Protein Biomarkers and Cardiovascular Outcomes in People With Type 2 Diabetes and Acute Coronary Syndrome: The ELIXA Biomarker Study
Hertzel C. Gerstein, Sibylle Hess, Brian Claggett, Kenneth Dickstein, Lars Køber, Aldo P. Maggioni, John J.V. McMurray, Jeffrey L. Probstfield, Matthew C. Riddle, Jean‐Claude Tardif, Marc A. Pfeffer
Abstract
OBJECTIVE: To use protein biomarkers to identify people with type 2 diabetes at high risk of cardiovascular outcomes and death. RESEARCH DESIGN AND METHODS: Biobanked serum from 4,957 ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial participants was analyzed. Forward-selection Cox models identified independent protein risk factors for major adverse cardiovascular events (MACE) and death that were compared with a previously validated biomarker panel. RESULTS: NT-proBNP and osteoprotegerin predicted both outcomes. In addition, trefoil factor 3 predicted MACE, and angiopoietin-2 predicted death (C = 0.70 and 0.79, respectively, compared with 0.63 and 0.66 for clinical variables alone). These proteins had all previously been identified and validated. Notably, C statistics for just NT-proBNP plus clinical risk factors were 0.69 and 0.78 for MACE and death, respectively. CONCLUSIONS: NT-proBNP and other proteins independently predict cardiovascular outcomes in people with type 2 diabetes following acute coronary syndrome. Adding other biomarkers only marginally increased NT-proBNP's prognostic value.