Disparities in Cardiovascular Disease in Women with Adverse Pregnancy Outcomes

Background: Although adverse pregnancy outcomes (APOs) have been linked to increased cardiovascular disease (CVD) risk, most studies have focused on homogenous populations. We tested the hypothesis that APOs and race and ethnicity synergistically increase the risk of CVD. Methods: We conducted retrospective analyses of data collected by All of Us, a large and diverse population study in the United States. We included women with a single lifetime delivery and no history of CVD before that delivery. Our exposures of interest were APOs (defined as any preeclampsia, eclampsia, gestational hypertension and diabetes, preterm delivery, fetal growth restriction, or placental abruption) and self reported race and ethnicity. Our primary outcome was incident CVD after 1 year postpartum, defined as any stroke (ischemic or hemorrhagic), myocardial infarction, or heart failure. Multivariable Cox proportional hazard models estimated the association between APO, race and ethnicity and CVD, and product terms were used to test for synergistic contributions (interaction) between APO and race and ethnicity. Results: We included 10,760 women in our analysis, who had a mean (SD) age of 30 (6) years at first delivery. Of these, 4,204 (39%) had at least one APO. After a median (interquartile range) follow-up of 7.02 (3.82-13.26) years, 217 (5.2%) women with APO sustained CVD, while only 252 (3.8%) without APO did (p<0.001). Multivariable Cox regressions confirmed these results, showing that women with APO had a significantly increased risk of CVD (HR: 1.45; 95%CI: 1.17-1.80). Race and ethnicity significantly modified the association between APO and CVD (interaction-p=0.003): compared with White women without APO, Black women with APO had a four-fold higher risk of CVD (HR: 4.04; 95%CI: 2.81-5.79), which was also substantially higher than the risk observed in White women with APO (HR: 2.01; 95%CI: 1.43-2.84). Conclusions: In a large and diverse cohort of American women with a single lifetime delivery, APOs were associated with an increased risk of CVD, and these risks were even greater among Black women. These findings highlight the potential to integrate reproductive health history and non-medical determinants of health to enhance CVD prevention and health equity using personalized medicine. Further research is needed to identify the mechanisms that lead to synergistic contributions by APOs and race and ethnicity.