Angiotensin profiling accurately identified ACEi (100% sensitivity, 99% specificity) and ARB adherence (80% sensitivity, 94% specificity), enabling drug-specific primary aldosteronism screening.
Cohort
Does angiotensin profiling accurately detect drug adherence and primary aldosteronism in patients with resistant hypertension on triple therapy including an ACEi or ARB?
Angiotensin profiling provides accurate mechanism-based drug monitoring and drug class-specific primary aldosteronism screening in patients on triple antihypertensive therapy, addressing a critical gap in current guidelines.
Objective: Contemporary guidelines endorse screening for primary aldosteronism (PA) in patients receiving first-line antihypertensive therapy. However, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) substantially alter renin and angiotensin peptides, complicating interpretation of PA biomarkers and obscuring drug non-adherence. Practical guidance for PA detection under RAAS blockade remains undefined. Design and method: In the Prospective Cohort: Resistant Hypertension (PRIO) study, patients with uncontrolled or resistant hypertension were transitioned to standardized triple therapy including an ACEi or ARB. At follow-up, standard biochemical screening for PA was performed with referral for adrenal vein sampling as indicated. Patients not meeting diagnostic criteria were classified as uncontrolled hypertension (UHTN). Using a validated LC-MS/MS platform, we retrospectively quantified angiotensin (Ang) peptides and aldosterone to evaluate drug class-specific effects on Ang II, ACE-Q (ratio of Ang II to Ang I), and the aldosterone-Ang II ratio (AA2-R). Drug adherence was determined by direct quantification of antihypertensive agents in serum (reference method). Receiver operating characteristic analyses defined cut-offs for ACE-Q and Ang II to detect ACEi and ARB adherence, respectively. “Clean” adherence thresholds were derived in UHTN patients without PA. Among biomarker-adherent patients, we established ACEi- and ARB-specific AA2-R cut-offs for PA detection and constructed a sequential clinical algorithm integrating drug monitoring and PA screening. Results: ACEi suppressed ACE-Q, and ARBs increased concentrations of Ang II, confirming mechanistic specificity of these two drug classes. ACE-Q and Ang II robustly identified ACEi and ARB adherence, respectively, with good performance sensitivity and specificity (ACE-Q 163 pM; 80% and 94%). Drug class – specific AA2-R thresholds for PA differed substantially between ACEi- and ARB-treated patients (20.4 and 1.84 pM/pM with respective sensitivity and specificity of 100% and 82%, and 92% and 98%). The integrated algorithm demonstrated excellent performance for simultaneous adherence assessment and PA detection. Conclusions: Angiotensin profiling enables mechanism-based drug monitoring and drug class-specific PA screening under triple therapy. This approach reduces ambiguity introduced by RAAS blockade and non-adherence, addresses a critical gap in current guidelines, and advances precision management of resistant hypertension.
Beger et al. (Fri,) conducted a cohort in uncontrolled or resistant hypertension. Angiotensin profiling was evaluated on Detection of ACEi and ARB adherence and primary aldosteronism. Angiotensin profiling accurately identified ACEi (100% sensitivity, 99% specificity) and ARB adherence (80% sensitivity, 94% specificity), enabling drug-specific primary aldosteronism screening.