Abstract 029: Proteins Linking Chronic Kidney Disease To Incident Heart Failure In Adults With Chronic Kidney Disease: The Atherosclerosis Risk In Communities Study

Abstract

Introduction: Decreased estimated glomerular filtration rate (eGFR), a kidney dysfunction marker, associates independently with an increased incident heart failure (HF) risk. Identifying mechanisms linking kidney dysfunction to incident HF may reveal potential therapeutic targets. We performed a proteome-wide analysis to identify eGFR-related pathways associated with incident HF. Methods: We studied ARIC participants at Visit 3 (n=10412) and Visit 5 (n=4841) who were free of HF and had aptamer-based proteomic data (SomaLogic, Boulder, CO). Multivariable linear regression models identified proteins associated with eGFR at Visits 3 and 5 at Bonferroni-adjusted P < 1x10 -5 . Incident HF associations were assessed for eGFR-related proteins with multivariable Cox proportional hazards regression models at Bonferroni-adjusted P < 1x10 -5 . All regression models were adjusted for demographics, hypertension, diabetes, coronary artery disease, atrial fibrillation, smoking status, eGFR and albuminuria. Pathway analysis (g:Profiler/KEGG) was performed using proteins associated with incident HF at a false discovery rate (FDR) of < 0.05. Results: The mean age at Visit 3 was 62±6 years, 52% were women, 22% were Black, and 1127 incident HF events occurred post-Visit 3 (median follow-up: 14.8 years). The mean age at Visit 5 was 76±5 years, 58% were women, 18% were Black, and 488 incident HF events occurred post-Visit 5 (median follow-up: 7.2 years). One thousand and seventy-three proteins associated with eGFR at Visits 3 and 5 (P < 1x10 -5 ). Of these eGFR-related proteins, 18 associated with incident HF at Visits 3 and 5 (P < 5x10 -5 ) ( Figure ). Complement and coagulation cascades and cytokine-cytokine receptor interaction pathways were enriched within the 226 proteins associated with incident HF at FDR < 0.05. Conclusions: Kidney dysfunction-related changes in innate immunity and thrombosis associate with an increased risk of incident HF.