28: Coronary Disease

The prevalence of cardiovascular disease (CVD) and especially coronary artery disease (CAD) is increasing. In the United States, 82.6 million people have CVD, and of these, 40.4 million are older than age 60 years. Among people free of CVD at age 50 years, there is a lifetime risk for developing it of 51.7% for men and 39.2% for women. The good news is that the overall rate of death attributable to CVD has declined 30.6% from 1998 to 2008 and the actual number of patients dying in the same period decreased by 14.1%. A large percentage of this decrease is related to better therapy for patients with acute coronary syndromes (ACSs) and chronic stable angina.

Analysis of National Health and Nutrition Examination Survey (NHANES) data comparing death rates attributable to CAD between 1980 and 2000 found that approximately 47% of the decrease in coronary deaths was attributable to medical and surgical treatments and approximately 44% to changes in coronary risk factors. Unfortunately, these decreases in risk factors were partially offset by increases in obesity and type II diabetes.

Increasing age is a major factor in the increasing incidence of CVD, including aortic stenosis and CAD. In the age group 85 to 94 years, the average annual rate of first cardiovascular events is 24 times that of those in the age group 35 to 44 years. For women, comparable rates occur about 10 years later in life, with the difference narrowing with advancing age. Older adults also have a greater number of comorbidities. At least partly for this reason, they also have fewer surgical and interventional procedures, more adverse events from medication, more polypharmacy, are less frequently referred for cardiac rehabilitation and have a higher morbidity and mortality than younger patients with similar CVD. Congestive heart failure is the most common diagnosis on hospital discharge and the majority of these patients are age 65 years or older. Finally, approximately 80% of people who die are ≥65 years of age and most die with CAD.

Cardiovascular Changes with Normal Aging

With normal aging there are a number of changes seen in the heart and other organs that alter function and are precursors to a variety of diseases seen in older adults (Table 28–1). These changes occur in everyone as they age and must be distinguished from changes related to diseases such as CAD and other vascular diseases. These normal changes associated with aging also do not occur at the same rate in everyone, so physiologic aging and chronologic aging differ from person to person.

Table 28–1 lists the consequences of these changes. The practical effect of these aging changes on cardiac function is no change in cardiac output at rest or with moderate exercise and no change in left ventricular ejection fraction or stroke volume. With stress (eg, trauma, disease, surgery) that requires an increase in cardiac output and increase in O₂ demand, there is less ability to meet this increased demand as a result of the decrease in cardiac reserve.

Risk factors for vascular disease, including CAD, have been identified for decades. Because their effect on the development of vascular disease is a function of the number of risk factors present, the concentration of the factors and the duration of exposure and cumulative damage, the risk factors are as important—if not more so—in the older patient. Whether a risk factor will affect the development of vascular disease is also partially genetically determined. For instance, everyone who smokes does not develop CAD. In addition, in older adults we do not have evidence that elimination of a particular risk factor will result in a decrease in the incidence of cardiovascular events. For some risk factors, for instance, hypertension, the evidence that controlling the blood pressure reduces cardiac events is excellent, including in older patients. Patients older than age 65 years with systolic blood pressure greater than 180 mm Hg have a 3–4-fold increase in CAD compared to those with a systolic blood pressure less than 120 mm Hg. Treating hypertension in patients older than age 70 years has resulted in a decrease in the incidence of stroke and reduced cardiac events. The Hypertension in the Very Elderly Trial (HYVET), which included almost 4000 patients older than age 80 years, showed that with blood-pressure-lowering treatment, the incidence of stroke was decreased by 30% and cardiac death by 23%.

In older adults, the prevalence of smoking decreases. In 2007 to 2009, among people ≥65 years of age, 9.3% of men and 8.6% of women were current smokers. Older smokers are less likely to quit smoking than younger smokers, but the older smokers, if quitting is attempted, are more likely to succeed. Absolute rates of disease incidence and mortality as a result of smoking increase steadily as age and duration of smoking increases. There is no evidence that the disease consequences of smoking decrease in older adults. The proportional benefits of smoking cessation are somewhat less among older adults because of the cumulative damage of a long duration of smoking and possibly because patients susceptible to the increased risk of coronary disease from smoking have died at a younger age, leaving those less susceptible. However, cessation is the only way to alter smoke-related disease risk.

Hyperlipidemia as a cardiac risk factor is more complex. Serum cholesterol concentration increases progressively until age 50 years in men and age 65 years in women, and then begins to decline. Age-related changes in the concentration of cholesterol are mainly caused by increases in low-density lipoprotein (LDL) cholesterol. High-density lipoprotein (HDL) level remains relatively stable with age and is approximately 10 mg/dL higher in women than in men. A high level of LDL cholesterol and low level of HDL cholesterol remain predictors for the development of CAD in older adults. Clinical trial data indicate that in older patients with established CAD, LDL-lowering therapy is beneficial and it is standard therapy for older patients who are at higher risk and otherwise in good health to be given LDL-lowering therapy.

