Prognostic significance of c-reactive protein in heart failure: a report from a global federated research network
M Busti, L Monzo, T Rastogi, G Baudry, N GirerdAbstract
Objective
Systemic inflammation is a key contributor to heart failure (HF) pathophysiology, yet its prognostic relevance in established HF remains uncertain. C-reactive protein (CRP), a widely available marker of inflammation, may capture residual risk beyond conventional clinical profiling. Using a large global federated electronic health records dataset, we explored whether CRP levels are associated with clinical outcomes.
Methods
We analyzed 125,078 patients with HF and available CRP measurements from the TriNetX Global Research Network, stratified by CRP levels (0.1-2 mg/L vs. 2-10 mg/L). The primary outcome was a composite of all-cause mortality (ACM) or HF events over a maximum of 3-year follow-up. Propensity score matching was used to balance key baseline characteristics including age, sex, race, ethnicity, BMI, comorbidities, and HF medications.
Results
After matching, 39,368 patients were included in each cohort. The mean age was 69 years, 53% were men, hypertension was present in ~57% of patients, diabetes mellitus in ~30%, prior coronary artery disease in ~54% and chronic kidney disease in ~21%. After a mean follow-up of about 18 months, 9,940 composite outcomes were observed. Patients with higher CRP levels (2-10 mg/L) had a significantly increased incidence of the primary composite outcome (HR 1.41, 1.36–1.47, p<0.001) (Figure 1), when compared to propensity-matched patients with CRP<2 mg/L. Patients with higher CRP levels (2-10 mg/L) also had a significantly increased incidence of the individual components of the primary outcome (ACM: HR 1.35, 1.30–1.40, p<0.001; HF hospitalization: HR 1.41, 1.31–1.51, p<0.001) (Figure 2) when compared with propensity-matched counterpart. A graded increase in risk was evident across CRP categories (HR for CRP 2-5 mg/L: 1.23, 1.18-1.29; HR for CRP 5-10 mg/L: 1.47, 1.40-1.53 vs. CRP <2 mg/L).
Conclusion
In this real-world analysis, elevated C-reactive protein levels were associated with a higher risk of adverse outcomes in chronic HF patients, highlighting the prognostic role of systemic inflammation in this setting.Figure 1For image description, please refer to the figure legend and surrounding text.Figure 2For image description, please refer to the figure legend and surrounding text.