Coronary artery disease (CAD) also known as atherosclerotic heart disease, coronary heart

disease, or ischemic heart disease (IHD), is the most common type of heart disease and cause of heart
attacks. The disease is caused by plaque building up along the inner walls of thearteries of the heart,
which narrows the arteries and reduces blood flow to the heart. While the symptoms and signs of
coronary artery disease are noted in the advanced state of disease, most individuals with coronary artery
disease show no evidence of disease for decades as the disease progresses before the first onset of
symptoms, often a "sudden" heart attack, finally arises. Symptoms of stable ischaemic heart disease
include angina (characteristic chest pain on exertion) and decreased exercise tolerance. Unstable IHD
presents itself as chest pain or other symptoms at rest, or rapidly worsening angina. The risk of artery
narrowing increases with age, smoking, high blood cholesterol, diabetes, high blood pressure, and is
more common in men and those who have close relatives with CAD. Other causes includecoronary
vasospasm,[5] a spasm of the blood vessels of the heart, it is usually called Prinzmetal's angina.[6]
Diagnosis of IHD is with an electrocardiogram, blood tests (cardiac markers), cardiac stress testing or
a coronary angiogram. Depending on the symptoms and risk, treatment may be with
medication, percutaneous coronary intervention (angioplasty) or coronary artery bypass surgery (CABG).

Signs and symptoms[edit]

Angina (chest pain) that occurs regularly with activity, after heavy meals, or at other predictable times is
termed stable angina and is associated with high grade narrowings of the heart arteries. The symptoms of
angina are often treated with betablocker therapy such as metoprolol or atenolol. Nitrate preparations
such as nitroglycerin, which come in short-acting and long-acting forms are also effective in relieving
symptoms but are not known to reduce the chances of future heart attacks. Many other more effective
treatments, especially of the underlying atheromatous disease, have been developed.
Angina that changes in intensity, character or frequency is termed unstable. Unstable angina may
precede myocardial infarction, and requires urgent medical attention. It may be treated with oxygen,
intravenous nitroglycerin, and aspirin. Interventional procedures such as angioplasty may be done. About
80% of chest pains have nothing to do with the heart.
Heart failure (difficulty in breathing or swelling of the extremities due to weakness of the heart muscle)

Risk factors[edit]
Risk factors can be classified as: fixed (such as age, sex, family history) and modifiable (such as
smoking, hypertension, diabetes mellitus, obesity, etc.)

Pathophysiology[edit]
Limitation of blood flow to the heart causes ischemia (cell starvation secondary to a lack of oxygen) of the
myocardial cells. Myocardial cells may die from lack of oxygen and this is called a myocardial
infarction (commonly called a heart attack). It leads to heart muscle damage, heart muscle death and
later myocardial scarring without heart muscle regrowth. Chronic high-grade stenosis of the coronary

arteries can induce transient ischemia which leads to the induction of a ventricular arrhythmia, which may
terminate into ventricular fibrillation leading to death.
Typically, coronary artery disease occurs when part of the smooth, elastic lining inside a coronary
artery (the arteries that supply blood to the heart muscle) develops atherosclerosis. With atherosclerosis,
the artery's lining becomes hardened, stiffened, and swollen with all sorts of "gunge" - including calcium
deposits, fatty deposits, and abnormal inflammatory cells - to form a plaque. Deposits of calcium
phosphates (hydroxyapatites) in the muscular layer of the blood vessels appear to play not only a
significant role in stiffening arteries but also for the induction of an early phase of coronaryarteriosclerosis.
This can be seen in a so-called metastatic mechanism of calcification as it occurs in chronic kidney
disease and haemodialysis (Rainer Liedtke 2008). Although these patients suffer from a kidney
dysfunction, almost fifty percent of them die due to coronary artery disease. Plaques can be thought of as
large "pimples" that protrude into the channel of an artery, causing a partial obstruction to blood flow.
Patients with coronary artery disease might have just one or two plaques, or might have dozens
distributed throughout their coronary arteries. However, there is a term in medicine called cardiac
syndrome X, which describes chest pain (Angina pectoris) and chest discomfort in people who do not
show signs of blockages in the larger coronary arteries of their hearts when an angiogram (coronary
angiogram) is being performed.[23]
No one knows exactly what causes cardiac syndrome X. One explanation is microvascular dysfunction.
[24]
It is not completely clear why women are more likely than men to have it however, hormones and other
risk factors unique to women may play a role.[25]
For symptomatic patients, stress echocardiography can be used to make a diagnosis for obstructive
coronary artery disease.[26] The use ofechocardiography is not recommended on individuals who are
exhibiting no symptoms and are otherwise at low risk for developing coronary disease. [26]
CAD has always been a tough disease to diagnose without the use of invasive or stressful activities. The
development of the Multifunction Cardiogram (MCG) has changed the way CAD is diagnosed. The MCG
consists of a 2 lead resting EKG signal is transformed into a mathematical model and compared against
tens of thousands of clinical trials to diagnose a patient with an objective severity score, as well as
secondary and tertiary results about the patients condition. The results from MCG tests have been
validated in 8 clinical trials[citation needed] which resulted in a database of over 50,000 patients where the
system has demonstrated accuracy comparable to coronary angiography (90% overall sensitivity, 85%
specificity). This level of accuracy comes from the application of advanced techniques in signal
processing and systems analysis combined with a large scale clinical database which allows MCG to
provide quantitative, evidence-based results to assist physicians in reaching a diagnosis. The MCG has
also been awarded a Category III CPT code by the American Medical Association in the July 2009 CPT
update[citation needed].
The diagnosis of "Cardiac Syndrome X" - the rare coronary artery disease that is more common in
women, as mentioned, an "exclusion" diagnosis. Therefore, usually the same tests are used as in any
patient with the suspicion of coronary artery disease:

Baseline electrocardiography (ECG)

Exercise ECG Stress test

Exercise radioisotope test (nuclear stress test, myocardial scintigraphy)

Echocardiography (including stress echocardiography)

Coronary angiography

Intravascular ultrasound

Magnetic resonance imaging (MRI)

The diagnosis of coronary disease underlying particular symptoms depends largely on the nature of the
symptoms. The first investigation is anelectrocardiogram (ECG/EKG), both for "stable" angina and acute
coronary syndrome. An X-ray of the chest and blood tests may be performed.

