Paradoxical association between lipid levels and incident atrial fibrillation according to statin usage

In epidemiology studies, a higher level of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) is associated with a lower risk of atrial fibrillation (AF). Statin use might exert possible confounding effects in the paradoxical relationship; however, the inverse link between AF and cholesterol level that distinguishes statin users from non-users has not been evaluated.

We investigated the epidemiological relationships of TC–AF and LDL-C–AF in statin users and non-users, respectively.

From the Korean National Health Insurance Service database, we included 9,778,014 adults who underwent a health examination in 2009 and had no prior AF history. The levels of TC and LCL-C at the health exam were categorized in quartile (Q) and decile (D) values of the total study population. The study population was grouped into statin users and non-users, and TC–AF and LDL-C–AF relationships were evaluated.

867,336 (8.9%) were on statin use among the total population. Statin users showed higher TC level (208.4±55.6 vs. 194.1±39.5 mg/dL, p<0.001) and LDL-C level (123.0±102.2 vs. 121.3±226.3, p<0.001) compared to non-users. Inverse associations of TC–AF and LCL-C–AF were observed; higher levels of TC and LDL-C were associated with a lower risk of AF. The hazard ratios (HR) and 95% confidence intervals (CI) were 0.797 (0.786–0.809) for the highest quartile of TC (Q4, TC ≥218) and 0.832 (0.82–0.843) for the highest quartile of LDL-C (Q4, LDL-C ≥135) when adjusted by age, sex, lifestyle behaviors, comorbidities, and low-income status. Statin users exhibited higher AF incidence rate than non-statin users, but the association in statin users generally tracked that seen among non-statin users demonstrating similar HR in Q4 of TC [0.812 (0.790–0.835) for statin users and 0.812 (0.798–0.826) for non-statin users] and LDL-C [0.842 (0.819–0.865) for statin users and 0.849 (0.835–0.863) for non-statin users].

The paradoxical relationship between lipid levels (TC and LDL-C) and incident AF remained consistent both in statin users and non-users. Further research is required to investigate an underlying mechanism for the cholesterol paradox of AF which still seems evident despite the pleiotropic effects of statin.

Type of funding sources: None.