Practice Essentials
Angina pectoris is the result of myocardial ischemia caused by an imbalance between myocardial blood supply and oxygen demand. It is a common presenting symptom (typically, chest pain) among patients with coronary artery disease (CAD). Approximately 9.8 million Americans are estimated to experience angina annually, with 500,000 new cases of angina occurring every year.
Signs and symptoms
Patients should be asked about the frequency of angina, severity of pain, and number of nitroglycerin pills used during episodes. Symptomatology reported by patients with angina commonly includes the following:
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Retrosternal chest discomfort (pressure, heaviness, squeezing, burning, or choking sensation) as opposed to frank pain
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Pain localized primarily in the epigastrium, back, neck, jaw, or shoulders
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Pain precipitated by exertion, eating, exposure to cold, or emotional stress, lasting for about 1-5 minutes and relieved by rest or nitroglycerin
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Pain intensity that does not change with respiration, cough, or change in position
Angina decubitus (a variant of angina pectoris that occurs at night while the patient is recumbent) may occur.
The following should be taken into account in the physical examination:
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For most patients with stable angina, physical examination findings are normal
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A positive Levine sign suggests angina pectoris
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Signs of abnormal lipid metabolism or of diffuse atherosclerosis may be noted
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Examination of patients during the angina attack may be more helpful
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Pain produced by chest wall pressure is usually of chest wall origin
See Clinical Presentation for more detail.
Diagnosis
Diagnostic studies that may be employed include the following:
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Chest radiography: Usually normal in angina pectoris but may show cardiomegaly in patients with previous MI, ischemic cardiomyopathy, pericardial effusion, or acute pulmonary edema
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Graded exercise stress testing: This is the most widely used test for the evaluation of patients presenting with chest pain and can be performed alone and in conjunction with echocardiography or myocardial perfusion scintigraphy
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Coronary artery calcium (CAC) scoring by fast CT: The primary fast CT methods for this application are electron-beam CT (EBCT) and multidetector CD (MDCT)
Other tests that may be useful include the following:
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ECG (including exercise with ECG monitoring and ambulatory ECG monitoring)
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Selective coronary angiography (the definitive diagnostic test for evaluating the anatomic extent and severity of CAD)
See Workup for more detail.
Management
General treatment measures include the following:
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Encouragement of smoking cessation
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Treatment of risk factors (eg, hypertension, diabetes mellitus, obesity, hyperlipidemia)
In patients with CAD, efforts should be made to lower the low-density lipoprotein (LDL) level (eg, with a statin). Current Adult Treatment Panel III (ATP III) guidelines are as follows [1] :
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In high-risk patients, a serum LDL cholesterol level of less than 100 mg/dL is the goal
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In very high-risk patients, an LDL cholesterol level goal of less than 70 mg/dL is a therapeutic option
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In moderately high-risk persons, the recommended LDL cholesterol level is less than 130 mg/dL, but an LDL cholesterol level of 100 mg/dL is a therapeutic option
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Non-high-density lipoprotein (HDL) cholesterol level is a secondary target of therapy in persons with high triglyceride levels (>200 mg/dL); the goal in such persons is a non-HDL cholesterol level 30 mg/dL higher than the LDL cholesterol level goal
Patients with established CAD and low HDL levels are at high risk for recurrent events and should be targeted for aggressive nonpharmacologic and pharmacologic treatment. The currently accepted management approach is as follows:
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In all persons with low HDL cholesterol levels, the primary target of therapy is to achieve the ATP III guideline LDL cholesterol level goals with diet, exercise, and drug therapy as needed
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After the targeted LDL level goal is reached, emphasis shifts to other issues; in patients with low HDL and high triglyceride levels, the secondary priority is to achieve the non-HDL cholesterol level goal (30 mg/dL higher than the LDL goal); in patients with isolated low HDL cholesterol levels and triglyceride levels below 200 mg/dL, drugs to raise HDL can be considered
Other pharmacologic therapies that may be considered include the following:
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Enteric-coated aspirin
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Clopidogrel
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Hormone replacement therapy
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Sublingual nitroglycerin
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Beta blockers
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Calcium channel blockers
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Angiotensin-converting enzyme (ACE) inhibitors
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Injections of autologous CD34+ cells [2]
Revascularization therapy (ie, coronary revascularization) can be considered in the following:
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Patients with left main artery stenosis greater than 50%
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Patients with 2- or 3-vessel disease and left ventricular (LV) dysfunction
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Patients with poor prognostic signs during noninvasive studies
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Patients with severe symptoms despite maximum medical therapy
The 2 main coronary revascularization procedures are (1) percutaneous transluminal coronary angioplasty, with or without coronary stenting, and (2) coronary artery bypass grafting. Considerations for choosing a procedure include the following:
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Patients with 1- or 2-vessel disease and normal LV function who have anatomically suitable lesions are candidates for percutaneous transluminal coronary angioplasty and coronary stenting.