Stable angina[edit]
Main article: Angina pectoris
In "stable" angina, chest pain with typical features occurring at predictable levels of exertion, various
forms of cardiac stress tests may be used to induce both symptoms and detect changes by way of
electrocardiography (using an ECG), echocardiography (using ultrasound of the heart)
orscintigraphy (using uptake of radionuclide by the heart muscle). If part of the heart seems to receive an
insufficient blood supply, coronary angiographymay be used to identify stenosis of the coronary arteries
and suitability for angioplasty or bypass surgery.

Acute coronary syndrome[edit]

Main article: Acute coronary syndrome
Diagnosis of acute coronary syndrome generally takes place in the emergency department, where ECGs
may be performed sequentially to identify "evolving changes" (indicating ongoing damage to the heart
muscle). Diagnosis is clear-cut if ECGs show elevation of the "ST segment", which in the context of
severe typical chest pain is strongly indicative of an acute myocardial infarction (MI); this is termed a
STEMI (ST-elevation MI), and is treated as an emergency with either urgent coronary
angiography and percutaneous coronary intervention (angioplasty with or without stent insertion) or
with thrombolysis ("clot buster" medication), whichever is available. In the absence of ST-segment
elevation, heart damage is detected by cardiac markers (blood tests that identify heart muscle damage). If
there is evidence of damage (infarction), the chest pain is attributed to a "non-ST elevation MI" (NSTEMI).
If there is no evidence of damage, the term "unstable angina" is used. This process usually necessitates
admission to hospital, and close observation on a coronary care unit for possible complications (such
as cardiac arrhythmias irregularities in the heart rate).
Depending on the risk assessment, stress testing or angiography may be used to identify and treat
coronary artery disease in patients who have had an NSTEMI or unstable angina.

Heart failure[edit]
Main article: Heart failure
In people with heart failure, stress testing or coronary angiography may be performed to identify and treat
underlying coronary artery disease.

Prevention[edit]
Prevention involves: exercise, decreasing obesity, treating hypertension, a healthy diet,
decreasing cholesterol levels, and stopping smoking. Medications and exercise are roughly equally
effective.[27]
In diabetes mellitus, there is little evidence that very tight blood sugar control improves cardiac risk
although improved sugar control appears to decrease other problems like kidney failure and blindness.
The World Health Organization (WHO) recommends "low to moderate alcohol intake" to reduce risk of
coronary artery disease although this remains without scientific cause and effect proof. [28]

Diet[edit]
Main article: Diet and heart disease
It has been suggested that coronary artery disease is partially reversible using an intense dietary regimen
coupled with regular cardiovascular exercise.[29] A high fiber diet appears to lower the risk.[30]

Vegetarian diet: Vegetarians have been shown to have a 24% reduced risk of dying of heart
disease.[31]

Cretan Mediterranean diet: The Seven Countries Study found that Cretan men had exceptionally
low death rates from heart disease, despite moderate to high intake of fat. The Cretan diet is similar
to other traditional Mediterranean diets: consisting mostly of olive oil, bread, abundant fruit and
vegetables, a moderate amount of wine and fat-rich animal products such as lamb, andgoat cheese.
[32][33]

The consumption of trans fat (commonly found in hydrogenated products such as margarine) has been
shown to cause the development of endothelial dysfunction, a precursor toatherosclerosis.[34] The
consumption of trans fatty acids has been shown to increase the risk of coronary artery disease [35]
Avoiding fats that are readily oxidized (e.g., trans-fats), and limiting carbohydrates and processed sugars
may reduce low density lipoproteins, triacylglycerol and apolipoprotein-B thus decreasing the risk.
Evidence does not support a beneficial role for omega-3 fatty acid supplementation in
preventing cardiovascular disease (including myocardial infarction and sudden cardiac death).[36]
[37]
Menaquinone (Vitamin K2), but not phylloquinone (Vitamin K1), intake may reduce the risk of
CAD mortality.[38]

Secondary prevention[edit]
Secondary prevention is preventing further sequelae of already established disease. Regarding coronary
artery disease, this can mean risk factor management that is carried out during cardiac rehabilitation, a 4phase process beginning in hospital after MI, angioplasty or heart surgery and continuing for a minimum
of three months. Exercise is a main component of cardiac rehabilitation along with diet, smoking
cessation, and blood pressure and cholesterol management. Beta blockers may also be used for this
purpose.[39]

Treatment[edit]
Therapeutic options for coronary artery disease[40] today are based on three principles:

1. Medical treatment - drugs (e.g. cholesterol lowering medications, beta-blockers, nitroglycerin,

calcium antagonists, etc.);

2. Coronary interventions as angioplasty and coronary stent-implantation;

3. Coronary artery bypass grafting (CABG - coronary artery bypass surgery).

Recent research efforts focus on new angiogenic treatment modalities (angiogenesis) and various
(adult) stem cell therapies.

Lifestyle[edit]
Lifestyle changes have been shown to be effective in reducing (and in the case of diet, reversing)
coronary disease:

A whole-food plant-based diet[41][42][43]

Weight control

Smoking cessation

Avoiding the consumption of trans fats (in hydrogenated oils)

Exercise Aerobic exercise, like walking, jogging, or swimming, can help decrease blood pressure
and the amount of blood cholesterol over time. [44]

Decrease psychosocial stress.[45]

In people with coronary artery disease, aerobic exercise can reduce the risk of mortality.[46] Separate to
the question of the benefits of exercise; it is unclear whether doctors should spend time counseling
patients to exercise. The U.S. Preventive Services Task Force, found 'insufficient evidence' to recommend
that doctors counsel patients on exercise, but "it did not review the evidence for the effectiveness of

physical activity to reduce chronic disease, morbidity and mortality", it only examined the effectiveness of
the counseling itself.[47] The American Heart Association, based on a non-systematic review, recommends
that doctors counsel patients on exercise.[48]

Medications[edit]

Statins, which reduce cholesterol, reduce risk of coronary disease

Nitroglycerin

ACE inhibitors, which treat hypertension and may lower the risk of recurrent myocardial

[49]

infarction[citation needed]

Calcium channel blockers and/or beta-blockers

Aspirin[42]

