Circulating neutrophil-related proteins associate with incident heart failure and cardiac dysfunction: The ARIC study

Aims: Neutrophil activity contributes to adverse cardiac remodelling in experimental acute cardiac injury and is modifiable with pharmacologic agents like colchicine. Methods and results: Neutrophil activity-related plasma proteins known to be affected by colchicine treatment were measured at Visit 3 (1993–1995) and Visit 5 (2011–2013) of the ARIC cohort study. A protein-based neutrophil activity score was derived from 10 candidate proteins using LASSO Cox regression. Associations with incident heart failure (HF) and with cardiac function using Cox proportional hazards regression and linear regression models, respectively. The mean ages at Visits 3 and 5 were 60 ± 6 and 75 ± 5 years, respectively, and 54% and 57% were women, respectively. Each 1-standard deviation increase in the neutrophil activity score was associated with a higher risk of incident HF in mid-life (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.25–1.37) and late-life (HR 1.23, 95% CI 1.14–1.34), with a higher HR for HF with preserved than reduced ejection fraction (HR 1.30, 95% CI 1.16–1.47 vs. HR 1.13, 95% CI 0.98–1.30). Higher neutrophil activity was associated with greater left ventricular end-diastolic volume index, mass index and diastolic and systolic dysfunction. Conclusions: Plasma proteins related to neutrophil function associate with incident HF in mid- and late-life and with adverse cardiac remodelling. Therapies that modify these proteins, such as colchicine, may represent promising targets for the prevention or treatment of HF.