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Drug-eluting stents can remarkably reduce the rate of in-stent restenosis
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Patients with significant left main coronary artery disease, 2- or 3-vessel disease and LV dysfunction, diabetes mellitus, or lesions anatomically unsuitable for percutaneous transluminal coronary angioplasty have better results with coronary artery bypass grafting
Other procedures that may be considered include the following:
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Intra-aortic balloon counterpulsation (in patients who continue to have unstable angina pectoris despite maximal medical treatment): This should be followed promptly by coronary angiography with possible coronary revascularization [3]
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Enhanced external counterpulsation (in patients whose angina is refractory to medical therapy and who are not suitable candidates for either percutaneous or surgical revascularization) [4]
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Laser transmyocardial revascularization (experimental) [5]
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Use of the Coronary Sinus Reducer (Neovasc Medical, Inc, Or Yehuda, Israel), a percutaneous implantable device designed to establish coronary sinus narrowing and elevate coronary sinus pressure (further studies needed)
See Treatment and Medication for more detail.
Background
Angina pectoris is the result of myocardial ischemia caused by an imbalance between myocardial blood supply and oxygen demand. Angina is a common presenting symptom (typically, chest pain) among patients with coronary artery disease. A comprehensive approach to diagnosis and to medical management of angina pectoris is an integral part of the daily responsibilities of health care professionals.
Pathophysiology
Myocardial ischemia develops when coronary blood flow becomes inadequate to meet myocardial oxygen demand. This causes myocardial cells to switch from aerobic to anaerobic metabolism, with a progressive impairment of metabolic, mechanical, and electrical functions. Angina pectoris is the most common clinical manifestation of myocardial ischemia. It is caused by chemical and mechanical stimulation of sensory afferent nerve endings in the coronary vessels and myocardium. These nerve fibers extend from the first to fourth thoracic spinal nerves, ascending via the spinal cord to the thalamus, and from there to the cerebral cortex.
Studies have shown that adenosine may be the main chemical mediator of anginal pain. During ischemia, ATP is degraded to adenosine, which, after diffusion to the extracellular space, causes arteriolar dilation and anginal pain. Adenosine induces angina mainly by stimulating the A1 receptors in cardiac afferent nerve endings. [6]
Heart rate, myocardial inotropic state, and myocardial wall tension are the major determinants of myocardial metabolic activity and myocardial oxygen demand. Increases in the heart rate and myocardial contractile state result in increased myocardial oxygen demand. Increases in both afterload (ie, aortic pressure) and preload (ie, ventricular end-diastolic volume) result in a proportional elevation of myocardial wall tension and, therefore, increased myocardial oxygen demand. Oxygen supply to any organ system is determined by blood flow and oxygen extraction. Because the resting coronary venous oxygen saturation is already at a relatively low level (approximately 30%), the myocardium has a limited ability to increase its oxygen extraction during episodes of increased demand. Thus, an increase in myocardial oxygen demand (eg, during exercise) must be met by a proportional increase in coronary blood flow.
