Department of Nutrition and Food Science, College of Agriculture & Natural Resources, University of Maryland, College Park.
Maryland Psychiatric Research Center, Department of Psychiatry.
J Hypertens. 2023 Nov 1;41(11):1811-1820. doi: 10.1097/HJH.0000000000003553. Epub 2023 Sep 5.
Elevated blood pressure (BP) is a modifiable risk factor associated with cognitive impairment and cerebrovascular diseases. However, the causal effect of BP on white matter brain aging remains unclear.
In this study, we focused on N = 228 473 individuals of European ancestry who had genotype data and clinical BP measurements available (103 929 men and 124 544 women, mean age = 56.49, including 16 901 participants with neuroimaging data available) collected from UK Biobank (UKB). We first established a machine learning model to compute the outcome variable brain age gap (BAG) based on white matter microstructure integrity measured by fractional anisotropy derived from diffusion tensor imaging data. We then performed a two-sample Mendelian randomization analysis to estimate the causal effect of BP on white matter BAG in the whole population and subgroups stratified by sex and age brackets using two nonoverlapping data sets.
The hypertension group is on average 0.31 years (95% CI = 0.13-0.49; P < 0.0001) older in white matter brain age than the nonhypertension group. Women are on average 0.81 years (95% CI = 0.68-0.95; P < 0.0001) younger in white matter brain age than men. The Mendelian randomization analyses showed an overall significant positive causal effect of DBP on white matter BAG (0.37 years/10 mmHg, 95% CI 0.034-0.71, P = 0.0311). In stratified analysis, the causal effect was found most prominent among women aged 50-59 and aged 60-69.
High BP can accelerate white matter brain aging among late middle-aged women, providing insights on planning effective control of BP for women in this age group.
高血压（BP）是一种可改变的风险因素，与认知障碍和脑血管疾病有关。然而，BP 对白质脑老化的因果效应尚不清楚。
在这项研究中，我们专注于具有基因型数据和临床 BP 测量值的 228473 名欧洲血统个体（103929 名男性和 124544 名女性，平均年龄为 56.49 岁，包括 16901 名有神经影像学数据可用的参与者），这些数据来自英国生物银行（UKB）。我们首先建立了一个机器学习模型，基于从扩散张量成像数据中得出的分数各向异性来计算白质微观结构完整性的结果变量脑龄差距（BAG）。然后，我们使用两个不重叠的数据集，在整个人群和按性别和年龄组分层的亚组中，进行两样本孟德尔随机化分析，以估计 BP 对白质 BAG 的因果效应。
高血压组的白质脑龄比非高血压组平均大 0.31 岁（95%CI=0.13-0.49；P<0.0001）。女性的白质脑龄比男性平均年轻 0.81 岁（95%CI=0.68-0.95；P<0.0001）。孟德尔随机化分析显示，DBP 对白质 BAG 有总体显著的正向因果效应（0.37 岁/10mmHg，95%CI 0.034-0.71，P=0.0311）。在分层分析中，这种因果效应在 50-59 岁和 60-69 岁的女性中最为明显。
高血压会加速中老年女性的白质脑老化，为这一年龄段女性有效控制血压提供了新的思路。
