Introduction: The placenta is a vascular organ that secretes angiogenic proteins during pregnancy. Abnormalities in these biomarkers are associated with higher risk for adverse pregnancy outcomes, which include hypertensive disorders of pregnancy (HDP) and gestational diabetes (GDM). However, the association between abnormalities in angiogenic proteins and long-term CVD risk is uncertain. Aims: To determine the association between angiogenic placental proteins measured in early pregnancy and predicted 30-year risk of CVD 2-7 years after delivery. Methods: In this analysis, we included nulliparous individuals from the prospective multicenter nuMoM2b Heart Health Study (nuMoM2b-HHS) with available data on angiogenic protein concentrations in the first trimester (vascular endothelial growth factor [VEGF], placental growth factor [PlGF], endoglin, and soluble fms-like tyrosine kinase-1 [sFLT-1]). The primary outcome was predicted 30-year risk of CVD based on the Framingham model, which integrates traditional risk factor levels into an absolute risk estimate. Multivariable linear regression estimated associations between log-transformed angiogenic protein concentrations and predicted 30-year risk of CVD, adjusting for maternal age, gestational age, insurance type, and smoking status at the first trimester visit. Analyses were repeated stratified by HDP or GDM. Results: Of 987 nuMoM2b-HHS participants included, the mean age was 26.9 (SD 5.9) years and the mean gestational age at biomarker assessment was 11.4 (1.6) weeks. Higher log-transformed concentrations of VEGF (per 1-SD) were associated with greater predicted 30-year risk of CVD by 0.68% (0.34, 1.02). Conversely, higher log-transformed concentrations of endoglin and sFlt-1 were associated with lower 30-year predicted risk of CVD by 0.85% (-1.15, -0.55) and 0.70% (-1.00, -0.41), respectively. There was no association between PlGF and 30-year predicted risk of CVD. Results were similar in those with or without HDP or GDM. Conclusions: Concentrations of VEGF, endoglin, and sFLt-1 measured in early pregnancy were associated with predicted long-term risk of CVD 2-7 years after delivery in all birthing individuals whether or not they experienced an adverse pregnancy outcome.
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