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. 2024 Apr 30:11:1401010.
doi: 10.3389/fcvm.2024.1401010. eCollection 2024.

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

Ji Cui #  1 , Qilong Zhai #  2 , Mengjie Chen  1 , Zhu Yang  1
Affiliations

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

Ji Cui et al. Front Cardiovasc Med. .

Erratum in

Abstract

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.

Keywords: GWAS; Mendelian randomization; cardiovascular disease; intrahepatic cholestasis of pregnancy; lipid.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) The basic assumptions of MR and (B) study design. SNP, single nucleotide polymorphisms; ICP, intrahepatic cholestasis of pregnancy; IVW, inverse variance weighted; WM, weighted median; CVD, cardiovascular disease; HTN, hypertension; CAD, coronary artery disease; GWAS, genome-wide association studies; IEU, integrative epidemiology unit open GWAS project.
Figure 2
Figure 2
The principle of two-step MR analysis. SNP, single nucleotide polymorphisms; ICP, intrahepatic cholestasis of pregnancy; CVD, cardiovascular disease; HTN, hypertension; CAD, coronary artery disease.
Figure 3
Figure 3
Three causal associations between ICP and CVD, HTN and CAD. ICP, intrahepatic cholestasis of pregnancy; CVD, cardiovascular disease; HTN, hypertension; CAD, coronary artery disease.
Figure 4
Figure 4
The results of the leave-one-out analyses about ICP, CVD and HTN. ICP, intrahepatic cholestasis of pregnancy; CVD, cardiovascular disease; HTN, hypertension.
See this image and copyright information in PMC

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