Chronic Stable Angina
Andrew M. Peterson
Christopher C. Roe
Cardiovascular disease was responsible for nearly 40.6% of deaths recorded in 2014, making it the leading cause of death in the United States (Go et al., 2014). Angina is a clinical syndrome caused by coronary heart disease (CHD) and affects nearly 10.2 million Americans. In 2010, the cost of cardiovascular disease was estimated to be nearly $315.4 billion (Go et al., 2014).
Fortunately, the overall mortality rate from CHD has been declining. The reason for this decline is the improved treatments for cardiovascular disease, including angina. Despite this hopeful note, angina remains a significant challenge for primary care management. Successful management depends on an in-depth understanding of the pathologic process, diagnosis, and treatment of this symptom complex.
Angina is a syndrome—a constellation of symptoms— that results from myocardial oxygen demand being greater than the oxygen supply (myocardial ischemia). By definition, angina is associated with reversible ischemia, so it does not result in permanent myocardial damage. Myocardial infarction (MI) is the result of irreversible ischemia when myocardial tissue is permanently damaged.
Patients with angina may report left-sided chest pain, discomfort, heaviness, or pressure, and the sensation may radiate to the back, neck, jaw, and throat or arms. Usually, these sensations last 1 to 15 minutes. Patients may also experience shortness of breath or fatigue. It is important to note, however, that not all patients present with “angina” in a typical fashion. For example, dyspnea on exertion may be the only presenting symptom. If a patient presents with unique symptoms, his or her group of symptoms associated with identified ischemia is called that patient’s “anginal equivalent.” Box 21.1 lists common and unique terms used to describe angina.
Angina is called stable when the paroxysmal chest pain or discomfort is provoked by physical exertion or emotional stress and is relieved by rest and/or nitroglycerin (NTG). Stable angina exists when the stimulating factors or activities and the degree and duration of discomfort have not changed for the past 60 days.
Anginal episodes that increase in frequency, duration, or severity are referred to as unstable. Unstable angina is experienced when the patient is at rest or if the episode is prolonged or progressive. Unstable angina has also been called preinfarction angina, crescendo angina, or intermittent coronary syndrome. It is differentiated from stable angina by the fact that symptoms may be triggered by minimal physical exertion or may be present at rest. Patients who experience unstable angina are at high risk for developing an MI.
Other types of angina include variant (or Prinzmetal) angina, nocturnal angina, angina decubitus, and postinfarction angina. Stable angina is frequently managed in the primary care setting and is the focus of this chapter.
CAUSES
The development of angina is directly related to the risk factors that have been identified for CHD. Nonmodifiable risk factors for CHD cannot be altered or improved by the patient; they include age, family history, and gender. Modifiable risk factors may be controlled or treated by lifestyle modifications or pharmacologic therapy to reduce the risk of morbidity or mortality from CHD. Modifiable risk factors include cigarette smoking, hypertension, dyslipidemia, diabetes, obesity, and physical inactivity. Box 21.2 lists the risk factors for chronic stable angina.
BOX 21.1
Words Patients Use to Describe Angina
Words Patients Use to Describe Angina
Ache, toothache-like, dull
Burning, heartburn, soreness, bursting, searing indigestion
Choking, strangling, compressing, constricting, tightness, viselike
Discomfort, fullness, swelling, heaviness, pressure, weight, uncomfortable
Nonmodifiable Risk Factors
Age
It is uncommon for men younger than age 40 and premenopausal women to have symptomatic CHD, but the incidence increases with age and is increased in women after menopause. More than 80% of patients who die of CHD are over age 65 (American Heart Association, 2010). This increasing incidence of CHD with age is likely linked to age-related changes in the vasculature and the higher prevalence of other CHD risk factors among older persons.
Heredity
A family history of premature CHD in a first-degree relative (i.e., mother, father, sister, or brother) is a strong predictor for CHD in an individual. Premature CHD is defined as occurring in a man younger than age 55 or in a woman younger than age 65. The strong association between family history and the development of CHD has been consistently demonstrated in several studies. Furthermore, race has been shown to be a factor. Data show that 44% of African Americans have high blood pressure versus 27.4% of Whites, thus increasing their risk of a cardiovascular event (Go et al., 2014). Therefore, individuals with a family history of CHD should be carefully screened for other CHD risk factors and managed appropriately.
