Hlatky and colleagues³³ found the exercise ECG to have a sensitivity of 84% and specificity of 70% for the diagnosis of CAD in persons older than 60 years. Newman and Phillips³⁴ found a sensitivity of 85%, specificity of 56%, and positive predictive value of 86% for the exercise ECG in diagnosing CAD. The increased sensitivity of the exercise ECG with increasing age found in these two treadmill exercise studies was probably due to the increased prevalence and severity of CAD in older adults.

Exercise stress testing also has prognostic value in older patients with CAD.^35–37 Deckers and associates³⁷ demonstrated that the 1-year mortality was 4% for 48 patients 65 years of age or older who were able to do an exercise stress test after acute MI and 37% for the 63 older patients unable to do the exercise stress test after acute MI.

Exercise stress testing using thallium perfusion scintigraphy, radionuclide ventriculography, and echocardiography is also useful for the diagnosis and prognosis of CAD.^38–40 Iskandrian and coworkers³⁸ showed that exercise thallium-201 imaging can be used for risk stratification of older patients with CAD. The risk for cardiac death or nonfatal MI at 25-month follow-up in 449 patients 60 years of age or older was less than 1% in patients with normal images, 5% in patients with a single-vessel thallium-201 abnormality, and 13% in patients with multivessel thallium-201 abnormality.

Ambulatory electrocardiography performed for 24 hours is also useful for detecting myocardial ischemia in older adults with suspected CAD who cannot perform treadmill or bicycle exercise stress testing because of advanced age, intermittent claudication, musculoskeletal disorders, heart failure, or pulmonary disease. Ischemic ST-segment changes demonstrated on 24-hour ambulatory ECGs correlate with transient abnormalities in myocardial perfusion and LV systolic dysfunction. The changes may be associated with symptoms, or symptoms may be completely absent, which is referred to as silent myocardial ischemia. Silent myocardial ischemia is predictive of future coronary events, including cardiovascular mortality in older adults with CAD.^{3–5,31,45–47} The incidence of new coronary events is especially increased in older adults with silent myocardial ischemia plus complex ventricular arrhythmias,³¹ abnormal LVEF,⁴⁵ or echocardiographic LV hypertrophy.⁴⁷

Multislice Computed Tomography and Magnetic Resonance Imaging

A direct comparison of multislice computed tomography angiography (MSCTA) with magnetic resonance imaging (MRI) for noninvasive coronary arteriography was performed in 129 patients, mean age 64 years, with suspected CAD.⁴⁹ Sensitivity for coronary stenoses larger than 50% of luminal diameter was 82% for MSCTA versus 54% for MRI; the respective specificities were 90% and 87%. The negative predictive value was slightly higher for MSCTA (95% vs. 90%). In this study, 74% of patients preferred MSCTA over MRI. The greater diagnostic accuracy of MSCTA over MRI in this study is consistent with meta-analyses of both tests.^50,51

64-MSCTA and coronary angiography were performed in 145 patients, mean age 67 years, and stress testing was done in 47 of these patients to determine the sensitivity, specificity, positive predictive value, and negative predictive value of these tests in diagnosing obstructive CAD in patients with suspected CAD.⁵² Of 145 patients, 64-MSCTA had a 98% sensitivity, 74% specificity, 90% positive predictive value, and 94% negative predictive value in diagnosing obstructive CAD. Of 47 patients, stress testing had a 69% sensitivity, 36% specificity, 78% positive predictive value, and 27% negative predictive value for diagnosing obstructive CAD, whereas 64-MSCTA had a 100% sensitivity, 73% specificity, 92% positive predictive value, and 100% negative predictive value for diagnosing obstructive CAD. 64-MSCTA has a better sensitivity, specificity, positive predictive value, and negative predictive value than stress testing in diagnosing obstructive CAD.⁵² The ability to estimate myocardial blood flow and fractional flow reserve with MSCTA may allow more accurate assessment of hemodynamically significant coronary lesions without the need for invasive coronary angiography.⁵³ Unrecognized MI can be detected by resting electrocardiography, echocardiography, nuclear imaging, or cardiovascular MRI.⁵⁴

Hypertension

Systolic hypertension in older adults is diagnosed if the systolic blood pressure is 140 mm Hg or higher from two or more readings on two or more visits.⁶¹ Diastolic hypertension in older adults is similarly diagnosed if the diastolic blood pressure is 90 mm Hg or higher.⁶¹ In a study of 1819 persons, mean age 80 years, living in the community, the prevalence of hypertension was 71% in older African Americans, 64% in elderly Asians, 62% in older Hispanics, and 52% in older whites.⁶²

