Study Details Causal Relationship Between Hypertensive Disorders of Pregnancy and Future Cardiovascular Risk

Siong Ng, MBBS, PhD
Image Courtesy: Imperial College London

A new study with data from more than 250,000 is providing further insight into associations of hypertensive disorders of pregnancy with future cardiovascular disease risk.

A genome-wide genetic association study led by investigators from the National Heart and Lung Institute at Imperial College London, results demonstrate genetically predicted hypertensive disorders of pregnancy were associated with an increased risk of coronary artery disease (CAD) and ischemic stroke, but investigators pointed out this risk could be partially mediated by cardiometabolic factors, which underlines the need for monitoring and treatment strategies.

“The results of this study add to current literature by providing evidence supporting an association between HDPs and higher risk of atherosclerotic cardiovascular disease,” wrote investigators.

Citing the potential for residual confounding and bias in observational studies examining hypertensive disorders of pregnancy with maternal and fetal morbidity, Siong Ng, MBBS, PhD, a clinical senior lecturer in Cardiac Electrophysiology at Imperial College London, the current endeavor was designed as a genome-wide genetic association study using mendelian randomization with the intent of describing genetic association estimates between hypertensive disorders of pregnancy and multiple forms of cardiovascular disease.

Data from genome-wide associations studies for the study were obtained from the FinnGen consortium’s 6th data release on January 24, 2022. From this data release, investigators identified uncorrelated (r² <.001) single-nucleotide variants for use as instrumental variations for exposures of interest, which were defined as any hypertensive disorder of pregnancy, gestational hypertension, and preeclampsia/eclampsia. From genome-wide association studies, investigators obtained information for genetic association estimates from 122,733 cases for CAD, 34,217 cases for ischemic stroke, 47,309 cases for heart failure, and 60,620 cases for atrial fibrillation.

Upon analysis, results indicated genetically predicted hypertensive disorders of pregnancy (Odds ratio [OR], 1.24 [95% CI, 1.08-1.43]; P=.002), genetically predicted gestational hypertension (OR, 1.08 [95% CI, 1.00-1.17]; P=.04), and genetically predicted preeclampsia/eclampsia (OR, 1.06 [95% CI, 1.01-1.12]; P=.03) were associated with a higher risk of CAD. For ischemic stroke, genetically predicted hypertensives disorders of pregnancy were associated with an increased risk of ischemic stroke (OR, 1.27 [95% CI, 1.12-1.44]; P = 2.87x10⁻⁴⁾, but this association was not observed for genetically predicted gestational hypertension (OR, 1.12 [95% CI, 0.93-1.36]; P=.23) or genetically predicted preeclampsia/eclampsia (OR, 1.04 [95% CI, 0.97-1.12]; P=.22). No associations for increased risk of 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).

In mediation analyses, investigators observed a partial attenuation of the effects of hypertensive disorders of pregnancy on CAD 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).¹

Investigators noted multiple limitations to consider before overinterpretation of study results. These limitations included use of GWAS data from European populations, analyses only being powered to detect differences of a certain size, inability to verify the occurrence of the mediator followed by the exposure in their mediation analysis.

“Cardiometabolic factors mediated part of the association between hypertensive disorders of pregnancy and CAD, highlighting key monitoring and treatment targets, but also highlighting a residual effect of a currently unclear source,” investigators added.¹“Broadly, these results support emerging recommendations to consider HDPs as important sex-specific risk factors for atherosclerotic cardiovascular disease.”

References

1. Rayes B, Ardissino M, Slob EAW, Patel KHK, Girling J, Ng FS. Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease. JAMA Netw Open. 2023;6(2):e230034. doi:10.1001/jamanetworkopen.2023.0034