Between 2005 and 2006 the prevalence of diabetes mellitus in adults ≥65 years of age was 17%. The prevalence of diabetes mellitus in the United States is projected to more than double from 2005 to 2050, with the largest increases in the oldest age groups, increasing by 220% in those ages 65–74 years and by 449% in those age ≥75 years. The presence of type II diabetes in the older age group doubles the risk of CAD, and when combined with hyperlipidemia, increases the risk 15-fold. At least 68% of people age 65 years or older with diabetes die of some form of heart disease; 16% die from stroke. Older adults are at increased cardiac risk from the constellation of signs known as the metabolic syndrome: central obesity, insulin resistance, dyslipidemia, and hypertension. The presence of the metabolic syndrome leads to an increased risk of CVD and renal events.

Physical inactivity in patients older than age 75 years is frequent, with 38% of men and 51% of women reporting no leisure-time physical activity. In patients 60–80 years old, frequent exercise raises HDL cholesterol, controls obesity, lowers blood pressure, and reduces insulin resistance, all protective effects against vascular disease.

General Principles in Older Adults

ACS has 3 components: ST-segment elevation myocardial infarction (STEMI), non–ST-segment elevation myocardial infarction (NSTEMI), and unstable angina (UA). All 3 share a common pathophysiologic origin related to progression of coronary plaque, instability, and rupture. STEMI refers to the elevation of the ST segment in at least 2 contiguous leads along with either biomarker evidence (troponin I or T; creatine kinase, myocardial bound [CK-MB]; myoglobin) of myocardial necrosis or symptoms consistent with ischemia. NSTEMI has a similar definition, but without elevation of the ST segment in at least 2 contiguous leads. UA is chest pain or discomfort that is accelerating in frequency or severity and can occur at rest, but does not result in myocardial damage as noted by negative cardiac biomarkers. Patients with UA are at increased risk for progression to myocardial infarction (MI). The percentage of ACS composed of STEMI varies from 29% to 47% but has been decreasing over time.

Of the estimated 1.2 million MIs or fatal coronary heart disease (CHD) events occurring annually in the United States, 67% occur in persons older than age 65 years and 44% occur in persons older than age 75 years. Older patients are more likely to have NSTEMI than STEMI. Case fatality rates increase markedly with age; 80% of all MI deaths occur in persons older than age 65 years. Although the incidence of MI is higher in men than in women at all ages, the total number of MIs or fatal CHD events is greater in women than men older than age 75 years, reflecting the fact that the proportion of women in the surviving population increases with age. The prevalence of silent or clinically unrecognized MI increases with age and prevalence may be twice as high as recognized MI in older adults. The long-term prognosis after clinically unrecognized MI is similar to that of recognized MI in older adults.

Prevention

Despite the high prevalence of CHD and ACS in industrialized countries, these disorders are potentially preventable or can be delayed through early and aggressive management of risk factors as discussed above. Although some risk factors, such as age, sex, and genetics, cannot be modified, lifelong adherence to behavior modification, including regular physical exercise; maintenance of desirable body weight; a diet rich in fruits, vegetables, and whole-grains but low in trans and saturated fats; and avoidance of tobacco products, can significantly reduce this risk.

Aspirin, adenosine diphosphatase (ADP) receptor antagonists, β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins have been shown to improve post-ACS prognosis. In addition, cardiac rehabilitation programs also reduce mortality and rehospitalizations after ACS.

Clinical Findings

Symptoms & Signs

The proportion of MI patients who have chest pain declines with age; <50% of MI patients older than 80 years complain of chest pain. Likewise, diaphoresis occurs less frequently in older patients with acute MI. Dyspnea is often the presenting manifestation of acute MI in older adults and is the most common initial symptom in persons older than 80 years. The prevalence of atypical symptoms (eg, gastrointestinal disturbances, overwhelming fatigue, dizziness, syncope, confusion, stroke) also increases with age, and up to 20% of patients older than 85 years with acute MI have neurologic complaints (see Chapter 63, “Addressing Chest Pain in Older Adults”).

Physical findings associated with ACS are nonspecific but may include signs of acute heart failure, occurring in up to 40% of older patients with MI. These signs include an S₃ or S₄ gallop, new mitral regurgitation murmur, or signs of pulmonary or systemic venous congestion, such as pulmonary rales or elevated jugular venous pressure (JVP). In patients with right ventricular infarction, the Kussmaul sign (rise in JVP with inspiration) may be present.