Aspirin[edit]
In those with no other heart problems aspirin decreases the risk of a myocardial infarction in men but not
women and increases the risk of bleeding, most of which is from the stomach. It does not affect the
overall risk of death in either men or women.[50] It is thus only recommended in adults who are at
increased risk for coronary artery disease[51] where increased risk is defined as 'men older than 90 years
of age, postmenopausal women, and younger persons with risk factors for coronary artery disease (for
example, hypertension, diabetes, or smoking) are at increased risk for heart disease and may wish to
consider aspirin therapy'. More specifically, high-risk persons are 'those with a 5-year risk 3%'. [citation needed]

Anti-platelet therapy[edit]
Clopidogrel plus aspirin reduces cardiovascular events more than aspirin alone in those with an STEMI.
In others at high risk but not having an acute event the evidence is weak. [52]

Angina pectoris
Angina pectoris commonly known as angina is chest pain due to ischemia of the heart muscle, due
in general to obstruction or spasm of thecoronary arteries.[1] The main cause of Angina pectoris
is coronary artery disease, due to atherosclerosis of the arteries feeding the heart. The term derives from
the Latin angina ("infection of the throat") from the Greek ankhon ("strangling"), and the
Latin pectus ("chest"), and can, therefore, be translated as "a strangling feeling in the chest".
There is a weak relationship between severity of pain and degree of oxygen deprivation in the heart
muscle (i.e., there can be severe pain with little or no risk of a Myocardial infarction (commonly known as
a heart attack), and a heart attack can occur without pain). In some cases, angina can be extremely

serious and has been known to cause death. People who suffer from average to severe cases of angina
have an increased percentage of death before the age of 55, usually around 60%. [vague][citation needed]
Worsening ("crescendo") angina attacks, sudden-onset angina at rest, and angina lasting more than 15
minutes are symptoms of unstable angina(usually grouped with similar conditions as the acute coronary
syndrome). As these may herald myocardial infarction (a heart attack), they require urgent medical
attention and are, in general, treated as a presumed heart attack.

Classification[edit]
Stable angina[edit]
Also known as effort angina, this refers to the more common understanding of angina related to
myocardial ischemia. Typical presentations of stable angina is that of chest discomfort and associated
symptoms precipitated by some activity (running, walking, etc.) with minimal or non-existent symptoms at
rest or with administration of sublingual nitroglycerin.[2] Symptoms typically abate several minutes
following cessation of precipitating activities and recur when activity resumes. In this way, stable angina
may be thought of as being similar to intermittent claudicationsymptoms.

Unstable angina[edit]
Unstable angina (UA) (also "crescendo angina"; this is a form of acute coronary syndrome) is defined as
angina pectoris that changes or worsens.[1]
It has at least one of these three features:
1. it occurs at rest (or with minimal exertion), usually lasting >10 min
2. it is severe and of new onset (i.e., within the prior 46 weeks)
3. it occurs with a crescendo pattern (i.e., distinctly more severe, prolonged, or frequent than
before).
UA may occur unpredictably at rest, which may be a serious indicator of an impending heart attack. What
differentiates stable angina from unstable angina (other than symptoms) is the pathophysiology of the
atherosclerosis. The pathophysiology of unstable angina is the reduction of coronary flow due to transient
platelet aggregation on apparently normal endothelium, coronary artery spasms, or coronary thrombosis.
[3][4]
The process starts with atherosclerosis, and when inflamed leads to an active plaque, which
undergoes thrombosis and results in acute ischemia, which finally results in cell necrosis after calcium
entry.[4] Studies show that 64% of all unstable anginas occur between 10 PM and 8 AM when patients are
at rest.[4][5]
In stable angina, the developing atheroma is protected with a fibrous cap. This cap (atherosclerotic
plaque) may rupture in unstable angina, allowing blood clots to precipitate and further decrease

the lumen of the coronary vessel. This explains why an unstable angina appears to be independent of
activity.[citation needed]

Microvascular angina[edit]
Microvascular Angina or Angina Syndrome X is characterized by angina-like chest pain, but the cause is
different. The cause of Microvascular Angina is unknown, but it appears to be the result of spasm in the
tiny blood vessels of the heart, arms, and legs. [6] Since microvascular angina is not characterized by
arterial blockages, it is harder to recognize and diagnose, but its prognosis is excellent. [7][8][9]

Signs and symptoms[edit]

This section needs additional citations for verification. Please help improve this
article by adding citations to reliable sources. Unsourced material may be challenged and
removed. (June 2013)

Angina pectoris can be quite painful, but many patients with angina complain of chest discomfort rather
than actual pain: The discomfort is usually described as a pressure, heaviness, tightness, squeezing,
burning, or choking sensation. Apart from chest discomfort, anginal pains may also be experienced in
the epigastrium (upper central abdomen), back, neck area, jaw, or shoulders. This is explained by the
concept of referred pain, and is due to the fact that the spinal level that receives visceral sensation from
the heart simultaneously receives cutaneous sensation from parts of the skin specified by that spinal
nerve's dermatome, without an ability to discriminate the two. Typical locations for referred pain are arms
(often inner left arm), shoulders, and neck into the jaw. Angina is typically precipitated by exertion or
emotional stress. It is exacerbated by having a full stomach and by cold temperatures. Pain may be
accompanied by breathlessness, sweating, and nausea in some cases. In this case, the pulse rate and
the blood pressure increases. Chest pain lasting only a few seconds is normally not angina (such
as Precordial catch syndrome).
Myocardial ischemia comes about when the myocardia (the heart muscles) receive insufficient blood and
oxygen to function normally either because of increased oxygen demand by the myocardia or because of
decreased supply to the myocardia. This inadequate perfusion of blood and the resulting reduced delivery
of oxygen and nutrients are directly correlated to blocked or narrowed blood vessels.
Some experience "autonomic symptoms" (related to increased activity of the autonomic nervous system)
such as nausea, vomiting, and pallor.
Major risk factors for angina include cigarette smoking, diabetes, high cholesterol, high blood
pressure, sedentary lifestyle, and family history of premature heart disease.
A variant form of angina (Prinzmetal's angina) occurs in patients with normal coronary arteries or
insignificant atherosclerosis. It is thought to be caused by spasms of the artery. It occurs more in younger
women.[10]

Cause[edit]
Major risk factors[edit]
[11]

Age ( 55 years for men, 65 for women)

Cigarette smoking

Diabetes mellitus (DM)

Dyslipidemia

Family history of premature cardiovascular disease (men <55 years, female <65 years old)

