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. 2023 Feb 1;6(2):e230034.
doi: 10.1001/jamanetworkopen.2023.0034.

Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease

Bilal Rayes  1 , Maddalena Ardissino  1   2 , Eric A W Slob  3   4   5 , Kiran Haresh Kumar Patel  1 , Joanna Girling  6 , Fu Siong Ng  1
Affiliations

Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease

Bilal Rayes et al. JAMA Netw Open. .

Abstract

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.

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 (r2<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.

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.

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.

Objective: To investigate the association of HDPs with multiple cardiovascular diseases.

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).

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Ardissino reported receiving grants from National Institute for Health Research (NIHR) during the conduct of the study. Dr Slob reported receiving NIHR Cambridge Biomedical Research Centre grant BRC-1215-20014 outside the submitted work. Dr Ng reported receiving grants from the British Heart Foundation and from the NIHR during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Data, Instrumental Variant Selection, and Analysis Flowchart
Genome-wide association study summary data were acquired from the FinnGen consortium on the 3 primary exposures. Mendelian randomization analysis was conducted for the outcomes of coronary artery disease, heart failure, atrial fibrillation, and acute ischemic stroke. R6 indicates release 6; SNV, single-nucleotide variant.
Figure 2.
Figure 2.. Mendelian Randomization Analysis of Hypertensive Disorders of Pregnancy and Cardiovascular Outcomes
Mendelian randomization estimates for the association of any hypertensive disorder in pregnancy, gestational hypertension, and preeclampsia/eclampsia with the outcomes of (A) coronary artery disease, (B) acute ischemic stroke, (C) heart failure, and (D) atrial fibrillation. OR indicates odds ratio.
See this image and copyright information in PMC

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