Nikita Makhnov: Primary aldosteronism: improving screening-based diagnostics and treatment

Abstract

Primary aldosteronism (PA, non-physiologic adrenal overproduction of aldosterone) causes about 10% of arterial hypertension, and substantially elevates morbidity and cardiovascular mortality compared to primary hypertension (HT) alone.  PA often lacks specific clinical traits, and remains mostly undiagnosed. Its diagnosis requires biochemical screening and confirmatory tests - which are quite difficult to perform and/or to interpret correctly. About a quarter of PA cases are lateralized (or unilateral, uPA) – and can be cured or significantly ameliorated by surgery, which gives the best long-term prognosis. Bilateral subtype (bPA) can be controlled by mineralocorticoid receptor antagonists. Even the current lateralizing procedures are technically demand-ing and invasive. The challenge of identifying PA and its subtypes to guide the treatment requires more straightforward and sensitive diagnostic methods.

Our first paper describes the project of screening of 1181 unselected primary care hypertensive patients for PA. The 53 found cases of PA (corresponding to a prevalence of 4,5%) were further evaluated and treated (surgically or medically) according to the current guidelines. The pathophysiologic and clinical aspects of the recommended diagnostic and treatment principles, and the follow-up results after at least 6 months after treatment initiation were presented and analyzed.

Our second and third papers present research of new peripheral blood markers that may support diagnostics of PA among hypertensive individuals, including differentiation between its lateralized and bilateral subtype. MicroRNAs (second paper) and proteomic profile (third paper) were analyzed in groups of well clinically studied patients with HT, bPA and uPA.

MicroRNAs have been shown to regulate both aldosterone production and its effects in the target-tissues. Using machine learning (ML), we demonstrate the potential of both microRNAs (analyzed by NGS) and proteomics (analyzed by Olink® Explore 384 Cardiometabolic Panel based on proximity extension assay) to differentiate PA from HT, and uPA from bPA. Further validating studies are needed to evaluate the constructed ML-models and the clinical utility of both microRNA and proteomic analysis in hypertensive patients.

The theoretic and practical experience of these studies confirms the necessity to actively screen hypertensive patients for PA and to further develop its diagnostic methods as specific treatment ameliorates the long-term prognosis.