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

Abstract

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.

Figure 1

Kaplan-Meier plot showing one minus cumulative cardiovascular event-free survival during follow up in quartiles (Q1 to Q4 with Q1 representing subjects with lowest values) of a multimarker score based on the summed standardized values (expressed as number of SD deviation from the mean) of N-BNP and CRP.

Figure 2

Kaplan-Meier plot showing one minus cumulative coronary event-free survival during follow up in quartiles (Q1 to Q4 with Q1 representing subjects with lowest values) of a multimarker score based on the summed standardized values (expressed as number of SD deviation from the mean) of N-BNP and MR-proADM.