| Title: | Cholesterol profiles and cholesterol-lowering medication in relation to the incidence of atrial fibrillation |
| Journal: | Heart Rhythm |
| Published: | 17 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41260453/ |
| DOI: | https://doi.org/10.1016/j.hrthm.2025.11.021 |
Publication 18913
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Abstract
BACKGROUND: Epidemiologic studies have suggested inverse associations between cholesterol levels and the risk of atrial fibrillation (AF).</p>
OBJECTIVE: This study aimed to investigate the associations of comprehensive cholesterol profiles, particle numbers, apolipoproteins, and cholesterol-lowering medication with AF incidence.</p>
METHODS: In 187,680 UK Biobank participants without baseline cardiovascular disease, lipoprotein cholesterol, and particle concentrations were quantified by nuclear magnetic resonance spectroscopy. Cox and Fine-Gray competing risk models with restricted cubic spline analyses evaluated associations and dose-response relationships. A separate cohort of 394,718 participants was analyzed to assess cholesterol-lowering medication use and AF incidence.</p>
RESULTS: Most cholesterol measures, including total, low-density lipoprotein, intermediate-density lipoprotein, very-low-density lipoprotein, remnant, and triglyceride-rich lipoprotein remnant cholesterol, were inversely associated with AF, whereas high-density lipoprotein cholesterol (HDL-C) showed a positive association. Small HDL-C was associated with lower AF risk, whereas large and very large HDL-C showed the opposite. Restricted cubic spline models suggested generally linear associations. Particle number analyses yielded consistent, size-dependent patterns, with small HDL particles showing inverse and large HDL particles showing positive associations. Adjustment for apolipoproteins revealed distinct cholesterol cargo conditional effects: low-density lipoprotein cholesterol and intermediate-density lipoprotein cholesterol associations were attenuated or reversed, whereas HDL-related associations persisted. Lecithin-cholesterol acyltransferase correlated with higher small HDL-C vs lower large HDL-C, in line with their respective associations with AF. The use of cholesterol-lowering medication, mainly representing statins, was modestly associated with a higher incidence of AF.</p>
CONCLUSION: Cholesterol and lipoprotein subfractions were heterogeneously associated with AF risk, potentially reflecting the biological effects of the distribution of different lipoprotein carriers and their cholesterol cargo, whereas cholesterol-lowering medication was linked to higher AF incidence.</p>
5 Authors
- Hongxuan Xu
- Bingxun Li
- Lifan Zhang
- Lei Ding
- Panhui Tian
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