Hypertension (HTN)

Kidney disease (microalbuminuria or GFR<60 mL/min)

Obesity (BMI 30 kg/m2)

Physical inactivity

prolonged psychosocial stress.[12]

Routine counselling of adults to advise them to improve their diet and increase their physical activity has
not been found to significantly alter behaviour, and thus is not recommended. [13]
Conditions that exacerbate or provoke angina
[14]

Medications

Vasodilators

Excessive thyroid replacement

Vasoconstrictors

polycythemia which thickens the blood causing it to slow its flow through the heart muscle

hypothermia

hypovolaemia

hypervolaemia

One study found that smokers with coronary artery disease had a significantly increased level
of sympathetic nerve activity when compared to those without. This is in addition to increases in
blood pressure, heart rate, and peripheral vascular resistance associated with nicotine, which may
lead to recurrent angina attacks. In addition, the Centers for Disease Control and Prevention(CDC)
reports that the risk of CHD (Coronary heart disease), stroke, and PVD (Peripheral vascular disease)
is reduced within 12 years of smoking cessation. In another study, it was found that, after one year,
the prevalence of angina in smoking men under 60 after an initial attack was 40% less in those
having quit smoking compared to those that continued. Studies have found that there are short-term
and long-term benefits to smoking cessation.[15][16][17][18]

Other medical problems[edit]

profound anemia

uncontrolled HTN

hyperthyroidism

hypoxemia

Other cardiac problems[edit]

tachyarrhythmia

bradyarrhythmia

valvular heart disease

hypertrophic cardiomyopathy[19][20]

Myocardial ischemia can result from:

1. a reduction of blood flow to the heart that can be caused by stenosis, spasm, or acute
occlusion (by an embolus) of the heart's arteries.
2. resistance of the blood vessels. This can be caused by narrowing of the blood vessels; a
decrease in radius.[21] Blood flow is proportional to the radius of the artery to the fourth
power [22]
3. reduced oxygen-carrying capacity of the blood, due to several factors such as a decrease in
oxygen tension and hemoglobin concentration.[23] This decreases the ability to of hemoglobin
to carry oxygen to myocardial tissue.[24]

Atherosclerosis is the most common cause of stenosis (narrowing of the blood vessels) of the heart's
arteries and, hence, angina pectoris. Some people with chest pain have normal or minimal narrowing
of heart arteries; in these patients, vasospasm is a more likely cause for the pain, sometimes in the
context of Prinzmetal's angina and syndrome X.
Myocardial ischemia also can be the result of factors affecting blood composition, such as reduced
oxygen-carrying capacity of blood, as seen with severe anemia (low number of red blood cells), or
long-term smoking.

Pathophysiology[edit]
Angina results when there is an imbalance between the heart's oxygen demand and supply. This
imbalance can result from an increase in demand (e.g., during exercise) without a proportional
increase in supply (e.g., due to obstruction or atherosclerosis of the coronary arteries).
However, the pathophysiology of angina in females varies significantly as compared to males. [25] Nonobstructive coronary disease is more common in females. [26][27]

Diagnosis[edit]
Angina should be suspected in people presenting with tight, dull, or heavy chest discomfort that is: [28]
1. Retrosternal or left-sided, radiating to the left arm, neck, jaw, or back.
2. Associated with exertion or emotional stress and relieved within several minutes by rest.
3. Precipitated by cold weather or a meal.
Some people present with atypical symptoms, including breathlessness, nausea, or epigastric discomfort
or burping. These atypical symptoms are particularly likely in older people, women, and those with
diabetes.[28]
Anginal pain is not usually sharp or stabbing or influenced by respiration. Antacids and simple analgesia
do not usually relieve the pain. If chest discomfort (of whatever site) is precipitated by exertion, relieved
by rest, and relieved by glyceryl trinitrate, the likelihood of angina is increased. [28]
In angina patients momentarily not feeling any chest pain, an electrocardiogram (ECG) is typically normal,
unless there have been other cardiac problems in the past. During periods of pain, depression, or
elevation of the ST segment may be observed. To elicit these changes, an exercise ECG test ("treadmill
test") may be performed, during which the patient exercises to his/her maximum ability before fatigue,
breathlessness, or pain intervenes; if characteristic ECG changes are documented (typically more than
1 mm of flat or downsloping ST depression), the test is considered diagnostic for angina. Even constant
monitoring of the blood pressure and the pulse rate can lead us to some conclusion regarding the angina.
The exercise test is also useful in looking for other markers of myocardial ischaemia: blood pressure

response (or lack thereof, in particular a drop in systolic pressure), dysrhythmia and chronotropic
response. Other alternatives to a standard exercise test include a thallium scintigram or sestamibi
scintigram (in patients unable to exercise enough for the purposes of the treadmill tests, e.g., due
to asthma or arthritis or in whom the ECG is too abnormal at rest) or Stress Echocardiography.
In patients in whom such noninvasive testing is diagnostic, a coronary angiogram is typically performed to
identify the nature of the coronary lesion, and whether this would be a candidate forangioplasty, coronary
artery bypass graft (CABG), treatment only with medication, or other treatments. There has been
research that concludes that a frequency is attained when there is increase in the blood pressure and the
pulse rate. This frequency varies normally but the range is 4550 kHz for the cardiac arrest or for the
heart failure.[clarification needed] In patients in hospital with unstable angina (or the newer term of "high-risk acute
coronary syndromes"), those with resting ischaemic ECG changes or those with raised cardiac enzymes
such as troponin may undergo coronary angiography directly.

