Exploring the causal effects of physical activity, diet, and nutrition on hypertension and hyperlipidemia: a multivariable Mendelian randomization analysis

Abstract

Background and aim: Hypertension and hyperlipidaemia are major risk factors for cardiovascular diseases, contributing to significant morbidity and mortality worldwide. Lifestyle interventions, including modifications in diet, nutrition, and physical activity, are commonly recommended, but their causal effects on these conditions remain uncertain. This study aims to explore the causal effects of these factors on hypertension and hyperlipidaemia using multivariate Mendelian randomisation analysis, providing insights for effective cardiovascular prevention strategies. Methods and results: Genetic data related to physical activity, diet, and nutrition were obtained from public databases and analyzed using multivariate Mendelian randomisation. The analysis employed MR Egger, weighted median, and inverse variance weighting (IVW) methods, with tests for heterogeneity and multiplicity ensuring the reliability of the results. In the hypertension analysis, low-calorie diets showed a positive association in weighted median and IVW analyses, with weighted median analysis showing an association of 1.122 (95% CI: 1.014-1.243, P = 0.026) and IVW analysis showing an association of 1.095 (95% CI: 1.013-1.184, P = 0.023). However, MR Egger's analysis showed no significant association (association of 0.688, 95% CI: 0.411-1.155, P = 0.230). Calcium supplements and dietary fibre did not demonstrate significant associations across all methods. Physical activity also did not show significant causal links with hypertension. Regarding hyperlipidaemia, calcium supplements exhibited significant effects across all methods, though with notable variation, while dietary fibre and physical activity showed no significant impacts. Conclusions: The study suggests a positive association between low-calorie diets and hypertension, as indicated by significant results from weighted median and IVW analyses. Other dietary factors, physical activity, and calcium supplementation exhibited varied or non-significant effects on hypertension and hyperlipidaemia. These findings highlight the need for further research to understand the underlying mechanisms and support the development of effective public health interventions.