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The question of whether moderately high serum or plasma levels of total homocysteine are a risk factor for coronary heart disease (CHD) and other atherothrombotic disorders has long been debated and is still unclear. The uncertainty mainly stems from the discrepant results obtained in case-control and prospective cohort studies. While case-control study results consistently showed a positive association between hyperhomocysteinemia and atherothrombotic events, prospective cohort studies gave conflicting results.¹

In 1999, I suggested that a clear distinction should be made between prospective cohort studies of subjects who were healthy at enrollment and prospective cohort studies of patients with overt atherothrombotic disease or other at-risk conditions.¹ While studies of healthy subjects gave conflicting results, study results of patients at risk consistently showed a positive association between baseline total homocysteine levels and the risk of future atherothrombotic events. Findings from subsequent studies published from 1999 to the present strengthened the hypothesis that . . . [Full Text of this Article]

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