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Although the association between sleep behavior and morbidity and mortality risk has been reported before, there is still uncertainty whether the observed associations are causal or confounding. Therefore, we investigated the causal relationships between sleep-behavioral traits and terminated healthspan risk using Mendelian randomization (MR). We conducted a one-sample MR analysis to evaluate causality between six sleep-behavioral traits (sleep duration, chronotype/morningness, napping, sleeplessness/insomnia, and getting up from bed) and risk of healthspan termination among 388, 909 UK Biobank (UKB) participants. Instrumental variables for sleep behaviors (N = 590) were obtained from recent genome-wide association studies (GWAS). We defined healthspan based on eight predominant health-terminating events associated with longevity (congestive heart failure, myocardial infarction, chronic obstructive pulmonary disease, stroke, dementia, diabetes, cancer, and death). We further constructed a sleep score and a weighted genetic risk score to increase the predictive ability of the sleep-behavioral traits. Cox regression models and Inverse Probability Treatment Weighting (IPTW) were implemented, followed by MR to assess causation. We used inverse-variance-weighted MR to estimate causal effects, and weighted-median and MR-egger for sensitivity analysis to test the pleiotropic effects. In IPTW, we observed a decreased risk of terminated healthspan for healthy sleep behaviors such as 'sleep duration 7-8h/d' (Hazard ratio, HR = 0.93; 95 % confidence interval, CI: 0.92–0.96; P < 0.001); 'morningness' (HR = 0.95; 95%CI: 0.93–0.98; P < 0.01); 'napping' (HR = 0.93; 95%CI: 0.91–0.94; P < 0.001); 'easy getting up from bed' (HR = 0.91; 95%CI: 0.88–0.93; P < 0.001); and, 'never/rarely experience sleeplessness/insomnia' (HR = 0.94; 95%CI: 0.92–0.96; P < 0.001). MR results further indicated causal associations between healthy sleep duration (OR = 0.98; 95%CI: 0.97–1.00; P = 0.036) and insomnia (OR = 1.02; 95%CI: 1.01–1.03; P < 0.001) with terminated healthspan. MR-egger did not suggest any potential pleiotropy. This study supports abnormal sleep duration and insomnia as potential causal risk factors for terminated healthspan. Thus, healthy sleep behavior is valuable for the extension of healthspan, and well-designed and tailored sleep health interventions are warranted. [ABSTRACT FROM AUTHOR]

Lack of physical activity (PA) and sarcopenia is a known risk factors for ischemic heart disease (IHD). However, considering their coexistence in the middle-aged and elderly population, the interaction of these two factors remains uncertain. Here, we investigated the interactive effects of PA and sarcopenia on IHD. We extracted 344,688 participants free of IHD at baseline from the UK Biobank. PA was classified into low, moderate, and high according to the International Physical Activity Questionnaire. Sarcopenia was identified in accordance with the European Working Group on Sarcopenia in Older People 2. Cox proportional hazard models were applied to estimate the effect of PA and sarcopenia on incident IHD and its subtypes. We also used objective PA data measured by wrist-worn devices to repeat these analyses. Over a median follow-up of 11.7 years, 24,809 (7.2%) participants developed incident IHD. Lack of PA was associated with a higher risk of IHD after adjusting for potential confounders. The hazard ratio (HR) was 1.09 (95% CI: 1.05–1.13) for individuals without sarcopenia and 1.29 (95% CI: 1.17–1.42) for those with sarcopenia. Regarding the joint effect, the combination of low PA and sarcopenia was associated with the highest risk of IHD, with an HR of 1.54 (95% CI: 1.44–1.66), and both additive and multiplicative interactions were significant (RERI 0.27, 95% CI: 0.14–0.39, p -interaction <0.01). For subtypes of IHD, the interaction was pronounced in acute myocardial infarction and chronic ischemic heart disease. These results suggest a synergistic interaction between lack of PA and sarcopenia on the risk of IHD. Findings from this study may help facilitate more effective primary prevention of IHD. [Display omitted] • Lack of physical activity (PA) and sarcopenia have synergistic interaction on ischemic heart disease (IHD). • The synergistic interaction is also found in subtypes of IHD. • Moderate volume of PA can provide beneficial protective effects. • Protective effects may only be achieved with moderate to high-intensity PA. [ABSTRACT FROM AUTHOR]