Cardiac Biomarkers and Risk of Incident Heart Failure in Chronic Kidney Disease: The CRIC (Chronic Renal Insufficiency Cohort) Study

Abstract

Background Cardiac biomarkers may signal mechanistic pathways involved in heart failure ( HF ), a leading complication in chronic kidney disease. We tested the associations of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity troponin T (hsTnT), galectin‐3, growth differentiation factor‐15 ( GDF ‐15), and soluble ST 2 ( sST 2) with incident HF in chronic kidney disease. Methods and Results We examined adults with chronic kidney disease enrolled in a prospective, multicenter study. All biomarkers were measured at baseline. The primary outcome was incident HF . Secondary outcomes included HF with preserved ejection fraction (EF≥50%) and reduced ejection fraction (EF<50%). Cox models were used to test the association of each cardiac biomarker with HF , adjusting for demographics, kidney function, cardiovascular risk factors, and medication use. Among 3314 participants, all biomarkers, with the exception of galectin‐3, were significantly associated with increased risk of incident HF (hazard ratio per SD higher concentration of log‐transformed biomarker): NT ‐pro BNP (hazard ratio, 2.07; 95% CI , 1.79–2.39); hsTnT (hazard ratio, 1.38; 95% CI , 1.21–1.56); GDF ‐15 (hazard ratio, 1.44; 95% CI , 1.26–1.66) and sST 2 (hazard ratio, 1.19; 95% CI, 1.05–1.35). Higher NT ‐pro BNP , hsTnT, and GDF ‐15 were also associated with a greater risk of HF with reduced EF ; while higher NT ‐pro BNP GDF ‐15 and sST 2 were associated with HF with preserved EF . Galectin‐3 was not associated with either HF with reduced EF or HF with preserved EF. Conclusions In chronic kidney disease, elevations of NT ‐pro BNP , hsTnT, GDF ‐15, sST 2 were associated with incident HF . There was a borderline association of galectin‐3 with incident HF . NT ‐pro BNP and hsTnT were more strongly associated with HF with reduced EF , while the associations of the newer biomarkers GDF ‐15 and sST 2 were stronger for HF with preserved EF.