Inflammation and heart failure risk in atrial fibrillation: Prospective evidence from UK Biobank

Although atrial fibrillation (AF) raises heart failure (HF) risk and inflammation is associated with cardiovascular disease, the role of inflammation in linking AF to HF remains unclear.

This study aimed to assess whether systemic inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), elevates HF risk in patients with AF.

This prospective study included 32,502 AF participants from the UK Biobank without baseline HF, significant mitral valve disease, or inflammatory conditions. Hs-CRP was analyzed both as quartiles and using a clinical cutoff value of ≥2 mg/dL. The association with incident HF was evaluated using Cox models and Fine-Gray regression. Sensitivity analyses included sequential exclusion of comorbidities and early events, as well as propensity score matching.

Over a median follow-up of 13.3 years, 6805 incident HF cases were documented. The cumulative incidence of HF increased significantly across hs-CRP quartiles, from 16.5% (1386 of 8419) in quartile 1 to 26.9% (2096 of 7786) in quartile 4 (log-rank P < .001). In fully adjusted models, quartile 4 had 61% higher HF risk than quartile 1 (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.51-1.73). Elevated hs-CRP (≥2 mg/dL) (HR 1.39; 95% CI 1.33-1.46) and per-standard-deviation increase (HR 1.12; 95% CI 1.10-1.15) were consistently associated with higher HF risk. These findings remained robust across all sensitivity analyses, subgroup comparisons, propensity score matching cohorts, and competing risk models.

Elevated hs-CRP is an independent predictor of increased HF risk in patients with AF, supporting its potential role in improving HF risk stratification.