The ability of the coronary arteries to increase blood flow in response to increased cardiac metabolic demand is referred to as coronary flow reserve (CFR). In healthy people, the maximal coronary blood flow after full dilation of the coronary arteries is roughly 4-6 times the resting coronary blood flow. CFR depends on at least 3 factors: large and small coronary artery resistance, extravascular (ie, myocardial and interstitial) resistance, and blood composition.
Myocardial ischemia can result from (1) a reduction of coronary blood flow caused by fixed and/or dynamic epicardial coronary artery (ie, conductive vessel) stenosis, (2) abnormal constriction or deficient relaxation of coronary microcirculation (ie, resistance vessels), or (3) reduced oxygen-carrying capacity of the blood.
Atherosclerosis is the most common cause of epicardial coronary artery stenosis and, hence, angina pectoris. Patients with a fixed coronary atherosclerotic lesion of at least 50% show myocardial ischemia during increased myocardial metabolic demand as the result of a significant reduction in CFR. These patients are not able to increase their coronary blood flow during stress to match the increased myocardial metabolic demand, thus they experience angina. Fixed atherosclerotic lesions of at least 90% almost completely abolish the flow reserve; patients with these lesions may experience angina at rest.
Coronary spasm can also reduce CFR significantly by causing dynamic stenosis of coronary arteries. Prinzmetal angina is defined as resting angina associated with ST-segment elevation caused by focal coronary artery spasm. Although most patients with Prinzmetal angina have underlying fixed coronary lesions, some have angiographically normal coronary arteries. Several mechanisms have been proposed for Prinzmetal angina: focal deficiency of nitric oxide production, [7] hyperinsulinemia, low intracellular magnesium levels, smoking cigarettes, and using cocaine.
Approximately 30% of patients with chest pain referred for cardiac catheterization have normal or minimal atherosclerosis of coronary arteries. A subset of these patients demonstrates reduced CFR that is believed to be caused by functional and structural alterations of small coronary arteries and arterioles (ie, resistance vessels). Under normal conditions, resistance vessels are responsible for as much as 95% of coronary artery resistance, with the remaining 5% being from epicardial coronary arteries (ie, conductive vessels). The former is not visualized during regular coronary catheterization. Angina due to dysfunction of small coronary arteries and arterioles is called microvascular angina. Several diseases, such as diabetes mellitus, hypertension, and systemic collagen vascular diseases (eg, systemic lupus erythematosus, polyarteritis nodosa), are believed to cause microvascular abnormalities with subsequent reduction in CFR.
The syndrome that includes angina pectoris, ischemialike ST-segment changes and/or myocardial perfusion defects during stress testing, and angiographically normal coronary arteries is referred to as syndrome X. Most patients with this syndrome are postmenopausal women, and they usually have an excellent prognosis. [8] Syndrome X is believed to be caused by microvascular angina. Multiple mechanisms may be responsible for this syndrome, including (1) impaired endothelial dysfunction, [9] (2) increased release of local vasoconstrictors, (3) fibrosis and medial hypertrophy of the microcirculation, (4) abnormal cardiac adrenergic nerve function, and/or (5) estrogen deficiency. [10]
A number of extravascular forces produced by contraction of adjacent myocardium and intraventricular pressures can influence coronary microcirculation resistance and thus reduce CFR. Extravascular compressive forces are highest in the subendocardium and decrease toward the subepicardium. Left ventricular (LV) hypertrophy together with a higher myocardial oxygen demand (eg, during tachycardia) cause greater susceptibility to ischemia in subendocardial layers.
Myocardial ischemia can also be the result of factors affecting blood composition, such as reduced oxygen-carrying capacity of blood, as is observed with severe anemia (hemoglobin, < 8 g/dL), or elevated levels of carboxyhemoglobin. The latter may be the result of inhalation of carbon monoxide in a closed area or of long-term smoking.
