Hypertensive Disorders in Pregnancy May Increase Long-Term Risk of Cardiovascular Events

Hypertensive disorders in pregnancy (HDPs) appeared to increase the maternal risk for major cardiovascular (CV) diseases (CVDs), particularly atherosclerotic CVDs such as coronary artery disease (CAD), according to a study published in JAMA Network Open.

“Observational evidence suggests that women who experience HDPs have a 2-fold higher long-term risk of future cardiovascular events compared with women who have normotensive pregnancy,” the study authors wrote. “In addition, recent data from the Nurses’ Health Study II cohort revealed that women with HDPs had a significantly higher rate of atherosclerosis in the years following pregnancy.”

Although clinical guidelines suggest screening for CVD risk factors and disease post-partum in women who had HDPs, these recommendations are not strongly followed, according to the study.

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

Nearly 10% of pregnancies are affected by HDPs, according to the study. Hypertensive disorder can either be gestational hypertension, preeclampsia, or eclampsia, and any of these 3 can also exacerbate the effects on patients with chronic hypertension. HDPs are the number 2 cause of death for pregnant women, and observational studies suggest that the impact on those who had HDP could have a 2-times greater risk of future CV events, but not enough studies can prove this.

In this study, investigators used mendelian randomization (MR) to understand the genetic risk of a CV event, including CAD, ischemic stroke, heart failure (HF), or atrial fibrillation (AF) from HDP. The team also studied whether traditional CV risk factors increased a patient’s risk of a CV event.

After analysis, risk of CAD was higher among women who had genetically predicted HDPs. The investigators observed this association in patients who had both gestational hypertension and preeclampsia or eclampsia. They hypothesize that this occurs because patients with preexistent hypertension have an underlying biological mechanism that increases their risk.

“Our results support the growing acceptance of HDPs as sex-specific risk factors for [CVD],” the study authors wrote.

Risk of ischemic stroke also appeared to be higher in patients with genetically predicted HDPs, however, there was no identifiable association between HDPs and risk of HF or AF.

Study limitations included that the study populations were limited to people living in Europe. Additionally, the testing was limited by study population size and available instruments. Further, estimates made via MR are not able to provide a holistic estimate of the lifetime effect of genetics on changes in mediated risk factors.

In further analysis, investigators observed that traditional CV risk factors, such as systolic blood pressure and type 2 diabetes, could partially mediate the association between CAD and HDPs. They suggest targeting these modifiable risk factors to prevent future CV events.

“Beyond demonstrating the association of HDPs with cardiovascular disease, it is important to consider underlying biological mechanisms with the aim of identifying actionable treatment targets. We performed mediation analysis using multivariable MR to explore the role of potential mediators of the association between HDPs and CAD,” the study authors wrote. “The results revealed only partial mediation by systolic blood pressure and type 2 diabetes. This has important implications: first, it identifies substantial actionable targets for primary prevention, and second, it identifies the presence of a key residual mechanism that is of an unclear source, representing an important target for future research.”

Despite American Heart Association guidelines that promote risk factor screening, rates are continually low—increasing follow-up and screening may further reduce the risk of CAD associated with HDPs.

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

Reference

Rayes B, Ardissino M, Slob E, et al. Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease. February 17, 2023. JAMA Netw Open. 2023;6(2):e230034. doi:10.1001/jamanetworkopen.2023.0034