Abstract 11936: Cardiorenal Prognostic Significance of IGFBP-7 Concentrations in Chronic Heart Failure: Findings From EMPEROR-Pooled

Abstract

Introduction: Insulin-like growth factor binding protein-7 (IGFBP-7) is a biomarker of tissue senescence with a role in heart failure (HF) pathophysiology. We examined the association of IGFBP-7 with risk of HF hospitalization or cardiovascular (CV) death and progression of renal disease in the EMPEROR-Reduced and EMPEROR-Preserved Trials. Methods: IGFBP-7 was measured in serum samples in the placebo and empaglifozin arms at baseline (N= 561, 564), 12 weeks (N=558, 557) and 52 weeks (N=355, 358). IGFBP-7 was measured using Roche Cobas Elecsys assay within the Biomarker Research Agreement of Boehringer Ingelheim, the sponsor of the EMPEROR trials and Roche Diagnostics International Ltd. Association between IGFBP-7 and risk of HF hospitalization or CV death, estimated glomerular filtration rate (eGFR) slope, and renal composite outcome of sustained eGFR reduction ≥40% or end-stage renal disease were evaluated using multivariable modeling. Results: Study participants with IGFBP-7 levels in the third tertile had a higher risk clinical profile compared to those with lower values. Empagliflozin was not meaningfully associated with change in IGFBP7 at 12 or 52 weeks. In Cox proportional hazards models adjusted for clinical variables, N-terminal pro-B type natriuretic peptide and high-sensitivity cardiac troponin T, baseline IGFBP-7 values above the second tertile predicted a higher risk of HF hospitalization or CV death (HR: 2.00 95% CI 1.28-3.10, p=0.002), higher rate of eGFR decline (β estimate: -2.45, 95% CI: -3.40 - -1.50, p for trend =0.005) and higher risk of renal composite endpoint (HR: 4.66, 95% CI: 1.61-13.53, p=0.005). Empagliflozin reduced risk for CV death/HF hospitalization irrespective of baseline IGFBP-7 (p-trend across IGFBP-7 tertiles=0.26). Concentrations of IGFBP-7 were moderately correlated with other prognostic HF biomarkers of tissue remodeling including fatty acid binding protein-3, growth differentiation factor-15, and angiopoietin-2. Conclusions: IGBP-7 was correlated with worse clinical presentation and associated with adverse cardiovascular outcomes even in models adjusted for conventional biomarkers. Empagliflozin did not significantly affect IGFBP-7 levels over time.