Abstract 17082: Translation From Highly Multiplexed Biomarker Discovery to a Targeted Protein Panel to Stratify Cardiovascular Risk in Patients With Coronary Heart Disease
Introduction: Failure to translate biomarkers from research publication to practical clinical measurements is well-recognized. The objective of this study was to transition from a research discovery of a prognostic model for cardiovascular (CV) events using large scale proteomic analysis to a clinical laboratory platform that offers simplicity, reduced assay costs, and consistency.
Hypothesis: Prognostic CV risk proteins discovered in plasma with a highly multiplexed proteomic array will translate to a panel suitable for clinical use.
Methods: CV prognostic proteins and a 9-protein model were previously validated with a modified aptamer microarray assay measuring 1054 proteins. These discoveries were translated to a panel assay suitable for clinical use by replacing the microarray with a low density array to reduce production cost, including QC/calibrators for the proteins chosen in validating the panel, and normalizing to an external reference standard to ensure consistency over time. Analytic validation was performed to CLIA standards. A Weibull parametric model to predict the 4-year probability of a CV event was derived from 937 individuals with stable coronary heart disease (CHD) and validated with 923 samples from an independent cohort. The composite CV endpoint was myocardial infarction, stroke, heart failure and all-cause death.
Results: A 7-protein model (CVD Panel) derived from the original microarray model provided the best combination of analytical and clinical performance. The median total coefficient of variation was <5%. CV event discrimination accuracy assessed by the C-statistic [95%CI] in the derivation study was 0.72 [0.70, 0.75] and 0.70 [0.66, 0.72] in validation. The validation quintile hazard ratio (HR) for predicting CV events was 8.5 [5.7, 12.6] and the HR per standard deviation was 2.1 [1.8, 2.3]. These results are statistically equivalent to the microarray-based model. In comparison, the validation C-statistic for the Framingham secondary prevention equation was 0.61 [0.58, 0.64] and the quintile HR was 2.2 [1.6, 3.2].
Conclusion: Discoveries made with a highly multiplexed modified aptamer array can be translated to a robust clinical assay that improves CV risk stratification compared to a standard clinical model.
Author Disclosures: R.K. DeLisle: Employment; Significant; SomaLogic. P. Ganz: None. E. Katilius: Employment; Significant; SomaLogic. S. Kato: Employment; Significant; NEC of America. R. Ostroff: Employment; Significant; SomaLogic. D. Sterling: Employment; Significant; SomaLogic. S. Williams: Employment; Significant; SomaLogic.
- © 2016 by American Heart Association, Inc.