The Relationship Between Physiological Risk Factors and Stroke: A Mendelian Randomization Study

Abstract Objective: Physiological risk factors play a crucial role in stroke development and prognosis. However, traditional epidemiological research methods cannot clearly establish a causal relationship between the physiological risk factors and stroke. Mendelian Randomization (MR) has recently emerged as a method of studying causal relationships. This study used a two-sample MR to explore the causal relationship between physiological risk factors and stroke. Methods: The four most commonly used MR methods were used in this analysis. All statistical analyses were performed using the "TwoSampleMR 0.5.7" package in R. The outcome variable was stroke (ischemic and hemorrhagic stroke), and the exposure factors were the five common physiological risk factors analyzed in the 2019 GBD study, including body mass index, fasting blood glucose, systolic blood pressure, LDL cholesterol, and renal dysfunction. The instrumental variables were genetic loci associated with ischemic or hemorrhagic stroke as derived from GWAS studies. Results: The results showed that there was a significant causal association between body mass index and ischemic stroke (OR = 1.21, 95% CI: 1.14~1.30, P = 3.55×10^-5), systolic blood pressure (OR = 1.61.04, 95% CI: 1.50~1.74, P = 8.26 Ö10^-36), and cholesterol (OR = 1.71, 95% CI: 1.12~2.62, P = 1.26×10^-6) with significant causal associations. There was also a significant causal association between body mass index and hemorrhagic stroke (OR = 1.45, 95% CI: 1.23~1.71, P = 1.27 × 10^-5), and systolic blood pressure (OR = 1.65, 95% CI: 1.38~1.97, P = 2.84 × 10^-8). Conclusion: Genetic variation-predicted physiological risk factor indicators, such as body mass index, systolic blood pressure, and cholesterol, were significantly associated with an increased risk of ischemic and hemorrhagic stroke and significantly increased the risk of stroke. Additionally, cholesterol is significantly associated with an increased risk of ischemic stroke but not with an increased risk of hemorrhagic stroke. Early detection and active management of body mass index, systolic blood pressure, and cholesterol are crucial for stroke prevention and prognosis and are important measures for preventing and controlling stroke. These risk factors can be effectively controlled by adjusting lifestyle and medical treatment, thereby reducing the risk of stroke.