Coronary artery disease

Coronary artery disease

Illustration depicting atherosclerosis in a coronary artery.
Classification and external resources
ICD-10 I20-I25
ICD-9 410-414, 429.2
MedlinePlus 007115
eMedicine radio/192
Patient UK Coronary artery disease
MeSH D003324

Coronary artery disease (CAD), also known as ischemic heart disease (IHD),[1] atherosclerotic heart disease,[2] atherosclerotic cardiovascular disease,[3] and coronary heart disease,[4] is a group of diseases that includes: stable angina, unstable angina, myocardial infarction, and sudden coronary death.[5] It is within the group of cardiovascular diseases of which it is the most common type.[6] A common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw.[7] Occasionally it may feel like heartburn.[7] Usually symptoms occur with exercise or emotional stress, last less than a few minutes, and gets better with rest.[7] Shortness of breath may also occur and sometimes no symptoms are present.[7] The first sign is occasionally a heart attack.[8] Other complications include heart failure or an irregular heartbeat.[8]

Risk factors include: high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, and excessive alcohol, among others.[9][10] Other risks include depression.[11] The underlying mechanism involves atherosclerosis of the arteries of the heart.[10] A number of tests may help with diagnoses including: electrocardiogram, cardiac stress testing, and coronary angiogram among others.[12]

Prevention is by eating a healthy diet, regular exercise, maintaining a healthy weight and not smoking.[13] Sometimes medication for diabetes, high cholesterol, or high blood pressure are also used.[13] There is limited evidence for screening people who are at low risk and do not have symptoms.[14] Treatment involves the same measures as prevention.[15][16] Additional medications such as aspirin, beta blockers, or nitrogylcerin may be recommended.[16] Procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) may be used in severe disease.[16][17] In those with stable CAD it is unclear if PCI or CABG in addition to the other treatments improve life expectancy or decreases heart attack risk.[18]

In 2013 CAD was the most common cause of death globally, resulting in 8.14 million deaths (16.8%) up from 5.74 million deaths (12%) in 1990.[6] The risk of death from CAD for a given age has decreased between 1980 and 2010 especially in the developed world.[19] The number of cases of CAD for a given age has also decreased between 1990 and 2010.[20] In the United States in 2010 about 20% of those over 65 had CAD, while it was present in 7% of those 45 to 64, and 1.3% of those 18 to 45.[21] Rates are higher among men than women of a given age.[21]

Signs and symptoms

Chest pain that occurs regularly with activity, after eating, or at other predictable times is termed stable angina and is associated with narrowings of the arteries of the heart.

Angina that changes in intensity, character or frequency is termed unstable. Unstable angina may precede myocardial infarction. In adults who go to the emergency with an unclear cause of pain, about 30% have pain due to coronary artery disease.[22]

Risk factors

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 high blood lipids.[23] Smoking is associated with about 36% of cases and obesity 20%.[24] Lack of exercise has been linked to 7–12% of cases.[24][25]

Job stress appears to play a minor role accounting for about 3% of cases.[24] 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.[26] 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.[26] Also, having a type A behavior pattern, a group of personality characteristics including time urgency, competitiveness, hostility, and impatience[27] is linked to an increased risk of coronary disease.[28]

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

Blood fats

Dietary cholesterol does not appear to have a significant effect on blood cholesterol and thus recommendations about its consumption may not be needed.[34]

Other

Pathophysiology

Micrograph of a coronary artery with the most common form of coronary artery disease (atherosclerosis) and marked luminal narrowing. Masson's trichrome.
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 calciphylaxis 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.[38]

No one knows exactly what causes cardiac syndrome X. One explanation is microvascular dysfunction.[39] 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.[40]

Diagnosis

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.[41] The use of echocardiography, stress cardiac imaging, and/or advanced non-invasive imaging is not recommended on individuals who are exhibiting no symptoms and are otherwise at low risk for developing coronary disease.[41][42]

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 patient's condition. The results from MCG tests have been validated in 8 clinical trials 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 .

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

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

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

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.[43]

Prevention

Prevention involves: exercise, decreasing obesity, treating hypertension, a healthy diet, decreasing cholesterol levels, and stopping smoking. Medications and exercise are roughly equally effective.[44]

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.[45]

Diet

A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death.[46] Vegetarians have a lower risk of heart disease,[47][48] possibly due to their greater consumption of fruits and vegetables.[49] Evidence also suggests that the Mediterranean diet[50] and a high fiber diet lower the risk.[51]

The consumption of trans fat (commonly found in hydrogenated products such as margarine) has been shown to cause a precursor to atherosclerosis[52] and increase the risk of coronary artery disease.[53]

Evidence does not support a beneficial role for omega-3 fatty acid supplementation in preventing cardiovascular disease (including myocardial infarction and sudden cardiac death).[54][55] There is tentative evidence that menaquinone (Vitamin K2), but not phylloquinone (Vitamin K1), intake may reduce the risk of CAD mortality.[56]

Secondary prevention

Secondary prevention is preventing further sequelae of already established disease. Lifestyle changes that have been shown to be effective to this goal include:

Management

There are a number of treatment options for coronary artery disease:[63]

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

Medications

Aspirin

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.[65] It is thus only recommended in adults who are at increased risk for coronary artery disease[66] 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%'.

Anti-platelet therapy

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.[67] In those who have had a stent more than 12 months of clopidogrel plus aspirin does not affect the risk of death.[68]

Surgery

Revascularization for acute coronary syndrome has a mortality benefit.[69] Revascularization for stable ischaemic heart disease does not appear to have benefits over medical therapy alone.[70] In those with disease in more than one artery coronary artery bypass grafts appear better than percutaneous coronary interventions.[71][72]

Epidemiology

Disability-adjusted life year for ischaemic heart disease per 100,000 inhabitants in 2004.[73]
  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.[74] This is up from 5.2 million deaths in 1990.[74] 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.[75] Males are affected more often than females.[75]

It is estimated that 60% of the world's cardiovascular disease burden will occur in the South Asian subcontinent despite only accounting for 20% of the world's population. This may be secondary to a combination of genetic predisposition and environmental factors. Organizations such as the Indian Heart Association are working with the World Heart Federation to raise awareness about this issue.[76]

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.[77] 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.[78] It is the most common reason for death of men and women over 20 years of age in the United States.[79] The Maasai of Africa have almost no heart disease.

Society and culture

Other terms sometimes used for this condition are "hardening of the arteries" and "narrowing of the arteries".[80]


Research

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.[81]

A more controversial link is that between Chlamydophila pneumoniae infection and atherosclerosis.[82] While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor. Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.[83]

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[84] 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[85][86] and utilization of endothelial progenitor cells.

Myeloperoxidase has been proposed as a biomarker.[87]

References

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