Genetically predicted lipids mediate the association between intrahepatic cholestasis of pregnancy and cardiovascular disease

作者全名：Cui, Ji; Zhai, Qilong; Chen, Mengjie; Yang, Zhu

作者地址：[Cui, Ji; Chen, Mengjie; Yang, Zhu] Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Chongqing, Peoples R China; [Zhai, Qilong] Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing, Peoples R China

通信作者：Chen, MJ; Yang, Z (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Chongqing, Peoples R China.

来源：FRONTIERS IN CARDIOVASCULAR MEDICINE

ESI学科分类：　

WOS号：WOS:001220523900001

JCR分区：Q2

影响因子：2.8

年份：2024

卷号：11

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：intrahepatic cholestasis of pregnancy; lipid; cardiovascular disease; Mendelian randomization; GWAS

摘要：Introduction Intrahepatic cholestasis of pregnancy (ICP), the most prevalent liver disorder specific to pregnancy, affects approximately 1.5%-4% of pregnancies. However, the influence of ICP on cardiovascular disease (CVD), including hypertension (HTN) and coronary artery disease (CAD), has not been thoroughly investigated.Methods This study explores the causal relationship between ICP and CVD (HTN, CAD) using Mendelian Randomization (MR). Utilizing summary-level data from Genome-Wide Association Studies (GWAS), we applied the inverse-variance weighted (IVW) method, supplemented by sensitivity and reverse MR analyses, to ascertain robustness.Results Our findings reveal significant causal links, indicating ICP notably increases the risk of CVD (P = 0.001), hypertension (HTN, P = 0.024), and coronary artery disease (CAD, P = 0.039). A two-step MR analysis highlighted the mediation role of lipid profiles, with LDL, TC, and Apo-B contributing to increased CVD risk by 25.5%, 12.2%, and 21.3%, respectively. Additionally, HTN was identified as a mediator in the ICP-CAD association, accounting for a 14.5% mediation effect.Discussion The results underscore the genetic predisposition of ICP to elevate CVD risk and the critical mediating role of lipid levels, emphasizing the need for vigilant lipid monitoring and early intervention in individuals with ICP.

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