C S P Lam, Johanna Contreras, Raed Darwesh, Aguinaldo F Freitas Junior, Søren Lund Kristensen, Koichiro Kuwahara, Andrew Ludman, Changsheng Ma, Nikolaus Marx, Jimmi Mathisen, Ann Marie Navar, Adam J. Nelson, Matteo Pirro, Hongye Ren, Shelley Zieroth, Adriaan A Voors
AIMS: Inflammation contributes to the pathophysiology of heart failure (HF), yet the global prevalence of elevated high sensitivity C-reactive protein (hsCRP) in patients with HF across the ejection fraction (EF) spectrum remains unclear. We sought to characterize the prevalence and clinical correlates of high inflammatory risk (defined as hsCRP ≥2 mg/L) in a global real-world HF cohort across the EF spectrum. METHODS AND RESULTS: POSEIDON prospectively enrolled 18,904 individuals across 317 sites in 18 countries (2023-2025) at routine visits, including 11,809 with HF and available hsCRP (3714 with preserved EF [HFpEF], 2176 with mildly reduced EF [HFmrEF], 5919 with reduced EF [HFrEF]), and excluding those with recent infections. Elevated hsCRP (≥2 mg/L) was found in 1442 (38.8%) patients with HFpEF, 830 (38.1%) with HFmrEF, and 2263 (38.2%) with HFrEF. Within each HF subtype, patients with elevated hsCRP were more likely to be female and to have chronic kidney disease, obesity, worse functional class, and higher N-terminal pro-B-type natriuretic peptide levels. In multivariable analyses, independent predictors of elevated hsCRP included smoking, rheumatic/autoimmune/inflammatory disease, obesity, reduced eGFR, dyslipidaemia and worse NYHA class. These predictors were consistent across HF subtypes (interaction p>0.05), except body mass index, which was more strongly associated with hsCRP in HFpEF (interaction p=0.001). Interleukin-6 correlated moderately with hsCRP across all HF subtypes. CONCLUSIONS: In a global HF population, high inflammatory risk is present in approximately 4 in 10 patients and is associated with more severe HF and a cardio-kidney-metabolic phenotype. These findings were consistent across HF subtypes.