Abstract
BACKGROUND: Few studies have examined how multiple types of adverse pregnancy outcomes across women's reproductive lives relate to long-term cardiovascular disease. METHODS: In 59 154 parous participants in Nurses' Health Study II, lifetime history of gestational diabetes, gestational hypertension, preeclampsia, preterm delivery, and low birthweight was self-reported, and cardiovascular events, including myocardial infarction, stroke, and coronary revascularization, were identified through June 2017. We used Cox proportional hazards models to estimate associations between adverse pregnancy outcomes and cardiovascular disease and quantified the extent to which these associations were explained by the later development of hypertension, diabetes, and hypercholesterolemia. We evaluated whether adding adverse pregnancy outcomes improved prediction of premature cardiovascular disease beyond established risk factors such as systolic blood pressure and diabetes. RESULTS: Each adverse pregnancy outcome was associated with a higher risk of long-term cardiovascular disease. Only gestational hypertension (hazard ratio, 1.62 [95% CI, 1.36-1.92]) and preeclampsia (1.31 [1.11-1.55]) retained independent associations after accounting for the cooccurrence of other adverse pregnancy outcomes. Postpregnancy hypertension, diabetes, and hypercholesterolemia jointly accounted for substantial attenuation (58.4% [38.7%-75.8%]) of the association between adverse pregnancy outcomes in the first pregnancy and later cardiovascular disease. Adding adverse pregnancy outcomes only modestly improved discrimination and slightly improved reclassification. CONCLUSIONS: Common adverse pregnancy outcomes, especially gestational hypertension and preeclampsia, are associated with higher future cardiovascular risk, with much of this association attenuated after accounting for subsequent cardiovascular risk factors. However, given the limited predictive gains, more nuanced integration of adverse pregnancy outcomes is needed to enhance their clinical utility in cardiovascular risk prediction.