Ambulatory ECG monitoring has shown that silent ischemia is a common phenomenon among patients with established coronary artery disease. In one study, as many as 75% of episodes of ischemia (defined as transient ST depression of 1 mm or above persisting for at least 1 min) occurring in patients with stable angina were clinically silent. Silent ischemia occurs most frequently in early morning hours and may result in transient myocardial contractile dysfunction (ie, stunning). The exact mechanism(s) for silent ischemia is not known. However, autonomic dysfunction (especially in patients with diabetes), a higher pain threshold in some individuals, and the production of excessive quantities of endorphins are among the more popular hypotheses. [11]
Etiology
Causes of angina pectoris include the following:
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Decrease in myocardial blood supply due to increased coronary resistance in large and small coronary arteries
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Increased extravascular forces, such as severe LV hypertrophy caused by hypertension, aortic stenosis, or hypertrophic cardiomyopathy, or increased LV diastolic pressures
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Reduction in the oxygen-carrying capacity of blood, such as elevated carboxyhemoglobin or severe anemia (hemoglobin, < 8 g/dL)
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Congenital anomalies of the origin and/or course of the major epicardial coronary arteries
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Risk factors
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Precipitating factors
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Preventive factors
Decrease in myocardial blood supply due to increased coronary resistance in large and small coronary arteries
Causes of such decreases in myocardial blood supply include the following:
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Significant coronary atherosclerotic lesion in the large epicardial coronary arteries (ie, conductive vessels) with at least a 50% reduction in arterial diameter
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Coronary spasm (ie, Prinzmetal angina)
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Abnormal constriction or deficient endothelial-dependent relaxation of resistant vessels associated with diffuse vascular disease (ie, microvascular angina) [12]
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Syndrome X
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Systemic inflammatory or collagen vascular disease, such as scleroderma, systemic lupus erythematous, Kawasaki disease, polyarteritis nodosa, and Takayasu arteritis
Congenital anomalies of the origin and/or course of the major epicardial coronary arteries
These include structural abnormalities of the coronary arteries (congenital coronary artery aneurysm or fistula, coronary artery ectasia, coronary artery fibrosis after chest radiation, coronary intimal fibrosis following cardiac transplantation).
Risk factors
Major risk factors for atherosclerosis include a family history of premature coronary artery disease, cigarette smoking, diabetes mellitus, hypercholesterolemia, or systemic hypertension.
Other risk factors include LV hypertrophy, obesity, and elevated serum levels of homocysteine, lipoprotein (a), plasminogen activator inhibitor, fibrinogen, serum triglycerides, or low high-density lipoprotein (HDL).
Metabolic syndrome has been characterized by the presence of hyperinsulinemia (fasting glucose level, ≥100 mg/dL), abdominal obesity (waist circumference, >40 in for men or >35 in for women), decreased HDL cholesterol levels (< 40 mg/dL for men or < 50 mg/dL for women), hypertriglyceridemia (>150 mg/dL), and hypertension (≥130/85 mm Hg). Based on data from the 2000 US census, an estimated 47 million Americans have the metabolic syndrome. Patients with the metabolic syndrome have a 3-fold increased risk for coronary atherosclerosis and stroke compared with those without this syndrome. [13]
Precipitating factors
These include factors such as severe anemia, fever, tachyarrhythmias, catecholamines, emotional stress, and hyperthyroidism, which increase myocardial oxygen demand.
Preventive factors
Factors associated with reduced risk of atherosclerosis are a high serum HDL cholesterol level, physical activity, estrogen, and moderate alcohol intake (1-2 drinks/d).
