Identifying Novel Biomarkers for Cardiovascular Events or Death in People With Dysglycemia
Background—Serum biomarkers may identify people at risk for cardiovascular (CV) outcomes. Bio-banked serum samples from 8494 participants with dysglycemia in the completed Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial were assayed for 284 biomarkers to identify those that could identify people at risk for a CV outcomes or death when added to clinical measurements.
Methods and Results—A multiplex analysis measured a panel of cardiometabolic biomarkers in 1 ml of stored frozen serum from every participant who provided bio-banked blood. After eliminating undetectable or unanalyzable biomarkers, 8401 participants who each had a set of 237 biomarkers were analyzed. Forward selection Cox regression models were used to identify biomarkers that were each independent determinants of 3 different incident outcomes: the composite of myocardial infarction, stroke or CV death; these plus heart failure hospitalization or revascularization; and all-cause death. When added to clinical variables, 10 biomarkers were independent determinants of the 1405 CV composite outcomes observed during follow-up; 9 biomarkers (including 8 of these 10) were independent determinants of the 2435 expanded composite outcomes; and 15 (including the 10 CV composite biomarkers) were independent determinants of the 1340 deaths. Adjusted C statistics increased from 0.64 for the clinical variables to 0.71, and 0.68 for the 2 CV composite outcomes respectively, with the greatest increase to 0.75 for death (P<0.001 for the change).
Conclusions—A systematic hypothesis-free approach identified combinations of up to 15 cardiometabolic biomarkers as independent determinants of CV outcomes or death in people with dysglycemia.
Clinical Trial Registration Information—clinicaltrials.gov. Identifier: NCT00069784.
- diabetes mellitus
- randomized controlled trial
- cardiovascular disease risk factors
- cardiovascular outcomes
- Received January 29, 2015.
- Revision received September 4, 2015.
- Accepted September 24, 2015.