BOX 21.2
Risk Factors for Chronic Stable Angina
Risk Factors for Chronic Stable Angina
NONMODIFIABLE RISK FACTORS
Age
Heredity
Gender
MODIFIABLE RISK FACTORS
Cigarette smoking
Hypertension
Dyslipidemia
Diabetes
Obesity
Physical inactivity
Gender
In general, the risk of CHD is higher for men than women. Male gender is considered a nonmodifiable risk factor for CHD. Differences for CHD susceptibility diminish, however, when comparing postmenopausal women and older men. In fact, after age 65, the incidence of CHD increases in women, but it does not reach that of men.
Modifiable Risk Factors
Cigarette Smoking
Cigarette smoking increases the risk of CHD by at least twofold to threefold. Smoking increases the incidence of atherosclerosis by a mechanism that is not clearly understood. It is thought to increase the release of catecholamines, which leads to elevated blood pressure due to an increased workload of the heart caused by an increase in the heart rate and peripheral vascular constriction. Catecholamines also increase the release of free fatty acids, which increases the amount of lipids in the blood. Smoking lowers high-density lipoprotein (HDL) levels and increases low-density lipoprotein (LDL) levels, and is thought to promote platelet activation, which increases the risk of clot formation in the arteries. All patients with CHD risk factors or established disease should be instructed to stop smoking. See Chapter 53 for a more detailed discussion of smoking cessation.
Hypertension
It is estimated that over 77.9 million Americans have elevated blood pressure (Go et al., 2014). Hypertension is a major risk factor for CHD and can lead to vascular complications that increase morbidity and mortality. Additionally, the higher the blood pressure, the higher the risk of MI and other cardiovascular events.
Atherosclerotic changes in the vasculature are exacerbated by increased pressure. Increased blood pressure alone also causes injury to the inner lining of the arteries, resulting in atherosclerotic changes and thrombus formation. As the arteries become stiff and narrow, the blood flow that normally increases during physical activity is restricted to a greater degree, resulting in ischemic symptoms. Chapter 19 provides further discussion of drug therapy for hypertension.
Dyslipidemia
Nearly half of the American population has high cholesterol (American Heart Association, 2010). Cholesterol plays a substantial role in the pathophysiology of atherosclerosis and CHD. High levels of LDL cholesterol and low levels of HDL cholesterol are associated with an increased risk of cardiovascular disease and occurrence of MI or other poor cardiovascular outcomes. Treatment of dyslipidemia in patients with CHD using pharmacologic and nonpharmacologic means has been
shown in multiple large-scale studies to reduce the risk of cardiovascular death. In 2014, a new guideline was released outlining the diagnosis and treatment of dyslipidemia in adults. See Chapter 20 for more detailed information on the treatment of dyslipidemia.
shown in multiple large-scale studies to reduce the risk of cardiovascular death. In 2014, a new guideline was released outlining the diagnosis and treatment of dyslipidemia in adults. See Chapter 20 for more detailed information on the treatment of dyslipidemia.
Diabetes
Cardiovascular disease is the most common cause of death in patients with diabetes. In fact, patients with diabetes have the same risk of having an MI as a patient who already has a history of an MI. Although data have not shown a clear or conclusive link between glucose control and cardiovascular risk reduction, an effort should be made to prevent or treat diabetes in these patients. For a complete discussion of diabetes treatment, see Chapter 45.
Obesity
In the United States, 68.2% of the population is considered overweight or obese (Go et al., 2014). The increasing incidence of obesity has been attributed to poorer nutrition and a more sedentary lifestyle.
Obesity is a risk factor for CHD in both men and women. Hypertension, dyslipidemia, and diabetes are more common in patients who are obese, but obesity also increases cardiovascular risk independent of these other risk factors by a mechanism that is not well understood. Even modest weight loss can improve blood pressure, hypertension, and insulin resistance and reduce cardiovascular risk. Weight loss is discussed in Chapter 54.
Physical Inactivity
A sedentary lifestyle predisposes patients to CHD. Regular physical exercise reduces blood pressure, maintains a healthy weight, and improves dyslipidemia, but it also reduces the risk of CHD independent of these changes. Patients should be carefully screened and counseled before beginning an exercise program. Exercise may include walking, running, cycling, or formalized aerobic exercise routines. It is recommended that patients get 30 to 60 minutes of aerobic exercise every day at least 5 days per week. Resistance training on 2 day/week may also be of benefit.