Electrocardiography—

Classic electrocardiographic features of a STEMI are ST-segment elevation of at least 1 mm in 2 or more contiguous leads corresponding to the anatomical distribution of a coronary artery (eg, leads II, III, avF), often with subsequent evolution to pathologic Q waves or new left bundle-branch block. ST elevation is not present in NSTEMI or UA, but there can be ST-segment depression or T-wave inversion, or both. Electrocardiographic changes often resolve with resolution of chest pain, so a nondiagnostic or even normal electrocardiogram (ECG) taken when the patient is free of symptoms does not exclude ischemia. However, the initial ECG is often nondiagnostic in older adults because of preexisting conduction system disease (eg, left bundle-branch block), presence of a ventricular pacemaker, prior infarct, left ventricular hypertrophy, metabolic abnormalities, or drug effects (eg, hypokalemia, digoxin), and the high prevalence of NSTEMI.

Atypical symptoms and physical findings, coupled with the high prevalence of nondiagnostic ECGs, often lead to delayed presentation and recognition of ACS. This time lag increases the risk of complications and reduces the window of opportunity for timely and effective intervention. Clinicians should maintain a high index of suspicion for ACS in all older patients with a wide range of unexplained symptoms and/or significant physical distress.

Cardiac biomarkers—

Definitive diagnosis of STEMI or NSTEMI requires abnormal cardiac biomarker elevation. Troponins I and T have become the gold standard for diagnosis because of their greater sensitivity and specificity compared with the CK-MB isoenzyme. Serial measures of biomarkers that exceed the normal range and exhibit a typical rise-and-fall pattern in a patient with clinical and/or electrocardiographic features of cardiac ischemia are diagnostic of MI. In the absence of recurrent ischemia, CK-MB levels rise within 4–6 hours, peak at approximately 24 hours after MI onset and return to normal within 36–48 hours. Troponin levels rise within 2–3 hours of onset of symptoms, peak at 24–72 hours, and may remain elevated for up to 10–14 days, especially in large infarctions.

Differential Diagnosis

The differential diagnosis of ACS in older adults includes other cardiovascular conditions as well as pulmonary, gastrointestinal, musculoskeletal, and neurologic disorders. Important cardiovascular conditions that should be considered include aortic dissection, pericarditis, myocarditis, acute pulmonary edema resulting from cardiomyopathy, valvular heart disease, and arrhythmia. Pulmonary disorders include pneumonia, pulmonary embolus, pneumothorax, pleurisy, and pleural effusion. Gastrointestinal disorders include esophagitis, esophageal spasm, esophageal rupture, gastroesophageal reflux, peptic ulcer disease, cholelithiasis, and pancreatitis. Musculoskeletal disorders include muscular strains, costochondritis, injuries involving the cervical or thoracic spine, disorders of the shoulder joint, and chest wall trauma. Neurologic conditions include stroke or transient ischemic attack, radiculopathy, and altered sensorium or delirium. Psychogenic conditions, including anxiety and hyperventilation syndrome, may also mimic the ACS symptoms.

Complications

Major MI complications include acute heart failure, conduction disturbances (eg bundle branch block, advanced atrioventricular [AV] block), atrial fibrillation, myocardial rupture, sudden death and cardiogenic shock. Each complication is associated with worse prognosis and occurs 2–4 times more frequently in older patients.

Treatment

Table 28–2 lists the major therapeutic options for ACS. Management of STEMI and NSTEMI differs with respect to the use of early reperfusion therapy but is otherwise similar. For UA, the primary goals of therapy are symptom relief and preventing progression to NSTEMI or STEMI. Guidelines recommend that older patients receive the same treatment as younger patients with close monitoring for adverse events and with the caution that their general health, comorbidities, cognitive status, and life expectancy be taken into account and that increased sensitivity to hypotension-inducing drugs and possible altered pharmacokinetics be considered.

General Measures

Maintenance of adequate arterial oxygenation and relief of chest discomfort are important goals. Intravenous morphine should be administered every 5–30 minutes as needed for relief of chest pain, monitoring closely for signs of respiratory depression, bradycardia, hypotension, and impaired sensorium, all of which are more common in older adults. Sublingual nitroglycerin should be administered acutely for the treatment of ischemic chest pain or dyspnea.

Patients with persistent chest pain or signs of pulmonary congestion should receive topical nitroglycerin ointment or an intravenous nitroglycerin infusion, titrated to control symptoms while avoiding excessive blood pressure (BP) reduction. In patients with signs of right ventricular infarction (ST elevation or depression in right precordial or inferior leads with elevated JVP and Kussmaul sign), nitroglycerin should be avoided as it may precipitate severe hypotension.

Reperfusion Therapy

Recanalization of the involved coronary artery as quickly as possible reduces mortality and morbid MI complications. Reperfusion can be achieved either pharmacologically with fibrinolytics or mechanically with percutaneous coronary intervention (PCI) with stent implantation. In general, mechanical reperfusion is more effective than fibrinolysis if it can be achieved in a timely manner. The recommended time from hospital presentation to reperfusion is 90 minutes.

Mechanical reperfusion has a lower risk of intracranial hemorrhage, particularly in patients older than 75 years, in whom the risk of intracranial bleeding is 1% to 2% with fibrinolysis. Mechanical reperfusion benefits patients with both STEMI and NSTEMI, whereas fibrinolytic therapy is only effective in STEMI and is contraindicated in treatment of NSTEMI.

