Investigating the causal interplay between sleep traits and risk of acute myocardial infarction: a Mendelian randomization study.

BACKGROUND: Few studies have investigated the joint effects of sleep traits on the risk of acute myocardial infarction (AMI). No previous study has used factorial Mendelian randomization (MR) which may reduce confounding, reverse causation, and measurement error. Thus, it is prudent to study joint effects using robust methods to propose sleep-targeted interventions which lower the risk of AMI. METHODS: The causal interplay between combinations of two sleep traits (including insomnia symptoms, sleep duration, or chronotype) on the risk of AMI was investigated using factorial MR. Genetic risk scores for each sleep trait were dichotomized at their median in UK Biobank (UKBB) and the second survey of the Trøndelag Health Study (HUNT2). A combination of two sleep traits constituting 4 groups were analyzed to estimate the risk of AMI in each group using a 2×2 factorial MR design. RESULTS: In UKBB, participants with high genetic risk for both insomnia symptoms and short sleep had the highest risk of AMI (hazard ratio (HR) 1.10; 95% confidence interval (CI) 1.03, 1.18), although there was no evidence of interaction (relative excess risk due to interaction (RERI) 0.03; 95% CI -0.07, 0.12). These estimates were less precise in HUNT2 (HR 1.02; 95% CI 0.93, 1.13), possibly due to weak instruments and/or small sample size. Participants with high genetic risk for both a morning chronotype and insomnia symptoms (HR 1.09; 95% CI 1.03, 1.17) and a morning chronotype and short sleep (HR 1.11; 95% CI 1.04, 1.19) had the highest risk of AMI in UKBB, although there was no evidence of interaction (RERI 0.03; 95% CI -0.06, 0.12; and RERI 0.05; 95% CI -0.05, 0.14, respectively). Chronotype was not available in HUNT2. CONCLUSIONS: This study reveals no interaction effects between sleep traits on the risk of AMI, but all combinations of sleep traits increased the risk of AMI except those with long sleep. This indicates that the main effects of sleep traits on AMI are likely to be independent of each other.

Self-reported insomnia symptoms, sleep duration, chronotype and the risk of acute myocardial infarction (AMI): a prospective study in the UK Biobank and the HUNT Study.

Insomnia and short/long sleep duration increase the risk of AMI, but their interaction with each other or with chronotype is not well known. We investigated the prospective joint associations of any two of these sleep traits on risk of AMI. We included 302 456 and 31 091 participants without past AMI episodes from UK Biobank (UKBB; 2006-10) and the Trøndelag Health Study (HUNT2; 1995-97), respectively. A total of 6 833 and 2 540 incident AMIs were identified during an average 11.7 and 21.0 years follow-up, in UKBB and HUNT2, respectively. Compared to those who reported normal sleep duration (7-8 h) without insomnia symptoms, the Cox proportional hazard ratios (HRs) for incident AMI in UKBB among participants who reported normal, short and long sleep duration with insomnia symptoms were 1.07 (95% CI 0.99, 1.15), 1.16 (95% CI 1.07, 1.25) and 1.40 (95% CI 1.21, 1.63), respectively. The corresponding HRs in HUNT2 were 1.09 (95% CI 0.95, 1.25), 1.17 (95% CI 0.87, 1.58) and 1.02 (95% CI 0.85, 1.23). The HRs for incident AMI in UKBB among evening chronotypes were 1.19 (95% CI 1.10, 1.29) for those who had insomnia symptoms, 1.18 (95% CI 1.08, 1.29) for those with short sleep duration, and 1.21 (95% CI 1.07, 1.37) for those with long sleep duration, compared to morning chronotypes without another sleep symptom. The relative excess risk for incident AMI in UKBB due to interaction between insomnia symptoms and long sleep duration was 0.25 (95% CI 0.01, 0.48). Insomnia symptoms with long sleep duration may contribute more than just an additive effect of these sleep traits on the risk of AMI.