Hypertensive Disorders of Pregnancy and Cardiovascular-Kidney-Metabolic Syndrome

Abstract

Background: Hypertensive disorders of pregnancy (HDP) affect over 10% of pregnancies worldwide, but their association with cardiovascular-kidney-metabolic (CKM) syndrome remains unexplored. Methods: The present study included parous UK Biobank participants. The primary exposure was HDP history. CKM syndrome was categorized from stage 0 (no risk factors) to 4 (cardiovascular disease). Logistic regression tested the association of HDP history with CKM stage, adjusted for age, age2, race, Townsend Deprivation Index, and smoking status. Cox models evaluated progression to stage 4, additionally adjusting for baseline CKM stage. Replication analyses were performed in the Women’s Health Initiative (WHI), with CKM stage assessed at two study visits. Results: Among 219,639 UK Biobank (mean age, 56.9 years) and 3,591 WHI participants (61.7 years at baseline, 78.1 years at the follow-up visit), 2,836 (1.3%) and 304 (8.4%), respectively, had a history of HDP. In the UK Biobank, HDP history was significantly associated with higher CKM stage (adjusted odds ratio [aOR], 3.40 [95% CI, 3.12–3.71]; P < 0.001) in ordinal logistic regression. Compared with CKM stage 0, HDP history was associated with higher odds of stages 2–4 (aORs 6.34, 11.20, and 7.43, respectively; all P < 0.001). Over a median follow-up of 13.6 years, prior HDP was associated with progression to stage 4 (adjusted hazard ratio, 1.24 [95% CI, 1.10–1.40]; P < 0.001). Replication in the WHI produced consistent results. Conclusions: HDP history was associated with greater CKM stage and progression to advanced CKM syndrome, supporting its use as an early-life predictor of adverse CKM trajectories.