Background

Angina pectoris (AP) represents the clinical syndrome occurring when myocardial oxygen
demand exceeds supply. The term is derived from Latin; the literal meaning is "the choking of
the chest;" angere, meaning "to choke" and pectus, meaning "chest." The first English-written
account of recurrent angina pectoris was by English nobleman Edward Hyde, Earl of Clarendon.
He described his father as having, with exertion, "a pain in the left armso much that the
torment made him pale". [1] The first description of angina as a medical disorder came from
William Heberden. Heberden, a prodigious physician, made many noteworthy contributions to
medicine during his career. He presented his observations on "dolor pectoris" to the Royal
College of Physicians in 1768. Much of his classic description retains its validity today. [2]

Angina pectoris has a wide range of clinical expressions. The symptoms most often associated to
angina pectoris are substernal chest pressure or tightening, frequently with radiating pain to the
arms, shoulders, or jaw. The symptoms may also be associated with shortness of breath, nausea,
or diaphoresis. Symptoms stem from inadequate oxygen delivery to myocardial tissue. No
definitive diagnostic tools that capture all patients with angina pectoris exist. This, combined
with its varied clinical expression, makes angina pectoris a distinct clinical challenge to the
emergency physician. The disease state can manifest itself in a variety of forms, including the
following:

Stable angina pectoris is classified as a reproducible pattern of anginal symptoms that

occur during states of increased exertion.
Unstable angina pectoris (UA) manifests either as an increasing frequency of symptoms
or as symptoms occurring at rest.
Prinzmetal angina or variant angina occurs as a result of transient coronary artery spasms.
These spasms can occur either at rest or with exertion. Unlike stable or unstable angina,
no pathological plaque or deposition is present within the coronary arteries that elicits the
presentation. On angiography, the coronary arteries are normal in appearance with spasm
on angiography.
Cardiac syndrome X occurs when a patient has all of the symptoms of angina pectoris
without coronary artery disease or spasm.

Pathophysiology
The past 2 decades has greatly expanded our overall understanding of the pathophysiology of
myocardial ischemic syndromes. The primary dysfunction in angina pectoris is decreased oxygen
delivery to myocardial muscle cells. The 2 predominant mechanisms by which delivery is
impaired appear to be coronary artery narrowing and endothelial dysfunction. Any other
mechanism that affects oxygen delivery can also precipitate symptoms.

Extracardiac causes of angina include, but are by no means limited to, anemia, hypoxia,
hypotension, bradycardia, carbon monoxide exposure, and inflammatory disorders. [3] The end
result is a shift to anaerobic metabolism in the myocardial cells. This is followed by a stimulation
of pain receptors that innervate the heart. These pain receptors ultimately are referred to afferent
pathways, which are carried in multiple nerve roots from C7 through T4. The referred/radiating
pain of angina pectoris is believed to occur because these afferent pathways also carry pain fibers
from other regions (eg, the arm, neck, and shoulders).

Coronary artery narrowing

Coronary artery narrowing appears to be the etiology of cardiac ischemia in the preponderance of
cases. This has clinical significance when atherosclerotic disease diminishes or halts blood flow
through the coronary arterial circulation, interfering with normal laminar blood flow. The
significance of even a small change in the diameter of a blood vessel can be profound. The
Poiseuille law predicts this outcomethe rate of flow is decreased exponentially by any change
in the radius of the lumen. As with a smaller pediatric airway, even relatively minute changes in
diameter have dramatic consequences in flow rates. Thus, when a lumen is narrowed by one
fifth, the flow rate is decreased by about one half. This predicts that even a small change in a
coronary artery plaque size can affect the oxygenation through that vessel's territory.

The epicardial vessel, where atherosclerosis often takes place, has the capacity to dilate via
autoregulatory mechanisms to respond to increased demand. Angina occurs as this compensatory
mechanism is overwhelmed either by large plaques (typically considered 70% or greater
obstruction) or by significantly increased myocardial demand. [4]

Endothelial factors

Endothelial factors also play an important role in angina pectoris. During sympathetic
stimulation, the endothelium is subjected to mediators of both vasoconstriction and
vasodilatation. Alpha-agonists (catecholamines) directly cause vasoconstriction, while
endothelial nitrous oxide synthase creates nitrous oxide (NO), which counteracts this constricting
force via vasodilatation.

