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

Abstract

BACKGROUND: Cardiovascular disease (CVD) prevalence is rising among younger women in the United States. Hypertensive disorders of pregnancy (HDP) are early indicators of cardiovascular risk, yet it remains unclear whether HDP independently increase CVD risk or reflect poor prepregnancy 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 used data from the All of Us research program, encompassing >50 health systems across the United States, to identify women with longitudinal pregnancy and postpartum data (n=17 357; between 2007 and 2022). Multivariable Cox regression estimated adjusted hazard ratios (aHRs) of HDP with CVD (ischemic heart disease, heart failure, or stroke), overall and stratified by prepregnancy cardiometabolic risk factors (hypertension, obesity, diabetes, hyperlipidemia, or chronic kidney disease). Analyses were replicated in an independent health system (n=56 549; between 2016 and 2025) using the Observational Medical Outcomes Partnership Common Data Model. RESULTS: Participants had a median [interquartile range] age of 30 [25, 35] years; 2719 (16%) identified as Black or African American, and 7267 (42%) identified as Hispanic or Latino. Among those who reported socioeconomic data, 4306 (35%) reported an income <$25 000, and 6429 (37%) a high school education at most. HDP occurred in 2098 (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 prepregnancy 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 prepregnancy 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.