Isolated systolic hypertension in older adults is diagnosed if the systolic blood pressure is 140 mm Hg or higher, with a diastolic blood pressure less than 90 mm Hg.⁶¹ Approximately two thirds of older adults with hypertension have isolated systolic hypertension.⁶²

Isolated systolic hypertension and diastolic hypertension are both associated with increased CAD morbidity and mortality in older adults.⁶³ Increased systolic blood pressure is a greater risk factor for CAD morbidity and mortality than increased diastolic blood pressure.⁶³ The higher the systolic or diastolic blood pressure, the greater the morbidity and mortality from CAD in older women and men. The Cardiovascular Health Study demonstrated in 5202 older men and women that a brachial systolic blood pressure greater than 169 mm Hg was associated with a 2.4-fold greater 5-year mortality.⁵⁵

At 30-year follow-up of persons 65 years and older in the Framingham Heart Study, systolic hypertension was related to a greater incidence of CAD in older men and women.⁶⁴ Diastolic hypertension correlated with the incidence of CAD in older men but not in older women.⁶⁴ At 40-month follow-up of 664 older men and 48-month follow-up of 1488 older women, systolic or diastolic hypertension was associated with a relative risk of new coronary events of 2.0 in men and 1.6 in women.⁵⁸ Data from the Framingham study have also suggested the importance of increased pulse pressure, a measure of large artery stiffness. Among 1924 men and women aged 50 to 79 years, at any given level of systolic blood pressure of 120 mm Hg or higher, the risk of CAD over 20 years rose with lower diastolic blood pressure, suggesting that higher pulse pressure was an important component of risk.⁶⁵ Among 1061 men and women aged 60 to 79 years in the Framingham Heart Study, the strongest predictor of CAD risk was pulse pressure (hazard ratio, 1.24).⁶⁶

Older adults with hypertension should be treated with salt restriction, weight reduction if necessary, cessation of drugs that increase blood pressure, avoidance of alcohol and tobacco, increase in physical activity, decrease of dietary saturated fat and cholesterol, and maintenance of adequate dietary potassium, calcium, and magnesium intake. In addition, antihypertensive drugs have been shown to reduce CAD events in older men and women with hypertension.^67–75

The Hypertension in the Very Elderly Trial (HYVET) randomized 3845 patients aged 80 years and older, mean age 84 years, with a sitting mean blood pressure of 173/90 mm Hg, to indapamide plus perindopril if needed versus a double-blind placebo.⁷⁵ The study was prematurely stopped at 2 years (median follow-up, 1.8 years) because antihypertensive drug therapy reduced fatal or nonfatal stroke by 30%, fatal stroke by 39%, all-cause mortality by 21%, death from cardiovascular causes by 23%, and heart failure by 64%.⁷⁵

Older adults with CAD should have their blood pressure reduced to less than 140/90 mm Hg and to less than 140/90 mm Hg if diabetes mellitus or chronic renal disease is present.⁶¹ Most older patients with hypertension will require two or more antihypertensive drugs to achieve this blood pressure goal.⁶¹ The drugs of choice for treating CAD with hypertension are β-blockers and angiotensin-converting enzyme (ACE) inhibitors.^61,76 If a third antihypertensive drug is needed, a thiazide diuretic should be administered.⁶¹

Left Ventricular Hypertrophy

Elderly men and women with ECG LV hypertrophy and echocardiographic LV have an increased risk of developing new coronary events hypertrophy.^{25–27,29,77} At 4-year follow-up of 406 older men and 735 older women in the Framingham study, echocardiographic LV hypertrophy was 15.3 times more sensitive in predicting new coronary events in older men and 4.3 times more sensitive in predicting new coronary events in older women than electrocardiographic LV hypertrophy.⁷⁷ At 37-month follow-up of 360 men and women with hypertension or CAD, mean age 82 years, echocardiographic LV hypertrophy was 4.3 times more sensitive in predicting new coronary events than electrocardiographic LV hypertrophy.²⁶

Physicians should try to prevent LV hypertrophy from developing or progressing in older men and women with CAD. A meta-analysis of 109 treatment studies found that ACE inhibitors were more effective than other antihypertensive drugs in decreasing LV mass.⁷⁸

