Coronary heart disease: causes and risk factors

Causes and pathophysiology of ischemic heart disease

IHD usually develops due to the appearance of atheromatous plaques in the intima of large and medium-sized coronary arteries, less often due to spasm of the coronary arteries. Rare causes of coronary heart disease include thromboembolism of the coronary arteries, dissection, aneurysm (eg, in Kawasaki disease) and vasculitis (eg, in systemic lupus erythematosus, syphilis).

Atherosclerosis of the coronary arteries is often distributed unevenly, with typical localizations being areas of turbulent blood flow (e.g., vascular branches). Progressive narrowing of the arterial lumen leads to ischemia (manifested as angina pectoris). The degree of stenosis that can lead to ischemia depends on the oxygen requirement.

Sometimes an atheromatous plaque ruptures or cracks. The reasons are unclear, but an inflammatory process that softens the plaque is probably important. As a result of the rupture, thrombogenic substances are released from the plaque, activating platelets and the coagulation process, which leads to acute thrombosis and ischemia. The consequences of acute ischemia, collectively known as acute coronary syndrome (ACS), depend on the location and severity of vascular obstruction and range from unstable angina to transmural myocardial infarction.

Coronary artery spasm is a transient local increase in vascular tone, resulting in a marked narrowing of the vessel lumen and a decrease in blood flow; this may result in symptomatic myocardial ischemia ("variant angina"). Significant narrowing may lead to thrombus formation, which causes myocardial infarction. Spasm may occur in arteries with or without atherosclerotic lesions. In arteries not affected by atherosclerosis, there is probably an initial increase in vascular tone and a hyperergic response to vasoconstrictor effects. The exact mechanism of variant angina is unclear, but an abnormality in nitric oxide synthesis or an imbalance between endothelium-constricting and dilating factors are suggested. In arteries altered by atherosclerosis, an atheromatous plaque may lead to increased contractility; Proposed mechanisms include a resulting loss of sensitivity to natural vasodilators (eg, acetylcholine) and increased formation of vasoconstrictors (eg, angiotensin II, endothelial cells, leukotrienes, serotonin, thromboxane) within the atherosclerotic plaque. Repeated spasms may damage the intima lining of the artery, leading to plaque formation. Use of substances with vasoconstrictor properties (eg, cocaine, nicotine) may cause coronary artery spasm.

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Risk factors for coronary heart disease

The risk factors for coronary heart disease are the same as for atherosclerosis: high levels of LDL cholesterol and lipoprotein A, low levels of HDL cholesterol in the blood, diabetes mellitus (especially type 2), smoking, excess body weight and physical inactivity. Smoking is the strongest predisposing factor to the development of myocardial infarction in women (especially under 45 years of age). Genetic predisposition and some diseases (such as hypertension, hypothyroidism) play a certain role. An important risk factor is high levels of apoprotein B, which may indicate the risk of developing atherosclerosis in cases where the amount of total cholesterol or LDL is normal.

High blood levels of C-reactive protein are a sign of plaque instability and inflammation and are more likely to predict ischemia than elevated LDL levels. High blood triglycerides and insulin (reflecting insulin resistance) may also be risk factors, but this is less well understood. The risk of coronary heart disease is increased in smokers, those with a high-fat, high-calorie diet, low fiber (found in fruits and vegetables) and vitamins C and E, relatively low levels of alpha-3(n-3) polyunsaturated fatty acids (PUFAs), at least in some people, and those with low stress resistance.

Anatomy

The right and left coronary arteries arise from the right and left coronary sinuses at the root of the aorta, just above the orifice of the aortic valve. The coronary arteries divide into large and medium-sized arteries that lie on the surface of the heart (epicardial coronary arteries) and then give off smaller arterioles into the myocardium. The left coronary artery begins as the left main artery and quickly divides into the left anterior descending and circumflex arteries. The left anterior descending artery is usually located in the anterior interventricular groove and (in some people) continues to the apex of the heart. This artery supplies the anterior portion of the septum, including the proximal conduction system and the anterior wall of the left ventricle (LV). The circumflex artery, which is usually smaller than the left anterior descending artery, supplies the lateral wall of the left ventricle. Most people have a right-sided blood flow predominance: the right coronary artery runs along the atrioventricular groove on the right side of the heart; it supplies the sinus node (in 55% of cases), the right ventricle, and (usually) the atrioventricular node and the inferior wall of the myocardium. About 10 to 15% of people have a left-sided blood flow predominance: in them, the circumflex artery is somewhat larger and, continuing along the posterior atrioventricular groove, supplies the posterior wall and the AV node.

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