Sleep duration and coronary disease: prospective observational and Mendelian randomization analyses in over 0.6M individuals

Research output: Contribution to journalArticle

  • External authors:
  • Iyas Daghlas
  • Hassan S. Dashti
  • Jacqueline Lane
  • Krishna G. Aragam
  • Richa Saxena
  • Celine Vetter

Abstract

Background— Observational studies suggest associations between extremes of sleep duration and coronary artery disease (CAD), but the causal contribution of sleep to CAD and its potential to mitigate genetic predisposition to CAD is unclear. Objectives— To investigate associations between sleep duration and incident myocardial infarction (MI), accounting for joint effects with other sleep traits and genetic risk of coronary artery disease (CAD), and to assess causality using mendelian randomization (MR). Methods— In 461,347 UK Biobank (UKB) participants free of relevant cardiovascular disease, we estimated multivariable adjusted hazard ratios (HR) for MI (5,128 incident cases) across habitual self-reported short (<6h) and long (>9h) sleep duration, and examined joint effects with sleep disturbance traits and a CAD genetic risk score. We conducted MR for continuous (78 SNPs) and short (27 SNPs) sleep duration with CAD in UKB (n=17,157 cases/320,375 controls) and replicated results in the CARDIoGRAMplusC4D cohort (60,801/123,504). Results—Compared to sleeping 6-9 hours/night, short sleepers had a 20% higher multivariable-adjusted risk of incident MI (HR=1.20, 95% confidence interval 1.07-1.33), and long sleepers had a 34% higher risk (1.34, 1.13-1.58); associations were independent of other sleep dimensions. Healthy sleep duration mitigated MI risk even amongst individuals with high genetic liability (0.82, 0.68-0.998). MR was consistent with a causal effect of short sleep duration on CAD (OR<7h 1.24, 1.11-1.38) and MI (1.19, 1.09-1.29). Conclusions— Prospective observational and MR analyses support short sleep duration as a potentially causal risk factor for coronary disease. Investigation of sleep extension to prevent coronary disease may be warranted.

Bibliographical metadata

Original languageEnglish
JournalJournal of the American College of Cardiology
Publication statusAccepted/In press - 2 Jul 2019