Persistence of a Proteomic Signature After a Hypertensive Disorder of Pregnancy

A hypertensive disorder of pregnancy is associated with a higher risk of cardiovascular disease later in life, but the potential mechanistic links are unknown.

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.

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.

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.