Biochemical risk markers and 10-year incidence of atherosclerotic cardiovascular disease: independent predictors, improvement in pooled cohort equation, and risk reclassification

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BackgroundThe recommendation for statins in primary atherosclerotic cardiovascular disease (ASCVD) prevention begins with risk estimation using the pooled cohort equation (PCE). However, treatment decisions may still remain uncertain after PCE-based assessment. We therefore developed a simple biomarker score that could supplement decision making.MethodsUsing the prospectively collected database of the Multi-Ethnic Study of Atherosclerosis, we identified biochemical risk markers that independently predicted 10-year risk of ASCVD and developed an aggregate biomarker score based on them. Thereafter, we assessed for incremental benefit of these markers over the PCE using C-statistic, net reclassification index (NRI), and integrated discrimination index (IDI).ResultsA total of 5,303 adults free of ASCVD at baseline were included in this study. Five biochemical risk markers—high-sensitivity C-reactive protein, homocysteine, albuminuria, N-terminal prohormone of brain natriuretic peptide, and troponin T—that predicted 10-year risk of ASCVD were combined into an aggregate biomarker score (CHAN2T3), which demonstrated a graded increase in the rate of incident ASCVD from 2.1% among participants with score of 0 to 25% among participants with score of 5. In addition, a biomarker score of ≥2 was associated with improvement in the C-statistic of the PCE (0.748 vs 0.734, P = .02), integrated discrimination index (P < .001), category-free NRI of 45% (95% CI, 31%-57%), and net categorical NRI of 5.4% in the full cohort. Lastly, a biomarker score of ≥4 resulted in 6% net reclassification across ASCVD risk cut point of 7.5% among nondiabetic individuals with LDL-C <190 mg/dL.ConclusionsA novel CHAN2T3 biomarker score could supplement risk-based discussion for ASCVD prevention, especially when treatment decision is uncertain. Further validation in other cohorts is however warranted

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