Logo: to the web site of Uppsala University

Objective: Primary aldosteronism (PA) is a common cause of hypertension. It entails elevated morbidity and mortality that do not sufficiently improve with conventional antihypertensive therapy. Screening for PA by plasma aldosterone–renin ratio (ARR) enables discovery and specific treatment of affected patients. By screening primary care patients with hypertension and evaluating them further according to the Endocrine Society guidelines, we aimed to assess the prevalence of PA, the factors affecting biochemical diagnostics, and the outcome of lateralization studies and of specific treatment of the discovered PA cases.

Design, patients, and methods: Prospective evaluation of screening for PA was conducted in 1,181 patients. Screening by ARR was performed under current therapy, but without mineralocorticoid receptor antagonists (MRA), under normokalemia, and confirmed by the intravenous saline suppression test, SST#1. Those with results in a defined gray zone underwent therapy adjustment and then completed SST#2. Plasma aldosterone and ARR were compared under different stages of the diagnostic process. All patients with PA were offered adrenal venous sampling, or, in certain cases, adrenocortical-specific positron emission tomography. Lateralizing cases were offered laparoscopic adrenalectomy. Patients with bilateral disease were treated with MRA. Treatment results were assessed after a minimum of 6 months.

Results: A total of 53 discovered cases of (mostly mild) PA corresponded to its prevalence of 4.5%. Initial seated ARR was higher than recumbent ARR before SST#1. At SST#2, initial ARR and final aldosterone were higher than at SST#1. Localizing studies (accepted by 45 patients) found 14 lateralized cases. Of the 11 operated cases, 4 had aldosterone-producing adenoma, and the remainder had micro- and macronodular histopathology. A total of 31 patients had bilateral PA. Both surgical and conservative treatments were well tolerated and led to improved blood pressure and higher renin, indicating risk amelioration.

Conclusions: PA is prevalent among primary care patients with hypertension and can be screened for under current antihypertensive therapy. Aldosterone-producing adenoma was rare in this cohort. The study results support active screening of primary care patients with hypertension for PA in order to offer appropriate treatment options.

Background: Primary aldosteronism (PA) is the principal cause of secondaryhypertension; it leads to significantly elevated cardiovascular morbidity andmortality, but only a fraction of its cases ever get detected, partially due todiagnostic procedures that are difficult to perform and to interpret. Morestraightforward diagnostic methods are needed. Lateralized, or unilateral PA(uPA), is best treated by surgery. Bilateral PA (bPA) is treated medically.Aim: The aim of our study was to explore microRNA (miRNA) in peripheral bloodas markers of PA, uPA and bPA.

Methods: In groups of subjects with primary hypertension (HT, n = 11), bPA (n =12), and uPA (n = 16), peripheral serum was used for isolation of total RNA, librarypreparation, and NGS sequencing to achieve a comparative analysis of miRNAexpression. Five-fold cross-validation support vector machine learning (ML)models were employed to search for miRNA that could be used as markers ofPA and its forms.

Results: In our cohort of patients, the discovered combinations of miRNAs could,with a high level of accuracy, sensitivity, and specificity, characterize thedifference between HT and PA, as well as between a combined group of HT +bPA vs. uPA. The differentiating parameters were moderately good forcomparison of bPA vs. uPA.

Conclusion: Within our patient cohort, and using ML, the study identifieddistinctly different miRNA profiles between HT and PA, as well as between bPAand uPA. Further validation studies may lead to the emergence of a new tool forclinical diagnostics of PA.

Purpose 

Primary aldosteronism (PA) is prevalent among hypertensive patients, and associated with worsened cardiovascular outcomes compared to primary hypertension (HT). Screening and diagnostics for PA are currently complicated and invasive, why new methods are needed. Unilateral PA (uPA) is best treated surgically, and bilateral PA (bPA) - medically. No validated proteomic diagnostic test has been found yet. Our aim was to explore proteomic markers in peripheral serum to discriminate between HT, PA, uPA and bPA. 

Methods

Eighty-eight hypertensive individuals were evaluated for PA, and diagnosed with HT (n=30); bPA (n=29); and uPA (n=29). Serum samples from these study groups were analyzed by Olink® Explore 384 Cardiometabolic Panel. A machine learning model based on ridge logistic regression with a stratified 5-fold cross-validation was used to identify HT, PA, bPA and uPA.

Results

In the study groups, 56 circulating proteins were significantly different, and some of them specifically: 4 between PA vs. HT;  3 between bPA vs. uPA; 1 between bPA vs. HT; 9 between uPA vs. HT; 1 between HT vs. bPA vs. uPA. Three proteins with strongest differentiation (Coagulation factor IX for PA vs. HT; dipeptidyl peptidase 4 for uPA vs. HT and bPA; heat shock protein B1 for bPA vs. uPA) were validated by enzyme-linked immunosorbent assay. Our machine learning model could successfully identify 95% of HT, bPA, and uPA samples.

Conclusion

Serum protein biomarkers may serve as a tool for discriminating HT, PA, uPA and bPA. Further studies are needed to support our results.