Epidemiology and Prevention Contribution of 30 Biomarkers to 10-Year Cardiovascular Risk Estimation in 2 Population Cohorts

Background—Cardiovascular risk estimation by novel biomarkers needs assessment in disease-free population cohorts, followed up for incident cardiovascular events, assaying the serum and plasma archived at baseline. We report results from 2 cohorts in such a continuing study. Methods and Results—Thirty novel biomarkers from different pathophysiological pathways were evaluated in 7915 men and women of the FINRISK97 population cohort with 538 incident cardiovascular events at 10 years (fatal or nonfatal coronary or stroke events), from which a biomarker score was developed and then validated in the 2551 men of the Belfast Prospective Epidemiological Study of Myocardial Infarction (PRIME) cohort (260 events). No single biomarker consistently improved risk estimation in FINRISK97 men and FINRISK97 women and the Belfast PRIME Men cohort after allowing for confounding factors; however, the strongest associations (with hazard ratio per SD in FINRISK97 men) were found for N-terminal pro-brain natriuretic peptide (1.23), C-reactive protein (1.23), B-type natriuretic peptide (1.19), and sensitive troponin I (1.18). A biomarker score was developed from the FINRISK97 cohort with the use of regression coefficients and lasso methods, with selection of troponin I, C-reactive protein, and N-terminal pro-brain natriuretic peptide. Adding this score to a conventional risk factor model in the Belfast PRIME Men cohort validated it by improved c-statistics (Pϭ0.004) and integrated discrimination (PϽ0.0001) and led to significant reclassification of individuals into risk categories (Pϭ0.0008). Conclusions—The addition of a biomarker score including N-terminal pro-brain natriuretic peptide, C-reactive protein, and sensitive troponin I to a conventional risk model improved 10-year risk estimation for cardiovascular events in 2 middle-aged European populations. Further validation is needed in other populations and age groups. C ardiovascular risk assessment based on classic risk factors does not fully explain the distribution of risk in the general population. 1– 4 Specifically, classic risk scores may provide variable results in different populations. 5 Recent data indicate that 9 simple risk factors, including abnormal apolipoprotein levels, smoking, diabetes mellitus, and hyper-tension, substantially account for the risk of acute myocardial infarction globally. 6 Importantly, most of these classic risk factors are modifiable, and intervention is likely to reduce the risk of cardiovascular disease (CVD). To improve risk estimation beyond what is possible with classic risk factors, many novel biomarkers have now been related to cardiovas-cular risk in community settings. 7 It seems that, overall, C-reactive protein and N-terminal pro-brain natriuretic pep-Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to …