Growth Differentiation Factor‐15 Predicts Death and Stroke Event in Outpatients With Cardiovascular Risk Factors: The J‐HOP Study

BACKGROUND: Growth differentiation factor‐15 (GDF‐15) has emerged as a novel biomarker to predict all‐cause death in community‐dwelling individuals and patients with cardiovascular disease. We evaluated the prognostic value of GDF‐15 in outpatients with cardiovascular risk factors. METHODS AND RESULTS: GDF‐15 levels were measured in 3562 outpatients with cardiovascular risk factors in the J‐HOP (Japan Morning Surge‐Home Blood Pressure) study, a nationwide prospective study. Participants were stratified according to tertiles of GDF‐15 and followed up for all‐cause death and cardiovascular disease. During a mean follow‐up period of 6.6 years, there were 155 all‐cause deaths, 81 stroke events including cerebral infarction and intracranial hemorrhage, and 141 cardiac events including cardiac artery disease and heart failure. Patients with higher GDF‐15 levels were associated with risks of all‐cause death and stroke events (except for cardiac events) after adjustment for traditional risk factors and other prognostic biomarkers (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], high‐sensitivity troponin T; all‐cause death, hazard ratio, 2.38; 95% CI, 1.26–4.48; P=0.007; stroke events, hazard ratio, 2.93; 95% CI, 1.31–6.56, P=0.009; compared with the lowest tertile). Furthermore, incorporating GDF‐15 to the predictive models for all‐cause death improved discrimination and reclassification significantly. For stroke events, GDF‐15 showed similar diagnostic accuracy to NT‐proBNP and high‐sensitivity troponin T. CONCLUSIONS: In Japanese outpatients with cardiovascular risk factors, GDF‐15 improves risk stratification for all‐cause death when compared with NT‐proBNP and high‐sensitivity troponin T. GDF‐15 was associated with increased risks of stroke events beyond conventional risk factors and other prognostic markers; however, the predictive ability for stroke events was equivalent to NT‐proBNP and high‐sensitivity troponin T. REGISTRATION: URL: http://www.umin.ac.jp/ctr.; Unique identifier: UMIN000000894.