How Useful is Homocysteine in Predicting Cardiovascular Disease Risk?

Source: Tufts University
January 17, 2003 (Reviewed: January 21, 2005)

Several studies have found an association between elevated blood homocysteine levels and increased risk for cardiovascular disease (CVD). But data are mixed on just how effective this marker is in predicting CVD risk. A recent meta-analysis found that elevated homocysteine only "modestly" predicted risk for ischemic heart disease (IHD) and stroke. The results are published in the Journal of the American Medical Association.

Compiling data from 30 studies

Researchers who form the Homocysteine Studies Collaboration aimed to investigate the relationship between elevated homocysteine levels and vascular disease risk by conducting a meta-analysis of studies on the subject. They identified 30 studies (both prospective and retrospective) that comprised a total of 5,073 cases of ischemic heart disease (IHD) and 1,113 cases of stroke.

In doing the meta-analysis, the researchers corrected for potential confounding factors, such as age, smoking status, and medical history. They also corrected for regression dilution bias, in which random fluctuations in homocysteine levels (caused, perhaps, by errors in measurement or by effects of treatment or disease) underestimated the true strength of the association between homocysteine level and CVD risk.

Associations found

After adjustment for confounding factors and correction for regression dilution bias, a 25% lower usual homocysteine level was associated with 11% lower IHD risk (Odds Ratio, or OR=0.89; 95% CI, 0.83-0.96) and 19% lower stroke risk (OR=0.81; 95% CI, 0.69-0.95). The authors estimate that a 25% lower homocysteine level is equal to the average change in plasma homocysteine concentration achieved by folic acid supplementation.

Different studies yield different associations

Retrospective studies, in which blood samples were collected after the onset of disease, yielded stronger associations between elevated homocysteine levels and CVD risk than did prospective studies, in which blood samples were collected before disease onset.

The authors say this "may reflect bias in retrospective studies because of the difficulties of selecting appropriate controls or the effects of changes in treatment, renal function, or other factors after the onset of disease that produce increases in homocysteine concentrations among the cases".

Applying these results to practice

These results, while useful in advancing the understanding of the association between homocysteine levels and CVD risk, do not indicate that measuring blood homocysteine levels is not useful in identifying people at risk for CVD. The authors state that if the modest associations observed in this study are indeed causal, then the impact of decreasing homocysteine levels across populations "could still be substantial".

They also point out that ongoing research into genetic causes of elevated homocysteine is providing support that these associations are causal, and they suggest that randomized clinical trials of vitamin supplementation to lower homocysteine levels will provide additional, much-needed evidence.

Homocysteine remains one of a number of factors continuing to be studied for its usefulness in predicting CVD risk. Practical advice to patients to consume a diet adequate in folate/folic acid - a B vitamin shown to keep homocysteine levels in check - remains warranted. Good sources of this nutrient include legumes, green leafy vegetables, orange juice, fortified foods (including breads and cereals in the USA) and vitamin supplements.

Source

• Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis.  The Homocysteine Studies Collaboration., JAMA, 2002, vol. 288, pp. 2015--2022

Related Links
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