Cardiovascular Inflammation Persists in Some Patients With CVD Despite Standard Treatment

Findings from the POSEIDON real-world study suggest that elevated high-sensitivity C-reactive protein (hsCRP) is common across heart failure subtypes and in patients with atherosclerotic cardiovascular (CV) disease (CVD) and chronic kidney disease (CKD), even among those receiving guideline-directed therapy.¹

The findings, presented at the 94th European Atherosclerosis Society (EAS) Congress in Athens, Greece, highlight a significant gap in residual CV risk management that pharmacists and other clinicians may need to address when supporting patients with complex cardiometabolic profiles.¹

“Frontline care teams may suspect high inflammatory risk based on a patient's clinical profile; however, suspicion is not measurement,” lead POSEIDON author 3Carolyn Lam, MBBS, PhD, FRCP, MS, FACC, FAMS, FASC, senior consultant cardiologist at the National Heart Center in Singapore, professor in the cardiovascular and metabolic disorders signature research program at Duke-NUS Medical School, told Pharmacy Times. “POSEIDON showed that elevated hsCRP travels with a cardio-kidney-metabolic phenotype—yet the overlap with patients with lower inflammatory risk is substantial.”

What Is POSEIDON?

POSEIDON is a cross-sectional, global, real-world prevalence study that prospectively enrolled 18,904 patients across 317 sites in 18 countries spanning Europe, North America, South America, and Asia-Pacific between 2023 and 2025. Patients were enrolled sequentially at routine clinical visits, and those with recent infections or acute hospitalizations were excluded to ensure that inflammatory markers reflected chronic CV inflammation rather than acute conditions.^1,2

CV inflammation was measured using high-sensitivity C-reactive protein (hsCRP), the most widely available and validated blood-based biomarker for this purpose. Elevated hsCRP was defined as a level of 2 mg/L or greater, consistent with published clinical thresholds and FDA review criteria.^1,3

Key Findings: Prevalence Across Patient Populations

Among the 13,475 patients in POSEIDON with atherosclerotic cardiovascular disease (ASCVD), 5,757 (42.7%) also had CKD, and about 2 in 5 of these patients had elevated hsCRP, indicating persistent inflammatory burden despite standard-of-care management.¹

A parallel analysis published in the European Journal of Heart Failure examined the 11,809 patients enrolled with heart failure (HF) across the full ejection fraction spectrum. Elevated hsCRP was found in approximately 38.8% of patients with HF with preserved ejection fraction (HFpEF), 38.1% of those with mildly reduced ejection fraction (HFmrEF), and 38.2% of those with reduced ejection fraction (HFrEF), a strikingly similar prevalence across all 3 subtypes.²

Within each HF subgroup, patients with elevated hsCRP were more likely to be female, have CKD, have obesity, exhibit worse New York Heart Association (NYHA) functional class, and have higher N-terminal pro-B-type natriuretic peptide levels compared with those whose hsCRP was below the threshold. In multivariable analyses, independent predictors of elevated hsCRP included smoking, rheumatic or autoimmune disease, obesity, reduced estimated glomerular filtration rate, dyslipidemia, and more severe HF symptoms—with these associations consistent across HF subtypes.²

“The key is what does not get measured does not get acted upon,” Lam noted. She offered reassurance in the form of the simplicity and affordability of hsCRP measurement, which only needs to be ordered when a patient is clinically stable and free of recent hospitalization or infection. “Pharmacists in medication therapy management are ideally placed here—the medication list is often where the actionable gap first becomes visible.”

