Abstract MP64: The Role of Aspirin in the Relationship Between Hypertensive Disorders of Pregnancy and Incident Maternal Cardiovascular Disease
Authors: Stuart Jennifer J , Tanz Lauren J , Rich-Edwards Janet W , Rimm Eric B , Mukamal Kenneth J , Curhan Gary C , Rexrode Kathryn M 
Published: March 2019

Introduction:
Hypertensive disorders of pregnancy (HDP; including gestational hypertension and preeclampsia) are associated with an increased risk of maternal cardiovascular disease (CVD). Low-dose aspirin reduces the risk of preterm preeclampsia, through proposed short-term effects on platelet and endothelial function. While low-dose aspirin is recommended for the prevention of preeclampsia in women at high risk, no recommendations exist for aspirin use following a pregnancy complicated by HDP.

Hypothesis:
We hypothesized that regular aspirin use after pregnancy would modify the association between HDP and CVD, lowering the magnitude of the association among aspirin users relative to non-users.

Methods:
Parous women free of CVD before first birth in the Nurses’ Health Study II comprised the analytic sample (n=60,392). Lifetime pregnancy history was reported in 2009. Women were followed for confirmed incident CVD (coronary heart disease [non-fatal or fatal MI, fatal CHD] or stroke [non-fatal or fatal]) from 1989 through 2013. Current regular aspirin use was self-reported at baseline in 1989 and updated every 2 years via biennial questionnaire. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the relationship between HDP in first pregnancy (using 3 mutually exclusive categories: normotension [ref], gestational hypertension, preeclampsia) and CVD, adjusted for age, race/ethnicity, parental education, family history of CVD <60y, and pre-pregnancy risk factors (smoking, physical activity, diet, alcohol intake, oral contraceptive use, BMI). Effect modification by aspirin was tested through a likelihood ratio test, comparing nested models with and without interaction terms between HDP history and time-varying aspirin use.

Results:
Nine percent of women (n=5,629) had HDP in first pregnancy. CVD events occurred in 657 women with normotension, 30 women with gestational hypertension, and 75 women with preeclampsia. Compared to women with normotension in first pregnancy, gestational hypertension was associated with stroke (HR=1.65; CI: 1.01-2.71) but not CHD (HR=1.21; CI: 0.70-2.12), while preeclampsia was associated with CHD (HR=2.27; CI: 1.69-3.04) but not stroke (HR=1.03; CI: 0.68-1.57). Current aspirin use was not a significant effect modifier of the relationship between HDP and CVD (p-value=0.53). Hazard ratios for the relationship between gestational hypertension and CVD were 1.58 (CI: 1.01-2.49) among aspirin non-users and 1.15 (CI: 0.61-2.18) among aspirin users. Hazard ratios for the relationship between preeclampsia and CVD were 1.52 (CI: 1.10-2.10) among aspirin non-users and 1.67 (CI: 1.16-2.40) among aspirin users.

Conclusion:
Aspirin use after pregnancy does not appear to modify the increased risk of CVD observed among women with a history of HDP compared to women with normotension in pregnancy.