Patients with UA who have severe or recurrent symptoms or electrocardiographic abnormalities should undergo coronary angiography followed by percutaneous or surgical revascularization based on anatomic findings. Patients who respond to medical therapy and have no further symptoms should undergo a symptom-limited stress test for risk stratification. Patients with severe ischemia, ischemia at low cardiac workload, or ischemia in association with reduced left ventricle (LV) systolic function should proceed to angiography and possibly revascularization. Those with less-severe ischemia or a normal stress test may be managed medically.

Fibrinolytics—

The 5 fibrinolytic agents approved for intravenous use for the treatment of STEMI in the United States are streptokinase, alteplase, anistreplase, reteplase, and tenecteplase. Use of fibrinolytic agents should be restricted to those who fulfill criteria for fibrinolysis and can be treated within 6 hours of symptom onset (Table 28–3). In-hospital mortality increases with increasing age along with the risk of intracranial hemorrhage and ventricular free wall rupture in older patients receiving fibrinolytics.

PCI—

Mechanical reperfusion (ie, PCI with or without stenting) is associated with improved outcomes in patients of all ages and is superior to fibrinolysis in older patients. Either bare metal stents or drug-eluting stents may be implanted. The latter are generally preferred, given the lower risk of restenosis, although they require a longer duration of treatment with dual antiplatelet agents. Early angiography and coronary intervention is associated with improved short- and long-term outcomes in patients with either STEMI or NSTEMI. In STEMI patients, the target door-to-balloon time is 90 minutes. Mechanical reperfusion, if available, is the preferred strategy in older patients with documented ACS, although used less often than in younger patients. Older patients do have a lower rate of angiographic success and less ST-segment resolution and more postinfarction complications.

Antithrombotic Therapy

Aspirin—

Aspirin is indicated for all patients with ACS. It is effective in older adults and should be continued indefinitely in all patients with documented CHD. The recommended dosage in the acute setting of ACS is 325 mg daily; dosages of 75–325 mg daily are suitable for long-term use.

Anticoagulation—

Anticoagulation is indicated in patients with NSTEMI and UA, although the benefits in STEMI are less well-established. Its benefit is even greater in ACS complicated by recurrent ischemia or atrial fibrillation. Anticoagulation is also indicated in patients receiving a short-acting fibrinolytic agent (eg, recombinant tissue-type plasminogen activator) and those receiving a glycoprotein IIb/IIIa inhibitor.

Anticoagulant options include unfractionated heparin (UFH), bivalirudin, low-molecular-weight heparin (LMWH) agents such as enoxaparin and dalteparin, and fondaparinux. LMWH provides more stable anticoagulation than UFH and offers the advantage of subcutaneous administration without the need to monitor activated partial thromboplastin time (aPTT). In addition, LMWHs have been associated with improved clinical outcomes although they are contraindicated in renal failure and have been associated with increased bleeding in older adults, which may be due to decreased creatinine clearance.

Antiplatelet therapy—

Antiplatelet agents that block the ADP receptor have been shown to reduce repeat major cardiac events after percutaneous coronary stent implantation in ACS patients. In addition, these agents reduce cardiovascular mortality, nonfatal MI, and nonfatal stroke by approximately 20% compared with aspirin alone during long-term therapy after NSTEMI. Currently available agents include clopidogrel, prasugrel, and ticagrelor. Prasugrel is more potent than clopidogrel but is not recommended in patients older than 75 years because of the bleeding risk. Clopidogrel recently became generic and is the most commonly used ADP receptor antagonist. The initial dosage is 300–600 mg orally followed by 75 mg daily.

Glycoprotein IIb/IIIa inhibitors—

These potent antiplatelet agents block the final pathway leading to platelet aggregation. Available agents include abciximab, eptifibatide, and tirofiban. Most data for these agents came prior to the routine use of ADP receptor antagonists, where they were shown to reduce the risk of recurrent ischemic events and improve clinical outcomes in patients with documented MI, particularly those undergoing percutaneous coronary revascularization. These agents similarly benefit younger and older patients, although the risk of bleeding is higher in those who are older; dosage adjustment may be necessary in patients with impaired renal function.

β Blockers

Early administration of intravenous β blockers reduces mortality partly because of reduced sudden cardiac death, recurrent ischemic events, and both supraventricular and ventricular tachyarrhythmias in appropriately selected ACS patients. Intravenous β-blocker therapy should be initiated as soon as possible in all patients with suspected ACS in the absence of contraindications (ie, heart rate <50 beats/min, systolic BP <90–100 mm Hg, PR interval ≥240 milliseconds, heart block greater than first degree, moderate or severe pulmonary congestion, or active bronchospasm).

