Identifying Novel Biomarkers for Cardiovascular Events or Death in People With Dysglycemia

Circulation. 2015 Dec 15;132(24):2297-304. doi: 10.1161/CIRCULATIONAHA.115.015744. Epub 2015 Oct 30.


Background: Serum biomarkers may identify people at risk for cardiovascular (CV) outcomes. Biobanked serum samples from 8494 participants with dysglycemia in the completed Outcome Reduction With Initial Glargine Intervention trial were assayed for 284 biomarkers to identify those that could identify people at risk for a CV outcome 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 biobanked 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: (1) the composite of myocardial infarction, stroke, or CV death; (2) these plus heart failure hospitalization or revascularization; and (3) 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: URL: Unique identifier: NCT00069784.

Keywords: biological markers; clinical trial; diabetes mellitus; risk.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / metabolism*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis*
  • Cardiovascular Diseases / mortality
  • Cause of Death / trends*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / mortality
  • Female
  • Heart Failure / blood
  • Heart Failure / diagnosis
  • Heart Failure / mortality
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors


  • Biomarkers
  • Blood Glucose

Associated data