Use of several older and newer biomarkers appears to offer minimal added benefit in the prediction of cardiovascular events compared to conventional risk factors such as high cholesterol and high blood pressure, according to a study in the July 1 issue of JAMA.
“Cost-effective cardiovascular prevention relies on the accurate identification of individuals at risk. However, a large proportion of individuals with cardiovascular events have 1 or fewer of the conventional risk factors, including smoking, diabetes, hypertension, or hyperlipidemia,” the authors write. As a result, the use of recently identified biomarkers to supplement standard risk algorithms has attracted increasing attention in recent years. However, prior studies have reached differing conclusions regarding the usefulness of biomarkers for cardiovascular risk prediction, according to background information in the article.
Olle Melander, M.D., Ph.D., of Lund University, Malmö, Sweden, and colleagues assessed several cardiovascular biomarkers, individually and in combination, regarding their usefulness in predicting future cardiovascular events, compared with conventional risk factors. The study included 5,067 participants (average age, 58 years; 60 percent women) without cardiovascular disease from Malmö, Sweden, who were examined at the beginning of the study, between 1991 and 1994. Participants underwent measurement of older biomarkers (C-reactive protein [CRP] and N-terminal pro-B-type natriuretic peptide [N-BNP]) and newer biomarkers (cystatin C, lipoprotein-associated phospholipase-2 [Lp-PLA2], midregional proadrenomedullin [MR-proADM], and midregional proatrial natriuretic peptide [MR-proANP]. There was follow-up until 2006, using the Swedish national hospital discharge and cause-of-death registers and the Stroke in Malmö register for first cardiovascular events (heart attack, stroke, coronary death). During median (midpoint) follow-up of 12.8 years, there were 418 cardiovascular events and 230 coronary events.
When considered individually, 5 of 6 biomarkers predicted future cardiovascular events and 3 (cystatin C, MR-proADM, and N-BNP) predicted future coronary events in models adjusting for conventional risk factors. “The best combinations of biomarkers were CRP and N-BNP for predicting cardiovascular events and MR-proADM and N-BNP for predicting coronary events. The use of multiple biomarkers minimally improved the accuracy of risk prediction models over and above conventional cardiovascular risk factors and did not reclassify a substantial proportion of individuals to higher or lower risk categories,” the authors write.
The researchers add that what may be relevant to clinical care, however, is not whether changes in predicted probabilities are statistically significant but whether they result in reclassification of individuals to new, clinically meaningful risk categories. “Our data indicate that a relatively small proportion of individuals are moved to new risk categories by the addition of biomarkers—8 percent or fewer when both upward and downward risk category movement are included and fewer than 1 percent when only the movements likely to lead to changes in therapy according to the Adult Treatment Panel III [cholesterol] guidelines are included. Furthermore, these reclassifications result in only modest improvements in the overall concordance between risk categories and actual event rates, as measured by the net reclassification improvement.”
“The challenge will be to find new cardiovascular biomarkers that alone or in combination with existing biomarkers can bring about improvements in risk assessment that are not just statistically significant but clinically significant as well,” the authors conclude.