Treatment[edit]
The most specific medicine to treat angina is nitroglycerin. It is a potent vasodilator that makes more
oxygen available to the heart muscle. Beta blockers and calcium channel blockers act to decrease the
heart's workload, and thus its requirement for oxygen. Nitroglycerin should not be given if certain
inhibitors such as Sildenafil (Viagra), Tadalafil (Cialis), or Vardenafil (Levitra) have been taken within the
previous 12 hours as the combination of the two could cause a serious drop in blood pressure.
Treatments for angina are balloon angioplasty, in which the balloon is inserted at the end of
a catheter and inflated to widen the arterial lumen. Stents to maintain the arterial widening are often used
at the same time. Coronary bypass surgery involves bypassing constricted arteries with venous grafts.
This is much more invasive than angioplasty.
The main goals of treatment in angina pectoris are relief of symptoms, slowing progression of the
disease, and reduction of future events, especially heart attacks and death. Beta blockers
(e.g.,carvedilol, propranolol, atenolol) have a large body of evidence in morbidity and mortality benefits
(fewer symptoms, less disability and longer life) and short-acting nitroglycerin medications have been
used since 1879 for symptomatic relief of angina. [29] Calcium channel blockers (such as nifedipine (Adalat)
and amlodipine), isosorbide mononitrate and nicorandil are vasodilators commonly used in chronic stable
angina[citation needed]. A new therapeutic class, called If inhibitor, has recently been made
available: Ivabradine provides pure heart rate reduction[30] leading to major anti-ischemic and antianginal
efficacy. ACE inhibitors are also vasodilators with both symptomatic and prognostic benefit. Statins are
the most frequently used lipid/cholesterol modifiers, which probably also stabilize existing atheromatous
plaque[citation needed]. Low-dose aspirin decreases the risk of heart attack in patients with chronic stable
angina, and was is part of standard treatment. However, in patients without established cardiovascular
disease, the increase in haemorrhagic stroke and gastrointestinal bleeding offsets any benefits and it is
no longer advised unless the risk of myocardial infarction is very high. [31]
Exercise is also a very good long-term treatment for the angina (but only particular regimens - gentle and
sustained exercise rather than intense short bursts), [32] probably working by complex mechanisms such as
improving blood pressure and promoting coronary artery collateralisation.

Identifying and treating risk factors for further coronary heart disease is a priority in patients with angina.
This means testing for elevated cholesterol and other fats in the blood, diabetes andhypertension (high
blood pressure), and encouraging smoking cessation and weight optimisation.
The calcium channel blocker nifedipine prolongs cardiovascular event- and procedure-free survival in
patients with coronary artery disease. New overt heart failures were reduced by 29% compared to
placebo; however, the mortality rate difference between the two groups was statistically insignificant. [33]
The fatty acid oxidation inhibitor mildronate is a clinically used anti-ischemic drug for the treatment
of angina and myocardial infarction.[34] Mildronate shifts the myocardial energy metabolism from fatty
acid oxidation to the more oxygen-sparing glucose oxidation under ischemic conditions,[35] by
inhibiting enzymes in the carnitine biosynthesis pathway[36][37][38] including gamma-butyrobetaine
dioxygenase.[39][40][41] Mildronate also inhibits carnitine acetyltransferase and therefore acts as a
myocardial energy metabolism regulator.[42]

Microvascular angina in women[edit]

Aggressive risk factor modification is required for effective treatment of microvascular angina where
exercise plays a major role.[43] Several other treatment strategies including b-blockers, angiotensinconverting enzyme inhibitors, ranolazine, l-arginine, statin drugs and potentially estrogen replacement
therapy have been shown to relieve anginal symptoms as well as improve vascular function. [43] Nitrates
may be effective for symptom relief.[43] Further studies are required to determine whether specific
treatments are associated with improved survival as well as decreased symptoms.

Suspected angina[edit]
Hospital admission for people with the following symptoms, as they may have unstable angina: Pain at
rest (which may occur at night), pain on minimal exertion, angina that seems to be progressing rapidly
despite increasing medical treatment. Refer urgently all people with suspected angina to a chest pain
evaluation service, for confirmation of the diagnosis and assessment of the severity of coronary heart
disease.[44]

Myocardial infarction
Myocardial infarction (from Latin: Infarctus myocardii, MI) or acute myocardial infarction (AMI) is the
medical term for an event commonly known as a heart attack. It happens when blood stops flowing
properly to part of the heart and the heart muscle is injured due to not receiving enough oxygen. Usually
this is because one of the coronary arteries that supplies blood to the heart develops a blockage due to
an unstable buildup of white blood cells, cholesterol and fat. The event is called "acute" if it is sudden and
serious.
A person having an acute MI usually has sudden chest pain that is felt behind the breast bone and
sometimes travels to the left arm or the left side of the neck. Additionally, the person may have shortness
of breath, sweating, nausea, vomiting, abnormal heartbeats, and anxiety. Women experience fewer of

these symptoms than men, but usually have shortness of breath, weakness, a feeling of indigestion,
and fatigue.[1] In many cases, in some estimates as high as 64%, the person does not have chest pain or
other symptoms.[2] These are called "silent" myocardial infarctions.
Important risk factors are previous cardiovascular disease, old age, tobacco smoking, high blood levels of
certain lipids (low-density lipoproteincholesterol, triglycerides) and low levels of high density
lipoprotein (HDL) cholesterol, diabetes, high blood pressure, lack of physical activity, obesity,chronic
kidney disease, excessive alcohol consumption, and the use of cocaine and amphetamines.[3][4] The main
way to determine if a person has had a myocardial infarction are electrocardiograms (ECGs) that trace
the electrical signals in the heart and testing the blood for substances associated with damage to the
heart muscle. Common blood tests are creatine kinase (CK-MB) and troponin. ECG testing is used to
differentiate between two types of myocardial infarctions based on the shape of the tracing. An ST section
of the tracing higher than the baseline is called an ST elevation MI (STEMI) which usually requires more
aggressive treatment.Immediate treatments for a suspected MI include aspirin, which prevents further
blood from clotting, and sometimes nitroglycerin to treat chest pain and oxygen.[5] STEMI is treated by
restoring circulation to the heart, called reperfusion therapy, and typical methods are angioplasty, where
the arteries are pushed open, and thrombolysis, where the blockage is removed using medications.
[6]
Non-ST elevation myocardial infarction (NSTEMI) may be managed with medication, although
angioplasty may be required if the person is considered to be at high risk. [7] People who have multiple
blockages of their coronary arteries, particularly if they also have diabetes, may also be treated
with bypass surgery (CABG).

