coronary heart disease

Coronary heart disease (CHD), also called coronary artery disease (CAD), ischaemic heart disease, atherosclerotic heart disease, is the end result of the accumulation of atheromatous plaques within the walls of the arteries that supply the myocardium (the muscle of the heart) with oxygen and nutrients. While the symptoms and signs of coronary heart disease are noted in the advanced state of disease, most individuals with coronary heart disease show no evidence of disease for decades as the disease progresses before the first onset of symptoms, often a "sudden" heart attack, finally arise. After decades of progression, some of these atheromatous plaques may rupture and (along with the activation of the blood clotting system) start limiting blood flow to the heart muscle. The disease is the most common cause of sudden death^[1], and is also the most common reason for death of men and women over 20 years of age.^{[citation needed]} According to present trends in the United States, half of healthy 40-year-old males will develop CHD in the future, and one in three healthy 40-year-old women.^[2] According to the Guinness Book of Records, Northern Ireland is the country with the most occurrences of CHD.

Overview

Atherosclerotic heart disease can be thought of as a wide spectrum of disease of the heart. At one end of the spectrum is the asymptomatic individual with atheromatous streaks within the walls of the coronary arteries (the arteries of the heart). These streaks represent the early stage of atherosclerotic heart disease and do not obstruct the flow of blood. A coronary angiogram performed during this stage of disease may not show any evidence of coronary artery disease, because the lumen of the coronary artery has not decreased in calibre.

Over a period of many years, these streaks increase in thickness. While the atheromatous plaques initially expand into the walls of the arteries, eventually they will expand into the lumen of the vessel, affecting the flow of blood through the arteries. While it was originally believed that the growth of atheromatous plaques was a slow, gradual process, recent evidence suggests that the gradual buildup may be complemented by small plaque ruptures which cause the sudden increase in the plaque burden due to accumulation of thrombus material.

Intravascular ultrasound image of a coronary artery (left), with color coding on the right, delineating the lumen (yellow), external elastic membrane (blue) and the atherosclerotic plaque burden (green). As the plaque burden increases, the lumen size will decrease.

Atheromatous plaques that cause obstruction of less than 70 percent of the diameter of the vessel rarely cause symptoms of obstructive coronary artery disease. As the plaques grow in thickness and obstruct more than 70 percent of the diameter of the vessel, the individual develops symptoms of obstructive coronary artery disease. At this stage of the disease process, the patient can be said to have ischemic heart disease. The symptoms of ischemic heart disease are often first noted during times of increased workload of the heart. For instance, the first symptoms include exertional angina or decreased exercise tolerance.

As the degree of coronary artery disease progresses, there may be near-complete obstruction of the lumen of the coronary artery, severely restricting the flow of oxygen-carrying blood to the myocardium. Individuals with this degree of coronary heart disease typically have suffered from one or more myocardial infarctions (heart attacks), and may have signs and symptoms of chronic coronary ischemia, including symptoms of angina at rest and flash pulmonary edema.

A distinction should be made between myocardial ischemia and myocardial infarction. Ischemia means that the amount of oxygen supplied to the tissue is inadequate to supply the needs of the tissue. When the myocardium becomes ischemic, it does not function optimally. When large areas of the myocardium becomes ischemic, there can be impairment in the relaxation and contraction of the myocardium. If the blood flow to the tissue is improved, myocardial ischemia can be reversed. Infarction means that the tissue has undergone irreversible death due to lack of sufficient oxygen-rich blood.

An individual may develop a rupture of an atheromatous plaque at any stage of the spectrum of coronary heart disease. The acute rupture of a plaque may lead to an acute myocardial infarction (heart attack).

Pathophysiology

Limitation of blood flow to the heart causes ischemia (cell starvation secondary to a lack of oxygen) of the myocardial cells. When myocardial cells die from lack of oxygen, this is called a myocardial infarction (commonly called a heart attack). It leads to heart muscle damage, heart muscle death and later scarring without heart muscle regrowth.

Myocardial infarction usually results from the sudden occlusion of a coronary artery when a plaque ruptures, activating the clotting system and atheroma-clot interaction fills the lumen of the artery to the point of sudden closure. The typical narrowing of the lumen of the heart artery before sudden closure is typically 20%, according to clinical research completed in the late 1990s and using IVUS examinations within 6 months prior to a heart attack. High grade stenoses as such exceeding 75% blockage, such as detected by stress testing, were found to be responsible for only 14% of acute heart attacks the rest being due to plaque rupture/ spasm. The events leading up to plaque rupture are only partially understood. Myocardial infarction is also caused, far less commonly, by spasm of the artery wall occluding the lumen, a condition also associated with atheromatous plaque and CHD.

CHD is associated with smoking, obesity, hypertension and a chronic sub-clinical lack of vitamin C. A family history of CHD is one of the strongest predictors of CHD. Screening for CHD includes evaluating homocysteine levels, high-density and low-density lipoprotein (cholesterol) levels and triglyceride levels.

Angina

Angina that occurs regularly with activity, upon awakening, 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 nitrate preparations such as nitroglycerin, which come in short-acting and long-acting forms, and may be administered transdermally, sublingually or orally. 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 is treated with morphine, oxygen, intravenous nitroglycerin, and aspirin. Interventional procedures such as angioplasty may be done.

