Prior studies have conflicted regarding how much information novel biomarkers add to cardiovascular risk assessment.
To evaluate the utility of biomarkers for predicting cardiovascular risk when added to conventional risk factors, using contemporary biomarkers and newer statistical approaches.
Design, Setting, Participants
Between 1991 and 1994, 5067 participants (mean age 58, 60% women) without cardiovascular disease from a prospective cohort in Malmö, Sweden underwent measurement of C-reactive protein (CRP), mid-regional-pro-atrial natriuretic peptide, N-terminal pro-B-type natriuretic peptide (N-BNP), mid-regional-pro-adrenomedullin (MR-proADM), lipoprotein-associated phospholipase-2, and cystatin C. Participants were followed until 2006. First cardiovascular events (myocardial infarction, stroke, coronary death) were ascertained using the Swedish national hospital discharge and cause-of-death registers. Low-, intermediate-, and high-risk were defined as 10-year risks of <6%, 6–19%, or ≥20%, respectively.
Main Outcome Measures
Incident cardiovascular and coronary events.
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], 0.734–0.781) and 0.760 (0.730–0.789) for cardiovascular and coronary events. Biomarkers retained in backward-elimination models were N-BNP and CRP for cardiovascular events, and N-BNP and MR-proADM for coronary events, which raised the c-statistic by 0.007 (p=0.04) and 0.009 (p=0.08), respectively. The proportion of participants reclassified was modest (8% for cardiovascular risk, 5% for coronary risk). The net reclassification improvement (NRI) was non-significant for cardiovascular events (0.0%, 95%CI, −4.3%–4.3%) and coronary events (4.7%, −0.76%–10.1%). Greater improvements were observed in analyses restricted to intermediate-risk individuals (cardiovascular events: 7.4%, 95%CI, 0.7%–14.1% [p=0.03]; coronary events: 14.6%, 5.0%–24.2% [p=0.003]). However, correct re-classification was almost entirely confined to down-classification of individuals without events, rather than up-classification of those with events.
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.