Cardioselective β blockers are preferred, and intravenous metoprolol and atenolol have been approved for treatment of ACS. Patients receiving intravenous β blockers should be carefully observed for bradyarrhythmias, hypotension, dyspnea, and bronchospasm. It is prudent to use lower dosages and a slower dose titration schedule in patients older than 75 years and in those with multiple comorbidities or unstable hemodynamics. Dose adjustment is necessary for atenolol in renal impairment.

Angiotensin-Converting Enzyme Inhibitors & Angiotensin Receptor Blockers

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are beneficial in patients 65–74 years of age, but there is no clear evidence of benefit in patients older than age 75 years. Data suggest that ACE inhibitors are particularly beneficial in patients with anterior STEMIs and MIs complicated by clinical heart failure or significant LV systolic dysfunction (LV ejection fraction <40%). Contraindications to ACE inhibitors include systolic BP <90–100 mm Hg, advanced renal insufficiency—especially if worsening renal function is evident, bilateral renal artery stenosis, and hyperkalemia. ACE inhibitor therapy can be initiated with captopril 6.25 mg 3 times a day or enalapril 2.5 mg twice daily. Once the maintenance dose has been achieved, changing to a once-daily agent at equivalent dosage (eg, lisinopril 20–40 mg) is appropriate. Throughout the initiation and titration phase of ACE inhibitor therapy, BP, serum creatinine, and potassium should be carefully monitored. ARBs are generally used for patients who do not tolerate ACE inhibitors because of cough.

Lipid-Lowering Agents

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors (statins) should be initiated early in the course of ACS at high doses (eg, atorvastatin 80 mg) and continued indefinitely. These agents have been shown to decrease mortality and recurrent ischemic events after NSTEMI and STEMI.

Nitrates

Nitrate preparations are effective in controlling ischemia, treating heart failure, and managing hypertension in patients with ACS. As noted above, the options include sublingual nitroglycerin, topical nitroglycerin ointment, and intravenous nitroglycerin infusion. Nitrate tolerance generally occurs within about 24 hours.

Calcium Channel Blockers

Calcium channel blockers have not been shown to improve mortality in ACS patients, and the use of short-acting dihydropyridines (eg, nifedipine) is contraindicated, as are the nondihydropyridines (eg, verapamil and diltiazem) in patients with heart failure and LV dysfunction.

Potassium & Magnesium

Potassium should be maintained within a range of 3.5–4.5 mEq/L and magnesium above 2.0 mEq/L.

Prognosis

Approximately 15% to 20% of patients with STEMI die before reaching the hospital, a proportion that likely increases with advancing age. Among patients with recognized ACS, both short- and long-term mortality increase progressively with age. Other factors associated with increased mortality include anterior MI, clinical heart failure, impaired LV systolic function, atrial fibrillation, complex ventricular arrhythmias, poor functional status, diabetes mellitus, and lack of guideline-based treatment. Although short-term prognosis is more favorable in NSTEMI than in STEMI, mortality rates at 2 years are similar.

General Principles in Older Adults

CHD is the leading cause of death in the United States in both men and women. Chronic stable angina is the most common form of CHD and is the initial form of presentation in 80% of patients. Although the incidence and prevalence of CHD are both higher in men than in women, the rates for women increase progressively after menopause, and the greater longevity of women compared with men results in a slight predominance of women in the total number of CHD cases. The prevalence of CHD increases progressively with age, affecting 16.1% of women and 18.6% of men older than 75 years.

Prevention

Primary prevention of CHD may be achieved through lifelong avoidance of tobacco products, participation in regular physical exercise, maintenance of desirable body weight, consumption of a diet rich in fruits, vegetables, and whole-grain foods, and limited consumption of foods high in trans and saturated fats and cholesterol. Early identification and aggressive treatment of risk factors as discussed above is essential.

Clinical Findings

Symptoms & Signs

The most common symptom of chronic CHD is central chest discomfort, often described as pressure, tightness, or heaviness, typically brought on by physical exertion or emotional stress and relieved by rest or nitroglycerin. The discomfort may radiate to or primarily be in the jaw, left or both arms, back or epigastrium. The discomfort typically lasts longer than a few minutes and up to 20 minutes. If longer than 20 minutes, ACS should be ruled out. Taking a breath, moving arms or body or coughing does not affect the discomfort. However, many older adults with CHD, including those with prior MI or UA, manifest atypical symptoms, such as dyspnea, fatigue, weakness, dizziness, or abdominal discomfort, whereas others, particularly diabetics, are entirely asymptomatic, in part because of the high prevalence of physical inactivity at older age (see Chapter 63, “Addressing Chest Pain in Older Adults”).

Myocardial ischemia occurs when the myocardial O₂ demands are not met by an increase in myocardial blood supply. The earliest events are increased myocardial stiffness of the ischemic myocardium, followed by decreased contractility, metabolic alterations resulting in increased lactic acid formation, changes in electrical repolarization, and finally the discomfort we recognize as angina. The symptoms and events created can be angina, dyspnea, or the development of malignant ventricular arrhythmias, including sudden death. If the volume of ischemic myocardium is large, symptoms of shortness of breath, exercise intolerance and even heart failure may occur.