Dyslipidemia

Numerous studies have demonstrated that a high serum total cholesterol level is a risk factor for new or recurrent coronary events in older men and women.^58,79–81 At 40-month follow-up of 664 older men and at 48-month follow-up of 1488 older women, an increment of 10 mg/dL of serum total cholesterol was associated with an increase in the relative risk of 1.12 for new coronary events in men and women.⁵⁸

A low-serum, high-density lipoprotein (HDL) cholesterol level is a risk factor for new coronary events in older men and women.^{58,79,82–84} In the Framingham study,⁷⁹ Established Populations for Epidemiologic Studies of the Elderly study,⁸¹ and a large cohort of nursing home patients,⁵⁸ a low serum HDL cholesterol level was a more powerful predictor of new coronary events than total serum cholesterol. At 40-month follow-up of 664 older men and 48-month follow-up of 1488 older women, a decrement of 10 mg/dL of serum HDL cholesterol increased the relative risk of new coronary events 1.70 times in men and 1.95 times in women.⁵⁸

Hypertriglyceridemia is a risk factor for new coronary events in older women but not in older men.^58,79 At 40-month follow-up of older men and 48-month follow-up of older women, the level of serum triglycerides was not a risk factor for new coronary events in men and was a very weak risk factor for new coronary events in women.⁵⁸

Numerous studies have demonstrated that statins reduce new coronary events in older men and women with CAD.^85–98 The absolute reduction in new coronary events in these studies is greater for older adults than for younger persons. In an observational prospective study of 488 men and 922 women, mean age 81 years, with prior MI and a serum low-density lipoprotein (LDL) cholesterol level of 125 mg/dL or higher, 48% of persons were treated with statins.⁸⁹ At 3-year follow-up, statins reduced new coronary events by 50%.⁸⁹ The lower the LDL cholesterol level achieved in this study, the greater the reduction in new coronary events.⁸⁹

In the 1263 persons aged 75 to 80 years at study entry and 80 to 85 years at follow-up in the Heart Protection Study, any major vascular event was significantly reduced 28% by simvastatin. Lowering the serum LDL cholesterol level from less than 116 mg/dL to less than 77 mg/dL by simvastatin caused a 25% significant reduction in vascular events.⁸⁸

In the Heart Protection Study, 3500 persons had initial serum LDL cholesterol levels less than 100 mg/dL.⁸⁸ A decrease of the serum LDL cholesterol level from 97 to 65 mg/dL by simvastatin in these persons caused a similar decrease in risk, as did treating patients with higher serum LDL cholesterol levels. The Heart Protection Study investigators recommended treating those at high risk for cardiovascular events with statins, regardless of the initial levels of serum lipids, age, or gender.⁸⁸

On the basis of these and other data,^89,95–98 the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines⁶⁰ and updated National Cholesterol Education Program III guidelines⁹⁹ stated that in very high-risk persons, working toward a serum LDL cholesterol level of less than 70 mg/dL is a reasonable clinical strategy.

A meta-analysis was performed in nine randomized trials of statins for secondary prevention in 19,569 patients aged 65 to 82 years.¹⁰⁰ Over 5 years, statins reduced all-cause mortality by 22%, CAD mortality by 30%, nonfatal by MI 26%, need for revascularization by 30%, and by stroke 25%. The estimated number needed to treat to save one life was 28.¹⁰⁰

The 2013 ACC/AHA lipid guidelines recommend the use of high-dose statins (20 to 40 mg daily of rosuvastatin or 40 to 80 mg daily of atorvastatin) to adults aged 75 years and younger with arteriosclerotic cardiovascular disease (ASCVD) unless contraindicated with a class I indication.¹⁰¹ Moderate-dose or high-dose statins are reasonable to administer to persons with ASCVD older than 75 years with a class IIa indication. Persons aged 21 years and older with a serum LDL cholesterol level of 190 mg/dL or higher should be treated with high-dose statins with a class I indication. For primary prevention in diabetics aged 40 to 75 years and a serum LDL cholesterol level between 70 to 189 mg/dL moderate-dose statins should be administered with a class I indication. For primary prevention in diabetics aged 40 to 75 years, a serum LDL cholesterol level between 70 to 189 mg/dL and a 10-year risk of ASCVD of 7.5% or higher calculated from the pooled cohort equation, high-dose statins should be administered with a class IIa indication. For primary prevention in diabetics aged 21 to 39 years or older than 75 years and a serum LDL cholesterol level between 70 to 189 mg/dL, moderate-dose statins or high-dose statins should be administered with a class IIa indication. Adults aged 40 to 75 years without diabetes mellitus or ASCVD with a serum LDL cholesterol level between 70 to 189 mg/dL and a 10-year risk of ASCVD of 7.5% or higher calculated from the pooled cohort equation should be treated with high-dose statins or moderate-dose statins with a class I indication. Adults aged 40 to 75 years of age without diabetes mellitus or ASCVD with a serum LDL cholesterol level between 70 to 189 mg/dL and a 10-year risk of ASCVD of 5% to 7.4%, calculated from the pooled cohort equation, should be treated with moderate-dose statins with a class IIa indication.¹⁰¹

