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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Reproduction
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1366023
This article is part of the Research Topic Maternal Factors and Vascular Remodelling in Pregnancy View all articles

Hypertensive disorders of pregnancy and stroke: a univariate and multivariate Mendelian randomization study

Provisionally accepted
Kang Qu Kang Qu 1Mingxi Li Mingxi Li 1Peng Yu Peng Yu 2Wei Jiang Wei Jiang 1Ming Dong Ming Dong 1*
  • 1 Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China
  • 2 Department of Ophthalmology, The second hospital of Jilin University, Changchun, Hebei Province, China

The final, formatted version of the article will be published soon.

    Background: Hypertensive disorders of pregnancy (HDP) are associated with an increased risk of stroke later in life in multiparous women. However, causality of these associations remains unclear. This study employed 2-sample univariate and multivariate Mendelian randomization (MR) to assess the causal connection between HDP and stroke.Methods: Genetic variants for HDP and two subtypes were identified from recent large-scale genome-wide association studies and the FinnGen consortium. Stroke summary data were obtained from the MEGASTROKE consortium. The primary analytical approach for univariate MR was the inverse variance weighting method. Sensitivity analyses incorporated methods such as MR-Egger regression, weighted median, and maximum likelihood to ascertain the robustness of the results. Additionally, multivariable MR analyses were conducted to account for potential associative effects of hypertension and type 2 diabetes.Results: Genetically predicted HDP was associated with a high risk of large artery atherosclerosis (odds ratio [OR]=1.50, 95% confidence interval [CI]: 1.17-1.91, P=1.13×10 - 3 ) and small vessel stroke (OR=1.29, 95% CI: 1.20-1.50, P=1.52×10 -3 ). HDP may also correlate with ischemic stroke (OR=1.13, 95% CI: 1.04-1.23, P=4.99×10 -3 ) and stroke (OR=1.11, 95% CI: 1.03-1.20, P=8. 85×10 -3 ). An elevated risk of small vessel stroke (OR=1.20, 95% CI: 1.01-1.43, P=3.74×10 -2 ) and large artery atherosclerosis (OR=1.22, 95% CI: 1.01-1.47, P=4.07×10 -2 ) may be related with genetically predicted susceptibility to gestational hypertension. Genetically predicted susceptibility to preeclampsia or eclampsia may be associated with an increased risk of stroke (OR = 1.10, 95% CI: 1.02-1.19, P = 1.16×10 -2 ) and ischemic stroke (OR = 1.10, 95% CI: 1.02-1.20, P = 1.84×10 -2 ). Type 2 2 diabetes mellitus and hypertension were identified as significant factors contributing to the association between HDP and stroke.This study provides genetic evidence supporting an association between HDP and increased stroke risk bolstering HDP as a cerebrovascular risk factor.

    Keywords: Hypertensive disorders of pregnancy, Preeclampsia, Gestational hypertension, Mendelian randomization, Stroke

    Received: 05 Jan 2024; Accepted: 07 Oct 2024.

    Copyright: © 2024 Qu, Li, Yu, Jiang and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ming Dong, Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China

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