Pregestational Cardiometabolic Biomarkers and Future Hypertensive Disorders of Pregnancy

Importance: Hypertensive disorders of pregnancy (HDP) are one of the leading causes of maternal morbidity and death. There is an urgent need to improve early identification of women at risk of HDP, and assessment of pregestational cardiometabolic biomarkers is a potential way forward. Objective: To investigate pregestational cardiometabolic disturbances with regard to risk of HDP. Design, Setting, and Participants: This prospective cohort study used data from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort, a population-based study set in the greater Stockholm area of Sweden, linked to the Swedish Medical Birth Register from January 1, 1985, to December 31, 2020. Participants were nulliparous women 18 years of age or older with blood biomarker data obtained before their first completed pregnancy. Data analyses were conducted from January 1 to October 31, 2025. Exposures: Pregestational cardiometabolic disturbances, identified through biomarkers of lipid and glucose metabolism and low-grade inflammation. Median time between blood sampling and the start of pregnancy was 4 to 6 years (range, 0-31 years). Main Outcomes and Measures: HDP, defined as gestational hypertension, preeclampsia, or superimposed preeclampsia. Results: Of 35 189 women included (mean [SD] age at delivery, 30.9 [4.8] years), 1938 (5.5%) had HDP. In groups identified with pregestational cardiometabolic disturbances, the percentages with HDP were between 5.5% and 12.8%, whereas the percentages in the comparison categories were between 4.1% and 5.3%. In multivariable logistic regression models, associations with increased risk of HDP were observed for quartile (Q) 4 (vs Q1) for total cholesterol (adjusted odds ratio [AOR], 1.23 [95% CI, 1.06-1.41]), low-density lipoprotein cholesterol (AOR, 1.41 [95% CI, 1.05-1.89]), triglycerides (AOR, 1.19 [95% CI, 1.03-1.37]), haptoglobin (AOR, 1.20 [95% CI, 1.02-1.42]), apolipoprotein (Apo) B (AOR, 1.90 [95% CI, 1.36-2.65]), ApoB/ApoA1 ratio (AOR, 1.59 [95% CI, 1.10-2.30]), and the triglyceride-glucose index (AOR, 1.21 [95% CI, 1.04-1.40]). For C-reactive protein (AOR, 0.97 [95% CI, 0.80-1.17]) and leukocyte counts (AOR, 0.98 [95% CI, 0.80-1.20]), there was no association with HDP risk. Conclusions and Relevance: In this cohort study, pregestationally assessed cardiometabolic biomarkers were associated with increased risk of HDP in nulliparous women. For some biomarkers, the increased risk was observed below standard cutoff levels for a clinical diagnosis, that is, at subclinical levels. These results suggest that assessment of cardiometabolic biomarkers may improve identification of women at risk of HDP, both in preconceptional counseling settings and at enrollment in antenatal health care.