Guidelines recommend use of the aldosterone-renin ratio (ARR) for the case detection of primary aldosteronism (PA) and “confirmatory” tests in patients with a baseline ARR value above a given cut-off to exclude false positive results from further diagnostic work-up.
We tested the hypothesis that the ARR carries important quantitative information, which could avoid confirmatory tests in a substantial proportion of the patients.
Design and method:
The study was carried out in two prospectively recruited large cohorts of hypertensive patients who underwent measurement of the ARR and the captopril challenge test, in which a conclusive diagnosis of aldosterone-producing adenoma (APA) was made by the “four corners” criteria. We analyzed the exploratory dataset based on ARR cut-off values corresponding to predefined false positive rates for the diagnosis of APA. The results obtained in the exploratory dataset were then tested in a sensitivity analysis of the validation cohort. To determine if the captopril challenge test yielded any diagnostic gain over the cut-off value, which maximized accuracy, the AUC of ROC curve of the post-captopril ARR was analyzed.
The exploratory dataset was analyzed at five predefined ARR cut-offs, that yielded a 1% stepwise decrease of false positive rates from 5% to 1%, showing that the positive and negative likelihood ratio progressively increased along with the ARR cut-off value. ARR values above 115.4 (ng/dl)/(ng/ml/h), e.g. the cut-off associated with a false positive rate of 2%, provided no incremental positive likelihood ratio. The diagnostic odds ratio progressively increased up to a peak at the cut-off value corresponding to a 2% false positive rate. After selection of patients with an ARR >115.4 the post-captopril ARR ROC curve (using the APA as diagnosis status) showed no diagnostic gain of the captopril challenge test (0.550 95% CI 0.369–0.732, p = 0.5 vs. the AUC identity line). These results were confirmed by the analysis of the validation dataset.
Our study showed that the ARR carries quantitative information and that values above the 115.4 cut-off identify patients with a high probability of APA, in whom the diagnostic yield of the captopril challenge test is null.