Leiden, the Netherlands - A small study has shown that, for primary prevention, homocysteine appears to be the best predictor of cardiovascular mortality in the very elderly [1]. The research also confirms what many had already suspected—that the Framingham Risk Score (FRS) is not very accurate at predicting risk in this age group. Dr Wouter de Ruijter (Leiden University Medical Center, the Netherlands) and colleagues report their findings online January 8, 2009 in BMJ.

"We found the FRS does not predict cardiovascular mortality in those 85 and older, and we think perhaps this problem with the FRS starts a little bit earlier than 85," de Ruijter told heartwire. "From our study, homocysteine seems a very good candidate instead of measuring classical risk factors. Those in the upper-third tertile of the homocysteine range had a very large five-year cardiovascular mortality risk."

However, he acknowledges that this current study could not establish a cutoff point for homocysteine above which treatment would be recommended, nor is there any indication that lowering homocysteine in this age group would be beneficial—all research on this approach so far has shown it to be an ineffective strategy, he notes.

"These preliminary findings call for validation in a separate cohort and, if confirmed, could eventually lead to a revision of current guidelines," he and his colleagues conclude.

De Ruijter et al investigated the performance of classic risk factors and some newer biomarkers in predicting cardiovascular mortality in very old people from the general population with no history of cardiovascular disease who were participating in the Leiden 85-plus Study, an observational prospective cohort study with five years of follow-up.

Of 302 participants (215 women and 87 men), 108 died during follow-up, and 32% of these (35/108 deaths) were from cardiovascular causes. Classic risk factors used in the FRS did not predict. Of the newer biomarkers assessed—homocysteine, folic acid, C-reactive protein (CRP), and interleukin-6—homocysteine had the most predictive power.

De Ruijter said this study confirms earlier findings of a fall in the predictive abilities of FRS in older populations for primary prevention and says the components of FRS may become "a little blurred" in even younger patients, aged 75 to 85, but that this study did not address this age group.

"The principal point is that doctors in daily practice tend to keep on focusing on these traditional risk factors," he commented. "But I would be glad if they would admit that this is not the sensible thing to do. For cardiovascular mortality prediction, in primary prevention in those aged 85 and over, it's absolutely useless to measure blood pressure, total cholesterol levels, etc," he said.

The researchers explain in their paper that the predictive power of homocysteine goes beyond that of classic risk factors and is equally robust without classic risk factors being included in the model.

"Homocysteine has for four decades been in the center of our attention for cardiovascular risk," de Ruijter told heartwire. "It is a good predictor of cardiovascular risk in younger age groups, and we have shown here that it keeps on doing so in the very elderly."

There was little association between the other newer biomarkers—folic acid, CRP, and interleukin-6—in this very elderly population, however, in contrast with findings in younger age groups, he notes.

With regard to potential treatment, de Ruijter et al suggest that the role of statins needs to be explored. It is possible that homocysteine levels could be used as a cutoff to decide who does and does not get statin therapy, they propose.

The beneficial effect of statins in secondary prevention in the elderly is evident, and such drugs could also be effective in primary prevention if the selection of patients at highest risk is accurate, de Ruijter says.

However, he concedes that before definite guidelines can be issued with regard to homocysteine, "we really need to validate our findings in a larger cohort and do some more work."