Epidemiology
United States statistics
Approximately 9.8 million Americans are estimated to experience angina annually, with 500,000 new cases of angina occurring every year. In 2009, an estimated 785 000 Americans will have a new coronary attack, and about 470 000 will have a recurrent attack. Only 18% of coronary attacks are preceded by angina. An additional 195,000 silent first myocardial infarctions are estimated to occur each year. [13]
Race-related demographics
The annual rates per 1000 population of new episodes of angina for those aged 45-54 years are as follows [13] :
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8.5 for nonblack men
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10.6 for nonblack women
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11.8 for black men
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20.8 for black women
The annual rates per 1000 population of new episodes of angina for those aged 55-64 years are as follows [13] :
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11.9 for nonblack men
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11.2 for nonblack women
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10.6 for black men
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19.3 for black women
The annual rates per 1000 population of new episodes of angina for those aged 65-74 years are as follows [13] :
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13.7 for nonblack men
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13.1 for nonblack women
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8.8 for black men
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10.0 for black women
Sex-related demographics
Angina pectoris is more often the presenting symptom of coronary artery disease in women than in men, with a female-to-male ratio of 1.7:1. It has an estimated prevalence of 4.6 million in women and 3.3 million in men. In one analysis, this female excess was found across countries and was particularly high in the American studies and higher among nonwhite ethnic groups than among whites. [14] The frequency of atypical presentations is also more common among women compared with men. Women have a slightly higher rate of mortality from coronary artery disease compared with men, in part because of an older age at presentation and a frequent lack of classic anginal symptoms. The estimated age-adjusted prevalence of angina is greater in women than in men.
Age-related demographics
The prevalence of angina pectoris increases with age. Age is a strong independent risk factor for mortality. More than 150,000 Americans killed by CVD in 2005 were younger than 65 years. However, in 2005, 32% of deaths from cardiovascular disease occurred before the age of 75 years, which is well before the average life expectancy of 77.9 years. [13]
Prognosis
Important prognostic indicators in patients with angina pectoris include LV function, severity and location of atherosclerotic lesions, and response of symptoms to medical treatment.
LV function is the strongest predictor of long-term survival. Elevated LV end-diastolic pressure and volume along with reduced LV ejection fraction ( (< 40%) are poor prognostic signs. Note the following:
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Critical lesions of left main and proximal left anterior descending coronary arteries are associated with a greater risk. Mortality rates are also directly associated with the number of epicardial arteries involved.
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Unstable angina, recent MI, or both is a sign of atherosclerotic plaque instability, which is a strong predictor of increased risk of short-term coronary events.
More recent studies indicate that epicardial adipose tissue thickness (EAT) can also be used to predict major adverse cardiac events. [15] In a study of 200 patients hospitalized with stable angina pectoris, unstable angina pectoris, or acute myocardial infarction who underwent coronary angiography, patients with a baseline EAT of more than 7 mm suffered significantly more revascularizations, nonfatal myocardial infarction, and cardiovascular death. [15]
A number of signs during noninvasive testing are predictive of a higher risk of coronary events, including ST-segment depression of more than 2 mm at a low workload, ST-segment depression that persists for more than 5 minutes after termination of exercise, and failure of blood pressure to rise or an actual drop in blood pressure.
Patients who continue to smoke after an MI have a 22-47% increased risk of reinfarction and death.
In general, Prinzmetal angina and syndrome X are associated with excellent long-term prognoses.
Morbidity/mortality
About every 25 seconds, an American will have a coronary event, and about every minute someone will die from one. Coronary heart disease (CHD) caused about 1 of every 5 deaths in the United States in 2005. Final 2005 coronary heart disease mortality in 2005 was 445,687 (232,115 males and 213,572 females). On the basis of 2005 mortality rate data, nearly 2,400 Americans die of cardiovascular disease (CVD) each day—an average of 1 death every 37 seconds. The 2006 overall preliminary death rate from cardiovascular disease was 262.9. [13]
Complications
Complications of angina pectoris include unstable angina, MI, and death.
Patient Education
Educating patients about the benefits of smoking cessation, a low-cholesterol diet, physical activity, and periodic screening for diabetes mellitus and hypertension is the prime component of a long-term management plan.
For patient education resources, see Cholesterol Center and Heart Health Center, as well as Coronary Heart Disease, Angina Pectoris, High Cholesterol, Cholesterol Charts (What the Numbers Mean), Lifestyle Cholesterol Management, Cholesterol-Lowering Medications, Chest Pain, and Heart Attack.