In the diseased coronary artery, NO production is reduced or absent. In this setting, the
catecholamine drive can overwhelm the autoregulatory mechanisms. In addition, the
endothelium of the plaque-laden artery may, in itself, be dysfunctional. This limits the ability of
the intra-arterial endothelium to produce mediators, which, in a healthy artery, would protect
against further vasoconstriction, assist dilatation, and provide protection from platelet
aggregation. Small lesions in these vessels may produce incompletely obstructing aggregates of
platelets. This would further impede flow through the affected vessel. [4]

In the diseased heart, these 2 factors, coronary artery narrowing and endothelial dysfunction,
synergistically result in reduced oxygen delivery to the myocardium. The net result is angina
pectoris.

Extrinsic factors

Extrinsic factors can also play a role in specific circumstances. The oxygen-carrying capacity of
blood is based on a number of factors. The most important of which is the amount of
hemoglobin. Any alteration in the ability of blood to carry oxygen can precipitate angina.
Anemia of any degree can result in anginal symptoms. Given a scenario where demand is
increased, such as climbing a flight of stairs, increased stress, or even sexual intercourse, the
anginal symptoms may appear. [5] Abnormal hemoglobin, such as methemoglobin,
carboxyhemoglobin, or any of a number of hemoglobinopathies, creates an environment at
greater risk for precipitating angina.

Other extrinsic factors that affect hemoglobin formation, such as lead poisoning or iron-
deficiency states, also lead to a similar decrease in oxygen-carrying capacity. Any mechanism
that impedes oxygen delivery to the red blood cells has a similar effect. Therefore, any number
of pulmonary causes, such as pulmonary embolism, pulmonary fibrosis or scarring, pneumonia,
or congestive heart failure, can exacerbate angina. A decreased oxygen environment, such as
travel to a higher elevation, has similar consequences due to the decrease in concentration of
atmospheric oxygen.

Variant angina

The etiology of variant angina is currently not well understood. Research suggests that
inflammatory mediators may result in focal coronary artery vasospasm. Another possibility is
that perfusion is decreased through microvascular circulation. Spasm or intermittent narrowing
of this microscopic lumen may result in transient areas of hypoperfusion and oxygen deprivation.
[6]

Syndrome X

Syndrome X is the triad of angina pectoris, a positive ECG stress test result, and a normal
coronary angiogram. The pathophysiology of this disease is not well understood. Many theories
exist as to the underlying pathology. Decreased oxygenation of the underlying myocardium may
be the result of impaired vasodilatation, dysfunctional smooth muscle cells, poor or deficient
microvascular circulation, or even structural problems on a cellular level (eg, an inappropriately
functioning sodium ion channel). [6]

Epidemiology
Frequency

United States

An average of 3.4 million US adults older than 40 years experience angina each year. Between
2007 and 2010, there were a total of 2.3 million office visits per year for angina. [7]

About 635,000 US adults with have a new coronary event (MI or CHD death), with an estimated
300,000 experiencing recurrent events. [7]

Conservative 2010 data show 625,000 acute coronary syndrome (ACS) discharges from
hospitals. [7]
Mortality/Morbidity

The prognosis of each patient is dependent upon individual factors and the progression of their
underlying disease.

The majority of coronary attacks are NOT preceded by long-standing angina pectoris (AP) (only
18%). [7]

Morbidity/mortality

Cardiovascular diseases, including heart disease and stroke, account for more than onethird
(33.6%) of all U.S. deaths. [7]

Coronary heart disease is the single greatest killer of American men and women. [7]

In 2010, the total costs of cardiovascular diseases in the United States were estimated to be $444
billion, with treatment of these diseases accounting for about $1 of every $6 spent on US
healthcare. [7]

Complications

Complications may occur from the progression of the patient's underlying disease or from failure
to intervene. Unfortunately, even the testing for underlying disease (eg, stress testing,
angiography) can lead to complications including progression to myocardial infarction and renal
failure. The risks and benefits of testing and treatment must be determined for and discussed with
each patient.

Race

The Centers for Disease Control and Prevention (CDC) note that the prevalence of angina and/or
coronary heart disease is highest and increasing in Hispanics followed by whites and black non-
Hispanics (5%, 4.2%, 3.7%, respectively). This information includes the 50 US states, the
District of Columbia, Puerto Rico, and the US Virgin Islands. [8, 9]

Sex

Among US adults aged 40-59 years and 80 years and older, the age-adjusted prevalence of
angina pectoris (AP) is higher among women than men; in those aged 60-79 years, it is higher
men than women. [7]

Age

The incidence of new and recurrent angina increases with age but then declines at around 85
years.