Biomarkers of Inflammation in Heart Failure Patients with Reduced and Preserved Ejection Fractions: Multi-Ethnic Study of Atherosclerosis

Abstract

Background: Limited evidence exists examining the relationship between biomarkers of inflammation and heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) subtypes. Purpose: Examine the relationships between biomarkers of inflammation and incident heart failure subtypes in a diverse, population-based sample. Methods: Study sample included 6,814 adult (45-84 years of age) participants in the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease at baseline. The upper quartile of log-transformed C-reactive protein (CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor-α receptor-1 (sTNFR1) was considered elevated. Heart failure participants with an ejection fraction (EF) <50% were considered HFrEF and those with a borderline EF (41-49%) or EF ≥50% were considered HFpEF. Results: During an average of 11.2 years of follow-up, there were 178 incident heart failure diagnoses; 57 with HFpEF, 86 with HFrEF, and 35 with unknown EF. Following adjustment for age, gender, race/ethnicity, blood pressure, waist circumference, smoking, LDL-C, triglycerides, HDL-C, atrial fibrillation, medications, and level of physical activity, logistic regression revealed significantly increased odds of HFrEF in those with elevated CRP (Odds Ratio [OR] 1.96; 95% Confidence Interval [CI] 1.18-3.13, p<0.01), sTNFR1 (OR 1.95; 95% CI 1.01-3.76, p=0.05) and IL-6 (OR 2.20; 95% CI 1.27-3.81, p<0.01). Comparatively, significantly increased odds of HFpEF were observed only in those with elevated IL-6 (OR 2.21; 95% CI 1.12-4.35, p<0.05). Conclusion: In a diverse sample of U.S. adults, elevated CRP, sTNFR1, and IL-6 levels were associated with increased odds of HFrEF and elevated IL-6 was significantly associated with HFpEF.