Hypertensive Disorders of Pregnancy and Premature Cardiovascular Disease in a Diverse Cohort of Young US Women

Background: Cardiovascular disease (CVD) prevalence is rising among younger women in the US. Hypertensive disorders of pregnancy (HDP) are early indicators of cardiovascular risk, yet it remains unclear whether HDP independently increase CVD risk or reflect poor pre-pregnancy health. We aimed to quantify the association between HDP and incident CVD in a diverse, real-world population, with replication of findings across health systems. Methods: We utilized data from the All of Us Research Program, encompassing >50 health systems across the US, to identify women with longitudinal pregnancy and postpartum data (n=17,357; between years 2007-2022). Multivariable Cox regression estimated adjusted hazards ratios (aHR) of HDP with CVD (ischemic heart disease, heart failure, stroke), overall and stratified by pre-pregnancy cardiometabolic risk factors (hypertension, obesity, diabetes, hyperlipidemia, and/or chronic kidney disease). Analyses were replicated in an independent health system (n=56,549; between years 2016-2025) using the Observational Medical Outcomes Partnership Common Data Model. Results: Participants were median [IQR] age 30 [25, 35] years; 2,719 (16%) identified as Black or African American and 7,267 (42%) identified as Hispanic or Latino. Among those who reported socioeconomic data, 4,306 (35%) reported an income under $25,000, and 6,429 (37%) at most a high school education. HDP occurred in 2,098 (12%) of pregnancies. Over a median of 4.6 years of follow-up, 701 women developed CVD. Overall, HDP were associated with elevated CVD risk (aHR 1.82 [95% CI: 1.49-2.22]). Regardless of pre-pregnancy cardiometabolic risk factors, HDP were independently associated with CVD risk (aHR 2.06 [95% CI: 1.55–2.74] among women without risk factors, and aHR 1.33 [95% CI: 1.00–1.77] among women with risk factors). Main findings showed similar effect estimates for the risk of HDP with composite CVD (aHR 2.62 [95% CI: 2.17-3.16]) in the external replication cohort. Conclusions: In a diverse, national sample of young US women, HDP were a significant marker of premature CVD risk, even in the absence of pre-pregnancy cardiometabolic risk factors. Integrating pregnancy complications into CVD risk stratification and promoting cardiometabolic health before, during and after pregnancy may reduce the growing burden of early-onset CVD among women.