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

Background Sleep duration and quality has been associated with cardiovascular disease, however the effect of sleep on peripheral artery disease (PAD) specifically remains unestablished. We conducted cohort, case-control, and Mendelian randomization (MR) analyses to assess the associations of sleep duration and quality with PAD risk. Methods Sleep traits were assessed for associations with incident PAD using cohort analysis among 53,416 Swedish adults. Replicated 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 study (UKB). Two-sample Mendelian randomization (MR) was used for casual inference-based analyses of sleep-related traits and 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 Maintenance