A retrospective longitudinal study on the association between urine metanephrines and cardiovascular events in patients in primary prevention without chromaffin tumors

Mirko Parasiliti Caprino; Martina Bollati; Elisa Febbraro; Daniele Giuseppe Candela; Matteo Procopio; Stefano Arata; Chiara Lopez; Fabio Bioletto; Federico Ponzetto; Giulio Mengozzi; Ezio Ghigo; Mauro Maccario

doi:10.1530/endoabs.110.P46

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Endocrine Abstracts (2025) 110 P46 | DOI: 10.1530/endoabs.110.P46

ECEESPE2025 Poster Presentations Adrenal and Cardiovascular Endocrinology (169 abstracts)

A retrospective longitudinal study on the association between urine metanephrines and cardiovascular events in patients in primary prevention without chromaffin tumors

Mirko Parasiliti Caprino ¹ , Martina Bollati ¹ , Elisa Febbraro ¹ , Daniele Giuseppe Candela ¹ , Matteo Procopio ¹ , Stefano Arata ¹ , Chiara Lopez ¹ , Fabio Bioletto ¹ , Federico Ponzetto ¹ , Giulio Mengozzi ² , Ezio Ghigo ¹ & Mauro Maccario ¹

Author affiliations

¹Endocrinology, Diabetes and Metabolism, University of Turin, Turin, Italy; ²Clinical Biochemistry Laboratory, University of Turin, Turin, Italy

JOINT2036

Background: Previous studies have suggested that urine metanephrines (metanephrine, dU-MT, and normetanephrine, dU-NMT), metabolites of catecholamines used in the diagnosis and follow-up of pheochromocytomas and paragangliomas (PPGL), may serve as markers of sympathetic nervous system (SNS) hyperactivation. SNS overactivity has been observed in various cardiometabolic disorders such as hypertension, heart failure, and metabolic syndrome. However, the predictive role of metanephrines in cardiovascular events (CVE) remains unexplored.

Objectives: This retrospective longitudinal study aims to assess the association between urine metanephrine levels and the development of CVE in patients in primary prevention without PPGL.

Methods: Adult patients who underwent measurement of 24-hour urine fractionated metanephrines at the Clinical Biochemistry Laboratory of the City of Health and Science University Hospital of Turin between 2007 and 2015 were included in the analysis. Patients were stratified into tertiles based on dU-MT and dU-NMT levels. Exclusion criteria encompassed a diagnosis of PPGL, prior CVE, interfering therapies, acute conditions at the time of testing, and stage IV-V chronic kidney disease. CVE development (coronary artery disease, stroke, symptomatic peripheral artery disease, arrhythmias, and heart failure) was assessed by retrieving pertinent discharge diagnoses from a regional database, restricting the evaluation to hospital admissions that occurred after the measurement of urine metanephrines.

Results: The final population consisted of 1,170 individuals (41.5% male, mean age 54±14 years), 86% of whom had arterial hypertension. During a mean follow-up period of 11.7±4.1 years, 14.7% of patients experienced a CVE. In univariate analysis, patients in the 2nd and 3rd tertiles of dU-NMT showed lower CVE-free survival compared to those in the 1st tertile (P=0.020 and P < 0.001, respectively). Multivariate Cox regression analysis revealed that patients in the 3rd tertile of dU-NMT had a 1.76-fold increased risk of CVE compared to those in the 1st tertile (P=0.010), regardless of traditional cardiovascular risk factors (age, sex, smoking status, family history of CVE, hypertension, and diabetes mellitus), renal function, number of antihypertensive drugs, and lipid-lowering therapy. Tertiles of dU-MT, however, did not show a significant difference in CVE risk.

Conclusions: This study reveals an association between higher dU-NMT levels and increased long-term risk of CVE, regardless of traditional risk factors, within a primary prevention cohort of patients without PPGL. These findings suggest that such metabolites could serve as a valuable tool for cardiovascular risk stratification.