MSACL 2016 US Abstract

The AA2-Ratio: Improved Screening for Primary Aldosteronism in Hypertension

Marko Poglitsch (Presenter)
Attoquant Diagnostics

Bio: Marko Poglitsch PhD., CEO Graduated from University of Vienna (Molecular Biology) and Technical University of Vienna (Biochemistry) and worked in the field of innate immunity during his PhD thesis at the Medical University of Vienna. Before he founded Attoquant Diagnostics, Dr. Poglitsch built up a mass spectrometry facility at Apeiron Biologics AG, a biotech company involved in cardiovascular drug development, where he developed the RAS-Fingerprint™ technology. Attoquant is specialized in the quantitative analysis of vasoactive peptides with a special focus on the peptides of the renin-angiotensin-system and offers LC-MS/MS based quantification of low-abundance peptide hormones in biological samples.

Authorship: Marko Poglitsch
Attoquant Diagnostics GmbH, Vienna, Austria

Short Abstract The Aldosterone-to-Angiotensin-II-Ratio (AA2-Ratio) is a novel LC-MS/MS based high-throughput test for primary aldosteronism (PA), a severe but curable form of hypertension. The test can be applied to standard collected serum samples and does not interfere with anti-hypertensive therapies including ACE inhibitors. These are major advantages over currently employed diagnostic procedures, building the basis for the implementation of the AA2-Ratio into clinical practice of therapeutic management of hypertension.

Long Abstract

Hypertension has been clearly shown to be the most important cause of morbidity and mortality worldwide, representing a severe challenge for healthcare systems in the future. The prevalence of hypertension in Europe is 30% among the adult population, affecting estimated 119 million people in in 2015. Numbers of hypertensive patients are constantly growing and an increase by 15% till 2025 is estimated. Up to 11,9 million people in Europe are referred to be resistant hypertensive, meaning that they cannot be cured by standard treatments and therefore have to face a severe cardiovascular risk. Primary aldosteronism (PA) is a frequent form of resistant hypertension affecting up to 20% of resistant hypertensive patients, up to 2,4 million Europeans.

PA can be can be cured by appropriate second-line drug treatments or surgical procedures, if detected. Recommendations of clinical societies suggest extensive screening efforts to facilitate the early detection of PA among resistant and high-risk hypertensive patients in order to reduce cardiovascular events. However, actual clinical practice does not adhere to these guidelines due to the lack of appropriate and cost effective screening procedures. A major issue in the diagnostic process of PA is that standard tests interfere with anti-hypertensive therapies, which needs to be discontinued before testing. This imposes a severe cardiovascular risk to affected patients, which is usually not taken by physicians leading to poor adherence to clinical guidelines. If PA remains undiagnosed, it causes severe hypertension frequently resulting in cardiovascular complications including heart attacks and strokes.

Primary aldosteronism (PA) is severe form of hypertension characterized by a strongly increased aldosterone secretion mediated by adenomas or other forms of adrenal hyper-activity. Once detected, PA can be usually cured by either surgical intervention or by appropriate pharmacologic treatments. This is also reflected in clinical guidelines of Endocrine Societies in Europe and the US, suggesting extensive PA screening activities among resistant hypertensive patients. The incidence of PA among hypertensive patients varies strongly between different studies, which is in part caused by the complex state-of-the-art testing procedure that is unfortunately far away from being a versatile PA screening tool. Despite strong limitations regarding selectivity and the interference with multiple anti-hypertensive drugs, the antibody-based determination of the aldosterone-renin-ratio (ARR) is widely used for PA case detection. However, there is still a strong demand for accurate and reliable and patient friendly PA case detection. The use of novel LC-MS/MS based assays for quantification of aldosterone might help to improve the power of the ARR as a diagnostic tool for PA. However, there is a big need for a versatile PA screening assay that doesn’t interfere with anti-hypertensive treatments and therefore allows the clear identification of PA patients without complex and risky treatment adaptions being necessary in the course of the diagnostic process. The Aldosterone-to-Angiotensin-II-Ratio (AA2-Ratio) is a novel LC-MS/MS based high-throughput test for PA that combines the plasma levels of aldosterone and physiologically active angiotensin II into a diagnostic ratio. The availability of innovative diagnostic approaches for the Renin-Angiotensin-Aldosterone-System (Equilibrium Analysis) paved the way for Angiotensin peptides to be used in clinical routine testing by solving pre-analytic problems of analyte stability. The test performance is superior to the ARR in terms of the diagnostic window and method accuracy and the AA2-Ratio does not interfere with standard anti-hypertensive drugs including ACE inhibitors. First data obtained in a proof-of-concept study investigating PA positive and negative patients proved the AA2-Ratio to be a powerful and cost-effective diagnostic tool for the diagnosis of PA in hypertension.

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