SUN-LB97 Targeted Metabolomics as a Screening Tool in the Diagnosis of Endocrine Hypertension

Arterial hypertension [HT] is a global epidemic that requires adequate treatment to reduce cardiovascular morbidity and mortality. Secondary causes of HT and specifically endocrine hypertension [EHT] (primary hyperaldosteronism [PA], pheochromocytoma/paraganglioma [PPGL] and Cushing syndrome [CS]) can potentially be cured by surgery or treated by targeted medication. However, diagnosis of EHT requires expertise in test selection and interpretation of test results. The availability of experts outnumbers its demand. Thus, preselecting tools are necessary to identify patients who require further referral to an expert. Since targeted metabolomics [TM] is a new method showing promising results in profiling cardiovascular diseases and endocrine conditions associated with HT, we tested the ability of TM in discriminating primary hypertension [PHT] from EHT cases. The study included 282 adult patients (52% female; mean age 49 years) from the European multicentre consortium ENSAT-HT (www.ensat-ht.eu). Of these, 59 were diagnosed with PHT and 223 with EHT (40 CS, 107 PA and 76 PPGL). TM was performed on stored blood samples with a mass spectrometry based approach using the AbsoluteIDQ(TM) p180 Kit (BIOCRATES Life Sciences, Austria). In total, 188 metabolites were determined, of which 155 were eligible for statistical analyses according to established selection criteria. To identify relevant discriminating metabolites, a series of univariate and multivariate analyses were applied. Since the distribution of the patients between the clinical entities was different according to sex (p<0.001) and age (p=0.001), analyses were also performed separately for each sex and age group (cut-off 50 years). Thereby, we identified 4 common metabolites (C18:1, C18:2, spermidine, ornithine) from the comparison of PHT with each endocrine hypertension subgroup (CS, PA, PPGL) separately. The ROC curve for discrimination between PHT and EHT built upon these 4 metabolites had an area under the curve (AUC) of 0.79 (95%CI 0.73-0.85). In the comparison of PHT and EHT as a common group 38 metabolites were identified. Using the top 15 metabolites from the latter comparison (C3-DC, C9, C16, C16:1, C18:1, C18:2, arginine, aspartate, glutamate, ornithine, spermidine, lysoPCaC20:4, PCaaC38:6, PCaaC40:6, PCaaC42:1) the AUC was 0.86 (95%CI 0.81-0.91). We conclude that TM is associated with distinct metabolic pattern in PHT and EHT and is a promising pre-screening tool for identifying EHT patients.