Signs and symptoms[edit]

The onset of symptoms in myocardial infarction (MI) is usually gradual, over several minutes, and rarely
instantaneous.[12] Chest pain is the most common symptom of acute MI and is often described as a
sensation of tightness, pressure, or squeezing. Chest pain due to ischemia (a lack of blood and hence
oxygen supply) of the heart muscle is termed angina pectoris. Pain radiates most often to the left arm, but
may also radiate to the lower jaw, neck, right arm, back, and epigastrium,[8][13] where it may
mimic heartburn. Levine's sign, in which patients localize the chest pain by clenching their fists over
their sternums, has classically been thought to be predictive of cardiac chest pain, although a prospective
observational study showed it had a poor positive predictive value. [14]
Shortness of breath (dyspnea) occurs when the damage to the heart limits the output of the left ventricle,
causing left ventricular failure and consequentpulmonary edema. Other symptoms
include diaphoresis (an excessive form of sweating),[15] weakness, light-headedness, nausea, vomiting,
andpalpitations. These symptoms are likely induced by a massive surge of catecholamines from
the sympathetic nervous system[16] which occurs in response to pain and the hemodynamic abnormalities
that result from cardiac dysfunction. Loss of consciousness (due to inadequate cerebral perfusion and
cardiogenic shock) and sudden death (frequently due to the development of ventricular fibrillation) can
occur in MIs.[8]
Female, elderly, and diabetic patients report atypical symptoms more frequently than their male and
younger counterparts.[17][18] Women also report more numerous symptoms compared with men (2.6 on
average vs. 1.8 symptoms in men).[17] The most common symptoms of MI in women include dyspnea,

weakness, and fatigue. Fatigue, sleep disturbances, and dyspnea have been reported as frequently
occurring symptoms that may manifest as long as one month before the actual clinically manifested
ischemic event. In women, chest pain may be less predictive of coronary ischemia than in men. [19] Women
may also experience back or jaw pain during an episode. [20]
At least one-fourth of all MIs are silent, without chest pain or other symptoms. [2][21] These cases can be
discovered later on electrocardiograms, using blood enzyme tests or at autopsy without a prior history of
related complaints. Estimates of the prevalence of silent MIs vary between 22 and 64%. [2] A silent course
is more common in the elderly,[2] in patients with diabetes mellitus[22] and after heart transplantation,
probably because the donor heart is not fully innervated by the nervous system of the recipient. [23] In
people with diabetes, differences in pain threshold, autonomic neuropathy, andpsychological factors have
been cited as possible explanations for the lack of symptoms. [22]
Any group of symptoms compatible with a sudden interruption of the blood flow to the heart are called
an acute coronary syndrome.[24]
The differential diagnosis includes other catastrophic causes of chest pain, such as pulmonary
embolism, aortic dissection, pericardial effusion causingcardiac tamponade, tension pneumothorax,
and esophageal rupture. Other noncatastrophic differentials include gastroesophageal reflux and Tietze's
syndrome

Causes[edit]
Many of these risk factors are modifiable, so many heart attacks can be prevented by maintaining a
healthier lifestyle. Physical activity, for example, is associated with a lower risk profile. [26] Nonmodifiable
risk factors include age, sex, and family history of an early heart attack, which is thought of as reflecting
a genetic predisposition.[citation needed] The effect of education is partially based on its effect on income
and marital status.[27]

Lifestyle[edit]
Smoking appears to be the cause of about 36% and obesity the cause of 20% of coronary artery disease.
[28]
Lack of exercise has been linked to 7-12% of cases. [28][29] Job stress appears to play a minor role,
accounting for about 3% of cases.[28] Chronic high stress levels may cause some cases.[30]
Tobacco smoking, including secondhand smoke[31] Short-term exposure to air pollution, including carbon
monoxide, nitrogen dioxide, and sulfur dioxide, but not ozone.[32] Lack of physical activity[3] Psychosocial
factors including, low socioeconomic status, social isolation, negative emotions and stress increase the
risk of and are associated with worse outcomes after MI.Socioeconomic factors such as a
shorter education and lowerincome (particularly in women), and unmarried cohabitation are also
correlated with a higher risk of MI.[27] Alcohol prolonged exposure to high quantities of alcohol can
increase the risk of heart attack.

Disease[edit]
Diabetes mellitus (type 1 or 2),[33] high blood pressure[31] dyslipidemia/hypercholesterolemia (abnormal
levels of lipoproteins in the blood), particularly high low-density lipoprotein, low high-density
lipoproteinand high triglycerides[31] Obesity[34] (defined by a body mass index of more than 30 kg/m, or
alternatively by waist circumference or waist-hip ratio).
A number of acute and chronic infections including: Chlamydophila pneumoniae, influenza, Helicobacter
pylori, and Porphyromonas gingivalis among others have been linked to atherosclerosis and myocardial
infarction. There is as of 2013 no evidence of benefit from antibiotics or vaccination, however, calling the
association into question.[35][36]

Other[edit]
Older age[3] Male sex: at any given age, men are more at risk than women, particularly
before menopause,[37] but because in general women live longer than men, ischemic heart disease
causes slightly more total deaths in women.[3] Family history of ischaemic heart disease or MI, particularly
if one has a first-degree relative (father, brother, mother, sister) who suffered a 'premature' myocardial
infarction (defined as occurring at or younger than age 55 years (men) or 65 (women). [3]
Oral contraceptive pill women who use combined oral contraceptive pills have a modestly increased risk
of myocardial infarction, especially in the presence of other risk factors, such as smoking. [38]
An increased incidence of a heart attack is associated with time of day especially in the morning hours,
more specifically around 9 am.[39][40][41]

Pathophysiology[edit]
Acute myocardial infarction refers to two subtypes of acute coronary syndrome, namely non-ST-elevated
and ST-elevated MIs, which are most frequently (but not always) a manifestation of coronary artery
disease.[42] The most common triggering event is the disruption of an atheroscleroticplaque in an
epicardial coronary artery, which leads to a clotting cascade, sometimes resulting in total occlusion of the
artery.[43][44] Atherosclerosis is the gradual buildup of cholesterol and fibrous tissue in plaques in the wall
of arteries (in this case, the coronary arteries), typically over decades.[45]Blood stream column
irregularities visible on angiography reflect artery lumen narrowing as a result of decades of advancing
atherosclerosis.[46] Plaques can become unstable, rupture, and additionally promote a thrombus (blood
clot) that occludes the artery; this can occur in minutes. When a severe enough plaque rupture occurs in
the coronary vasculature, it leads to MI (necrosis of downstream myocardium). [43][44]
If impaired blood flow to the heart lasts long enough, it triggers a process called the ischemic cascade;
the heart cells in the territory of the occluded coronary artery die (chiefly through necrosis) and do not
grow back. A collagen scar forms in their place. Recent studies indicate that another form of cell
death, apoptosis, also plays a role in the process of tissue damage subsequent to MI. [47] As a result, the
patient's heart will be permanently damaged. This myocardial scarring also puts the patient at risk for

