Persistent C-reactive protein elevation and incident heart failure in adults at increased cardiovascular risk: A multinational electronic health record study.

BACKGROUND: Systemic inflammation has been associated with heart failure (HF) development. C-reactive protein (CRP) is a sensitive marker of inflammation, but its prognostic association with incident HF remains incompletely defined. We explored whether persistent CRP elevation was associated with incident HF among adults at increased cardiovascular (CV) risk. METHODS: We identified 64,743 adults aged 40-80 years from the TriNetX Global Research Network with available body mass index, at least two cardiovascular risk factors, and at least two consecutive CRP measurements within the same predefined range. Participants were categorized as having low (0.1-3.0 mg/L) or elevated CRP (3.1-10.0 mg/L). The primary outcome was incident HF over a maximum follow-up of 10 years. Propensity-score matching was used to balance key baseline characteristics (including CV risk factors). RESULTS: After matching, each group included 19,547 participants. Elevated CRP was associated with higher risks of incident HF (overall: HR 1.34 [95% CI 1.22-1.48]), all-cause mortality (HR 1.90 [95% CI, 1.67-2.17]), and their composite (HR 1.49 [95% CI 1.37-1.62]). In exploratory phenotype-specific analyses, directionally consistent associations were observed for code-defined HFrEF (HR, 1.53; 95% CI, 1.30-1.80) and HFpEF (HR, 1.44; 95% CI, 1.24-1.66). Exploratory subgroup analyses suggested a stronger association among participants without obesity (P for heterogeneity =0.004). CONCLUSIONS: In this selected cohort of adults at increased CV risk, persistent CRP elevation was associated with higher risk of incident HF and all-cause mortality. These findings may suggest the prognostic relevance of elevated CRP and warrant further study of inflammation in HF development.