Risk factors

The following are confirmed independent risk factors for the development of CAD, in order of decreasing importance:

1. Hypercholesterolemia (specifically, serum LDL concentrations)
2. Smoking
3. Hypertension (high systolic pressure seems to be most significant in this regard)
4. Hyperglycemia (due to diabetes mellitus or otherwise)
5. Type A Behavioural Patterns, TABP. Added in 1981 as an independent risk factor after a majority of research into the field discovered that TABP's were twice as likely to cause CHD than any other personality type.
6. Hereditary differences in such diverse aspects as lipoprotein structure and that of their associated receptors, homocysteine processing/metabolism, etc.

Significant, but indirect risk factors include:

• Lack of exercise
• Stress
• Diet rich in saturated fats
• Diet low in antioxidants
• Obesity
• Men over 60; Women over 65 [1]

Prevention

Coronary heart disease is the most common form of heart disease in the Western world. Prevention centers on the modifiable risk factors, which include decreasing cholesterol levels, addressing obesity and hypertension, avoiding a sedentary lifestyle, making healthy dietary choices, and stopping smoking. There is some evidence that lowering uric acid and homocysteine levels may contribute. In diabetes mellitus, there is little evidence that blood sugar control actually improves cardiac risk. Some recommend a diet rich in omega-3 fatty acids and vitamin C. The World Health Organization (WHO) recommends "low to moderate alcohol intake" to reduce risk of coronary heart disease.^[3]

An increasingly growing number of other physiological markers and homeostatic mechanisms are currently under scientific investigation. Among these markers are low density lipoprotein and asymmetric dimethylarginine. Patients with CHD and those trying to prevent CHD are advised to avoid fats that are readily oxidized (e.g., saturated fats and trans-fats), limit carbohydrates and processed sugars to reduce production of Low density lipoproteins while increasing High density lipoproteins, keeping blood pressure normal, exercise and stop smoking. These measures limit the progression of the disease. Recent studies have shown that dramatic reduction in LDL levels can cause mild regression of coronary heart disease.

Exercise

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 (USPSTF), based on a systematic review of randomized controlled trials, found 'insufficient evidence' to recommend that doctors counsel patients on exercise.^[4] However, the American Heart Association, based on a non-systematic review, recommends that doctors counsel patients on exercise ^[5]

Preventive diets

Main article: Diet and Heart Disease

It has been suggested that coronary heart disease is partially reversible using an intense dietary regimen coupled with regular cardio exercise.^[6]

• Vegetarian diet: Vegetarians have been shown to have a 24% reduced risk of dying of heart disease.^[7]

• Cretan Mediterranean diet: The Seven Country 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, sausage and goat cheese.^[8][9][10] However, the Cretan diet consisted of less fish and wine consumption than some other Mediterranean-style diets, such as the diet in Corfu, another region of Greece, which had higher death rates.^{[citation needed]}

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.^[11]

Aspirin

Aspirin, in doses of less than 75 to 81 mg/d^[12], can reduce the incidence of cardiovascular events.^[13] The U.S. Preventive Services Task Force 'strongly recommends that clinicians discuss aspirin chemoprevention with adults who are at increased risk for coronary heart disease'.^[14] The Task Force defines increased risk as 'Men older than 40 years of age, postmenopausal women, and younger persons with risk factors for coronary heart 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%'. A risk calculator is available.^[15]

Regarding healthy women, the more recent Women's Health Study randomized controlled trial found insignficant benefit from aspirin in the reduction of cardiac events; however there was a signficant reduction in stroke.^[16] Subgroup analysis showed that all benefit was confined to women over 65 years old.^[16] In spite of the insignficant benefit for women < 65 years old, recent practice guidelines by the American Heart Association recommend to 'consider' aspirin in 'healthy women' <65 years of age 'when benefit for ischemic stroke prevention is likely to outweigh adverse effects of therapy'.^[17]

Omega-3 fatty acids

The benefit of fish oil is controversial with conflicting conclusions reached by a negative meta-analysis^[18] of randomized controlled trials by the international Cochrane Collaboration and a partially positive systematic review^[19] by the Agency for Healthcare Research and Quality. Since these two reviews, a randomized controlled trial reported a reduction on coronary events in Japanese hypercholesterolemic patients.^[20]

Omega-3 fatty acids are also found in some plant sources including flax seed oil, hemp seed oil, and walnuts. Plant sources may be safer as fish products have been shown to contain heavy metals and other fat soluble pollutants.

Secondary prevention

Secondary prevention is preventing further sequelae of already established disease. Regarding coronary heart 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.

Anti-platelet therapy

A meta-analysis of randomized controlled trials by the international Cochrane Collaboration found "that the use of clopidogrel plus aspirin is associated with a reduction in the risk of cardiovascular events compared with aspirin alone in patients with acute non-ST coronary syndrome. In patients at high risk of cardiovascular disease but not presenting acutely, there is only weak evidence of benefit and hazards of treatment almost match any benefit obtained.".^[21]

Recent research

Further information: atheroma and atherosclerosis

A 2006 study by the Cleveland Clinic found a region on Chromosome 17 was confined to families with multiple cases of myocardial infarction.^[22]

A more controversial link is that between Chlamydophila pneumoniae infection and atherosclerosis.^[23] 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.^[24]

References

See also

• Diet and Heart Disease
• ApoA-1 Milano

External links

• Risk Assessment of having a heart attack or dying of coronary heart disease, from the American Heart Association.
• The InVision Guide to a Healthy Heart An interactive website on the development and function of the cardiovascular system and cardiovascular diseases and consequences. The website also features treatment options and preventative measures for maintaining a healthy heart.

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