Diabetes Mellitus

Diabetes mellitus is a risk factor for new coronary events in older men and women.^58,79,102 In the Cardiovascular Health Study, an elevated fasting glucose level (>130 mg/dL) increased 5-year mortality by 1.9-fold.⁵⁵ At 40-month follow-up of 664 older men and 48-month follow-up of 1488 older women, diabetes mellitus increased the relative risk of new coronary events by 1.9-fold in men and 1.8-fold in women.⁵⁸ Older diabetics without CAD have a higher incidence of new coronary events than older nondiabetics with CAD.¹⁰³

Persons with diabetes mellitus are more often obese and have higher serum LDL cholesterol and triglyceride levels and lower serum HDL cholesterol levels than nondiabetics. Diabetics also have a higher prevalence of hypertension and LV hypertrophy than nondiabetics. These risk factors contribute to the increased incidence of new CAD events in diabetics compared to nondiabetics. Increased age can further amplify these risk factor differences and contribute to greater CAD risk.

Diabetics with microalbuminuria have more severe angiographic CAD than diabetics without microalbuminuria.¹⁰⁴ Diabetics also have a significant increasing trend of HbA1c levels over the increasing number of vessels with CAD.¹⁰⁵

Older adults with diabetes mellitus should be treated with dietary therapy, weight reduction if necessary, and appropriate drugs if necessary to control hyperglycemia. The HbA1c level should be maintained at less than 7%.^60,106,107 Other risk factors such as smoking, hypertension, dyslipidemia, obesity, and physical inactivity should be controlled. Diabetics should be treated with statins, as recommended by the 2013 ACC/AHA lipid guidelines.¹⁰¹ The blood pressure should be reduced to less than 140/90 mm Hg.⁶¹ Metformin is the drug of choice.¹⁰⁷ Sulfonylureas should be avoided in persons with CAD.^108,109

Obesity

Obesity was an independent risk factor for new CAD events in older men and women in the Framingham Heart Study.¹¹⁰ Disproportionate distribution of fat to the abdomen assessed by the waist-to-hip circumference ratio has also been shown to be a risk factor for cardiovascular disease, mortality from CAD, and total mortality in older men and women.^111,112

Obese men and women with CAD must undergo weight reduction. Weight reduction is also a first approach to controlling mild hypertension, hyperglycemia, and dyslipidemia. Regular aerobic exercise should be used in addition to diet to treat obesity. The body mass index should be reduced to 18.5 to 24.9 kg/m².⁵⁴

Physical Inactivity

Physical inactivity is associated with obesity, hypertension, hyperglycemia, and dyslipidemia. At 12-year follow-up in the Honolulu Heart Program, physically active men 65 years of age or older had a relative risk of 0.43 for CAD compared with inactive men.¹¹³ Lack of moderate or vigorous exercise increased 5-year mortality in older men and women in the Cardiovascular Heart Study.⁵⁵

Moderate exercise programs suitable for older adults include walking, climbing stairs, swimming, and bicycling. However, care must be taken in prescribing any exercise program because of the high risk of injury in this age group. Group or supervised sessions, including aerobic classes, offered by senior health care plans are especially appealing. Exercise training programs are not only beneficial in preventing coronary heart disease (CHD) but have also been found to improve endurance and functional capacity in older adults after MI.^114,115

Treatment of Unstable Angina Pectoris and Non–ST-Segment Elevation Myocardial Infarction

Treatment of patients with unstable angina pectoris and NSTEMI should be initiated in the emergency department. Reversible factors precipitating unstable angina pectoris should be identified and corrected. Oxygen should be administered to patients who have cyanosis, respiratory distress, congestive heart failure, or high-risk features. Oxygen therapy should be guided by arterial oxygen saturation and should not be given if the arterial oxygen saturation is more than 94%. Morphine sulfate should be administered IV when anginal chest pain is not immediately relieved with nitroglycerin or when acute pulmonary congestion and/or severe agitation is present.

