1. Angina Pectoris http://emedicine.medscape.com/article/150215-overview
Author: Jamshid Alaeddini, MD, FACC; Chief Editor: Eric H Yang, MD more...
Updated: Aug 10, 2011
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.[1]
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,[2] hyperinsulinemia, low intracellular magnesium levels, smoking cigarettes, and using cocaine.
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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.[3] Syndrome X is believed to
be caused by microvascular angina. Multiple mechanisms may be responsible for this syndrome, including (1)
impaired endothelial dysfunction,[4] (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.[5]
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 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.[6]
Epidemiology
Frequency
United States
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.[7]
Mortality/Morbidity
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.[7]
Race
The annual rates per 1000 population of new episodes of angina are as follows:[7]
Age 45-54 years
8.5 for nonblack men
10.6 for nonblack women
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3. Angina Pectoris http://emedicine.medscape.com/article/150215-overview
11.8 for black men
20.8 for black women
Age 55-64 years
11.9 for nonblack men
11.2 for nonblack women
10.6 for black men
19.3 for black women
Age 65-74 years
13.7 for nonblack men
13.1 for nonblack women
8.8 for black men
10.0 for black women
Sex
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.[8] 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
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.[7]
Contributor Information and Disclosures
Author
Jamshid Alaeddini, MD, FACC Clinical Cardiac Electrophysiologist, Inland Cardiology Associates
Jamshid Alaeddini, MD, FACC is a member of the following medical societies: American College of Cardiology and
American Heart Association
Disclosure: Boston Scientific Honoraria Speaking and teaching; Medtronic Honoraria Speaking and teaching; St.
Jude Honoraria Speaking and teaching; Reliant Honoraria Speaking and teaching
Coauthor(s)
Jamshid Shirani, MD Director of Cardiology Fellowship Program, Director of Echocardiography Laboratory, St
Luke's Hospital and Health Network
Jamshid Shirani, MD is a member of the following medical societies: American Association for the Advancement of
Science, American College of Cardiology, American College of Physicians, American Federation for Medical
Research, American Heart Association, American Society of Echocardiography, and Association of Subspecialty
Professors
Disclosure: Nothing to disclose.
Specialty Editor Board
Alan D Forker, MD Professor of Medicine, University of Missouri at Kansas City School of Medicine; Director,
Outpatient Lipid Diabetes Research, MidAmerica Heart Institute of St Luke's Hospital
Alan D Forker, MD is a member of the following medical societies: Alpha Omega Alpha, American College of
Cardiology, American College of Physicians, American Heart Association, American Medical Association, American
Society of Hypertension, and Phi Beta Kappa
Disclosure: Research Grant Grant/research funds Hospital contracts to do research; I am a hospital employee with
no personal profit; Speakers Bureau Honoraria Speaking and teaching
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4. Angina Pectoris http://emedicine.medscape.com/article/150215-overview
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Steven J Compton, MD, FACC, FACP Director of Cardiac Electrophysiology, Alaska Heart Institute, Providence
and Alaska Regional Hospitals
Steven J Compton, MD, FACC, FACP is a member of the following medical societies: Alaska State Medical
Association, American College of Cardiology, American College of Physicians, American Heart Association,
American Medical Association, and Heart Rhythm Society
Disclosure: Nothing to disclose.
Amer Suleman, MD Private Practice
Amer Suleman, MD is a member of the following medical societies: American College of Physicians, American
Heart Association, American Institute of Stress, American Society of Hypertension, Federation of American
Societies for Experimental Biology, Royal Society of Medicine, and Society of Cardiac Angiography and
Interventions
Disclosure: Nothing to disclose.
Chief Editor
Eric H Yang, MD Associate Professor of Medicine, Director of Interventional Cardiology Fellowship Program,
Henry Ford Hospital
Eric H Yang, MD is a member of the following medical societies: Alpha Omega Alpha
Disclosure: Nothing to disclose.
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