THE EFFECT OF RAMIPRIL ON THE ALDOSTERONE/RENIN RATIO AND THE ALDOSTERONE/ANGIOTENSIN II RATIO IN PATIENTS WITH PRIMARY ALDOSTERONISM

Abstract

Objective: The aldosterone/renin ratio (ARR) is recommended for case detection of PA. However, many anti-hypertensive medications [such as angiotensin-converting enzyme (ACE) inhibitors] and physiological factors have been reported to affect renin and aldosterone, thereby causing false-negative ARR screening results. We sought to investigate the diagnostic performance of the ARR and aldosterone/AngII ratio (AA2R) among PA patients receiving ramipril treatment. Design and method: Blood samples from 60 PA and 40 non-PA patients were collected, aiming to predict optimal PA screening cut-offs for the ARR and AA2R (using ROC analysis). Another 26 PA patients were recruited and were administered ramipril (5 mg tablet, once daily) for 2 weeks. Blood was collected in the morning of day 0 (basal), day 14 (2 h after taking ramipril) and day 15 (26 h after last dose ramipril). Plasma aldosterone (PAC), equilibrium AngI and AngII (eqAngI and eqAngII) were measured by LC-MS/MS, while renin concentration (DRC) and activity (PRA) were measured by immunoassays. Results: When PAC was measured by LC-MS/MS, the predicted PA screening cut-offs for the ARR_DRC, ARR_PRA and AA2R were 53.9 (pmol/mU), 495.9 (pmol/L)/(ng/ml/h) and 8.3 (pmol/pmol), respectively. Compared to the basal levels, eqAngII and ACE activity (ACE-S, eqAngII/eqAngI) both decreased (P < 0.01) after ramipril treatment, whereas DRC, PRA and eqAngI all increased (P < 0.01 or P < 0.05). Although median PAC tended to fall from 504.9 (day 0) to 458.3 (day 14) and to 488.0 (day 15) pmol/L, the changes were not statistically significant. On day 14, five patients displayed false-negative results in both ARR_DRC and ARR_PRA, whereas no false-negative AA2R result was observed. On day 15, three patients still demonstrated false-negative screening results, including one with both false-negative ARR_DRC and ARR_PRA, one with both false-negative ARR_DRC and AA2R, and one with false-negative ARR_PRA only. Conclusions: Although PAC did not change significantly, the changes of renin, eqAngI, eqAngII and ACE-S were consistent with ramipril's effect on ACE. Unlike the ARR which can be affected by ACE inhibitors causing false-negative screening results, the AA2R seems to be superior in PA screening among subjects who are receiving ACE inhibitors.