Systolic blood pressure is associated with abnormal alterations in brain cortical structure: Evidence from a Mendelian randomization study

Background: Hypertension has been recognized as a significant risk factor for cerebrovascular diseases and cognitive decline. However, the specific impact of hypertension, systolic/diastolic blood pressure, pulse pressure (PP) and mean arterial pressure (MAP) on brain cortical structure remains unclear. Mendelian randomization (MR) provides a robust approach to investigate the causal relationship between blood pressure components and brain cortical changes. Methods: In this MR study, data from large-scale genome-wide association studies for blood pressure components and neuroimaging were utilized to conduct our analyses. We leveraged genetic variants associated specifically with hypertension (122,620 cases and 332,683 controls), systolic (469,767 individuals), diastolic (490,469 individuals) blood pressure, PP (810,865 individuals) and MAP (over 1 million individuals) to evaluate their effects on brain cortex surficial area (51,665 individuals) and cortex thickness (51,665 individuals). Results: Our findings revealed a significant correlation between systolic blood pressure and abnormal reduction in brain cortex surficial area (beta=-1330.69, 95% confident interval [CI]: -2655.35 to -6.02, p = 0.0489); however, no significant relationship was found between systolic blood pressure and brain cortex thickness (beta=-0.0078, 95% CI: -0.0178 to 0.0022, p = 0.1287). Additionally, no significant associations were observed between hypertension (beta=-200.05, p = 0.6884; beta=-0.0051, p = 0.1179, respectively), diastolic blood pressure (beta=-460.63, p = 0.5160; beta=0.0047, p = 0.2448, respectively), PP (beta=1041.84, p = 0.3725; beta=-0.0112, p = 0.2212, respectively), MAP (beta=-18.84, p = 0.8841; beta=0.0002, p = 0.7654, respectively) and both brain cortex surficial area and brain cortex thickness. Conclusion: Our MR study provides evidence supporting the hypothesis that systolic blood pressure, rather than diastolic blood pressure, PP or MAP, is associated with abnormal changes in brain cortical structure.