronic or terminal illness (110). Moreover, studies have shown that patient surrogates, including spouses and physicians, are unable to reliably predict a patient’s wishes in specific end-of-life scenarios. In order to ensure that a patient’s wishes are honored if and when the patient is no longer capable of communicating his or her preferences, the physician should make an effort to address these issues at a time when the patient is still competent and lucid. The patient should also be encouraged to develop a living will and appoint a durable power of attorney. In addition, in patients with a progressive illness such as HF, it is helpful to discuss where the patient wishes to spend his or her final days. Potentially suitable environments include the home, a chronic-care facility, or a hospital. Palliative care through a reputable hospice should also be considered in older patients with terminal cardiovascular disease.

SUMMARY AND CONCLUSIONS

Aging is associated with extensive changes in cardiovascular structure and physiology, many of which have a direct impact on the clinical manifestations, response to treatment, and prognosis of cardiovascular disease in older adults. As a general principle, older patients are at increased risk for adverse outcomes, and the potential benefits to be derived from specific therapeutic interven- tions are therefore greater in older than in younger patients. Although additional research is needed to define the precise role of many therapies in older patients, the available evidence strongly sug- gests that age alone is not a sufficient justification for withholding treatment. Similarly, it is evident that more effective preventive strategies are needed to reduce the tremendous physical, emotional, and financial burden imposed on our society by cardiovascular disease in our ever-expanding elderly population.

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