The Role of Inflammation in CVD

Inflammation has been established as a central pathophysiological driver of ASCVD and a contributor to its progression. Multiple studies have shown that patients with elevated hsCRP face increased risk of major adverse cardiovascular events, including myocardial infarction, stroke, and CV death, independent of traditional risk factors such as low-density lipoprotein cholesterol. In HF, inflammation is believed to contribute through oxidative stress, tissue fibrosis, and microvascular dysfunction, mechanisms that differ somewhat by ejection fraction subtype but appear to converge on shared inflammatory pathways.^1,4,5

The relationship between CKD and inflammation adds further complexity. Inflammation contributes to CKD progression, and impaired kidney function itself promotes inflammatory signaling, creating a feedback cycle that amplifies overall CV risk.⁶

Implications for Clinical Practice

The POSEIDON data underscore an important clinical reality: even when patients are receiving recommended therapies for cholesterol, blood pressure, and blood sugar, a substantial proportion continue to carry elevated inflammatory risk. A prior analysis of statin-treated patients found that those with hsCRP of at least 2 mg/L—regardless of LDL levels—had significantly higher rates of CV events, supporting the notion that residual inflammatory risk operates as an independent dimension of CV vulnerability.^4,5

“The most important message is to optimize treatment with what we already have,” Lam noted. Patients in POSEIDON were less likely to be on guideline-directed statin therapy; pharmacists can start by recommending pillars of heart failure therapy to at-risk patients, while considering newer, incretin-based therapies for weight loss.

Current CV prevention guidelines from the American Heart Association (AHA), the American College of Cardiology (ACC), and the European Society of Cardiology (ESC) already include elevated hsCRP as a risk-modifying biomarker to inform more intensive preventive interventions in select patients. These data from POSEIDON may further support the routine incorporation of hsCRP measurement into the management of high-risk patients with ASCVD, CKD, or HF.^7,8

“Measuring hsCRP today does double duty: it stratifies residual risk now, and it defines the very patients who stand to benefit from precision anti-inflammatory therapy tomorrow,” Lam summarized.

Looking Ahead

The POSEIDON findings represent one of the largest contemporary global assessments of CV inflammation prevalence in high-risk populations, and they are expected to inform the design of interventional trials targeting inflammation directly. Pharmacists involved in chronic disease management, medication therapy management, or specialty cardiology programs are well-positioned to help identify patients who may benefit from hsCRP screening and to support shared decision-making about emerging anti-inflammatory strategies as the evidence base continues to develop.

REFERENCES

1. Novo Nordisk global observational study reveals 2 in 5 people with cardiovascular disease have cardiovascular inflammation, increasing their risk of heart attack and stroke. News Release. Novo Nordisk. May 26, 2026. Accessed June 29, 2026. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916553

2. Lam CSP, Contreras J, Darwesh R, et al. Prevalence and predictors of high inflammatory risk in heart failure subtypes: findings from the global POSEIDON study. Eur J Heart Fail. 2026Lxuag155. doi:10.1093/ejhf/xuag155

3. Review criteria for assessment of C-reactive protein (CRP), high sensitivity C-reactive protein (hsCRP) and cardiac C-reactive assays. Last Updated August 24, 2018. Accessed June 29, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/review-criteria-assessment-c-reactive-protein-crp-high-sensitivity-c-reactive-protein-hscrp-and

4. Ridker PM, Bhatt DL, Pradhan AD, et al. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials. Lancet. 2023;401(10384):1293–1301. doi:10.1016/S0140-6736(23)00215-5

5. Ridker PM, Lei L, Louie MJ, et al. Inflammation and cholesterol as predictors of cardiovascular events among 13,970 contemporary high-risk patients with statin intolerance. Circulation. 2024;149(1):28–35. doi:10.1161/CIRCULATIONAHA

6. Lawler PR, Bhatt DL, Godoy LC, et al. Targeting cardiovascular inflammation: next steps in clinical translation. Eur Heart J. 2021;42(1):113–131. doi:10.1093/eurheartj/ehaa099

7. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;74(10):e177–e232. doi:10.1016/j.jacc.2019.03.010

8. Visseren FLJ, Mach F, Smulders YM, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42(34):3227–3337. doi:10.1093/eurheartj/ehab484