Rampant Inflammation In Heart Failure: Can Anything Be Done About It?

TL;DR

Before you orderOffer from Amazon

Get health and wellness essentials delivered free with Prime

• Fast, free delivery on millions of items
• Prime Video, Amazon Music and more included
• Member-only deals all year

Start your free Prime trial →Free trial for eligible customers · Cancel anytime

As an affiliate, we earn on qualifying purchases.Hide

A U.S. analysis of the POSEIDON registry found elevated hsCRP, a marker of inflammation, in about half of participants across three heart failure types. Researchers said the findings point to substantial residual inflammatory risk, but no dedicated treatment has been established, and two ziltivekimab trials were stopped early for futility.

A U.S. analysis of the POSEIDON registry found that about half of participants with heart failure had elevated high-sensitivity C-reactive protein (hsCRP), a marker used to assess inflammation. Presented by Duke University’s Marat Fudim at the Heart Failure Society of America annual conference, the findings highlight a common risk signal for which researchers say there is no dedicated, proven treatment.

Elevated hsCRP was defined in the analysis as 2 milligrams per liter or higher. Among U.S. participants, the proportion above that threshold was 50.8% for heart failure with preserved ejection fraction (HFpEF), 44.7% for mildly reduced ejection fraction (HFmrEF), and 50.3% for reduced ejection fraction (HFrEF). The results come from a cross-sectional analysis, which describes the participants’ measurements rather than showing that inflammation caused their heart failure or subsequent outcomes.

The U.S. percentages were higher than those reported across POSEIDON’s full international heart-failure population: 38.8% for HFpEF, 38.1% for HFmrEF, and 38.2% for HFrEF. That broader registry enrolled 18,904 adults with atherosclerotic cardiovascular disease and/or heart failure across 18 countries from 2023 to 2025. The U.S. heart-failure groups in this analysis included 315 people with HFpEF, 94 with HFmrEF, and 392 with HFrEF.

Fudim said elevated hsCRP was associated with higher levels of interleukin-6 (IL-6) and NT-proBNP across the three heart-failure types. He also said residual inflammatory risk remained despite use of guideline-directed heart-failure medication. The report identified obesity, diabetes, and chronic kidney disease as important comorbidities linked to inflammation, while noting higher insulin and diuretic use among participants with elevated hsCRP.

Inflammation Persists Despite Heart Failure Care

The findings draw attention to a risk marker that may be present in many patients even when they are receiving standard heart-failure treatment. About one in two U.S. participants in each ejection-fraction group met the study’s hsCRP threshold, suggesting that inflammatory risk is not confined to one type of heart failure. The comparison with the full international registry also points to a higher measured prevalence in the U.S. cohort, although the analysis does not establish why the difference exists.

For clinicians and patients, the gap between a widespread marker and a treatment that has shown benefit matters. Fudim described hsCRP as a practical way to identify residual risk and said he uses the result to inform risk discussions. He pointed to lifestyle measures, exercise, weight loss, and management of conditions such as chronic kidney disease as possible parts of care, but the report does not present these as a substitute for individualized medical treatment or as proof that lowering hsCRP improves heart-failure outcomes.

Registry Findings Meet Trial Setbacks

The POSEIDON analysis was presented at the Heart Failure Society of America annual conference and examines a subset of a registry that prospectively enrolled adults receiving routine care. Its cross-sectional design offers a snapshot of hsCRP prevalence, not a test of whether a particular anti-inflammatory treatment works. The U.S. subgroup sizes also differed substantially by heart-failure type, particularly the smaller HFmrEF group.

The treatment outlook has been complicated by recent trial results. Novo Nordisk announced in September that two placebo-controlled trials of the IL-6 inhibitor ziltivekimab, HERMES and ATHENA, had been stopped early for futility. The studies were designed to test clinical and other outcomes in heart-failure patients with high hsCRP. Before those stops, ziltivekimab had also failed to reduce major adverse cardiovascular events in the ZEUS trial among people with atherosclerotic cardiovascular disease, chronic kidney disease, and inflammation.

At the conference, discussant Amanda Vest of Cleveland Clinic described a history of neutral or negative studies targeting particular inflammatory pathways. Fudim suggested that approaches acting on multiple pathways may merit attention, mentioning GLP-1 drugs as an example of medicines that can affect inflammation in different ways. These comments are researchers’ views, not evidence from the POSEIDON analysis that a broad anti-inflammatory strategy benefits heart-failure patients.

“We are very inflamed as a nation of HF patients.”

— Marat Fudim, MD, MHS, Duke University Medical Center

What the Registry Cannot Establish

The analysis does not show whether elevated hsCRP predicts future events in these specific participants, whether it directly contributes to heart failure, or whether lowering it would improve survival or symptoms. It also does not explain the difference between the U.S. and international rates. The report gives no randomized comparison of lifestyle measures or anti-inflammatory therapies, and the U.S. subgroup results cannot establish that the same pattern applies to all patients.

It remains unclear whether another targeted drug, a medicine acting on multiple pathways, or a combination of approaches can reduce clinically meaningful outcomes without excessive interference with immune function. The available report does not provide further trial details or a timeline for replacement studies after HERMES and ATHENA stopped early.

Research Must Link Markers to Outcomes

The immediate next step is to interpret the registry results alongside clinical trials rather than treat hsCRP prevalence as evidence that an anti-inflammatory drug will work. Researchers will need to show whether using hsCRP to guide care changes outcomes and whether any intervention can reduce heart-failure events or improve patients’ health safely. Further information about the discontinued ziltivekimab trials and any new studies could clarify which treatment strategies remain under consideration.

For now, Fudim described hsCRP as a tool for risk discussion, with attention to lifestyle and related conditions such as obesity, diabetes, and kidney disease. Decisions about testing or treatment remain matters for patients and their qualified health professionals; the registry report does not establish a specific care plan.

Key Questions

What did the POSEIDON analysis find?

It found hsCRP of 2 mg/L or higher in 50.8% of U.S. participants with HFpEF, 44.7% with HFmrEF, and 50.3% with HFrEF.

Does elevated hsCRP prove that inflammation caused heart failure?

No. This was a cross-sectional analysis of a biomarker. It describes how common elevated hsCRP was in the groups but does not establish cause and effect or predict outcomes for an individual.

Is there a dedicated anti-inflammatory treatment for heart failure?

Fudim said there is no dedicated treatment established for this purpose. The report also notes that two ziltivekimab heart-failure trials were stopped early for futility; it does not establish that another anti-inflammatory approach is effective.

What did the report suggest about managing inflammatory risk?

Fudim cited exercise, lifestyle measures, weight loss, and attention to conditions including chronic kidney disease. The analysis did not test these strategies or show that they reduce heart-failure outcomes; patients should discuss care decisions with a qualified health professional.

Source: rss