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Is Widespread Homocysteine Screening Worth It?

Data from 2 meta-analyses help to answer this question.

Homocysteine elevation has shown some promise as a marker of cardiovascular risk: Retrospective studies have pointed to an association, whereas prospective studies have yielded mixed results. Two meta-analyses offer some clarity.

In the first, investigators combined data from 30 prospective and retrospective observational studies to estimate the predictive value of elevated homocysteine level for ischemic heart disease (IHD) and stroke. IHD events numbered 5073, and strokes numbered 1113. In a meta-analysis of individual patient data, adjusted for interstudy differences and potential clinical confounders, a 25% lower long-term average homocysteine level for an individual was associated with an 11% lower risk for IHD and a 19% lower risk for stroke than was a more typical long-term average level.

The second meta-analysis focused on a genetic marker for high homocysteine level: a common polymorphism (MTHFR677CT) of the gene that encodes the methylene tetrahydrofolate reductase enzyme. The researchers identified 40 case-control studies (involving 11,162 cases and 12,758 controls) that addressed the relation between the MTHFR 677 TT genotype and coronary heart disease risk. People with the TT genotype were found to have a 16% higher risk for CHD than people with the CC genotype.

Comment: The data from these 2 meta-analyses suggest that cardiovascular risk is, at best, modestly associated with elevated homocysteine level and with a genetic marker for homocysteine elevation. The findings do not support population-wide homocysteine screening. Ongoing studies will further clarify the relation among B vitamins, homocysteine levels, and cardiovascular risk.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology January 17, 2003

Citation(s):

The Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: A meta-analysis. JAMA 2002 Oct 23/30; 288:2015-22.

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• Medline abstract (Free)

Klerk M et al. and the MTHFR Studies Collaboration Group. MTHFR 677CT polymorphism and risk of coronary heart disease: A meta-analysis. JAMA 2002 Oct 23/30; 288:2023-31.

• Original article (Subscription may be required)
• Medline abstract (Free)

Wilson PWF. Homocysteine and coronary heart disease: How great is the hazard? JAMA 2002 Oct 23/30; 288:2042-3.

• Original article (Subscription may be required)
• Medline abstract (Free)