Elevated hsCRP unmasks a distinct metabolic-inflammatory HFpEF phenotype
E Verghote, A Achten, J Weerts, S G J Mourmans, A Barandiaran Aizpurua, C Knackstedt, V Van EmpelAbstract
Background
Heart failure with preserved ejection fraction (HFpEF) is an inflammation-driven syndrome characterized by multiple comorbidities such as hypertension, obesity, kidney disease and diabetes mellitus. High-sensitive C-reactive protein (hsCRP) is a widely used biomarker of systemic inflammation and is commonly elevated in patients with HFpEF, also when no infection is present. Several clinical studies have used hsCRP ≥2 mg/L to identify HFpEF patients with a heightened inflammatory state and an elevated risk of adverse outcomes. We aimed to evaluate whether hsCRP ≥2 mg/L defines a distinct clinical HFpEF phenotype, and evaluate its prognostic association.
Methods
This single-centre prospective observational cohort study included patients diagnosed with HFpEF via a specialised outpatient clinic between January 2016 and November 2023. Clinical features were compared between patients with low (<2 mg/L) and high (≥2 mg/L) hsCRP levels at diagnosis. Factors associated with high hsCRP were evaluated using univariable and multivariable logistic regression models. Prognostic value of hsCRP was assessed through Kaplan-Meier survival analysis and Cox regression for the composite endpoint of heart failure hospitalisation or all-cause mortality.
Results
The study included 412 patients with HFpEF (mean age, 75 years; 68% female) with median hsCRP of 2.4 mg/L [1.2, 5.6]. Low and high hsCRP was measured in 171 (41%) and 241 (59%) patients, respectively. Patients with high hsCRP were more often obese (56% vs 31%, p < 0.001), whereas the prevalence of diabetes mellitus was not significantly different (20.5% vs 28.2%, p = 0.09). In multivariable logistic regression analysis, high hsCRP was independently associated with higher body mass index (OR 1.09, 95% CI 1.04-1.15, p < 0.001), lower transferrin saturation (OR 0.97, 95% CI 0.94-1.00, p = 0.023) and increased low-density lipoprotein concentrations (OR 1.34, 95% CI 1.03-1.76, p = 0.033) (Table 1). Prognosis was worse in patients with high versus low hsCRP (99 (41.1%) vs 45 (26.3%) events, log rank p = 0.0094, Figure 1), and this association remained significant after adjustment for age, sex and comorbidities (HR 1.20, 95% CI 1.02-1.59, p = 0.031).
Conclusion
HFpEF patients with hsCRP ≥ 2 mg/L were associated with obesity, altered iron metabolism, and higher low-density lipoprotein, suggesting a distinct metabolic-inflammatory profile. These insights provide a basis for data-driven identification of patients with elevated hsCRP, who may potentially benefit from emerging anti-inflammatory therapies.Factors associated with hsCRPFor image description, please refer to the figure legend and surrounding text.hsCRP-stratified prognosisFor image description, please refer to the figure legend and surrounding text.