potentially life-threatening arrhythmias, and may result in the formation of aventricular aneurysm that can
rupture with catastrophic consequences.
Injured heart tissue conducts electrical impulses more slowly than normal heart tissue. The difference in
conduction velocity between injured and uninjured tissue can trigger re-entry or a feedback loop that is
believed to be the cause of many lethal arrhythmias. The most serious of these arrhythmias is ventricular
fibrillation (V-Fib/VF), an extremely fast and chaotic heart rhythm that is the leading cause of sudden
cardiac death. Another life-threatening arrhythmia is ventricular tachycardia (V-tach/VT), which may or
may not cause sudden cardiac death. However, VT usually results in rapid heart rates that prevent the
heart from pumping blood effectively. Cardiac output and blood pressure may fall to dangerous levels,
which can lead to further coronary ischemia and extension of the infarct.
The cardiac defibrillator device was specifically designed to terminate these potentially fatal arrhythmias.
The device works by delivering an electrical shock to the patient to depolarize a critical mass of the heart
muscle, in effect "rebooting" the heart. This therapy is time-dependent, and the odds of successful
defibrillation decline rapidly after the onset of cardiopulmonary arrest.
Myocardial infarction results from atherosclerosis.[8] Inflammation is known to be an important step in the
process ofatherosclerotic plaqueformation.[48] C-reactive protein (CRP) is a sensitive but
nonspecific marker for inflammation. Elevated CRP blood levels, especially measured with high-sensitivity
assays, can predict the risk of MI, as well as stroke and development of diabetes.[48] Moreover, some
drugs for MI might also reduce CRP levels.[48] The use of high-sensitivity CRP assays as a means
of screening the general population is advised against, but it may be used optionally at the physician's
discretion in patients who already present with other risk factors or known coronary artery disease.
[49]
Whether CRP plays a direct role in atherosclerosis remains uncertain. [48]
Calcium deposition is another part of atherosclerotic plaque formation. Calcium deposits in the coronary
arteries can be detected with CT scans. Several studies have shown that coronary calcium can provide
predictive information beyond that of classical risk factors. [50][51][52]
Hyperhomocysteinemia (high homocysteine) in homocysteinuria is associated with premature
atherosclerosis,[53]whether elevated homocysteine in the normal range is causal is contentious. [54]

Pathological types[edit]
The two main types of acute myocardial infarction, based on pathology, are:

Transmural AMI is associated with atherosclerosis involving a major coronary artery. It can be
subclassified into anterior, posterior, inferior, lateral, or septal. Transmural infarcts extend through the
whole thickness of the heart muscle and are usually a result of complete occlusion of the area's blood
supply.[55] In addition, on ECG, ST elevation and Q waves are seen.

Subendocardial AMI involves a small area in the subendocardial wall of the left ventricle,
ventricular septum, or papillary muscles. The subendocardial area is particularly susceptible to
ischemia.[55] In addition, ST depression is seen on ECG.

Diagnosis[edit]
Main article: Myocardial infarction diagnosis
A cardiac troponin rise accompanied by either typical symptoms, pathological Q waves, ST elevation or
depression, or coronary intervention is diagnostic of MI. [56]
WHO criteria[57] formulated in 1979 have classically been used to diagnose MI; a patient is diagnosed with
MI if two (probable) or three (definite) of the following criteria are satisfied:
1. Clinical history of ischaemic type chest pain lasting for more than 20 minutes
2. Changes in serial ECG tracings
3. Rise and fall of serum cardiac biomarkers
At autopsy, a pathologist can diagnose an MI based onanatomopathological findings.

Classification[edit]
Myocardial infarctions are generally classified into ST elevation MI (STEMI) and non-ST elevation
MI (NSTEMI).[42] A STEMI is the combination of symptoms related to poor oxygenation of the heart with
elevation of the ST segments on the electrocardiogram followed by an increase in proteins in the blood
related to heart muscles death.[58] They make up abut 25 to 40 percent of cases.[58]
The phrase "heart attack" is often used none specifically to refer to a myocardial infarction and to sudden
cardiac death. A MI is different from, but can cause cardiac arrest, which is the stopping of the heartbeat.
It is also distinct from heart failure, in which the pumping action of the heart is impaired. However; an MI
may lead to heart failure.[8]
A 2007 consensus document classifies MI into five main types: [59]

Type 1 spontaneous MI related to ischemia due to a primary coronary event such as plaque
erosion and/or rupture, fissuring, or dissection

Type 2 MI secondary to ischemia due to either increased oxygen demand or decreased supply,
e.g. coronary artery spasm, coronary embolism, anaemia, arrhythmias, hypertension, or hypotension

Type 3 sudden unexpected cardiac death, including cardiac arrest, often with symptoms
suggestive of myocardial ischaemia, accompanied by new ST elevation, or new LBBB, or evidence of
fresh thrombus in a coronary artery by angiography and/or at autopsy, but death occurring before
blood samples could be obtained, or at a time before the appearance of cardiac biomarkers in the
blood

Type 4 associated with coronary angioplasty or stents:

Type 4a MI associated with PCI

Type 4b MI associated with stent thrombosis as documented by angiography or at

autopsy

Type 5 MI associated with CABG

Electrocardiogram[edit]
For a person to quality as having an STEMI, the ECG must show new ST elevation in two or
more contiguous leads.[58] This must be greater than 2 mm (0.2 mV) for males and greater than 1.5 mm
(0.15mV) in females if in leads V2 and V3 or greater than 1 mm (0.1 mV) if it is in other ECG leads.
[58]
A left bundle branch block (LBBB) that is believed to be new used to be considered the same as ST
elevation; however, no longer is.[58] In early STEMIs there may just be peaked T wave with ST elevation
developing latter.[58]

Cardiac biomarkers[edit]
While there are a number of different biomarkers, tropinins, are considered to be the best.[58]

