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Homocysteine improves cardiovascular risk estimation

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Measuring homocysteine improves the accuracy of estimated risk of cardiovascular events, according to an analysis of data from two different sources.

“Our observations are novel and demonstrated that elevated homocysteine concentration predicts future CVD (cardiovascular disease) and CHD (coronary heart disease) events in disparate, representative populations of U.S. adults across ethnic subgroups,” conclude Dr. Luis Afonso, at Wayne State University, Detroit, Michigan and colleagues in their report in the August 30 issue of the Journal of the American College of Cardiology.

They note that traditional risk factors such as those in the Framingham risk score do not always identify individuals who will or who will not experience adverse cardiovascular events. The level of homocysteine has shown promise in refining cardiovascular risk classification, but several studies that have tried to quantify the risk conferred by homocysteine have had inconsistent results.

To investigate further, the team examined data from the Multiethnic Study of Atherosclerosis (MESA) on 6450 individuals without prior cardiovascular disease, and the National Health and Nutrition Examination Survey III (NHANES III) that surveyed and followed a nationally representative sample of individuals.

The MESA analysis looked at homocysteine levels in relation to all CVD events and “hard” CHD events (i.e., MI, resuscitated cardiac arrest, or death due to CHD). The researchers found that after adjustment for traditional risk factors and C-reactive protein, a homocysteine level greater than 15 micromol/L significantly predicted CVD events (adjusted hazard ratio 1.79; p=0.006) and hard CHD events (aHR 2.22; p=0.01).

In the NHANES III analysis, the primary outcome of interest was death due to CVD and CHD, and again a high homocysteine level predicted increased risk with adjusted hazard ratios of 2.72 and 2.61 (p<0.001 for both), respectively.

When the homocysteine level was added to the Framingham risk score, it reclassified 12.9% of the MESA cohort and 18.3% of the NHANES cohort, Dr. Afonso and colleagues estimated.

“Our results lend support to previously published data exploring the association between homocysteine and CVD and CHD events,” they conclude.

The author an accompanying editorial points out that it has yet to be shown that lowering homocysteine reduces cardiovascular risk. “Should we consider homocysteine as a mere bystander?”, asks Dr. Arduino A. Mangoni, at the University of Aberdeen, UK.

He concludes, “If homocysteine is to be used as a screening tool in primary prevention, it is imperative that further trials are conducted in low- and intermediate-risk patients without previous CVD. Only then can the real value of measuring homocysteine as a nontraditional CVD risk factor or risk marker be quantified.”

Homocysteine and Reclassification of Cardiovascular Disease Risk
J Am Coll Cardiol 2011;58:1025–1035.