Copeptin Levels Consistently Elevated in Preeclampsia, Revealing Geographic and Genetic Links to AVP System

Preeclampsia (PE) is a severe, life-threatening pregnancy complication characterized by new-onset hypertension and organ dysfunction. Current diagnostic methods often rely on clinical symptoms, which can delay intervention. Literature suggests elevated copeptin (CPP), a stable surrogate marker for arginine vasopressin (AVP) secretion from the hypothalamic-neurohypophyseal system (HNS), precedes PE onset. Understanding the dynamic role of the AVP system, beyond a primary driver, could offer new avenues for early detection and personalized management strategies for this critical condition.

This systematic review and meta-analysis investigated copeptin levels in women with preeclampsia, exploring the AVP system's association with clinical progression. Researchers searched five databases (Google Scholar, Embase, Scopus, PubMed, Semantic Scholar) using terms like "preeclampsia-AND-vasopressin-OR-copeptin-OR-oxytocin". Study quality was assessed via the Newcastle-Ottawa Scale. A Gaussian Mixture Model (GMM) algorithm, after Kernel Principal Component Analysis (kPCA), was applied to predict preeclamptic or healthy normotensive pregnancies based on copeptin concentrations. The review included 39 registries, with 20 observational studies documenting copeptin concentrations across all three trimesters.

The meta-analysis, encompassing 1025 cases within 2446 pregnancies, consistently found elevated copeptin (CPP) concentrations in women with preeclampsia. Observational and experimental studies confirmed an association between the development of PE and circulating CPP levels, alongside pharmacological manipulations involving AVP. Notably, no such association was observed for oxytocin levels. Geographic comparisons revealed a significant gene-environment link: > A greater effect of higher concentrations of CPP on preeclamptic cases was observed in Asian and African populations. This suggests a potential regional influence on the AVP system's role in PE. Furthermore, gestational hypertension was associated with single nucleotide polymorphisms (SNPs) in the AVP and ERAP2 genes, where ERAP2 encodes an endopeptidase that cleaves and inactivates AVP, highlighting a genetic component to AVP regulation in hypertensive pregnancy.