Background: Conventional factors do not fully explain the distribution of cardiovascular outcomes. Biomarkers are known to
participate in well-established pathways associated with cardiovascular disease, and may therefore provide further information
over and above conventional risk factors. This study sought to determine whether individual and/or combined assessment of
9 biomarkers improved discrimination, calibration and reclassification of cardiovascular mortality.
Methods: 3267 patients
(2283 men), aged 18-95 years, at intermediate-to-high-risk of cardiovascular disease were followed in this prospective cohort
study. Conventional risk factors and biomarkers were included based on forward and backward Cox proportional stepwise selection
Results: During 10-years of follow-up, 546 fatal cardiovascular events occurred. Four biomarkers (interleukin-6,
neutrophils, von Willebrand factor, and 25-hydroxyvitamin D) were retained during stepwise selection procedures for subsequent
analyses. Simultaneous inclusion of these biomarkers significantly improved discrimination as measured by the C-index (0.78,
P = 0.0001), and integrated discrimination improvement (0.0219, P < 0.0001). Collectively, these biomarkers improved net
reclassification for cardiovascular death by 10.6% (P < 0.0001) when added to the conventional risk model.
In terms of adverse cardiovascular prognosis, a biomarker panel consisting of interleukin-6, neutrophils, von Willebrand factor,
and 25-hydroxyvitamin D offered significant incremental value beyond that conveyed by simple conventional risk factors.