Dottorato in ARTERIAL HYPERTENSION AND VASCULAR BIOLOGY

Titolo della tesi: Feasibility of Screening and Subtyping of Primary Aldosteronism during Mineralocorticoid Receptor Antagonists (MRA) treatment

Background: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRA) before primary aldosteronism (PA) screening and subtyping, but this practice can cause severe hypokalemia and/or uncontrolled high blood pressure (BP). Recently, the results EMIRA study showed that MRA, at doses able to control BP and potassium levels, do not lower aldosterone or increase renin levels, hence they do not interfere with PA screening. Aims of the study: Our main aim was to verify the feasibility of using MRAs during subtyping of PA by adrenal vein sampling (AVS). Secondary aims were to evaluate the effect of MRAs on AVS indexes and to investigate the accuracy of subtyping PA with AVS as a function of the level of renin suppression. Methods. We compared the rate of uPA identification between patients with and without MRA treatment in large datasets of patients submitted to AVS while off renin-angiotensin system blockers and beta-blockers. In sensitivity analyses, the between-group differences of lateralization index (LI) values after propensity score matching and the rate of uPA identification in subgroups with undetectable (≤ 2 mUI/L), suppressed (< 8.2 mUI/L) and unsuppressed (≥ 8.2 mUI/L) direct renin concentration (DRC) levels were also evaluated. Results: Plasma aldosterone concentration, DRC, and BP values were similar in non-MRA- (n=779) and MRA-treated (n=61) PA patients, but the latter required more antihypertensive agents (p = 0.001) and showed a higher rate of adrenal nodules (82% vs 67%, p = 0.022) and adrenalectomy (72% vs 54%, p = 0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the ROC curve (AUROC) of lateralization index (LI), both under unstimulated conditions and post-cosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels. Conclusions: Treatment with MRAs, at doses that controlled BP and potassium levels, does not preclude screening and subtyping of PA, allowing for the control of hypertension and hypokalemia.