Aspirin should be administered to all patients with unstable angina pectoris and NSTEMI unless contraindicated and continued indefinitely.^134,135 The first dose of aspirin should be chewed rather than swallowed to ensure rapid absorption.

The ACC/AHA 2011 guidelines have updated conditions for which clopidogrel should be administered in addition to indefinite use of aspirin in hospitalized patients with unstable angina pectoris and NSTEMI for whom an early noninterventional approach or PCI is planned. Clopidogrel should be withheld for 5 to 7 days in patients for whom elective coronary artery surgery is planned.¹³⁵ Prasugrel may be considered instead of clopidogrel if PCI is planned if there is a low bleeding risk, no history of stroke or ischemic attack, age younger than 75 years, body weight more than 60 kg, and the need for CABS considered unlikely.¹³⁶ Ticagrelor may also be used instead of clopidogrel if PCI is planned, but the aspirin dose must not be more than 100 mg daily.^137,138 When possible, ticagrelor should be stopped at least 5 days prior to any surgery. On the basis of data from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial^139,140 and Clopidogrel for the Reduction of Events During Observation (CREDO) trial,¹⁴¹ 81 mg of aspirin daily plus 75 mg of clopidogrel daily should be administered to patients with unstable angina and NSTEMI for at least 1 year.

Nitrates should be administered immediately in the emergency department to patients with unstable angina and NSTEMI.^135,142 Patients whose symptoms are not fully relieved with three 0.4-mg sublingual nitroglycerin tablets or a spray taken 5 minutes apart and initiation of an IV β-blocker should be treated with continuous IV nitroglycerin.^135,142 Topical or oral nitrates are alternatives for patients without ongoing refractory symptoms.^135,142

β-Blockers should be administered IV in the emergency department unless there are contraindications to their use, followed by oral administration and continued indefinitely.^135,142 Metoprolol may be given in 5-mg IV increments over 1 to 2 minutes and repeated every 5 minutes until 15 mg has been given, followed by oral metoprolol 100 mg twice daily. The target resting heart rate is 50 to 60 beats/min.

An oral ACE inhibitor should also be given unless there are contraindications to its use and continued indefinitely.^135,142 In patients with continuing or frequently recurring myocardial ischemia despite nitrates and β-blockers, verapamil or diltiazem should be added to their therapeutic regimen in the absence of LV systolic dysfunction (class IIa indication).^135,142 The benefit of calcium channel blockers in the treatment of unstable angina pectoris is limited to symptom control.^135,142 Intraaortic balloon pump counterpulsation should be used for severe myocardial ischemia that is continuing or occurs frequently, despite intensive medical therapy, or for hemodynamic instability in patients before or after coronary angiography.^135,142

A platelet glycoprotein IIb/IIIa inhibitor should also be administered in addition to aspirin and clopidogrel and heparin in patients in whom coronary angioplasty is planned.^135,142 Abciximab can be used for 12 to 24 hours in patients with unstable angina/NSTEMI in whom coronary angioplasty is planned within the next 24 hours.^135,142 Eptifibatide or tirofiban should be administered in addition to aspirin and low-molecular-weight heparin or unfractionated heparin to patients with continuing myocardial ischemia, an elevated cardiospecific troponin I or T, or with other high-risk features in whom an invasive management is not planned.^135,142

IV thrombolytic therapy is not recommended for the treatment of unstable angina and NSTEMI.^135,142 Prompt coronary angiography should be performed without noninvasive risk stratification in patients who fail to stabilize with intensive medical treatment.¹⁴² Coronary revascularization should be performed in patients with high-risk features to reduce coronary events and mortality.^{135,142–144}

On the basis of the available data, the ACC/AHA 2013 guidelines have recommended the use of statins in all patients with acute coronary syndromes without contraindications.¹⁰¹ Statins should be continued indefinitely after hospital discharge.^{95,99,101,142,145}

Patients should be discharged on aspirin plus clopidogrel, β-blockers, and ACE inhibitors in the absence of contraindications. Nitrates should be given for ischemic symptoms. A long-acting nondihydropyridine calcium channel blocker may be given for ischemic symptoms that occur, despite treatment with nitrates plus β-blockers. Hormone therapy should not be administered to postmenopausal women.^146,147