Higher Cardiovascular Inflammation Prevalent Across All Heart Failure Subtypes

Elevated cardiovascular inflammation (CVI) affects roughly 50% of US patients with heart failure (HF) across the spectrum, potentially corresponding to HF severity through higher IL-6 and NT-proBNP.¹

These data, a subanalysis of the POSEIDON study, were presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026 in Phoenix, Arizona, by Marat Fudim, MD, an associate professor at Duke University Health and a member of the American Heart Association’s Heart Technology Advisory Group.¹

“The real reason this registry was put into place is because there is a cadre of clinical trials going on – a couple of these trials were halted and are going to be terminated because there was no apparent benefit to blocking IL-6 versus placebo,” Fudim told HCPLive in an exclusive interview. “Now this is very disappointing, but it does not mean that this registry has no value anymore. Quite the opposite: it shows that we may have lost the battle, but we have not lost the war.”

POSEIDON was a cross-sectional, global, real-world prevalence study spanning 317 sites in 18 countries. Patients were eligible if they had atherosclerotic cardiovascular disease (ASCVD) and/or HF, as well as serum creatinine in the medical chart within 24 months prior to signing of informed consent. Patients with a hospitalization of any kind within the last 60 days or clinical evidence or suspicion of active infection within the same period, among other criteria, were excluded.^2,3

The POSEIDON study ultimately enrolled 18,904 individuals, including 11,809 with HF and available hsCRP. Of these, 3714 had preserved ejection fraction (HFpEF), 2176 had mildly reduced EF (HFmrEF), and 5919 had reduced EF (HFrEF). Elevated hsCRP was found in 1442 patients with HFpEF, 830 with HFmrEF, and 2263 with HFrEF. In each subtype, patients with elevated hsCRP were more likely to be female and have chronic kidney disease (CKD), obesity, worse functional class, and higher NT-proBNP. These predictors were also consistent across HF subtypes, with the exception of body mass index (BMI).³

In the present analysis, Fudim and colleagues brought a cohort of US-based patients from the POSEIDON study into the clinic for a singular study visit with a blood sample collection. A total of 810 patients were included in this substudy, and CVI risk was categorized as either low (hsCRP <2 mg/L) or high (hsCRP ≥2 mg/L). Of these patients, 315 had HFpEF, 94 had HFmrEF, and 392 had HFrEF.¹

Fudim and colleagues found that nearly 50% of patients across the HF spectrum had CVI risk: in the HFpEF group, 49% of patients had hsCRP ≥2 mg/L, while 55% in the HFmrEF group and 50% in the HFrEF group had hsCRP ≥2 mg/L. The team noted that these measures represented residual inflammatory risk persisting despite current management; additionally, CVI risk was numerically higher in the US cohort than in the global POSEIDON study. The team also recorded a potential association between hsCRP ≥2 mg/L and higher IL-6 and NT-proBNP across all HF phenotypes and risk subgroups.¹

Ultimately, Fudim and colleagues noted that CVI risk may potentially provide a link between inflammatory pathway activation and HF severity. They also noted that its frequent presence across all HF phenotypes could present an opportunity for further research into anti-inflammatory approaches to reducing cardiovascular risk.¹

“First of all, I would want to know if treatment of inflammation really results in better outcomes; we haven’t had many successful stories there,” Fudim said. “That’s A. B is whether the risk of CVI change over time in the same individuals. It would have been nice to longitudinally track and see if people change their risk over time, and then to also understand what it is that led to that risk reclassification. So, yes, longitudinal data would be amazing.”

Editors’ Note: Fudim reports disclosures with Alleviant, the American Heart Association, Bayer, Impulse Dynamics, Novo Nordisk, Summacor, and others.

References

1. Fudim M, Contreras J, Ibrahim H, et al. Prevalence of Cardiovascular Inflammation and Associated Patient Characteristics and Biomarker Profiles Across the Heart Failure Spectrum in the United States: Results From the POSEIDON Study. Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026, Phoenix, AZ. October 9-12, 2026.

2. Novo Nordisk A/S. Levels of Inflammation in People With Cardiovascular Disease (POSEIDON) (POSEIDON). ClinicalTrials.gov Identifier: NCT06122961. Updated May 9, 2026. Accessed November 4, 2026. https://clinicaltrials.gov/study/NCT06122961?term=NCT06122961&rank=1

3. Lam CS, Contreras J, Darwesh R, et al. Prevalence and predictors of high inflammatory risk in heart failure subtypes: Findings from the Global Poseidon Study. European Journal of Heart Failure. Published online May 10, 2026. doi:10.1093/ejhf/xuag155