Hypertensive Disorders of Pregnancy Raise Long-Term CVD Risk by 63%

After adjustment for known cardiovascular risk factors, investigators found women with a hypertensive disorder of pregnancy, including preeclampsia and gestational hypertension, during their first pregnancy had a 63% greater risk of future cardiovascular disease compared to women with normotensive pregnancies.

New research from Brigham and Women’s Hospital details the association between hypertensive disorders of pregnancy and long-term risk of cardiovascular disease among women.

An analysis of data from the Nurses’ Health Study (NHS) II, results of the study suggest women with a hypertensive disorder of pregnancy during their first pregnancy had a 63% greater risk of cardiovascular disease, with those experiencing preeclampsia at a 72% greater risk and those with gestational hypertension experiencing a 41% greater risk.

“Women with a history of gestational hypertension or preeclampsia should be informed that they are at increased risk for cardiovascular disease events. Screening and prevention efforts in those with a history of gestational hypertension or preeclampsia should target the established cardiovascular disease risk factors of chronic hypertension, hypercholesterolemia, type 2 diabetes mellitus, and overweight/obesity,” said study investigator Jennifer Stuart, ScD, of the Division of Women’s Health at Brigham and Women’s Hospital, in a statement. “We are eager to continue investigating strategies to reduce long-term cardiovascular risk following hypertensive pregnancy and to empower and equip these patients to improve their cardiovascular health in the years and decades after delivery.”

Among the largest prospective investigations into the risk factors for major chronic diseases in women, the NHS II provided investigators with data related to 116,429 female registered nurses aged 25-42 years at enrollment in 1989 for inclusion in the current analysis. Of the 116,429 women included in NHS II, 60,379 were porous women free of cardiovascular disease before their first pregnancy with information available on their first pregnancy.

The primary outcome of interest for the study was the relationship between hypertensive disorders of pregnancy and cardiovascular disease. Investigators noted Cox proportional hazards models were used to estimate hazard ratios (HRs) and adjust for potential confounders, including prepregnancy BMI, smoking, and parental history of cardiovascular disease. Investigators also pointed out the difference method was used to quantify the proportion of the associations jointly accounted for by chronic hypertension, hypercholesterolemia, type 2 diabetes, and changes in BMI.

Of the 60,379 women identified for inclusion, 57,974 were considered eligible for inclusion in the investigators’ mediation analysis and 57,137 were included in the secondary analysis examining lifetime pregnancy exposure. At the end of the follow-up period, the 60,379-person cohort gad a median age of 61 (IQR, 57-64) years and a median follow-up of 34 (IQR, 29-40) years since first birth. A total of 1789 patients were identified as having gestational hypertension during their first pregnancy and 3834 as having preeclampsia during their first pregnancy, with the remaining 54,756 had normotensive pregnancies.

Upon analysis, results suggested women with a hypertensive disorder of pregnancy during their first pregnancy had a 63% higher rate of cardiovascular disease than women with normotensive pregnancies (HR, 1.63 [95% CI, 1.37-1.94]), but this association was mediated by established cardiovascular disease risk factors (proportion mediated 64%). Analysis according to specific hypertensive disorder of pregnancy suggested the risk of future cardiovascular disease associated with preeclampsia (HR, 1.72 [95% CI, 1.42-2.10]) was greater than the observed risk associated with gestational hypertension (HR, 1.41 [95% CI, 1.03-1.93]). Investigators pointed out established cardiovascular disease risk factors accounted for 57% of the increase risk of cardiovascular ride for women with preeclampsia and 84% for women with gestational hypertension (both P <.0001).

“To our knowledge, this study presents the most complete control of prepregnancy confounding in the relationship between HDP and long-term CVD and is the first to estimate the proportion of this association jointly mediated by chronic hypertension, hypercholesterolemia, T2DM, and changes in BMI. Even after adjustment for prepregnancy confounders, HDP in first pregnancy remained associated with a 63% higher rate of CVD later in life,” wrote investigators in their conclusion.

This study, “Cardiovascular Risk Factors Mediate the Long-Term Maternal Risk Associated with Hypertensive Disorders of Pregnancy,” was published Journal of the American College of Cardiology.