Evaluation of the Paradoxical Association Between Lipid Levels and Incident Atrial Fibrillation According to Statin Usage: A Nationwide Cohort Study

Objective: Higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are associated with a lower risk of atrial fibrillation (AF). Statin use might exert confounding effects on the paradoxical associations; however, the relationships that distinguish statin users from non-users have not been thoroughly evaluated. Methods: From the Korean National Health Insurance Database, we included 9,778,014 adults who underwent a health examination in 2009. The levels of TC and LDL-C at the health examination were categorized into quartile values of the total study population. We grouped the study population into statin users and non-users and investigated the associations between TC, LDL-C, and the risk of incident AF. Results: Of the total population, 867,336 (8.9%) were taking statins. During a mean follow-up of 8.2 years, inverse associations of TC – AF and LDL-C – AF were observed; higher levels of TC and LDL-C were associated with the lower risk of AF in the total population. Overall, statin users showed higher AF incidence rate than non-users, but the inverse associations of TC – AF and LDL-C – AF were consistently observed irrespective of statin usage; adjusted hazard ratio with 95% confidence interval was 0.81 (0.79–0.84) for statin users and 0.81 (0.80–0.83) for non-users in the highest TC quartile, and 0.84 (0.82–0.87) for statin users and 0.85 (0.84–0.86) for non-users in the highest LDL-C quartile (all p<0.001). Conclusion: The paradoxical relationship between lipid levels (TC and LDL-C) and the risk of AF remains consistent in both statin users and non-users.