Angina is graded using the Canadian Cardiovascular Society Classification system based on the level of activity required to produce symptoms (Table 28–4).

The physical examination in patients with chronic CAD can be entirely normal. In other patients, physical findings are nonspecific but may include an S₃ or S₄ gallop, mitral regurgitation murmur, a laterally displaced or dyskinetic apical impulse (especially in patients with prior MI), or signs of heart failure (eg, pulmonary rales, elevated JVP, peripheral edema).

Special Tests

Basic laboratory tests can reveal factors that contribute to the pathophysiology of stable angina such as complete blood count (anemia), thyroid-stimulating hormone (TSH) (hyperthyroidism), and toxicology screen (cocaine or amphetamine use).

Electrocardiography—

The ECG may demonstrate pathologic Q waves in patients with prior MI. Other ECG findings are nonspecific. The ECG is especially informative if done while the patient is experiencing chest discomfort. At such times, flat or down-sloping ST depression may be seen. If the patient is not experiencing angina at the time the ECG is done, it may be entirely normal.

Stress tests—

The noninvasive procedure of choice for diagnosing CHD is an exercise test or pharmacologic stress test using adenosine, dipyridamole, regadenoson, or dobutamine, usually accompanied by echocardiographic or radionuclide imaging. Meta-analysis suggests that an ECG exercise test without imaging has a mean sensitivity of 68% and a specificity of 77%. However, because of selection bias, the sensitivity is nearer to 50% with a specificity of 85% to 90%. The ability of the older patient to achieve 85% of maximal estimated heart rate for age and sex is markedly reduced compared to younger patients. Also, an exercise ECG stress test can only be interpreted if the resting ECG is normal or has minor ST–T-wave changes. The presence of LVH, moderate ST–T-wave changes, Wolff-Parkinson-White syndrome, or left bundle-branch block makes changes in the exercise ECG non-interpretable.

The exercise ECG stress test provides 80% to 90% sensitivity and specificity for diagnosing CHD, although the predictive accuracy of the test is dependent on the pretest likelihood of CHD. In general, it is preferable to perform an exercise test if the patient is capable of doing so, as the duration of exercise is an independent powerful predictor of prognosis. However, because many older patients are limited by arthritis, neurologic conditions, or poor physical conditioning, it is often necessary to perform a pharmacologic stress test (eg, dobutamine echo, adenosine sestamibi).

Coronary angiography—

Coronary angiography remains the gold standard for determining the presence, extent, and severity of CHD as well as the suitability for percutaneous or surgical revascularization. Older patients are more likely to have multivessel disease and left main CAD.

Other tests—

Multidetector cardiac CT with coronary calcium quantification showing a high burden of coronary calcium is associated with extensive CAD and worse prognosis, but routine use of this technology is controversial. CT with contrast coronary angiography can also demonstrate proximal coronary disease and its severity. However, it requires special expertise and is not generally available.

Differential Diagnosis

The differential diagnosis of chest pain includes:

1. Cardiac: coronary vasospasm, pericarditis, cardiomyopathy, arrhythmias, syndrome X or microvascular coronary artery dysfunction, cocaine or amphetamine vasospasm

2. Vascular: aortic dissection, arteritis

3. Gastrointestinal: esophageal reflux, esophageal spasm, duodenal ulcer, pancreatitis, cholecystitis

4. Pulmonary: pulmonary embolus, pneumothorax, pleurisy, pneumonia

5. Neurologic: shingles, neuropathy

6. Musculoskeletal: costochondritis, rib fracture, arthritis, muscle pain

7. Psychogenic causes: panic attacks, hyperventilation, anxiety

Angina as a result of myocardial ischemia can occur whenever there is an imbalance between myocardial O₂ demand and supply. Other diseases where angina is a symptom without epicardial CAD are valvular aortic stenosis, hypertrophic cardiomyopathy, and myocarditis. With nonobstructive coronary artery plaques, an unusual increase in myocardial O₂ demand can result in myocardial ischemia and angina: hyperthyroidism, arteriovenous fistulae, and excessive sympathetic stimulation. Patients with anemia, hypoxemia, and hyperviscosity can have decreased O₂ delivery resulting in angina.

Complications

The major complications of chronic CHD are progression to ACS, development of heart failure because of the cumulative effects of myocardial injury or infarction (ischemic cardiomyopathy), and development of conduction abnormalities or arrhythmias, including ventricular tachycardia and ventricular fibrillation. Sudden cardiac death is the initial manifestation of CHD in up to 20% of cases.

Risk Stratification

The patients at highest risk are those with ACS. In patients with chronic CAD, the risk increases with higher Canadian Class, decreased LV function (LV ejection fraction), location, severity and extent of coronary artery stenosis, high-risk noninvasive stress test, general physical health, comorbidities, and uncontrolled vascular risk factors.