PATHOPHYSIOLOGY
Angina is a symptomatic manifestation of reversible myocardial ischemia, which occurs when demand for oxygen in the myocardium exceeds available supply. This imbalance between oxygen supply and demand is caused by limited blood supply due to narrowing of the blood vessels that supply the heart muscle. The most common cause of this narrowing of the coronary arteries is atherosclerotic disease. Rarely, vasospasm of the coronary arteries narrows the arteries, thereby limiting the blood supply to the heart muscle. Other even more uncommon sources of anginal symptoms are thrombosis, aortic stenosis, primary pulmonary hypertension, and severe hypertension.
Atherosclerotic Disease
The pathophysiology of angina involves atherosclerosis, a disorder of lipid metabolism resulting in the deposit of cholesterol in the blood vessel. Over time, this causes a reactive endothelial injury that eventually results in a narrowing of the vessels by episodes of acute thrombosis. The narrow arteries impair the ability of oxygen and nutrients to reach the myocardium. This reduction in blood supply, or ischemia, impairs myocardial metabolism. The myocardial cells remain alive but cannot function normally. Once the blood supply is restored, cardiac function returns to normal. If the ischemia is caused by complete occlusion of the coronary artery, an MI (cell death) occurs.
Regardless of the risk factors that cause the development of atherosclerosis and resulting restriction of coronary blood supply, the pathophysiologic process is essentially the same. The three layers of the arterial wall—intima, media, and adventitia—are affected by structural changes that lead to CHD. The intima is a single layer of endothelial cells, constituting the innermost surface of the artery. It is impermeable to the substances in the blood. The media is the middle layer of the artery and is made up almost entirely of smooth muscle. The outer layer, or adventitia, consists mainly of smooth muscle cells, fibroblasts (which are normally only in this layer), and loose connective tissue. Atherosclerotic changes in the artery occur in stages. Normally, the intima is thin and contains only an occasional muscle cell. As a person ages, the intima slowly increases in thickness and muscle cells proliferate.
Atherosclerosis primarily affects the intima of the arterial wall. It normally takes years to develop, and clinical manifestations do not occur until the disorder is well advanced. CHD progresses through three developments—the fatty streak, the fibrous plaque, and the complicated lesion.
The Fatty Streak
Thought to begin in childhood, the fatty streak is caused by the development of fatty, lipid-rich lesions that result from macrophages adhering to the intact endothelial surface. The macrophages take in lipids, which leads to a thickening of the intimal layer. Smooth muscle cells migrate to the intima and become lipid laden. The lesions at this stage do not obstruct the artery. However, on examination, fatty streaks appear in the coronary arteries as early as age 15. They continue to enlarge through the third decade of life and appear to be a precursor to plaque formation, although the process is not clearly understood.
The Fibrous Plaque
The raised fibrous plaque is a white, elevated area on the surface of the artery. It signals the beginning of progressive changes in the arterial wall, including protrusion of the lesion into the lumen of the artery. These more advanced lesions begin to develop at approximately age 30 in most patients. The major change in the arterial intima during this phase is the migration and proliferation of smooth muscle cells and the formation of a fibrous cap over a deeper deposit of extracellular lipid and cell
debris. The lipid accumulation directly or indirectly reduces the blood supply. The decrease in blood supply is permanent and results in cell necrosis and cell debris.
debris. The lipid accumulation directly or indirectly reduces the blood supply. The decrease in blood supply is permanent and results in cell necrosis and cell debris.
The Complicated Lesion
A complicated lesion contains a fibrous plaque, calcium deposits, and a thrombus formed by hemorrhage into the plaque. The complicated lesion results from continuing cell degeneration. As the complicated lesion, with its lipid, necrotic center, becomes larger, it calcifies. The intimal surface may develop open or ruptured areas that degenerate into an ulcer. The damage is most likely to occur in areas where blood flow creates the greatest amount of stress in the vessel, such as at branches and bifurcations. The damaged surface allows blood from the artery lumen to enter the lipid core. Then, platelets adhere and thrombus formation begins. The thrombus expands and distorts the plaque, which becomes larger and begins to block the lumen of the artery. The blockage impedes the blood flow needed to supply extra oxygen and nutrients to meet the increased workload of the heart. The result is cardiac ischemia and anginal symptoms. These symptoms are relieved when either the workload of the heart is decreased or administration of vasodilating drugs increases blood flow to the myocardium. Complete blockage can cause permanent myocardial death because the cells are entirely deprived of oxygen and blood flow cannot be restored in time to revive the cardiac cells, resulting in an MI.
