Key result
Hypertensive pregnancy disorders are linked to persistent mid-life differences in complement and coagulation proteins.
Why the study?
Hypertensive disorders of pregnancy are associated with higher risks of cardiovascular disease later in life, but potential mechanistic links remain unknown.
Are there persistent proteomic signature differences in women with a history of a hypertensive disorder of pregnancy compared to those with a normotensive pregnancy?
Case-Control (n=249)
Are there persistent proteomic signature differences in women with a history of a hypertensive disorder of pregnancy compared to those with a normotensive pregnancy?
Effect estimate: c-index 0.72
May identify plasma protein links between hypertensive pregnancy disorders and later CVD; hypothesis-generating, needs prospective validation.
BACKGROUND: A hypertensive disorder of pregnancy is associated with a higher risk of cardiovascular disease later in life, but the potential mechanistic links are unknown. METHODS: We recruited 2 groups of women, 1 during pregnancy and another at least 2 years after delivery. Cases had a hypertensive disorder of pregnancy, and controls had a normotensive pregnancy. The pregnancy cohort had study visits antepartum and postpartum; the mid-life group made a single study visit. We assayed 7288 plasma proteins, applied machine learning to identify proteomics signatures at each time point, and performed enrichment analyses to identify relevant biological pathways. RESULTS: The pregnancy cohort (58 cases and 46 controls) had a mean age of 33.8 years, and the mid-life group (71 cases and 74 controls) had a mean age of 40.8 years. Protein levels differed significantly between cases and controls at each time point: 6233 antepartum, 189 postpartum, and 224 in mid-life. The postpartum protein signature discriminated well between cases and controls (c-index=0.78), and it also discriminated well in the independent mid-life samples (c-index=0.72). Pathway analyses identified differences in the complement and coagulation cascades that persisted across the antepartum, postpartum, and mid-life samples. The 28 proteins present in both the postpartum and mid-life signatures included 5 complement factors (3, B, H, H-related-1, and C1r-subcomponent-like) and coagulation factor IX. CONCLUSIONS: Differences in protein expression persist for years after a hypertensive disorder of pregnancy. The consistent differences in the complement and coagulation pathways may contribute to the increased risk of later life cardiovascular disease.
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Hlatky et al. (2025) conducted a case-control in Hypertensive disorder of pregnancy (n=249). Hypertensive disorder of pregnancy vs. Normotensive pregnancy was evaluated on Discrimination between cases and controls using a postpartum protein signature in independent mid-life samples (c-index 0.72). A hypertensive disorder of pregnancy was associated with persistent differences in complement and coagulation proteins, with a postpartum signature discriminating cases in mid-life (c-index=0.72).
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