Renin-Angiotensin-Aldosterone System Triple-A Analysis for the Screening of Primary Aldosteronism

Hypertension. 2020 Jan;75(1):163-172. doi: 10.1161/HYPERTENSIONAHA.119.13772. Epub 2019 Nov 25.


Primary aldosteronism is recognized as the most frequent cause of secondary hypertension, and its screening is expected to become a routine evaluation in most patients with hypertension. The interference of antihypertensive therapies with the aldosterone-to-renin ratio during screening process is a major confounder. Renin-angiotensin-aldosterone system Triple-A analysis is a novel liquid chromatography/tandem mass spectrometry diagnostic assay that allows simultaneous quantification of aldosterone, equilibrium Ang I (angiotensin I), and Equilibrium Ang II in a single sample of serum. We performed a comparative evaluation of the diagnostic performance of the aldosterone-to-Ang II ratio and 5 renin-based diagnostic ratios, differing in methods to determine aldosterone levels and renin activity in a cohort of 110 patients with hypertension (33 patients with confirmed primary aldosteronism and 77 with essential hypertension). All ratios showed comparable areas under the curves ranging between 0.924 and 0.970 without significant differences between each other. The evaluation of the Ang II-to-Ang I ratio revealed persistent drug intake in some patients as cause for suppressed renin-based diagnostic ratios, while aldosterone-to-Ang II ratio remained unaffected. The Youden index optimal cutoff value for the aldosterone-to-Ang II ratio was 6.6 ([pmol/L]/[pmol/L]) with a sensitivity of 90% and a specificity of 93%, proving noninferiority compared with the aldosterone-to-renin ratio while pointing to the potential for an interference-free application in patients under ACE (angiotensin-converting enzyme) inhibitor therapy. This study shows for the first time the accuracy and reliability of renin-angiotensin-aldosterone system triple-A analysis for the screening of primary aldosteronism that can be applied in clinical routine.

Keywords: adrenal glands; aldosterone; angiotensin II; mass spectrometry; renin-angiotensin system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aldosterone / blood*
  • Angiotensin I / blood*
  • Angiotensin II / blood*
  • Essential Hypertension / blood
  • Essential Hypertension / diagnosis*
  • Female
  • Humans
  • Hyperaldosteronism / blood
  • Hyperaldosteronism / diagnosis*
  • Male
  • Middle Aged
  • Renin-Angiotensin System*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry


  • Angiotensin II
  • Aldosterone
  • Angiotensin I