Hypertension as the main risk for cardiovascular events
Uncontrolled hypertension affects more than 50% of patients treated for their high blood pressure. Underlying causes are manifold and it is therefore challenging to identify the cause of inefficient blood pressure lowering therapy in clinical practice. Diagnostic tools that have been available so far to screen for frequent forms of secondary hypertension, like primary aldosteronism, suffer from interference with anti-hypertensive therapies and require drug withdrawal before screening, leading to very low screening rates. However, more than every 10th high blood pressure patient is affected by primary aldosteronism. General practitioners frequently have to go the trial and error path when seeking to control hypertension in their patients. Without knowing the underlying molecular causes, this might result in frustration among patients, inappropriate drug prescriptions and also increases in the overall cardiovascular risk due to a long time to blood pressure control.
What is RAAS Triple-A™ analysis?
The Renin-Angiotensin-Aldosterone-System (RAAS) is critically involved in the regulation of fluid balance and blood pressure. It serves as a major target for the pharmacologic treatment of hypertension. The RAAS Triple-A™ hormones (Angiotensin I, Angiotensin II and Aldosterone) and their receptors represent key molecular players in mediating physiologic hormonal effects.
Up until now, the laboratory evaluation of the RAAS has been primarily based on measuring Renin, which is the upstream precursor of Angiotensin II, the actual effector hormone of the RAAS. Recent doubts related to the reliability of such methods led to a surge in clinical LC-MS/MS for Aldosterone, while an LC-MS/MS based method for the simultaneous measurement of Renin is still not available yet.
For the first time, RAAS-Triple-A™ analysis, and subsequent calculation of Angiotensin-based biomarkers paved the way for the simultaneous LC-MS/MS based assessment of Aldosterone concentration, renin activity and ACE activity in standard serum samples. This allows for an in-depth assessment of RAAS dynamics, which includes screening for secondary hypertension (primary aldosteronism, PA) using the Aldosterone-to-Angiotensin II ratio (AA2-R).
Angiotensin-based biomarkers
PRA-S: Angiotensin based marker for renin, the pacemaker enzyme of the Renin-Angiotensin-Aldosterone system (RAAS).
Renin is secreted by the kidney and is regulated by renal hemodynamics, fluid and salt balance as well as Angiotensin II itself. Most antihypertensive drugs have direct or indirect effects on Renin secretion.
ACE-S: Angiotensin based marker for the activity of Angiotensin converting enzyme (ACE), which is the main vascular and systemic producer of Angiotensin II. ACE-S is obtained by calculating the ratio between Angiotensin II and Angiotensin I. ACE-S in a patient sample is a measure for the pharmacologic efficacy of an ongoing ACE inhibitor therapy.
AA2-Ratio: The ratio of Aldosterone to Angiotensin II reflects the responsiveness of adrenal glands for Angiotensin II. In primary aldosteronism, which affects up to 10 % of hypertensive patients, this ratio is increased because excess Aldosterone secretion is largely independent of Angiotensin II. In patients with essential hypertension treated with ARBs, the AA2-Ratio is suppressed and can be used to monitor drug efficacy
RAAS Triple-A™ Kit
The RAAS Triple-A™ kit (CE-IVD) is a powerful routine laboratory support tool providing all necessary reagents, quality control samples, calibrators, and consumables required for the LC-MS/MS based quantification of Angiotensin I, Angiotensin II and Aldosterone in clinical samples. An optional software tool can be used to calculate angiotensin-based biomarkers that have been validated to screen for secondary causes of hypertension and to monitor antihypertensive drug efficacy.
Process overview
RAAS Triple-A™ analysis requires the collection of a serum sample of at least 0.5 ml. Patients should be on their standard antihypertensive treatment. With a bench stability of at least 8 hours at room temperature, the assay is highly robust and compatible with routine laboratory procedures. Samples may optionally be shipped or stored frozen until analysis, allowing interval workup of clinical routine samples as well as retrospective assessment of study samples, if needed.
More information
More research using our technology for RAAS profiling can be found here
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