Coronary Artery Vasospasm
A less common cause of restricted coronary blood supply may be coronary vasospasm, a narrowing of the coronary artery lumen. This narrowing is produced by an arterial muscle spasm and limits the blood supply to the myocardium. The exact cause is unknown, but it is thought to occur when the smooth muscles of the coronary arteries contract in response to neurogenic stimulation. Cigarette smoking and hyperlipidemia appear to play a role in this type of angina because they interfere with normal neurogenic control of the arterial intima.
Spasm is suspected of playing a role in acute MI, as well as in triggering anginal episodes. Coronary artery spasm also can occur with abrupt nitrate withdrawal, cocaine use, and direct mechanical irritation from cardiac catheterization. However, the exact mechanisms leading to spasm are still unclear.
Activation of Ischemic Episodes
Regardless of the existing pathophysiologic process, ischemic episodes that result in anginal pain are usually activated by two situations occurring simultaneously or independently: (1) ambient factors that increase myocardial oxygen demand and (2) circumstances that decrease oxygen supply. For example, the person with atherosclerosis (noncompliant arteries) climbs a flight of stairs. The activity increases the workload of the heart, and the myocardium needs more oxygen. The damaged arteries are unable to meet this demand. In some situations, the arteries may be so constricted that they are unable to deliver an adequate amount of oxygen even if the person is in a resting state. Therapy is directed at resolution or control of these situations so that the heart can receive the oxygen it needs to meet the physical demands of the body. Control of the blood flow to the heart by increasing it when necessary prevents the pathophysiologic process responsible for the myocardial ischemia.
DIAGNOSTIC CRITERIA
Health History
The health history is an important part of the diagnosis and management of angina. The chief complaint for most patients is usually chest pain or discomfort, but other symptoms may predominate, such as neck or jaw pain or shortness of breath. The patient should be asked to describe the duration, quality, location, severity, and radiation of the pain. Additionally, the practitioner should inquire about potential triggers of the pain and any accompanying symptoms, such as dyspnea, diaphoresis, nausea, or palpitations. The practitioner also should explore what interventions relieved the patient’s pain or symptoms, such as rest or NTG.
For all patients with angina, an assessment of CHD risk factors should be performed to determine an individual patient’s risk for CHD and to better target pharmacologic and nonpharmacologic management. Practitioners should ask patients about both nonmodifiable and modifiable risk factors, including family history, cigarette smoking, hypertension, dyslipidemia, diabetes, and physical inactivity. A past history of cerebrovascular disease or the presence of peripheral vascular disease also increases a patient’s risk of CHD.
Physical Findings
Most commonly, practitioners will not have the opportunity to examine a patient during an acute anginal episode. In that case, the physical examination should focus on the assessment of risk factors and the cardiovascular system as a whole. For example, the practitioner should assess a patient for obesity during the physical examination. Additionally, the vasculature may be evaluated by looking for funduscopic changes or decreased peripheral pulses. Hypertension may be evident from taking the patient’s blood pressure, and clinical signs and symptoms of heart failure may include murmurs, gallops, changes in the heart sounds, edema, rales, or organomegaly. Patients with dyslipidemia may exhibit xanthomas or cholesterol nodules.
If a physical exam is performed during an episode of anginal pain, a variety of findings may be present. These may include extra heart sounds, mild hypertension, tachycardia, or tachypnea. A paradoxical split of S2 may indicate altered left ventricular (LV) heart function associated with the ischemic discomfort.
Diagnostic Tests
Before therapy for angina can be properly prescribed, diagnostic testing is necessary to identify a cardiac cause of the patient’s chest pain. Diagnostic testing includes electrocardiography, echocardiography, exercise tolerance testing, radioisotope imaging, and coronary artery angiography.
