Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.
J Neurol. 2023 May;270(5):2724-2733. doi: 10.1007/s00415-023-11604-6. Epub 2023 Feb 11.
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.
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.
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.
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.
特发性正常压力脑积水(iNPH)患者高血压和糖尿病的患病率较高。然而,这些血管危险因素对 iNPH 的因果作用尚不清楚。本研究旨在探讨血管危险因素(VRFs)与 iNPH 之间的因果关系。
我们对 iNPH 进行了孟德尔随机化(MR)分析。我们将与高血压、糖尿病、血脂、肥胖、吸烟、饮酒、运动、睡眠和心血管事件相关的 19 个血管危险因素作为暴露因素纳入分析。我们使用逆方差加权法进行因果效应估计,并使用加权中位数、最大似然和 MR Egger 回归法进行敏感性分析。
我们发现,遗传预测原发性高血压(OR=1.608(1.330-1.944),p=0.013)和增加睡眠时间(OR=16.395(5.624-47.799),p=0.009)与 iNPH 的患病风险增加相关。1 型糖尿病(OR=0.869(0.828-0.913),p=0.004)与 iNPH 的患病风险降低相关。对于其他 16 个 VRFs,没有证据表明它们与 iNPH 有显著关联。敏感性分析表明,原发性高血压和 1 型糖尿病与 iNPH 显著相关。
在我们关于 VRFs 和 iNPH 的 MR 研究中,我们发现原发性高血压是 iNPH 的一个因果危险因素。这表明高血压可能参与了 iNPH 的病理生理机制。