Homocysteine - An Emerging Cardiovascular Risk Factor

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US Cardiology 2004;2004:1(1):1-4

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The Clinical Significance of Elevated Plasma Homocysteine

Although about half of Americans have levels of cholesterol that place them at high risk of coronary artery disease, hypercholesterolemia is now considered only one risk factor within a complex amalgam of factors. An elevated homocysteine level predicts a risk of coronary disease or death perhaps even more effectively than other traditional factors including cholesterol. The nine traditional risk factors - advancing age, heredity, male gender, cigarette smoking, high blood pressure, diabetes, obesity, lack of physical activity, and abnormal blood cholesterol levels - can help predict the likelihood of heart attacks and strokes; however, these factors explain only about 60% of the incidences of heart disease. Patients with myocardial infarction or carotid stenosis often have normal range cholesterol levels. An early study by McCully found that in two thirds of cases of severe arteriosclerosis, the disease developed without the traditional risks of elevated serum cholesterol, diabetes or hypertension.1

Numerous epidemiological studies have demonstrated the relationship between even moderate hyperhomocysteinemia and the occurrence of vascular diseases; cerebral, coronary, and peripheral artery diseases; and venous thrombosis.2,3 Analysis of the results of over 80 research studies conducted in the 1990s advanced elevated homocysteine from a non-traditional risk factor to a generally accepted predictor of several cardiovascular diseases. For example, in one study, homocysteine was an independent risk factor for premature vascular disease with an odds ratio of greater than 3:2.4

The question now in clinical trials is what, if any, is the cause-and-effect relationship of elevated homocysteine levels and disease.5,6 Research has identified an elevated homocysteine plasma level as an independent and possibly causal risk factor for developing cardiovascular disease and atherosclerotic lesions.7,8,9 Epidemiological studies clearly associate moderate to high homocysteine levels with increased risk for coronary heart disease, stroke and peripheral vascular disease and mortality. Accumulating evidence now links high homocysteine levels with death from heart disease.10 Verhoef et al. in a 1996 study calculated that each three-unit increase in homocysteine resulted in a 35% increase in heart attack risk.11 Indeed, a study at the Johns Hopkins University concluded that a 5╬╝mol/L increase in homocysteine level is associated with a 50% increase in the risk of cerebrovascular diseases (stroke) and other thrombotic events.12

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