POSEIDON enrolled 18,904 individuals at 317 sites in 18 countries (2023–2025); 11,809 had HF with hsCRP available. Elevated hsCRP (≥2 mg/L) was present in ~38% of patients across HFpEF, HFmrEF and HFrEF — strikingly consistent across the EF spectrum. Patients with elevated hsCRP were more likely female with a cardio-kidney-metabolic phenotype: CKD, obesity, worse NYHA, higher NT-proBNP. Smoking, autoimmune/inflammatory disease, obesity and reduced eGFR were independent predictors. The findings define the target population for IL-6 trials (ATHENA, HERMES with ziltivekimab) also announced at HF26.
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 (hsCRP ≥2 mg/L) in a global real-world HF cohort across the EF spectrum.
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 HFpEF, 2176 with HFmrEF, 5919 with 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 NT-proBNP levels. Independent predictors of elevated hsCRP included smoking, rheumatic/autoimmune/inflammatory disease, obesity, reduced eGFR, dyslipidaemia and worse NYHA class — 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.
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, consistently across HF subtypes.
