IMPROVING HYPERTENSION CONTROL BY MOLECULAR STRATIFICATION OF FIRST-LINE NON-RESPONDERS USING RAAS TRIPLE-A TESTING

Abstract

Objective: According to new European guidelines, first-line anti-hypertensive therapies include either an ACE inhibitor (ACEi) or an angiotensin receptor blocker (ARB) in a single pill combination with a calcium channel blocker (CCB) or a diuretic. Insufficient therapeutic effects could be caused by various factors ranging from compliance issues, patient specific PK/PD profiles, or secondary forms of hypertension. Altogether these factors contribute to blood pressure control rates ranging around 50% of patients on antihypertensive treatment. Design and method: RAAS Triple-A testing is based on a clinical high-throughput mass-spectrometry assay for simultaneous quantification of Angiotensin-I (Ang-I), Angiotenisn-II (Ang-II) and Aldosterone in standard serum or plasma samples by RAAS equilibrium analysis. Equilibrium angiotensin (eqAng-I, eqAng-II) and aldosterone levels are used to calculate markers for plasma-renin-activity (PRA-S), plasma angiotensin-converting-enzyme activity (ACE-S) and adrenal function (AA2-Ratio) that have been validated in healthy volunteers and hypertensive patients on therapy. The diagnostic performance of the AA2-Ratio in screening for primary aldosteronism (PA) has been compared to the aldosterone-to-renin ratio (ARR) as putative gold standard in resistant hypertensive patients, revealing major advantages of the AA2-Ratio especially in terms of usability and drug interference. Results: A diagnostic scheme for the stratification of first-line non-responding hypertensive patients has been developed to improve the control rates for hypertension and to provide an easy-to-handle diagnostic tool for physicians involved in first-line treatment of hypertension. The complex functional relations and the impact of anti-hypertensive drugs on selected angiotensin derived biomarkers are combined into a diagnostic scheme that allows for easy evaluation of compliance and dosing efficiency while effectively screening for major forms of secondary hypertension including PA, potentially without the need of withdrawing ACE inhibitors before screening. Conclusions: The RAAS Triple-A analysis for the first time provides insights into a patient's RAAS at the level of effector hormones, molecular regulation and patient specific pharmacologic responses to anti-hypertensive therapies. RAAS Triple-A testing allows for simultaneous diagnostic assessment of multiple causes for uncontrolled hypertension and has the potential to result in significant changes in hypertension care in clinical practice by introducing personalized treatments based on an easy and effective diagnostic tool.