Author + information
- Received March 14, 2019
- Revision received June 7, 2019
- Accepted July 2, 2019
- Published online September 2, 2019.
- Iyas Daghlas, BSa,b,
- Hassan S. Dashti, PhD, RDa,b,
- Jacqueline Lane, PhDa,b,c,
- Krishna G. Aragam, MD, MSa,b,d,
- Martin K. Rutter, MDe,f,
- Richa Saxena, PhDa,b,c and
- Céline Vetter, PhDa,g,∗ (, )@iyas_daghlas@DrCelineVetter
- aBroad Institute of MIT and Harvard, Cambridge, Massachusetts
- bCenter for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts
- cAnesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- dCardiology Division, Massachusetts General Hospital, Boston, Massachusetts
- eDivision of Endocrinology, Diabetes and Gastroenterology, Faculty of Biology, Medicine and Health, School of Medical Sciences, University of Manchester, Manchester, United Kingdom
- fManchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
- gDepartment of Integrative Physiology, University of Colorado at Boulder, Boulder, Colorado
- ↵∗Address for correspondence:
Dr. Céline Vetter, Department of Integrative Physiology, University of Colorado at Boulder, 1725 Pleasant Street, Ramaley N368, 354 UCB, Boulder, Colorado 80309-0354.
Background Observational studies suggest associations between extremes of sleep duration and myocardial infarction (MI), but the causal contribution of sleep to MI and its potential to mitigate genetic predisposition to coronary disease is unclear.
Objectives This study sought to investigate associations between sleep duration and incident MI, accounting for joint effects with other sleep traits and genetic risk of coronary artery disease, and to assess causality using Mendelian randomization (MR).
Methods In 461,347 UK Biobank (UKB) participants free of relevant cardiovascular disease, the authors estimated multivariable adjusted hazard ratios (HR) for MI (5,128 incident cases) across habitual self-reported short (<6 h) and long (>9 h) sleep duration, and examined joint effects with sleep disturbance traits and a coronary artery disease genetic risk score. The authors conducted 2-sample MR for short (24 single nucleotide polymorphisms) and continuous (71 single nucleotide polymorphisms) sleep duration with MI (n = 43,676 cases/128,199 controls), and replicated results in UKB (n = 12,111/325,421).
Results Compared with sleeping 6 to 9 h/night, short sleepers had a 20% higher multivariable-adjusted risk of incident MI (HR: 1.20; 95% confidence interval [CI]: 1.07 to 1.33), and long sleepers had a 34% higher risk (HR: 1.34; 95% CI: 1.13 to 1.58); associations were independent of other sleep traits. Healthy sleep duration mitigated MI risk even among individuals with high genetic liability (HR: 0.82; 95% CI: 0.68 to 0.998). MR was consistent with a causal effect of short sleep duration on MI in CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis plus Coronary Artery Disease Genetics Consortium) (HR: 1.19; 95% CI: 1.09 to 1.29) and UKB (HR: 1.21; 95% CI: 1.08 to 1.37).
Conclusions Prospective observational and MR analyses support short sleep duration as a potentially causal risk factor for MI. Investigation of sleep extension to prevent MI may be warranted.
- coronary artery disease
- genetic risk score
- Mendelian randomization
- myocardial infarction
- sleep duration
- UK Biobank
This work was supported by the National Institutes of Health, NIH/NIDDK grant R01DK105072 (Dr. Saxena) and R01DK107859 (Dr. Saxena), and the Phyllis and Jerome Lyle Rappaport MGH Research Scholar Award (Dr. Saxena). Dr. Rutter is supported by The University of Manchester Research Infrastructure Fund. The funders had no role in the study design; data collection; data analysis and interpretation; writing of the report; or the decision to submit for publication. Dr. Rutter has been a consultant and Advisory Board member for GlaxoSmithKline, Novo Nordisk, Roche, and Merck Sharp & Dohme; has received lecture fees from Merck Sharp & Dohme; and has received grant support from Novo Nordisk, Merck Sharp & Dohme, and GlaxoSmithKline. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received March 14, 2019.
- Revision received June 7, 2019.
- Accepted July 2, 2019.
- 2019 American College of Cardiology Foundation
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