Validation of the ORIGIN Cardiovascular Biomarker Panel and the Value of Adding Troponin I in Dysglycemic People

Background: Analyses of stored blood from the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) trial identified biomarkers that supplemented clinical risk factors for cardiovascular (CV) events or death. Their performance in participants with diabetes in the Heart Outcomes Prevention Evaluation (HOPE) study and the incremental value of adding high-sensitivity assays of serum troponin I (hsTnI) in the ORIGIN study were assessed. Methods: Levels of the 10 ORIGIN biomarkers for the composite CV outcome of myocardial infarction, stroke, or CV death were measured in 350 HOPE study participants with diabetes and stored serum that included all 77 who experienced this outcome. The effect of adding hsTnI levels to this panel, and the previously identified ORIGIN biomarkers for this composite outcome, this outcome, or revascularization or heart failure, and for mortality was also analyzed. Results: Within the HOPE cohort, the ORIGIN biomarker panel increased the C statistic from 0.63 for clinical risk factors alone to 0.67 with the addition of the 10 biomarkers, and the net reclassification improvement was 0.14 (95% confidence interval, 0.01, 0.28). Within the ORIGIN cohort, hsTnI levels predicted all three outcomes during follow-up both alone, and independently of the other biomarkers, which all remained independent predictors of outcomes after inclusion of the hsTnI levels. The hsTnI level interacted with follow-up time such that it was a stronger predictor of earlier vs later events. Conclusion: The ORIGIN biomarkers predicted CV outcomes in the independent HOPE cohort. Adding hsTnI levels to the previously identified models in ORIGIN modestly improved their performance.