Hypertensive Disorders of Pregnancy and Maternal Cardiovascular Disease

Abstract

Women with a history of hypertensive disorders of pregnancy (HDP)—gestational hypertension and preeclampsia—have a two-fold increased risk of cardiovascular disease (CVD), compared to women with a history of normotensive pregnancies. However, much of the literature remains uncontrolled for important shared risk factors—including pre-pregnancy body mass index, smoking, and family history. The trajectory of CVD risk factor development after pregnancy and the extent to which these risk factors mediate the HDP-CVD association remain unknown. Further, whether HDP improves CVD risk prediction in women has not been tested. We use observational data from a large, longitudinal cohort study to estimate associations of HDP with CVD risk factors and events and to evaluate the utility of incorporating HDP into a CVD risk score. In Chapter 1, we examine the association between HDP and CVD, adjusting for shared pre-pregnancy risk factors, and calculate the proportion mediated by CVD risk factors after pregnancy. We find that women with a hypertensive disorder in first pregnancy have a 1.5 -fold increased rate of myocardial infarction and stroke, compared to women with a normotensive first pregnancy; nearly 75% of this association is mediated by the development of chronic hypertension, type 2 diabetes mellitus (T2DM), hypercholesterolemia, and weight changes after pregnancy. In Chapter 2, we investigate the associations between HDP and chronic hypertension, T2DM, and hypercholesterolemia. We find that women with HDP in first pregnancy develop CVD risk factors earlier and have a 2-3-fold increased rate of chronic hypertension, 70% higher rate of T2DM, and 30% higher rate of hypercholesterolemia, compared to women with normotensive first pregnancies, adjusting for shared pre-pregnancy risk factors. In Chapter 3, we provide the first test of including HDP in an established CVD risk prediction model. While inclusion of HDP and parity improved model fit at younger ages (40-49 years), they did not improve CVD risk prediction model performance in this relatively young cohort of women at low risk for CVD. Taken together, these findings suggest that established CVD risk factors—chronic hypertension, type 2 diabetes, hypercholesterolemia, and weight gain—are suitable screening targets for women with a history of HDP.