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The association between short sleep duration and subsequent incident peripheral artery disease (PAD) was clarified and supported by complementary analyses of various large cohorts.

Based on a group of 50,000 Swedish adults, excess PAD risk was more likely in people sleeping less than 5 hours a day or 8 hours or more, a U-shaped relationship that was replicated in Million Veteran Program and U.K. Biobank participants, according to Susanna Larsson, PhD, an epidemiologist at the Karolinska Institutet in Stockholm, and colleagues.

However, only short sleep duration was tied to excess PAD risk upon Mendelian randomization (MR) analysis -- designed to minimize residual confounding and reverse causality by using genetic variants as instrumental variables to estimate potential causal effects -- favoring a linear, inverse association between sleep duration and PAD (OR 0.79 per hour increase, 95% CI 0.55-0.89), Larsson's group reported in .

"Reverse causality, whereby PAD-related pain leads to poor sleep quality but increased time in bed, might explain the discordant results of the observational and MR analyses. Our reverse MR analysis provides support for such a bidirectional relationship, where increased liability to PAD leads to shorter actigraphy-assessed sleep duration," the investigators wrote.

"These results provide consistent support for short sleep duration as a harmful risk factor for PAD and highlight the possibility of reverse causality leading to distorted effects in observational analyses of sleep and PAD," they added.

For clinical practice, the implication is that interventions to improve sleep may prevent or treat PAD, and interventions to treat PAD may improve sleep, Larsson and team said.

These findings "are consistent with prior studies that have suggested sleep duration (and poor sleep quality) are associated with risk of heart disease and stroke. Many lines of evidence support the value of a good night of uninterrupted sleep to cardiovascular health," commented Deepak Bhatt, MD, MPH, of the Icahn School of Medicine at Mount Sinai in New York City, who was not involved with the study.

Strengthening evidence for the links between sleep and cardiovascular health has led the American Heart Association to incorporate sleep as a key component of "Life's Essential 8," its checklist of cardiometabolic health. This document gives adults full points in the sleep category for sleeping 7-9 hours daily, though it acknowledges that the evidence is evolving.

For this study, Larsson and colleagues utilized complementary study designs.

Sleep traits were assessed for associations with PAD using a cohort analysis of 53,416 Swedish adults, and replication was sought in a cohort of 452,028 individuals from the U.K. Biobank study and a case-control study of 28,123 PAD cases and 128,459 controls from the Veterans Affairs Million Veteran Program.

Two-sample MR analysis was performed according to sleep-related genetic traits in 31,307 PAD cases and 211,753 controls.

Although the observational cohorts suggested a positive association between daytime napping and increased risk of PAD, this was not verified by MR, Larsson and team noted.

Objective polysomnography studies should be conducted to confirm the study's findings, they said.

They acknowledged the potential for bias and errors in their study due to a reliance on data collected from self-administrated questionnaires completed just once at participant enrollment. They also lacked medication data and were therefore unable to adjust for related confounding in their observational analyses.

Moreover, the results may not be generalizable to younger, diverse individuals, as the cohort analyses largely included middle-age and older people of European ancestry.

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