Marinobufagenin in essential hypertension and primary aldosteronism: a cardiotonic steroid with clinical and diagnostic implications

Abstract

Background: The cardiotonic steroid marinobufagenin (MBG) is increasingly suggested to be responsible for some of the cardiovascular injury that has been previously attributed to aldosterone. We examined the clinical correlates of circulating MBG concentrations in hypertensive patients and tested the hypothesis that MBG serves as a reliable diagnostic tool for detecting primary aldosteronism (PA).

Methods: Plasma MBG concentrations (mean: 0.51 ± 0.25 nmol/l) were measured in the morning fasting samples in 20 patients with PA and 20 essential hypertensive (EH) controls matched for age, sex, body mass index, renal function, urinary sodium and intake of antihypertensive medication (mean age: 51.6 years; 52.2% women).

Results: Overall, plasma MBG was directly correlated with plasma aldosterone, aldosterone to active renin ratio (AARR), diastolic blood pressure, mean carotid intima-media thickness, serum sodium, urinary protein to creatinine ratio and inversely with serum potassium levels. Plasma MBG levels were significantly higher in patients with PA compared to EH (mean: 0.68 ± 0.12 versus 0.35 ± 0.24 nmol/l; p < 0.001). ROC analysis yielded a greater AUC for plasma MBG compared to the AARR, PAC and serum potassium levels for detecting PA. Youden's Index analyses yielded the optimal plasma MBG cut-off score for diagnosing PA at > 0.49 nmol/l with specificity and sensitivity values of 0.85 and 0.95, respectively, which were higher than those at the optimum AARR cut-off at > 3.32 ng/dl/µU/ml.

Conclusions: In a well-characterized cohort, values of plasma MBG were significantly related to clinical correlates of cardiovascular and renal disease. Plasma MBG emerged as a valuable alternative to the AARR for screening of PA.

• Aldosterone
• cardiovascular
• hypertension
• marinobufagenin
• primary aldosteronism

Acknowledgements

We thank the whole staff of the outpatient clinic and the laboratory at the Department of Endocrinology and Metabolism as well as the laboratory at Clinical Institute of Medical and Chemical Laboratory Diagnostics of the Medical University of Graz for supporting us with the Graz Endocrine Causes of Hypertension study. The anti-MBG antibody, MBG-BSA conjugate and MBG were a kind gift from Alexei Bagrov MD, PhD, National Institute on Aging, National Institutes of Health, Baltimore, MD.

Declaration of interest

A.T. is partially supported by the project EU-MASCARA (“Markers for Sub-Clinical Cardiovascular Risk Assessment”; [HEALTH.2011.2.4.2-2]; Grant agreement no: 278249) and by the project EU-HOMAGE (“Validation of -omics-based biomarkers for diseases affecting the elderly” [HEALTH.2012.2.1.1-2]; Grant agreement no: 305507) and EU-SYSVASC ([HEALTH.2013.2.4.2-1]; “Systems Biology To Identify Molecular Targets For Vascular Disease Treatment”; Grant agreement no: 603288). M.G. is supported by funding from the Austrian National Bank (Jubilaeumsfond: project numbers: 13878 and 13905). N.V. is supported by funding from the Austrian National Bank (Jubilaeumsfond: project numbers: 14621). The authors report no conflicts of interest. A.T., G.P. and S.P. take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Supplementary material available online

Supplementary Figure S1