Abstract 16378: Growth Differentiation Factor-15 Independently Predicts 2 Year Mortality in Patients With Acute Coronary Syndrome: Observations From the A to Z Trial
BACKGROUND: Growth Differentiation Factor-15 (GDF-15) is an inflammatory biomarker upregulated in the setting of myocardial stress that we and others have shown to have potential prognostic value in cardiovascular (CV) disease. However, any role for GDF-15 along with traditional CV risk factors and biomarkers in predicting long term mortality after ACS remains investigational.
METHODS: We measured the plasma concentration of GDF-15 after stabilization of ACS in 4,179 patients (pts) presenting with UA/NSTEMI or STEMI enrolled in the A to Z Trial. Established, pre-specified cutoffs of GDF-15 (<1200, 1200-1800, and >1800 ng/L) were used for analysis. Outcomes were followed through the end of the study (median 2 years).
RESULTS: Pts with GDF-15 >1800 ng/L had significantly higher 2 year mortality rates than those with levels of 1200-1800 or <1200 ng/L (14.8%, 9.7%, and 3.2%, respectively; P<0.001, Fig-1A). After adjusting for age, sex, hypertension, diabetes, renal function, STEMI vs NSTEACS, heart failure, B-type natriuretic peptide (BNP) and C-reactive protein (CRP), pts with GDF-15 >1800 ng/L were at a significantly higher risk of death at 2yr (HR 1.88; 95% CI, 1.25-2.83) compared to those with GDF-15 levels <1200 ng/L. Even in pts with low baseline BNP levels (<80 pg/mL), a GDF-15 level >1800 ng/L was associated with higher mortality risk compared with pts with levels of 1200-1800 or <1200 ng/L (11.8%, 7.9%, and 3.0% respectively; P<0.001, Fig-1B). Addition of GDF-15 to a model including traditional cardiovascular risk factors, BNP, and CRP resulted in significant net reclassification improvement (P<0.001).
CONCLUSIONS: GDF-15 obtained in patients with established CAD stabilized after ACS is independently associated with increased mortality at 2 yrs. GDF-15 identifies additional mortality risk not currently captured by cardiovascular risk factors, BNP, or CRP. This finding supports GDF-15 as a potential aid for prognostic assessment in patients with ACS.
Author Disclosures: E.C. Kosova: None. J.A. de Lemos: Research Grant; Significant; Abbott, Roche. Consultant/Advisory Board; Significant; Abbott, Diadexus. P. Jarolim: Research Grant; Significant; Abbott, Merck, Roche, Beckman Coulter, Daiichi Sankyo, AstraZeneca. J. Guo: None. E. Braunwald: Research Grant; Significant; Merck. M.S. Sabatine: Research Grant; Significant; Abbott Laboratories, Amgen, AstraZeneca, AstraZeneca / Bristol-Myers Squibb Alliance, Critical Diagnostics, Daiichi-Sankyo, Eisai, Genzyme, GlaxoSmithKline, Intarcia, Merck, Roche Diagnostics, Sanofi-Aventis, Takeda. Consultant/Advisory Board; Modest; Amgen, AstraZeneca, Bristol-Myers Squibb, Intarcia, MyoKardia, Pfizer, Sanofi-Aventis, Zeus. D.A. Morrow: Research Grant; Significant; Abbott, Amgen, AstraZeneca, Beckman Coulter, BG Medicine, BRAHMS, Bristol-Myers Squibb, Critical Diagnostics, CV Therapeutics, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Johnson & Johnson, Merck and Co, Novartis Pharmaceuticals, Roche Diagnostics, Sanofi-Aventis, and Singulex. Consultant/Advisory Board; Modest; Abbott Laboratories, DiaDexus, Eli Lilly, Gilead, Instrumentation Laboratory, Konica Minolta, Johnson & Johnson, Merck, Roche Diagnostics, and Servier.
- © 2014 by American Heart Association, Inc.