Measured and genetic LDL-C and the risk of incident atrial fibrillation

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: None. BACKGROUND: Preventive therapy for atrial fibrillation (AF) is lacking, and association between hyperlipidemia and incident atrial fibrillation has been reported. We examined whether measured and genetically predicted low density lipoprotein cholesterol (LDL-C) can detect incident atrial fibrillation (AF) independent of clinical risk for AF. METHODS: A total of 339,023 individuals aged 39 to 73 without pre-existing ASCVD (coronary artery disease, ischemic stroke or transient ischemic attack, peripheral artery occlusive disease) and AF were included from the UK biobank. Clinical risk for AF was based on tertiles of CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology- Atrial Fibrillation) score. We calculated the risk of incident AF per SD increase in measured and genetic LDL, and its association with CHARGE-AF. RESULTS: Over a median 11.9 (11.2-12.6) years, the primary outcome occurred in 17,504 patients. Among those with low, moderate, and high CHARGE-AF, each SD increase in measured LDL-C was associated with hazard ratio of 1.09 (95% CI 0.85-1.38, p=0.502), 1.32 (95% CI 1.13-1.54, p<0.001), and 1.23 (95% CI 1.12-1.37, p<0.001). Among these same categories, each SD increase in genetic LDL-C was associated with hazard ratios of 1.10 (95% CI 1.04-1.16, p<0.001), 1.07 (95% CI 1.03-1.11, p<0.001), and 1.05 (95% CI 1.03-1.07, p<0.001). Among those with normal LDL, untreated hyperlipidemia, and treated hyperlipidemia, each SD increase in genetic LDL-C was associated with hazard ratios of 1.11 (95% CI 1.04-1.18, p=0.001), 1.07 (95% CI 1.05-1.09, p<0.001), and 1.02 (0.99-1.05, p=0.25). CONCLUSION: LDL cholesterol polygenic risk score may augment identification of individuals at heightened AF risk, including those with low CHARGE-AF or normal LDL-C. Whether it may also guide antilipidemic initiation or intensification requires further study. [Figure: see text]