Abstract 11460: Sleep Duration, Quality, and Risk of Peripheral Artery Disease: Multinational Cohort and Mendelian Randomization Studies

Introduction: Sleep duration and quality have been linked to atherosclerosis, however the effects on peripheral artery disease (PAD) specifically have not been well characterized. We conducted cohort, case-control, and Mendelian randomization analyses across three large multinational samples (Sweden, United Kingdom, United States) to evaluate associations between sleep traits and risk of PAD. Hypothesis: Abnormal sleep duration and poor sleep quality are associated with increased risk of PAD. Methods: Sleep traits (including duration, subjective quality, daytime napping, snoring, apnea, and insomnia) were assessed for associations with incident PAD using Cox proportional hazards regression within a cohort of 53,416 Swedish adults. Replication was sought in a case-control study of 28,123 PAD cases and 128,459 controls from the VA Million Veteran Program (MVP) and a cohort study of 452,028 individuals from the UK Biobank (UKB). Two-sample Mendelian randomization (MR) was used to estimate causal effects of sleep-related traits on PAD (31,307 PAD cases 211,753 controls). Results: Observational analyses demonstrated a U-shaped association between sleep duration and PAD risk. In Swedish adults, incident PAD risk was higher in those with short sleep (<5 hours; hazard ratio (HR) 1.74; 95% confidence interval (CI) 1.31-2.31) or long sleep (≥8 hours; HR 1.24; 95% CI 1.08-1.43), compared to individuals with a sleep duration of 7 to <8 hours/night. This finding was supported by case-control analysis in MVP and cohort analysis in UKB. Observational analysis also revealed positive associations between poor sleep quality (HR 1.81; 95% CI 1.13-2.90) and daytime napping (HR 1.32; 95% CI 1.18-1.49) with PAD. MR analysis supported an inverse association between sleep duration (odds ratio per hour increase, 0.79, 95% CI, 0.55, 0.89) and PAD, and an association between short sleep and increased PAD (odds ratio, 1.20, 95% CI, 1.04-1.38). MR also found an association between insomnia with PAD (OR 1.10; 95% CI 1.05-1.15) and a reverse association of PAD on shorter sleep (OR 1.05; 95% CI 1.01-1.10). Conclusions: Short sleep duration and measures of poor sleep quality may be causal risk factors for PAD. Maintenance of healthy sleep habits may help prevent PAD.