Abstract 2386: Growth-Differentiation Factor-15 is a Strong Predictor of Adverse Outcomes in Heart Failure: Results from Val-HeFT.
Background: Growth-Differentiation Factor-15 (GDF-15) is a member of the TGF-β family that is induced in the heart after myocardial injury. In patients with non-ST segment elevation ACS, GDF-15 is increased and provides prognostic information. Its role in heart failure is unknown. Methods & Results: GDF-15 was measured in 1125 Val-HeFT patients at baseline. Baseline median GDF-15 was 2027 ng/L (IQ range 1447 to 2942) and was abnormal (>1200 ng/L) in 86% of patients. Patients with GDF-15 above the median had higher NYHA class, greater volume load, lower LVEF and eGFR, higher hsCRP, norepinephrine, BNP and aldosterone, lower use of beta-blockers and higher use of diuretics (all p<0.01). In a multivariate COX model including all baseline variables, GDF-15 was a significant independent predictor of death (HR, 1.5, 95% CI, 1.06–2.14), first morbid event (HR 1.56, 95% CI, 1.19–2.04), and hospitalizations for HF (HR, 1.93, 95% CI, 1.33–2.80), as was BNP for all the three endpoints (HR, 1.7, 95% CI, 1.27–2.3), (HR 1.84, 95% CI, 1.45–2.35), and (HR, 1.98, 95% CI, 1.43–2.7). Spearman correlation of BNP with GDF-15 was 0.33 p<0.001. To test whether GDF-15 adds prognostic information over that provided by BNP, patients were sub-grouped using the median BNP (96 pg/mL) and GDF-15 (2027 ng/L). Figure shows survival curves for the four subgroups. In a multivariate COX analysis when both GDF-15 and BNP were above the median, the risk of death was nearly three times as great (HR 2.75, 95% CI 1.75–4.30, p<0.001) compared to those with both below the median. Conclusion: GDF-15 is an important prognostic marker in HF, independent of other markers and adds prognostic information to that provided by BNP alone.