Lipids and atrial fibrillation: New insights into a paradox

Although the prevalence of cardiovascular comorbidities and associated risk factors such as diabetes mellitus, chronic kidney disease, and obesity increase with age, lipid levels may go through several changes over the course of a lifetime, associated with sex, ethnicity, and metabolic profile [1].The association between lipid levels and atherosclerotic disease is well established [2], but the association between lipid levels and incidence of atrial fibrillation (AF) has not been fully elucidated.Despite the association between high lipoprotein levels and the increased risk of atherosclerosis and coronary artery disease (CAD), which, in turn, may lead to an increased risk of AF [3], several studies have suggested that high levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) are associated with a lower risk of AF [4].The clinical significance and pathophysiological mechanisms of this paradoxical inverse association between lipid levels and AF risk remain unclear [4].In an accompanying study in PLOS Medicine, Mozhu Ding and colleagues conducted a large population-based study of >65,000 adults aged 45 to 60 years without any history of cardiovascular disease, using data from the Swedish National Patient Register and Cause of Death Register [5].Using International Classification of Diseases (ICD) codes from discharge diagnoses of hospital visits and causes of death captured in these registries, participants were followed up for up to 35 years for incident AF.Higher levels of TC and LDL-C were associated with lower risk of AF within the first 5 years (hazard ratios [HRs]: 0.61, 95% confidence intervals [CIs]: 0.41 to -0.99; HR: 0.64, 95% CI: 0.45 to 0.92), but the effect was attenuated after 5 years of follow-up.Conversely, lower levels of HDL-C, high triglyceride (TGAU : PleasenotethatTGhasb ) levels and high TG/HDL-C ratio were consistently associated with a higher risk of AF over 3 decades of follow-up (HRs ranging from 1.13 [95% CI: 1.07 to 1.19, p < 0.001] to 1.53 [95% CI: 1.12 to 2.00]).Previous longitudinal studies have demonstrated that levels of the majority of lipoproteins increase significantly between the ages of 20 to 50 years before plateauing in older age; this pattern is observed mainly in men, while in women, increasing lipoproteins are associated with menopause [6].These early findings were recently confirmed in a cross-sectional study in a Chinese population, in which TC and LDL-C were found to plateau between the ages of 40 and 60 in men and 60 years of age in women, before declining markedly [7].Considering the inverse association of TC and LDL-C with aging, and the association between aging and higher prevalence of AF, this may partially explain the inverse association of TC and LDL-C with AF.