Treatment

Goals of Treatment

The goals of therapy for chronic CHD are to control symptoms, prevent or slow progression and prevent major complications. Since myocardial ischemia is the basis for the symptoms, the factors involved in myocardial O₂ demand must be considered. The major requirements for myocardial O₂ demand are myocardial contractility and LV wall tension, the determinants of which are the systolic BP, the LV diastolic radius, the LV wall thickness, and the heart rate. The coronary blood flow to the myocardium depends on the degree of coronary artery obstruction and changes that effect patency determined by the severity of the atherosclerotic plaque, plaque rupture with platelet aggregation or thrombus, varying degrees of coronary vascular tone, and coronary spasm. The pharmacologic approach to therapy addresses these factors:

1. Decrease in myocardial O₂ demand: β blockers, ACE inhibitors, ARBs, treatment of hypertension, lowering of heart rate.

2. Increase coronary blood flow: nitrates, Ca⁺⁺ channel blockers.

3. Decrease factors causing obstruction: nitrates, antiplatelet drugs.

4. Open or bypass obstruction: coronary bypass surgery, PCI with and without stenting.

5. Optimal treatment: involves lifestyle modifications, attention to risk factors, pharmacologic interventions, and, in selected patients, percutaneous or surgical revascularization.

Lifestyle Modifications

All patients with CHD should be strongly advised to discontinue all tobacco products. Gradual weight reduction through diet and regular exercise should be encouraged in overweight patients (body mass index >25–30 kg/m²). Patients with CHD should eat a balanced diet rich in fruits, vegetables, and whole grains while limiting intake of trans and saturated fats (including partially hydrogenated oils) and cholesterol. Patients should also engage in a total of at least 20–30 minutes of moderate intensity physical activity on most days of the week unless limited by active cardiovascular symptoms or other medical conditions. Walking, stationary cycling, and swimming are suitable exercise modalities for older adults with mild functional impairments. When beginning an exercise program, patients should be instructed to start at a slow and comfortable pace, gradually increasing the duration of exercise over a period of weeks. Patients who have suffered an MI or who have had coronary bypass surgery should be strongly encouraged to participate in a formal cardiac rehabilitation program. Such programs have been associated with reduced mortality, improved exercise tolerance and quality of life, and enhanced mood and sense of well-being.

Pharmacotherapy

Aspirin—

Long-term use of aspirin in CHD patients markedly reduces the risk of death, MI, and stroke. The absolute benefit is greatest in high-risk patients, including those older than 65 years. The optimal dose of aspirin is unknown, but 75 or 81 mg once daily provides benefits equivalent to higher doses with a lower risk of side effects, including bleeding. In patients intolerant to low-dose aspirin, clopidogrel 75 mg daily is an acceptable alternative.

β Blockers—

β Blockers reduce the risk of death and reinfarction after MI. β Blockers are also highly effective antianginal agents and appear to reduce the incidence of coronary events in patients with chronic CHD. It is reasonable to start and continue β blockers indefinitely in all patients who have had ACS or have LV dysfunction with or without heart failure symptoms unless contraindicated. In patients without prior MI, the optimal dose of β blockers is unknown, but a rational therapeutic goal is to gradually increase the dose until the patient has no or minimal ischemic symptoms and the resting heart rate is <60 beats/min. Older patients may be less tolerant of β blockers because of the effects of aging on sinus node function and the presence of comorbidities (eg, pulmonary disease); dosages should, therefore, be adjusted accordingly and heart rate should be followed for bradycardia.

Nitrates—

Sublingual nitroglycerin remains the drug of choice for treatment of an acute episode of angina. As a result of drying of the oral mucosa in older adults, nitroglycerin spray may be more effective than tablets for older patients. Older patients may also be more likely to experience orthostatic hypotension with nitroglycerin; they should be advised to take the medication in a sitting or reclining position. Long-term nitrates, such as isosorbide mononitrate, are effective antianginal agents, but have not been shown to improve clinical outcomes. In addition, tolerance to nitrates develops rapidly, requiring a daily 6- to 8-hour nitrate-free interval. Several oral and transdermal nitrate preparations are available for chronic use. If the patient has taken a phosphodiesterase-5 (PDE-5) inhibitor within 48 hours, any organic nitrate is strictly contraindicated because of the possibility of excessive hypotension.

Calcium channel blockers—

Calcium channel blockers are effective antihypertensive and antianginal agents, but they have not been shown to improve clinical outcomes in CHD patients. In addition, they may be associated with worsening heart failure and, with the exception of amlodipine and felodipine, should be avoided in patients with impaired LV systolic function. Verapamil and diltiazem slow the heart rate and conduction through the AV node, especially when used in combination with a β-blocker, thus increasing the risk of bradyarrhythmias and syncope in older patients with sinus node dysfunction (sick sinus syndrome) or impaired AV nodal conduction. Verapamil and, to a lesser extent, diltiazem also impair gastrointestinal motility and may lead to constipation or ileus.

