Coronary artery disease

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Coronary artery disease
Classification and external resources
RCA atherosclerosis.jpg
Micrograph of a coronary artery with the most common form of coronary artery disease (atherosclerosis) and marked luminal narrowing. Masson's trichrome.
ICD-10 I20-I25
ICD-9 410-414, 429.2
MedlinePlus 007115
eMedicine radio/192
MeSH D003324

Coronary artery disease (CAD) also known as atherosclerotic heart disease,[1] atherosclerotic cardiovascular disease,[2] coronary heart disease,[3] or ischemic heart disease (IHD),[4] is the most common type of heart disease and cause of heart attacks.[5] The disease is caused by plaque building up along the inner walls of the arteries 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 include coronary vasospasm,[6] a spasm of the blood vessels of the heart, it is usually called Prinzmetal's angina.[7]

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).

It was as of 2012 the most common cause of death in the world,[8] and a major cause of hospital admissions.[9] There is limited evidence for population screening, but prevention (with a healthy diet and sometimes medication for diabetes, cholesterol and high blood pressure) is used both to prevent IHD and to decrease the risk of complications.

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. About 80% of chest pains have nothing to do with the heart.

Risk factors[edit]

Coronary artery disease has a number of well determined risk factors. The most common risk factors include smoking, family history, hypertension, obesity, diabetes, lack of exercise, stress, and hyperlipidemia.[10] Smoking is associated with about 54% of cases and obesity 20%.[11] Lack of exercise has been linked to 7–12% of cases.[11][12]

Job stress appears to play a minor role accounting for about 3% of cases.[11] In one study, women who were free of stress from work life saw an increase in the diameter of their blood vessels, leading to decreased progression of atherosclerosis.[13] Contrastingly, women who had high levels of work-related stress experienced a decrease in the diameter of their blood vessels and significantly increased disease progression.[13] Also, having a type A behavior pattern, a group of personality characteristics including time urgency, competitiveness, hostility, and impatience[14] is linked to an increased risk of coronary disease.[15]

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]

Illustration depicting atherosclerosis in coronary artery.
Illustration depicting coronary artery disease

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 coronary arteriosclerosis. 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.[24]

No one knows exactly what causes cardiac syndrome X. One explanation is microvascular dysfunction.[25] 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.[26]

Diagnosis[edit]

Coronary angiogram of a man
Coronary angiogram of a woman

For symptomatic patients, stress echocardiography can be used to make a diagnosis for obstructive coronary artery disease.[27] The use of echocardiography is not recommended on individuals who are exhibiting no symptoms and are otherwise at low risk for developing coronary disease.[27]

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:

The diagnosis of coronary disease underlying particular symptoms depends largely on the nature of the symptoms. The first investigation is an electrocardiogram (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) or scintigraphy (using uptake of radionuclide by the heart muscle). If part of the heart seems to receive an insufficient blood supply, coronary angiography may be used to identify stenosis of the coronary arteries and suitability for angioplasty or bypass surgery.

Acute coronary syndrome[edit]

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.

Risk assessment[edit]

There are various risk assessment systems for determining the risk of coronary artery disease, with various emphasis on different variables above. A notable example is Framingham Score, used in the Framingham Heart Study. It is mainly based on age, gender, diabetes, total cholesterol, HDL cholesterol, tobacco smoking and systolic blood pressure.[28]

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.[29]

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.[30]

Diet[edit]

It has been suggested that coronary artery disease is partially reversible using an intense dietary regimen coupled with regular cardiovascular exercise.[31] A high fiber diet appears to lower the risk.[32]

  • Vegetarian diet: Vegetarians have been shown to have a 24% reduced risk of dying of heart disease.[33]
  • 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, and goat cheese.[34][35]

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 to atherosclerosis.[36] The consumption of trans fatty acids has been shown to increase the risk of coronary artery disease[37]

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).[38][39] Menaquinone (Vitamin K2), but not phylloquinone (Vitamin K1), intake may reduce the risk of CAD mortality.[40]

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 4-phase 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.[41]

Treatment[edit]

There are three main treatment options for coronary artery disease:[42]

  1. Medical treatment - drugs (e.g. cholesterol lowering medications, beta-blockers, nitroglycerin, calcium antagonists, etc.);
  2. Coronary interventions as angioplasty and coronary stent;
  3. Coronary artery bypass grafting (CABG)

Lifestyle[edit]

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

  • 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(LDL) over time. It also increases HDL cholesterol which is considered as a " good cholesterol "[46][47]
  • Decrease psychosocial stress.[48]

In people with coronary artery disease, aerobic exercise can reduce the risk of mortality.[49] 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.[50] The American Heart Association, based on a non-systematic review, recommends that doctors counsel patients on exercise.[51]

Medications[edit]

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.[53] It is thus only recommended in adults who are at increased risk for coronary artery disease[54] 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.[55]

Surgery[edit]

Revascularization for acute coronary syndrome has a mortality benefit.[56] Revascularization for stable ischaemic heart disease does not appear to have benefits over medical therapy alone.[57] In those with disease in more than one artery coronary artery bypass grafts appear better than percutaneous coronary interventions.[58][59]

Epidemiology[edit]

Disability-adjusted life year for ischaemic heart disease per 100,000 inhabitants in 2004.[60]
  no data
  <350
  350–700
  700–1050
  1050–1400
  1400–1750
  1750–2100
  2100–2450
  2450–2800
  2800–3150
  3150–3500
  3500–4000
  >4000

CAD as of 2010 was the leading cause of death globally resulting in over 7 million deaths.[61] This is up from 5.2 million deaths in 1990.[61] It may affect individuals at any age but becomes dramatically more common at progressively older ages, with approximately a tripling with each decade of life.[8] Males are affected more often than females.[8]

Coronary heart disease (CHD) is the leading cause of death for both men and women and accounts for approximately 600,000 deaths in the United States every year.[62] According to present trends in the United States, half of healthy 40-year-old males will develop CAD in the future, and one in three healthy 40-year-old women.[63] It is the most common reason for death of men and women over 20 years of age in the United States.[64] The Maasai of Africa have almost no heart disease.

Research[edit]

Further information: atheroma and atherosclerosis

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

A region on Chromosome 17 was confined to families with multiple cases of myocardial infarction.[65]

A more controversial link is that between Chlamydophila pneumoniae infection and atherosclerosis.[66] While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor.[citation needed] Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.[67]

Since the 1990s the search for new treatment options for coronary artery disease patients, particularly for so called "no-option" coronary patients, focused on usage of angiogenesis[68] and (adult) stem cell therapies. Numerous clinical trials were performed, either applying protein (angiogenic growth factor) therapies, such as FGF-1 or VEGF, or cell therapies using different kinds of adult stem cell populations. Research is still going on - with first promising results particularly for FGF-1[69][70] and utilization of endothelial progenitor cells.

Myeloperoxidase has been proposed as a biomarker.[71]

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