Inflammatory Markers and Risk of Heart Failure with Reduced, Mid-Range and Preserved Ejection Fraction

Background Chronic systemic inflammation is associated with an increased risk of HF. We sought to determine the association between markers of systemic inflammation (interleukin-6 (IL6), interleukin-2 (IL2), tumor necrosis factor-alpha (TNF-a), and c-reactive protein (CRP)) with HF and its subtypes. Hypothesis We hypothesize that inflammatory biomarkers IL6, IL2, TNF-a, and CRP are associated with HF and its subtypes. Methods We included participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective population-based cohort study (2000-2002), without a history of HF and with available baseline inflammatory biomarkers. We explored the association of IL6, IL2, TNFα, and CRP with incident HF, HF with reduced ejection fraction (LVEF less than 40%, HFrEF), HF with mid-range EF (LVEF 40-50%, HFmEF), and HF with preserved ejection fraction (LVEF more than 50%, HFpEF). Results Among 6814 participants, 195 developed HF over 10.9 years (56 HFrEF, 30 HFmrEF, and 57 HFpEF). In the models adjusted for clinical risk factors of heart failure, IL6 (Hazard ratio [HR] 1.33 per doubling; 95% CI: 1.10-1.60), TNFα (HR 2.49 per doubling; 95% CI: 1.18-5.28), and CRP (HR 1.18 per doubling; 95% CI: 1.06 -1.30) were associated with all HF, IL6 (HR 1.51 per doubling; 95% CI: 1.09-2.10), and CRP (HR 1.21 per doubling; 95% CI: 1.01-1.45) were associated with incident HFpEF, while none of the examined biomarkers were associated with HFmrEF or HFrEF. Conclusion Inflammatory biomarkers (IL6, TNFα, and CRP) are independently associated with incident HF. IL6 and CRP were associated with incident HFpEF but not HFrEF or HFmrEF. These findings suggest that activation of the IL6/CRP pathway (as cause, consequence, or epiphenomenon) may be unique to HFpEF, which may have therapeutic implications.