Imaging[edit]
A chest radiograph and routine blood tests may indicate complications or precipitating causes, and are
often performed upon arrival to an emergency department. New regional wall motion abnormalities on
an echocardiogram are also suggestive of an MI. Echo may be performed in equivocal cases by the oncall cardiologist.[60] In stable patients whose symptoms have resolved by the time of
evaluation, technetium (99mTc) sestamibi (i.e. a "MIBI scan") or thallium-201 chloride can be used
in nuclear medicine to visualize areas of reduced blood flow in conjunction with physiological or
pharmacological stress.[60] Thallium may also be used to determine viability of tissue, distinguishing
whether nonfunctional myocardium is actually dead or merely in a state of hibernation or of being
stunned.[61]
Medical societies recommend that the physician confirm a person is at high risk for myocardial infarction
before conducting imaging tests to make a diagnosis. [62] Patients who have a normal ECG and who are
able to exercise, for example, do not merit routine imaging. [62] Imaging tests such as stress
radionuclide myocardial perfusion imaging or stressechocardiography can confirm a diagnosis when a
patient's history, physical exam, ECG, and cardiac biomarkers suggest the likelihood of a problem. [62]

Prevention[edit]
The risk of a recurrent MI decreases with strict blood pressure management and lifestyle changes,
chiefly smoking cessation, regular exercise, a sensible diet for those with heart disease, andlimitation of
alcohol intake. People are usually started on several long-term medications after an MI, with the aim of

preventing further cardiovascular events such MIs, congestive heart failure, orcerebrovascular accident.
Unless contraindicated, such medications may include: [63][64]

Antiplatelet drug therapy such as aspirin and/or clopidogrel should be continued to reduce the risk
of plaque rupture and recurrent MI. Aspirin is first-line, owing to its low cost and comparable efficacy,
with clopidogrel reserved for patients intolerant of aspirin. The combination of clopidogrel and aspirin
may further reduce risk of cardiovascular events, but the risk of hemorrhage is increased.[65]

Beta blocker therapy such as metoprolol or carvedilol should be started.[66] These have been
particularly beneficial in those who are high-risk such as those with left ventricular dysfunction and/or
continuing cardiac ischaemia.[67] -Blockers decrease mortality and morbidity. They also improve
symptoms of cardiac ischemia in NSTEMI.

ACE inhibitor therapy should be commenced 2448 hours after MI in those who are
hemodynamically stable, particularly with a history of MI, diabetes mellitus, hypertension, anterior
location of infarct (as assessed by ECG), and/or evidence of left ventricular dysfunction. ACE
inhibitors reduce mortality, the development of heart failure, and decrease ventricular remodelling.[68]

Statin therapy has been shown to reduce mortality and morbidity.[69] The effects of statins may be
more than their LDL lowering effects. The general consensus is that statins have plaquestabilization
and multiple other ("pleiotropic") effects that may prevent myocardial infarction in addition to their
effects on blood lipids.[70]

The aldosterone antagonist agent eplerenone has been shown to further reduce risk of
cardiovascular death after MI in patients with heart failure and left ventricular dysfunction, when used
in conjunction with standard therapies above.[71] Spironolactone, another option, is sometimes
preferable to eplerenone due to cost.

Evidence supports the consumption of polyunsaturated fats instead of saturated fats as a

measure of decreasing coronary heart disease.[72] In high-risk people, no clear-cut decrease in
potentially fatal arrhythmias occurs due to omega-3 fatty acids.[73] And they may increase risk in some
groups.[73]

Giving heparin to people with heart conditions like unstable angina and some forms of heart
attacks reduces the risk of having another heart attack. However, heparin also increases the chance
of minor bleeding.[74]

Management[edit]
Main article: Myocardial infarction management
An MI requires immediate medical attention. Treatment attempts to save as much myocardium as
possible and to prevent further complications, hence the phrase "time is muscle". [75] Oxygen, aspirin, and
nitroglycerin may be administered. Morphine was classically used if nitroglycerin was not effective;

however, it may increase mortality in the setting of NSTEMI. [76] Reviews of high flow oxygen in myocardial
infarction found increased mortality and infarct size, calling into question the recommendation about its
routine use.[77][78] Other analgesics such as nitrous oxide are of unknown benefit.[7]

STEMI[edit]
Immediate[edit]
Percutaneous coronary intervention (PCI) is the treatment of choice for STEMI if it can be performed in a
timely manner.[79] If PCI cannot be performed within 90 to 120 minutes then fibrinolysis, preferably within
30 minutes, is recommended.[80][81] If after fibrinolysis, significant cardiogenic shock, continued severe
chest pain, or less than a 50% improvement in ST elevation after 90 minutes occurs, then rescue PCI is
indicated emergently.[81][82] After PCI, people are generally placed on dual antiplatelet therapy for at least a
year (which is generally aspirin andclopidogrel).[83]

Long term[edit]
Beta blockers are recommended in those without signs off heart failure or a heart block.[58] If used they
should be started in the first 24 hours.[58]

Prognosis[edit]
The prognosis after MI varies greatly, depending on a person's health, the extent of the heart damage,
and the treatment given.
In those who have an STEMI in the United States between 5 to 6 percent die before leaving hospital and
7 to 18 percent die within a year.[58]
Using variables available in the emergency room, people with a higher risk of adverse outcome can be
identified. One study found 0.4% of patients with a low-risk profile died after 90 days, whereas in high-risk
people it was 21.1%.[84]
Some risk factors for death include: age, hemodynamic parameters (such as heart failure, cardiac
arrest on admission, systolic blood pressure, or Killip class of two or greater), ST-segment deviation,
diabetes, serum creatinine, peripheral vascular disease, and elevation of cardiac markers.[84][85]
[86]
Assessment of left ventricular ejection fraction may increase the predictive power.[87]Prognosis is worse
if a mechanical complication such as papillary muscle or myocardial free wall rupture occurs.[88] Morbidity
and mortality from myocardial infarction has improved over the years due to better treatment. [89]

Complications[edit]
Main article: Myocardial infarction complications
Complications may occur immediately following the heart attack (in the acute phase), or may need time to
develop (a chronic problem). Acute complications may include heart failure if the damaged heart is no

longer able to pump blood adequately around the body; aneurysm or rupture of the myocardium; mitral
regurgitation, in particular if the infarction causes dysfunction of the papillary muscle; Dressler's
syndrome; and arrhythmias, such as ventricular fibrillation, ventricular tachycardia, atrial fibrillation, and
heart block. Longer-term complications include heart failure, atrial fibrillation, and the increased risk of a
second MI.