Clinical determinants of systemic inflammation in a real-world heart failure cohort

Background - Systemic inflammation plays a central role in cardiovascular disease and has been implicated in the pathophysiology of heart failure (HF). High-sensitivity C-reactive protein (hsCRP) represents an accessible marker of low-grade inflammatory activity; however, the clinical determinants of elevated hsCRP within heart failure populations remain incompletely defined. Purpose - To identify independent clinical determinants of hsCRP levels in a real-world cohort of patients with established HF and elevated inflammatory burden. Methods - We analysed 252 consecutive patients with confirmed HF, NT-proBNP>300mg/mL and hsCRP ≥2 mg/L. Demographic and clinical characteristics, cardiovascular risk factors, renal function and HF phenotype(preserved vs reduced ejection fraction) were recorded(baseline characteristics detailed in Figure 1). HsCRP demonsrated a right-skewed distribution and was log-transformed for regression analyses. Multivariable linear regression was performed to identify independent predictors of log-hsCRP. In addition, the association between EF phenotype and hsCRP was evaluated both unadjusted and after multivariable adjustment. To further characterise the inflammatory spectrum, patients were stratified according to hsCRP quartiles;the upper quartile(Q4) was defined as hsCRP>10.77mg/L and was considered to represent the highest inflammatory phenotype. Results - Mean age was 74.2 ± 9.1 years; 69% were male and 78% had preserved EF. Median hsCRP was 6.07 mg/L (IQR 3.37–10.77). In multivariable analysis(presented in Figure 2), lower eGFR (B −0.010, 95% CI −0.016 to −0.004; p<0.001), higher BMI (B 0.025, 95% CI 0.005–0.046; p=0.015), former smoking (B 0.381, 95% CI 0.078–0.685; p=0.014) and current smoking (B 0.419, 95% CI 0.064–0.774; p=0.021) were independently associated with higher hsCRP levels. EF phenotype was not associated with hsCRP either in unadjusted comparisons (p=0.296) or after multivariable adjustment (p=0.879). Patients in the highest hsCRP quartile (hsCRP >10.77 mg/L; n=62, 24.6%) demonstrated a highest prevalence of diabetes, greater renal dysfunction and increased smoking exposure compared with lower quartiles. Conclusions - In this real-world HF cohort, systemic inflammation was independently associated with adiposity, smoking and impaired renal function, but not with HF phenotype. Although diabetes did not emerge as an independent linear predictor, its greater prevalence in the highest hsCRP quartile indicates clustering of metabolic and renal dysfunction among patients with more pronounced inflammatory activation. These findings support the concept of a cardio-metabolic–renal inflammatory profile in HF and may help identify patient subgroups who might benefit from future targeted anti-inflammatory therapies.