Abstract 9846: Association Between Neutrophil Activity and Incident Heart Failure: The Atherosclerosis Risk in Communities Study

Abstract

Introduction: Inflammation-reduction with colchicine improves outcomes in coronary disease, possibly through effects on neutrophil activity. Inflammation also may contribute to incident heart failure (HF) and the association of neutrophil activity with HF is unclear. We assessed the association between 10 neutrophil-associated proteins that were altered by colchicine in two previous proteomic studies with incident HF. Methods: We studied 10,317 ARIC participants who were free of HF and had aptamer-based proteomic measurements (Somalogic, Colorado) at Visit 3 (1993-1995). Candidate proteins were included in a LASSO Cox regression model which were used to derive a neutrophil activity score. The association of the neutrophil activity score with incident HF was then assessed after adjustment for age, sex, race, study field center, hypertension, smoking history, diabetes, coronary disease, BMI, Visit 3 blood pressure, eGFR, and hsCRP and neutrophil-to-lymphocyte ratio. Results: The mean age was 60±6 years, 54% were women and 20% were black. Over a mean follow-up of 13 years, 1314 participants developed incident HF. Five of the 10 candidate proteins were associated with incident HF in multivariable uni-protein models (myeloperoxidase, suPAR, antichymotrypsin, BPIP, S100A12) at p <0.05. LASSO model retained 4 proteins (suPAR, antichymotrypsin, BPIP, S100A12), from which a neutrophil activity score was developed. Higher neutrophil activity score was associated with older age, higher prevalence of cardiovascular comorbidities, and higher hsCRP. Higher neutrophil activity score was associated with greater risk of incident HF in multivariable models after adjustment for clinical risk factors, hsCRP and neutrophil-to-lymphocyte ratio ( Figure ). Conclusions: Increased neutrophil activity may contribute to incident heart failure in the community. These findings provide a putative mechanism by which treatment with colchicine may influence risk of HF.