Screening for primary aldosteronism on and off interfering medications

Abstract

To determine whether antihypertensives will affect diagnostic accuracy of the ARR to an extent that is clinically relevant. MethodsCon rmatory tests were used to con rm or exclude PA diagnosis. Area under the receiver operating characteristic curve (AUC), speci city and sensitivity of ARR performance in different conditions were calculated. Results208 PA and 78 essential hypertension (EH), and 125 PA and 206 EH patients, were included in the retrospective and prospective cohort, respectively. AUC of ARR on interfering medications was comparable to ARR off interfering medications (retrospective: 0.82 vs. 0.87, p = 0.20; prospective: 0.78 vs. 0.84, p = 0.07). At a threshold of 20 pg/µIU, the sensitivity of ARR on interfering medications was lower (11.1-23.2%) while the speci city was higher (10.2-15.2%) than ARR off interfering medications.However, when the ARR threshold on interfering medications was lowered to 10 pg/µIU, both the sensitivity (retrospective: 0.91 vs. 0.90, p = 0.61; prospective: 0.86 vs. 0.82, p = 0.39) and speci city (retrospective: 0.49 vs. 0.59, p = 0.20; prospective: 0.58 vs. 0.66, p = 0.10) were comparable to the ARR threshold off interfering medications. ConclusionUsing ARR to screen for PA whilst taking interfering antihypertensive drugs is feasible in most cases, but the ARR threshold needs to be reduced. Trial RegistrationClinicalTrials.gov identi er: NCT04991961 [3][4][5]. International PA management guidelines recommend using the plasma aldosteronism-to-renin ratio (ARR) to screen for possible cases of PA [6][7][8]. However, commonly used antihypertensive drugs have been reported to affect plasma aldosterone and/or renin concentration. β receptor blockers can decrease both aldosterone and renin concentration, resulting in an increased ARR, while diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) and dihydropyridine calcium channel blockers (CCB) can increase renin and lower the ARR [9,10]. Hence, it is currently recommended that, if possible, antihypertensive that affect the ARR be withdrawn or switched to drugs with lesser effects on the ARR (eg. non-dihydropyridine CCB, α-adrenergic-receptor blocker) before screening [6]. However, this procedure can require multiple clinic visits and might render clinicians and/or patients reluctant to screen for PA [11]. In addition, changing medications may alter electrolyte status and blood pressure, affecting patients' well-being [12]. Thus, knowing the diagnostic accuracy of the ARR in the setting of ongoing antihypertensive treatment is particularly important for PA screening.Two studies reported that the accuracy of ARR screening for PA off or on interfering antihypertensive drugs is not signi cantly different [13,14]. Due to their small sample size, with 27 and 15 PA patients respectively, the data are not conclusive. We therefore sought to compare the accuracy of the ARR for PA detection either with or without the concurrent use of interfering antihypertensive drugs in a large patient cohort. ...

Challenges in Diagnosing and Managing the Spectrum of Primary Aldosteronism

“…A relatively small prospective study of 27 patients with PA and 151 patients with essential hypertension found no significant difference in the area under the receiver operated curve of the ARR on or off interfering medications when using a cutoff of 91 pmol/mU [ 22 ]. However, a larger cohort study of 331 patients (125 with PA and 206 with essential hypertension) who had ARR measured on and off interfering medications demonstrated an overall decrease in renin concentration and increase in ARR following cessation of interfering medications [ 23 ]. While on interfering medications (except β-blockers), a lower ARR cutoff of 27 pmol/mU showed comparable sensitivity and specificity to an ARR threshold of 54 pmol/mU off interfering medications.…”

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