Development of chronic hypertension among women with a history of de novo hypertension disorders during pregnancy: the role of metabolites

Background Hypertensive disorders of pregnancy, including gestational hypertension (GH) and preeclampsia (PE), are associated with an elevated long-term risk of chronic hypertension (CH). However, evidence regarding the underlying mechanisms and effective risk prediction models remains limited. Methods This study utilized baseline metabolomics data from the UK Biobank, focusing on women with a history of GH or PE. Their CH status was assessed both at enrollment and during follow-up. In Phase I, a cross-sectional study employing logistic regression and Mendelian randomization analyses identified metabolites significantly associated with CH. The discriminatory performance of these metabolites for CH at enrollment was evaluated using the area under the receiver operating characteristic curve. In Phase II, a prospective study assessed the predictive performance of the identified metabolites for incident CH at three and five years. Results The study recruited 281 women with a history of GH or PE. Among them, 75 had prevalent CH at enrollment. Of the remaining 206 women without CH at baseline, 27 developed incident CH during follow-up. Nine metabolites were significantly associated with CH, including glycine and lipid components in lipoprotein subclasses. Notably, adding the metabolic profile to a conventional prediction model significantly improved the predictive performance for CH. Conclusion The findings suggest that metabolic dysregulation, particularly in lipid metabolism, is involved in the progression to CH following GH or PE. The identified metabolic profile may enhance CH risk prediction in this high-risk population.