Physical Activity, sleep disorders and hypertension: observational and Mendelian randomization analyses

The interrelationships between physical activity (PA), sleep disorders, and hypertension remain incompletely characterised, 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 randomisation (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 personalised activity prescriptions for cardiovascular risk optimisation. Notably, no significant interaction was observed between PA and sleep disorders, suggesting that their effects on hypertension are likely independent. This study integrated observational and genetic data (Mendelian randomisation) from 18,052 adults to investigate the relationships between physical activity (PA), sleep disorders, and hypertension. Key findings demonstrate:Non-Linear PA-Hypertension Association: Analyses revealed a significant S-shaped dose-response relationship (<i>P</i>-non-linear &lt;0.001) Both insufficient and excessive PA were linked to higher hypertension risk, challenging linear assumptions.Causal Role of PA Intensity: Genetic analyses confirmed causal protective effects of light and vigorous-intensity PA on hypertension risk. Findings also indicated a need for re-evaluation of moderate-intensity PA recommendations.Sleep Disorders as an Independent Risk Factor : Sleep disorders significantly increased hypertension risk (OR = 1.61, 95% CI:1.10–2.35, <i>P</i> = 0.015) .No significant interaction with PA was found, indicating independent biological pathways. Non-Linear PA-Hypertension Association: Analyses revealed a significant S-shaped dose-response relationship (<i>P</i>-non-linear &lt;0.001) Both insufficient and excessive PA were linked to higher hypertension risk, challenging linear assumptions. Causal Role of PA Intensity: Genetic analyses confirmed causal protective effects of light and vigorous-intensity PA on hypertension risk. Findings also indicated a need for re-evaluation of moderate-intensity PA recommendations. Sleep Disorders as an Independent Risk Factor : Sleep disorders significantly increased hypertension risk (OR = 1.61, 95% CI:1.10–2.35, <i>P</i> = 0.015) .No significant interaction with PA was found, indicating independent biological pathways. In conclusion, sleep disorders are a key target for hypertension prevention alongside PA. The non-monotonic relationship underscores the need for personalised PA prescriptions. The lack of interaction suggests that sleep and PA interventions should be implemented as distinct, parallel public health strategies. Future guidelines should incorporate these findings..