Placental anti-angiogenic and inflammatory markers and postpartum cardiovascular risk following preeclampsia

BACKGROUND Preeclampsia (PE) increases lifetime maternal cardiovascular disease (CVD) risk. Placental transcriptomic and histological evidence suggests distinct PE subtypes-hypoxic (malperfusion, elevated FLT-1/ENG), inflammatory (immune infiltration, pro-inflammatory mediators), and maternal maladaptation (minimal placental disease)-which may differentially influence long-term CVD risk. This study evaluated whether subtype-specific immunohistochemical (IHC) biomarkers and placental pathology predict postpartum CVD risk. METHODS In this pilot study, placental IHC for FLT-1, ENG, and CD68 was performed on biopsies from 41 women (35 with PE and 6 normotensive controls). Postpartum CVD risk was assessed at six months using validated lifetime risk algorithms. Biomarker intensity, histopathological scores for maternal vascular malperfusion (MVM) and inflammation, and clinical covariates were analyzed using logistic regression and receiver operating characteristic (ROC) modeling. Correlation analyses examined associations between cardiovascular measures, placental biomarkers, and pathology. RESULTS Biomarker expression did not differ significantly between high- and low-risk groups. A biomarker-only model showed limited discrimination (AUC = 0.59), whereas combining biomarkers with clinical and pathological variables improved performance (AUC = 0.84; sensitivity 62.5%, specificity 90.5%). MVM, FLT-1, and ENG correlated positively with systolic blood pressure and total cholesterol, while CD68 correlated inversely. Precision analysis indicated only large effects were detectable given the pilot sample size. CONCLUSIONS Integrating placental biomarkers, pathology, and clinical data enhances prediction of postpartum CVD risk after PE. These exploratory findings highlight the potential of placental profiling for individualized CVD risk stratification following hypertensive pregnancy.