Association between vascular risk factors and idiopathic normal pressure hydrocephalus: a Mendelian randomization study

Background and objective Patients with idiopathic normal pressure hydrocephalus (iNPH) have a higher prevalence of hypertension and diabetes. However, the causal effects of these vascular risk factors on iNPH remain unclear. This study aimed to explore the causal relationship between vascular risk factors (VRFs) and iNPH. Methods We conducted the Mendelian randomization (MR) analysis of iNPH. We included nineteen vascular risk factors related to hypertension, diabetes, lipids, obesity, smoking, alcohol consumption, exercise, sleep, and cardiovascular events as exposure factors. We used the inverse-variance weighted method for causal effect estimation and weighted median, maximum likelihood, and MR Egger regression methods for sensitivity analyses. Results We found that genetically predicting essential hypertension (OR = 1.608 (1.330–1.944), p = 0.013) and increased sleep duration (OR = 16.395 (5.624–47.799), p = 0.009) were associated with higher odds of iNPH. Type 1 diabetes (OR = 0.869 (0.828–0.913), p = 0.004) was associated with lower odds of iNPH. For the other 16 VRFs, there was no evidence that they were significantly associated with iNPH. Sensitivity analyses showed that essential hypertension and type 1 diabetes were significantly associated with iNPH. Conclusion In our MR study on VRFs and iNPH, we found essential hypertension to be a causal risk factor for iNPH. This suggests that hypertension may be involved in the pathophysiological mechanism of iNPH.