DOI: 10.6084/m9.figshare.30272547.v1
title: Physical Activity, Sleep Disorders and Hypertension: Observational and Mendelian Randomization Analyses

description: The interrelationships between physical activity (PA), sleep disorders, and hypertension remain incompletely characterized, particularly regarding potential interactions between PA and sleep disorders on hypertension risk. This study aimed to investigate these associations using complementary epidemiological approaches. We conducted a population-based observational analysis of 18,052 adults aged ≥18 years using data from the National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey (2005-2018). Weighted multivariate logistic regression models were used to examine the associations between PA, sleep disorders, and hypertension, as well as the interaction effect of PA and sleep disorders on hypertension. Additionally, we performed a two-sample Mendelian randomization (MR) analysis was conducted to assess the causal relationship between PA, sleep disorders, and hypertension. The analysis of observational data shows that sleep disorders are significantly associated with a higher risk of hypertension, with an odds ratio (OR) of 1.61 (95% CI: 1.10–2.35, <i>P</i> = 0.015). Restricted Cubic Spline (RCS) analysis revealed an S-shaped dose-response relationship between PA and hypertension (P-non-linear &lt; 0.001). The MR analysis results were consistent with these findings. Convergent evidence from observational and genetic analyses identified sleep disorders as an independent risk factor for hypertension. The non-monotonic S-shaped association between PA and hypertension underscored the importance of personalized activity prescriptions for cardiovascular risk optimization. Notably, no significant interaction was observed between PA and sleep disorders, suggesting that their effects on hypertension are likely independent. This study integrated observational epidemiology and genetic causal inference (Mendelian randomization) to elucidate the relationships between physical activity (PA), sleep disorders, and hypertension in 18,052 adults. Key findings demonstrate: 1.Non-Linear PA-Hypertension Association: Restricted cubic splines revealed a significant S-shaped dose-response relationship (<i>P</i>-non-linear &lt;0.001) between PA levels and hypertension risk. Both insufficient and excessive PA were associated with elevated hypertension risk, challenging conventional linear dose-response assumptions. 2.Causal Role of PA Intensity: Mendelian randomization analyses confirmed causal protective effects of both light and vigorous-intensity PA on hypertension risk. Findings also indicated a need for re-evaluation of moderate-intensity PA recommendations. 3.Sleep Disorders as an Independent Risk Factor Without Interaction with PA: Sleep disorders were significantly associated with increased hypertension risk (OR = 1.61, 95% CI:1.10–2.35, <i>P</i> = 0.015) and no significant interaction was found between PA and sleep disorders, indicating that they influence hypertension through independent biological pathways rather than synergistic effects. Conclusions and Implications: Convergent evidence identifies sleep disorders as a target for hypertension prevention alongside PA. The non-monotonic PA-hypertension relationship underscores the necessity for personalized PA prescriptions based on individual risk thresholds. The lack of interaction suggests that sleep and PA interventions should be addressed as distinct, parallel strategies in public health initiatives. Future clinical guidelines require refinement to incorporate these findings, and intervention trials are warranted to establish optimal PA thresholds and evaluate combined PA-sleep interventions for hypertension control.