Abstract MP63: Established Cardiovascular Disease Risk Factors Mediate The Relationship Between Hypertensive Disorders In First Pregnancy And Maternal Cardiovascular Disease
Authors: Stuart Jennifer J , Tanz Lauren J , Rimm Eric B , Spiegelman Donna , Missmer Stacey A , Rexrode Kathryn M , Mukamal Kenneth J , Rich-Edwards Janet W 
Published: March 2020

Introduction:
Women with a history of hypertensive disorders in pregnancy (HDP; gestational hypertension [GHTN] or preeclampsia) have an increased risk of CVD risk factors and events compared to women with normotensive pregnancies. However, the extent to which the relationship between HDP and CVD events is mediated by established CVD risk factors is less clear.

Hypothesis:
We hypothesized that a large proportion of the HDP-CVD relationship would be mediated by subsequent CVD risk factors — chronic hypertension (CHTN), type 2 diabetes (T2D), hypercholesterolemia, and BMI.

Methods:
Parous women free of prior CVD events, CHTN, T2D, and hypercholesterolemia at first birth in the Nurses’ Health Study II comprised the analytic sample (n=57,974). Pregnancy history was retrospectively reported in 2009. Women were followed for confirmed CVD events (coronary heart disease [non-fatal or fatal MI, fatal CHD] or stroke [non-fatal or fatal]) from first birth through 2015. Potential mediators were self-reported on biennial questionnaires. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the relationship between HDP in first pregnancy (preeclampsia or GHTN vs. normotension [ref]) and CVD, adjusting for age, race/ethnicity, parental education, family history of CVD before age 60, and pre-pregnancy risk factors (e.g., smoking, diet, and BMI). To evaluate the proportion of the HDP-CVD association that was jointly mediated by the CVD risk factors we used the difference method, comparing a model including these four factors to a model without them.

Results:
Nine percent of women (n=5,306) had a history of HDP in first pregnancy (preeclampsia: 6.3%; GHTN: 2.9%). CVD events occurred in 650 women with normotension in first pregnancy, 30 with GHTN, and 81 with preeclampsia. Adjusting for pre-pregnancy confounders, women with HDP in first pregnancy had a 63% higher rate of incident CVD (CI: 1.33-2.00) compared to women with normotension in first pregnancy; in particular, the strongest association was observed between preeclampsia and CHD (HR=2.18, CI: 1.62-2.93). The overall HDP-CVD association was largely mediated by the group of four CVD risk factors (HDP: proportion mediation [PM]=65%, CI: 35-87; preeclampsia: PM=57%, CI: 21-87; GHTN: PM=99%, CI: inestimable). All CVD risk factors contributed to mediation, but chronic hypertension accounted for the largest proportion.

Conclusions:
While approximately 40% of the association between preeclampsia and CVD remained unexplained, almost all the increased risk of CVD conferred by a history of GHTN was jointly accounted for by the development of established risk factors postpartum. Screening for CHTN, T2D, hypercholesterolemia, and overweight/obesity after pregnancy may be especially helpful in CVD prevention among women with a history of HDP.