CIRCULATING BIOMARKERS IN MALIGNANT HYPERTENSION: INSIGHTS FROM THE IVAMA STUDY

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Objective: Malignant hypertension (MHT) is a rare but life-threatening condition characterized by abrupt and severe elevation in blood pressure, associated to acute damage in multiple target organs. Despite its clinical severity, the molecular mechanisms underlying MHT remain poorly understood. The IVAMA study was designed to identify molecular pathways driving organ injury in MHT. Design and method: IVAMA is a multicenter, prospective case-control study coordinated by CHU Bordeaux. It enrolled 30 patients with MHT and 15 matched controls with grade 2–3 essential hypertension. Blood and urine samples were collected at baseline and one month later (M1) to measure angiogenic, inflammatory, and vasoactive biomarkers using Luminex and Mesoscale platforms. Statistical analyses included repeated measures ANOVA, PCA, MFA, and multinomial logistic regression. Results: At inclusion, MHT patients had significantly higher SBP and DBP than controls, with marked retinal, renal, and cardiac damage. Biomarker analysis revealed elevated levels of ANGPT2, ANGPTL4, GAL-1, TREM-1, VEGFD, IL1-RA, and ET-1 in MHT patients. These markers showed significant correlations with organ injury parameters and remained elevated or evolved differently over time compared to controls. Renal injury was characterized by elevated creatinine, reduced eGFR, and increased proteinuria (UPCR, UACR), which correlated strongly with VEGFD, GAL-1, IL1-R1, and TREM-1. Cardiac injury, assessed via BNP, troponin, and echocardiography, was associated with ANGPT2, GAL-1, VEGFD, and IL33R. Retinal damage, including papilledema and hemorrhages, correlated with ET-1, ANGPTL4, and PTX-3. Multivariate analyses identified distinct biomarker clusters predictive of organ-specific injury. PCA and MFA revealed that inflammatory and endothelial markers drive the principal dimensions of disease heterogeneity. Logistic regression confirmed VEGFD, GAL-1, TREM-1, IL33R, and ANGPT2 as key predictors of organ damage clusters. Conclusions: The IVAMA study demonstrates that MHT is a biologically distinct entity within the spectrum of severe hypertension, characterized by specific inflammatory and angiogenic biomarker profiles. These molecular signatures are closely linked to organ damage and persist over time, distinguishing MHT from essential hypertension.

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