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.