Systemic inflammation and the risk of adverse clinical outcomes in heart failure with preserved ejection fraction.

INTRODUCTION: Systemic inflammation is implicated in the pathogenesis of cardiovascular disease, including heart failure (HF). We examined the association between systemic inflammation, indicated by elevated high-sensitivity C-reactive protein (hsCRP), and adverse clinical outcomes in individuals with HF with preserved ejection fraction (HFpEF). METHODS: This retrospective cohort study identified individuals with HFpEF from the Komodo Healthcare Map™ database (01/01/2016 to 12/31/2023) using a validated algorithm. Systemic inflammation status was established by hsCRP testing: with systemic inflammation if ≥1 hsCRP value of 2-10 mg/L and without systemic inflammation if all hsCRP values <2 mg/L. The relationship between hsCRP and risk for HF events, including all-cause mortality, HF hospitalization and urgent HF visits was examined using Cox proportional hazards models with multivariable adjustment. RESULTS: A total of 11,015 individuals with HFpEF and a qualifying hsCRP measurement were identified (mean age 66.4 years; 44% with systemic inflammation). The incidence rate of the composite HF endpoint was 103.2 per 1,000 person-years for those with systemic inflammation versus 83.3 for those without. Systemic inflammation was associated with a 21% increased risk of the composite HF endpoint (HR 1.21, 95% CI 1.11-1.31). Systemic inflammation was associated with increased risk of HF hospitalization (HR 1.17, 95% CI 1.03-1.33) and urgent HF visits (HR 1.21, 95% CI 1.08-1.35) but not all-cause mortality (HR 1.14, 95% CI 0.98-1.32). CONCLUSION: Systemic inflammation was associated with increased risk of future adverse CV-related outcomes in individuals with HFpEF, highlighting unmet clinical needs for this population and the potential to optimize their care.