Low-density lipoprotein cholesterol levels and in-hospital bleeding in patients with atrial fibrillation: findings from CCC-AF project

Front Cardiovasc Med. 2025 Jun 12:12:1574796. doi: 10.3389/fcvm.2025.1574796. eCollection 2025.

Abstract

Background and aims: Emerging evidence indicates a relationship between low-density lipoprotein cholesterol (LDL-C) levels and bleeding. However, data regarding the relationship between LDL-C levels and bleeding events in patients with atrial fibrillation (AF) remain unfilled. This study is aimed to examine the relationship between LDL-C levels and the risk of in-hospital bleeding in patients with AF.

Methods and results: In this multi-centered observational study, 25,380 patients with AF were enrolled; 14,071 (55.4%) and 11 309 (44.6%) were men and women, respectively, and the mean age was 69.51 ± 11.88 years. After adjusting for covariates, with LDL-C ≥ 70 mg/dl as the reference, LDL-C < 70 mg/dl was associated with a higher risk of any bleeding event [adjusted odds ratio [aOR]: 1.63, 95% confidence interval [CI]: 1.12-2.35; P = 0.009], major bleeding events (aOR: 1.48, 95% CI: 0.99-2.20; P = 0.05), and gastrointestinal bleeding events (aOR: 2.11, 95% CI: 1.27-3.50; P = 0.004) in the multivariate logistic regression model. The restricted cubic spline model showed an L-shaped relationship for bleeding events, with a higher risk at lower LDL-C levels. The nonlinear relationship between LDL-C levels and the risk of bleeding persisted among the subgroups.

Conclusions: This nationwide and multi-centered AF registry study found an L-shaped relationship between LDL-C levels at admission and in-hospital bleeding events, with a greater risk at lower LDL-C levels. Further studies are needed to establish LDL-C as a factor for risk stratification and management of bleeding events in patients with AF.

Clinical trial registration: [http://www.clinicaltrials.gov], identifier [NCT02309398].

Keywords: CCC-AF project; atrial fibrillation; bleeding risk; low-density lipoprotein cholesterol; nonlinear relationship.

Associated data

  • ClinicalTrials.gov/NCT02309398