Purpose Examine the relationships between high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor-α receptor-1 (sTNF-R1) and the cumulative risk of heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fractions in a diverse, population-based sample. Methods Study sample included 6,814 adult (45-84 years of age) men and women who participated in the Multi-Ethnic Study of Atherosclerosis and were free of cardiovascular disease at baseline. Cox regression was used to calculate the hazard ratios (HR) associated with elevated baseline hs-CRP (\u3e 3-10 mg/L), IL-6 (\u3e 75th percentile) and sTNF-R1 (\u3e 75th percentile) and risk of overall HF, HFrEF (ejection fraction [EF] \u3c 50%), and HFpEF (EF ≥ 50%). Results During ~11.2 years of follow-up there were 178 incident HF diagnoses. Elevated hs-CRP, IL-6 and sTNF-R1 were associated with a significant increased risk of HF overall (HR 1.76; 95% Confidence interval [CI] 1.22-2.52, HR 1.57; 95% 1.07-2.30, and HR 1.91; 95% CI 1.08-3.38, respectively). Elevated hs-CRP was a significant predictor in both HFrEF and HFpEF (HR 2.05; 95% CI 1.26-3.35, and HR 1.89; 95% CI 1.09-3.28, respectively). Baseline IL-6 concentrations were significantly associated with increased risk of HFrEF in nonsmokers only (HR 2.33; 95% CI 1.04-5.23) and of HFpEF in African Americans only (HR 5.89; 95% CI 1.52-22.80).Conclusions In a diverse sample of U.S. adults, elevated hs-CRP, IL-6 and sTNF-R1 were significant predictors of HF. Furthermore, both hs-CRP and IL-6 were significant predictors in HFrEF and HFpEF
