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Primary aldosteronism (PA) causes cardiovascular damage in excess to the blood pressure elevation, but there are no prospective studies proving a worse long-term prognosis in adrenalectomized and medically treated patients. We have, therefore, assessed the outcome of PA patients according to treatment mode in the PAPY study (Primary Aldosteronism Prevalence in Hypertension) patients, 88.8% of whom were optimally treated patients with primary (essential) hypertension (PH), and the rest had PA and were assigned to medical therapy (6.4%) or adrenalectomy (4.8%). Total mortality was the primary end point; secondary end points were cardiovascular death, major adverse cardiovascular events, including atrial fibrillation, and total cardiovascular events. Kaplan–Meier and Cox analysis were used to compare survival between PA and its subtypes and PH patients. After a median of 11.8 years, complete follow-up data were obtained in 89% of the 1125 patients in the original cohort. Only a trend ( P =0.07) toward a worse death-free survival in PA than in PH patients was observed. However, at both univariate (90.0% versus 97.8%; P =0.002) and multivariate analyses (hazard ratio, 1.82; 95% confidence interval, 1.08–3.08; P =0.025), medically treated PA patients showed a lower atrial fibrillation–free survival than PH patients. By showing that during a long-term follow-up adrenalectomized aldosterone-producing adenoma patients have a similar long-term outcome of optimally treated PH patients, whereas, at variance, medically treated PA patients remain at a higher risk of atrial fibrillation, this large prospective study emphasizes the importance of an early identification of PA patients who need adrenalectomy as a key measure to prevent incident atrial fibrillation.

Background Current guidelines recommend use of the aldosterone‐renin ratio ( ARR ) for the case detection of primary aldosteronism followed by confirmatory tests to exclude false‐positive results from further diagnostic workup. We investigated the hypothesis that this could be unnecessary in patients with a high ARR value if the quantitative information carried by the ARR is taken into due consideration. Methods and Results We interrogated 2 large data sets of prospectively collected patients studied with the same predefined protocol, which included the captopril challenge test. We used an unambiguous diagnosis of aldosterone‐producing adenoma as reference index. We also assessed whether the post‐captopril ARR and plasma aldosterone concentration fall furnished a diagnostic gain over baseline ARR values. We found that the false‐positive rate fell exponentially, and, conversely, the specificity increased with rising ARR values. At receiver operating characteristics curves and diagnostic odds ratio analysis, the high baseline ARR values implied very high positive likelihood ratio and diagnostic odds ratio values. The baseline and post‐captopril ARR showed similar diagnostic accuracy (area under the receiver operating characteristics curve) in both the exploratory and validation cohorts, indicating lack of diagnostic gain with this confirmatory test (between‐area under the curve difference, 0.005; 95% CI , −0.031 to 0.040; P =0.7 for comparison, and 0.05; 95% CI , −0.061 to 0.064; P =0.051 for comparison, respectively). Conclusions These results indicate that the ARR conveys key quantitative information that, if properly used, can simplify the diagnostic workup, resulting in saving of money and resources. This can offer the chance of diagnosis and ensuing adrenalectomy to a larger number of hypertensive patients, ultimately resulting in better control of blood pressure.

Introduction: Several studies have now revealed the direct deleterious effects of excess aldosterone, especially in cardiovascular disease, independent of the usual effect of aldosterone on electrolyte transport [1,2]. These new pathologic findings appear to be direct effects of aldosterone on cardiovascular and other tissues, leading to tissue remodeling and fibrosis. Interestingly, very little attention has been directed toward the kidney and renal damage in primary aldosteronism (PA). In fact, only two publications from the same institution have examined renal function in PA in a limited approach, noting early microalbuminuria when compared to subjects with primary hypertension (PH) [3,4]. In general, studies of renal pathology in PA are lacking. This omission is quite surprising for a disease involving often severe hypertension, and given the new information on the direct effects of aldosterone on tissue fibrosis [5]. Recent knowledge holds that PA is a much more frequent cause of secondary hypertension than previously thought, being as high as 12% of all the hypertensive population, thus involving millions of individuals in the world, further increasing the demand for world organization of screening and evaluation protocols and high-standard special centers [6]. Further information on PA and renal function is mandatory, especially with the newer screening tests to monitor progression of chronic kidney disease (CKD) and the renoprotective features indicating that PA be part of the new tests in nephrology, such as urinary albumin excretion (UAE) and estimated glomerular filtration rate (GFR). The Primary Aldosteronism Prevalence in Italy (PAPY) study is a prospective survey of 1180 consecutive newly diagnosed hypertensive patients referred to specialized hypertension centers in Italy to detect the prevalence of PA and intensely study several of its characteristic features [7]. In this study, 490 subjects were deemed justified for an intensified evaluation for PA, aldosterone-producing adenomas (APA) were found in 4.8% of subjects, and idiopathic hyperaldosteronism (IHA) in 6.4%, for a total incidence of PA of 11.2% in the Italian hypertensive population [7]. The main feature examined for renal function was the UAE, but previous renal function studies also showed serum and urine hyperfiltration and increased microalbuminuria in PA; however, these studies were limited by size and the fact that they studied only patients with APA. As is also well known, increased UAE is a key determinant for cardiovascular damage and endothelial dysfunction in high-risk patients. Thus, UAE would also serve an important role in patients with PA as a marker of their overall cardiovascular burden.