Longitudinal Changes in the Endothelial Activation and Stress Index (EASIX) in Patients with Preeclampsia

Background: Endothelial dysfunction is a central pathophysiological hallmark of preeclampsia. Laboratory and clinical features of preeclampsia can rapidly deteriorate and evidence on appropriate surveillance strategies is scarce. We aimed to evaluate the prognostic value of longitudinal changes in the "Endothelial Activation and Stress Index" (EASIX) for adverse outcomes in patients with preeclampsia. Methods: Patients with preeclampsia who delivered at Heidelberg University Hospital between 2017 and 2022 were included in this retrospective analysis. We assessed EASIX, derived from lactate dehydrogenase, creatinine and platelets, longitudinally between first admission and diagnosis of an adverse outcome. Composite adverse outcomes included pulmonary edema, HELLP syndrome, kidney injury, eclampsia, postpartum hemorrhage and death. We applied logistic and mixed linear regression modeling adjusted for age, gestational age and body mass index. Results: In total, 1733 EASIX measurements of 443 patients were included in the analysis, of which 81 patients experienced an adverse outcome. Both the first EASIX (aOR 2.81 [1.86;4.37]) and the absolute change per day (aOR 4.35 [1.77; 12.05]) were independently associated with adverse outcomes. Addition of the absolute change in EASIX to the model including the first EASIX (AUC 0.74 [0.68-0.81]) did not substantially improve the discriminatory performance (AUC 0.76 [0.70; 0.82]). Linear mixed regression modeling demonstrated that patients with adverse outcomes had a steeper rise in EASIX compared to patients without adverse outcomes (β = 0.024 [0.013, 0.034]). Conclusions: In patients with preeclampsia, EASIX diverged over time with steeper slopes in patients who developed adverse maternal outcomes. Our findings suggest that longitudinal EASIX monitoring may correlate with endothelial dysfunction and capture individual disease dynamics that are not apparent from a single measurement.