Abstract

Introduction: Biomarkers can facilitate the prediction of events in primary prevention. Few studies have been conducted in the community setting with analyses that incorporate many biomarkers. Hypothesis: We tested whether a multi biomarker model would outperform clinical factors and individual biomarkers for predicting MACE and Stroke/MI in subjects without known CAD. Methods: A retrospective cohort study assessed composite outcomes MACE (MI, CABG, PCI, stroke, and death) and Stroke/MI. Cox proportional hazard models were fit for individual biomarkers, adjusted for age, gender, BMI, hypertension, CAD, and GFR. Multi biomarker models were developed based on AIC values from the single-biomarker models. Bootstrap tests compared survival C-statistics and relative Integrated Discrimination Index (IDI). Results: 1131 patients in Olmsted County, MN were studied. Median age was 63.1 years, 97.5% were Caucasian, and 52.2% were female. Median BMI was 27.8. Kaplan Meier rates of MACE and Stroke/MI were 29.2% (CI = 26.5-31.8%) and 12.3% (CI = 10.3% - 14.3%), at 10 years. Adjusted NT proBNP models showed a 31% increased risk of MACE/death (HR = 1.31; CI = 1.17-1.46) and a 31% increased risk for stroke/MI (HR = 1.31; CI = 1.08-1.58). Adjusted Ceramide score models showed a 13% increased risk of MACE/death (HR = 1.13; CI = 1.04-1.24) and a 29% increased risk for stroke/MI (HR = 1.29; CI = 1.11-1.51). NT proBNP and the Ceramide score with clinical factors was better than clinical factors alone for MACE/Death (Relative IDI = 29.7%; p = 0.003) and Stroke/MI (Relative IDI = 36.1%; p = 0.034). This combined model did not outperform the strongest single biomarker model for Stroke/MI or MACE/Death. Other biomarkers were not significant when added to the combined model. Discussion: Ceramide score and NT proBNP alone and together improve the prediction of MACE and Stroke/MI in a community primary prevention cohort.

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