Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease

医学 孟德尔随机化 子痫前期 内科学 混淆 疾病 优势比 全基因组关联研究 冲程(发动机) 冠状动脉疾病 怀孕 遗传关联 子痫 妊娠高血压 心脏病学 产科 单核苷酸多态性 遗传学 基因型 生物 基因 遗传变异 机械工程 工程类
作者
Bilal Rayes,Maddalena Ardissino,Eric A. W. Slob,Kinesh Patel,Joanna Girling,Fu Siong Ng
出处
期刊:JAMA network open [American Medical Association]
卷期号:6 (2): e230034-e230034 被引量:19
标识
DOI:10.1001/jamanetworkopen.2023.0034
摘要

Importance Hypertensive disorders in pregnancy (HDPs) are major causes of maternal and fetal morbidity and are observationally associated with future maternal risk of cardiovascular disease. However, observational results may be subject to residual confounding and bias. Objective To investigate the association of HDPs with multiple cardiovascular diseases. Design, Setting, and Participants A genome-wide genetic association study using mendelian randomization (MR) was performed from February 16 to March 4, 2022. Primary analysis was conducted using inverse-variance-weighted MR. Mediation analyses were performed using a multivariable MR framework. All studies included patients predominantly of European ancestry. Female-specific summary-level data from FinnGen (sixth release). Exposures Uncorrelated ( r 2 <0.001) single-nucleotide variants (SNVs) were selected as instrumental variants from the FinnGen consortium summary statistics for exposures of any HDP, gestational hypertension, and preeclampsia or eclampsia. Main Outcomes and Measures Genetic association estimates for outcomes were extracted from genome-wide association studies of 122 733 cases for coronary artery disease, 34 217 cases for ischemic stroke, 47 309 cases for heart failure, and 60 620 cases for atrial fibrillation. Results Genetically predicted HDPs were associated with a higher risk of coronary artery disease (odds ratio [OR], 1.24; 95% CI, 1.08-1.43; P = .002); this association was evident for both gestational hypertension (OR, 1.08; 95% CI, 1.00-1.17; P = .04) and preeclampsia/eclampsia (OR, 1.06; 95% CI, 1.01-1.12; P = .03). Genetically predicted HDPs were also associated with a higher risk of ischemic stroke (OR, 1.27; 95% CI, 1.12-1.44; P = 2.87 × 10 −4 ). Mediation analysis revealed a partial attenuation of the effect of HDPs on coronary artery disease after adjustment for systolic blood pressure (total effect OR, 1.24; direct effect OR, 1.10; 95% CI, 1.02-1.08; P = .02) and type 2 diabetes (total effect OR, 1.24; direct effect OR, 1.16; 95% CI, 1.04-1.29; P = .008). No associations were noted between genetically predicted HDPs and heart failure (OR, 0.97; 95% CI, 0.76-1.23; P = .79) or atrial fibrillation (OR, 1.11; 95% CI, 0.65-1.88; P = .71). Conclusions and Relevance The findings of this study provide genetic evidence supporting an association between HDPs and higher risk of coronary artery disease and stroke, which is only partially mediated by cardiometabolic factors. This supports classification of HDPs as risk factors for cardiovascular disease.
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