Patients with new, current, or recent chest pain should have an electrocardiogram (ECG) to detect signs of cardiac ischemia. During an acute anginal episode, ST segment depressions with or without symmetric T-wave inversions may be noted in the leads that correspond to the myocardium affected. During pain-free intervals, however, the ECG reverts to baseline. ECG changes that may be present in the patient with chronic CHD include evidence of a prior MI, LV hypertrophy, and repolarization abnormalities.
Echocardiography is recommended if valvular disease or heart failure is suspected, if the patient has a history of MI, or if the patient experiences ventricular arrhythmias. Most patients with intermittent episodes of chest pain should undergo an exercise tolerance test with ECG monitoring (also called a stress test) to evaluate the risk of future cardiac events. Those suspected of having coronary ischemia based on the presence of anginal symptoms should undergo testing within 72 hours of symptoms (Fihn et al., 2012). One notable exception would be patients with a high probability of CHD, such as a patient with known coronary disease and classical angina symptoms; these patients should be referred to a specialist for potential advanced interventional therapies. Further testing with radioisotope perfusion testing or coronary artery angiography may be indicated for subgroups of patients. If diagnostic testing confirms cardiac ischemia as the cause of anginal symptoms, drug therapy is warranted.
INITIATING DRUG THERAPY
The treatment goals for the management of angina include relieving the acute anginal episode, preventing additional anginal episodes, preventing progression of CHD, reducing the risk of MI, improving functional capacity, and prolonging survival. These goals should be accomplished while maintaining the patient’s quality of life and avoiding adverse events associated with therapy.
Nonpharmacologic therapy is the cornerstone of treatment for patients with angina. The practitioner must assess the patient’s modifiable risk factors and work with him or her to reduce the risk for CHD. Practitioners should counsel patients on smoking cessation at each clinic visit and provide support and access to pharmacologic treatment if necessary. Patients should be instructed to maintain a normal weight by consuming a low-fat, low-cholesterol diet, and practitioners should provide dietary counseling and refer interested patients to dietitians for further support. Finally, practitioners should encourage patients to engage in regular aerobic exercise. Further details on these lifestyle modifications are provided in Chapters 19, 20, 53, and 54.
The practitioner should emphasize to the patient that nonpharmacologic therapy and lifestyle modifications supplement drug therapy and should continue indefinitely.
Goals of Drug Therapy
After the patient has been properly instructed on nonpharmacologic therapy for angina, appropriate drug therapy may be initiated. A summary of selected agents is provided in Table 21.1. Several classes of medications are used to treat angina, including angiotensin-converting enzyme (ACE) inhibitors, nitrates, beta-blockers, calcium channel blockers, and antiplatelet agents.
Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers
The 2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease recommends that patients with ejection fractions of less than 40% or those with hypertension, diabetes, or kidney disease be placed on an ACE inhibitor unless contraindicated (Fihn et al., 2012). When patients cannot take an ACE inhibitor, an angiotensin receptor blocker (ARB) may be used (Fihn et al., 2012). ACE inhibitors include captopril (Capoten), ramipril (Altace), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), perindopril (Aceon), and lisinopril (Prinivil, Zestril). ARBs include losartan (Cozaar), valsartan (Diovan), candesartan (Atacand), telmisartan (Micardis), eprosartan (Teveten), olmesartan (Benicar), and irbesartan (Avapro).
Mechanism of Action
ACE inhibitors affect the enzyme responsible for the conversion of angiotensin I to angiotensin II. ARBs block the vasoconstriction and aldosterone-secreting effects of angiotensin II by selectively blocking angiotensin II from binding to angiotensin II receptors found in many tissues. Angiotensin II is a potent vasoconstrictor and also stimulates aldosterone secretion. Blocking the production of angiotensin II results in reduced vasoconstriction and sodium and water retention, thus reducing preload, afterload, and ejection fraction. These benefits are helpful in chronic stable angina, heart failure (Chapter 22), and hypertension (Chapter 19).
Dosage
ACE inhibitors and ARBs should be initiated at low doses and followed by gradual dosage increases if the lower doses are well tolerated. Renal function and serum potassium should be assessed within 1 to 2 weeks of starting therapy and periodically thereafter, especially in patients with preexisting diabetes or those receiving potassium supplementation. Table 21.1 shows the doses of some common ACE inhibitors and ARBs when used to treat chronic stable angina.
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