Angiotensin-converting enzyme inhibitors—

ACE inhibitors do not exert a direct antiischemic effect, but ramipril reduces mortality and major cardiovascular events in a broad range of patients with established vascular disease or diabetes. In addition, ACE inhibitors improve outcomes in patients with reduced LV systolic function with or without symptoms. ACE inhibitors should be given as first-line therapy in patients with CHD, especially those with hypertension, reduced LV function, diabetes and/or chronic renal disease. Thus, initiation of an ACE inhibitor should be strongly considered in all older adults with established CHD in the absence of contraindications.

Angiotensin receptor blockers—

ARBs have been shown to improve outcomes in patients with diabetes and in hypertensive patients with LV hypertrophy; however, the value of these agents in patients with CHD is unproven. Both ACE inhibitors and ARBs have been shown in patients with coronary disease to improve endothelial function by increasing the availability of nitric oxide that should prove beneficial. A meta-analysis showed that compared to controls, ARBs reduce the risk of strokes, heart failure and new onset diabetes. Currently, routine use of an ARB in patients with CHD is not recommended, but they are an appropriate alternative in patients who require an ACE inhibitor but are intolerant of these agents because of cough.

Lipid-lowering agents—

Statins reduce mortality and cardiovascular morbidity in patients with CHD, and the benefits extend to patients at least up to the age of 85. Statins have been shown to reduce adverse cardiovascular events even in patients who have LDL cholesterol below 100 mg/dL. This beneficial effect has been attributed to the cholesterol-independent pleiotropic effects of statins including improvement in endothelial function, enhancing the stability of atherosclerotic plaques, decreasing vascular oxidative stress and inflammation, and inhibiting the thrombogenic response. Therefore, all patients with CHD or diabetes should be on statins to lower LDL cholesterol to ≤70 mg/dL if not contraindicated. As with other medications, it is advisable to start with a lower dose and titrate the drug more slowly in patients older than 75 years.

Warfarin—

Warfarin is indicated in patients with CHD complicated by atrial fibrillation or LV mural thrombus with embolization. Warfarin can also be used as an alternative to aspirin in aspirin-intolerant patients. Older patients are at increased risk for bleeding complications with warfarin, especially during concomitant treatment with nonsteroidal antiinflammatory drugs (NSAIDs).

Other therapies—

Mainly for patients with angina refractory to maximal treatment with the above drugs are spinal cord stimulation and external counterpulsation, but there is not enough data to recommend these. A new antianginal drug is ranolazine, a partial fatty acid oxidation inhibitor that shifts adenosine triphosphate (ATP) production from fatty acids to more oxygen-efficient carbohydrate oxidation. However, it prolongs the QT interval. Because it does not affect heart rate or BP, it is useful in those patients who have not responded to maximally-tolerated other antianginal medications.

Revascularization

Patients with stable CAD who can perform ordinary activity without symptoms on optimal medical therapy and who have normal or only moderately depressed LV function can be managed medically. Supporting this recommendation is the COURAGE trial, where patients with stable angina, objective evidence of myocardial ischemia, and an LV ejection fraction ≥30% with coronary vessels suitable for PCI were randomized to optimal medical management or PCI with optimal medical management. In a follow-up of 2.5–7 years (median: 4.6 years), there was no difference between optimal medical management with or without PCI in the composite of MI, stroke, and death.

PCI and coronary artery bypass surgery are highly effective in improving symptoms and quality of life in older patients with CHD; >50% of all revascularization procedures in the United States are now performed in patients older than 65 years. On the other hand, both coronary angioplasty with and without stents and bypass surgery are associated with increased mortality and major complications in the very old, especially in patients older than age 80 years; thus, careful selection of candidates for revascularization procedures is of paramount importance. In general, percutaneous coronary revascularization is associated with lower mortality and major morbidity (including stroke, delirium) as well as much more rapid recovery compared with coronary bypass surgery in older patients. However, the need for repeat revascularization procedures is higher after angioplasty, and long-term outcomes are similar. Thus, both procedures represent suitable options for older patients with severe symptomatic CHD, and the choice of procedure should be based on anatomical considerations, prevalent comorbidities, and patient preferences. Up to 50% of older patients undergoing coronary bypass surgery may experience a decline in cognitive function in the perioperative period. Although these cognitive deficits are transient in many patients, a significant proportion may exhibit persistent cognitive impairment during long-term follow-up.

Prognosis

The prognosis of chronic CHD is highly variable. Although some patients remain minimally symptomatic or asymptomatic for decades, others experience marked disability despite multiple therapeutic interventions. Still others succumb to the disease after suffering a large MI or fatal arrhythmia. Factors that adversely influence prognosis include older age, male gender, more severe CHD, more severe heart failure or LV systolic dysfunction (lower ejection fraction), more severe symptoms or functional limitations, presence of diabetes or atrial fibrillation, and presence of significant ventricular arrhythmias (Table 28–5).