Novel and conventional biomarkers for prediction of incident cardiovascular events in the community

Context: Prior studies have demonstrated conflicting results regarding how much information novel biomarkers add to cardiovascular risk assessment. Objective: To evaluate the utility of contemporary biomarkers for predicting cardiovascular risk when added to conventional risk factors. Design, Setting, and Participants: Cohort study of 5067 participants (mean age, 58 years; 60% women) without cardiovascular disease from Malmö, Sweden, who attended a baseline examination between 1991 and 1994. Participants underwent measurement of C-reactive protein (CRP), cystatin C, lipoprotein-associated phospholipase 2, midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide, and N-terminal pro-B-type natriuretic peptide (N-BNP) and underwent 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 (myocardial infarction, stroke, coronary death). Main Outcome Measures: Incident cardiovascular and coronary events. Results: During median follow-up of 12.8 years, there were 418 cardiovascular and 230 coronary events. Models with conventional risk factors had C statistics of 0.758 (95% confidence interval [CI], 0.734 to 0.781) and 0.760 (0.730 to 0.789) for cardiovascular and coronary events, respectively. Biomarkers retained in backward-elimination models were CRP and N-BNP for cardiovascular events and MR-proADM and N-BNP for coronary events, which increased the C statistic by 0.007 (P=.04) and 0.009 (P=.08), respectively. The proportion of participants reclassified was modest (8% for cardiovascular risk, 5% for coronary risk). Net reclassification improvement was nonsignificant for cardiovascular events (0.0%; 95% CI, -4.3% to 4.3%) and coronary events (4.7%; 95% CI, -0.76% to 10.1%). Greater improvements were observed in analyses restricted to intermediate-risk individuals (cardiovascular events: 7.4%;95%CI, 0.7% to 14.1%; P=.03; coronary events: 14.6%; 95% CI, 5.0% to 24.2%; P=.003). However, correct reclassification was almost entirely confined to down-classification of individuals without events rather than up-classification of those with events. Conclusions: Selected biomarkers may be used to predict future cardiovascular events, but the gains over conventional risk factors are minimal. Risk classification improved in intermediate-risk individuals, mainly through the identification of those unlikely to develop events.