Background. Despite being widely recognized as the most common form of secondary hypertension, the true prevalence of primary aldosteronism (PA) and its main subtypes, aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH), among the general hypertensive population remains a matter of debate. Objectives. To determine the prevalence and clinical phenotype of PA in a large cohort of unselected hypertensive patients, consecutively referred to our Hypertension Unit, by 19 general practitioners from Torino, Italy. Methods. Patients were screened for PA using the serum aldosterone to plasma renin activity ratio after withdrawal from all interfering medications and PA was diagnosed according to the Endocrine Society guidelines. The diagnosis was confirmed/excluded by an i.v. saline infusion test or captopril challenge test and subtype differentiation was performed by adrenal CT scanning and adrenal vein sampling (AVS) using strict criteria to define both successful cannulation and lateralization of aldosterone production. Results. A total of 1,672 primary care hypertensive patients, 569 newly diagnosed hypertensives and 1,103 patients already diagnosed with arterial hypertension, were included in the study. A total of 99 patients (5.9%) were diagnosed with PA and conclusive subtype differentiation by AVS was made in 91 patients (27 patients with an APA and 64 patients with BAH). The overall prevalence of PA increased with the severity of hypertension, from 3.9% in hypertensives stage I to 11.8% in hypertensives stage III. Patients with PA more frequently displayed target organ damage and cardiovascular events compared to non-PA hypertensives, independent of confounding variables. Conclusions.The results from the present study demonstrated that PA is a frequent cause of secondary hypertension even in the general hypertensive population and indicates that the majority of hypertensive patients should be screened for PA. Keywords: Primary aldosteronism, aldosterone-producing adenoma, bilateral adrenal hyperplasiaAbbreviation list AC = aldosterone concentration APA = aldosterone-producing adenoma AVS = adrenal vein sampling ARR = serum aldosterone to plasma renin activity ratio BAH = bilateral adrenal hyperplasia CV events = cardiovascular events GP = general practitioner HT = hypertension LREH = low renin essential hypertensives MRA= mineralocorticoid receptor antagonist PA = primary aldosteronism PATO = primary aldosteronism in Torino Condensed AbstractThe prevalence of primary aldosteronism (PA) among general hypertensive population remains unknown. We screened 1,672 primary care hypertensives and 5.9% were diagnosed with PA (27 3 with an aldosterone-producing adenoma and 64 with bilateral adrenal hyperplasia). PA prevalence increased with the severity of hypertension, from 3.9% in hypertensives stage I to 11.8% in stage III. PA patients more frequently displayed target organ damage and cardiovascular events compared to non-PA hypertensives. The study demonstrated that PA is a frequent cause ...

Extracellular vesicles (EVs) including plasma membrane–derived microvesicles and endosomal-derived exosomes aggregate by unknown mechanisms, forming microcalcifications that promote cardiovascular disease, the leading cause of death worldwide. Here, we show a framework for assessing cell-independent EV mechanisms in disease by suggesting that annexin A1 (ANXA1)–dependent tethering induces EV aggregation and microcalcification. We present single-EV microarray, a method to distinguish microvesicles from exosomes and assess heterogeneity at a single-EV level. Single-EV microarray and proteomics revealed increased ANXA1 primarily on aggregating and calcifying microvesicles. ANXA1 vesicle aggregation was suppressed by calcium chelation, altering pH, or ANXA1 neutralizing antibody. ANXA1 knockdown attenuated EV aggregation and microcalcification formation in human cardiovascular cells and acellular three-dimensional collagen hydrogels. Our findings explain why microcalcifications are more prone to form in vulnerable regions of plaque, regulating critical cardiovascular pathology, and likely extend to other EV-associated diseases, including autoimmune and neurodegenerative diseases and cancer.

P rimary aldosteronism (PA) is the most common form of secondary hypertension, with a prevalence of 5% to 15% among hypertensive patients and is characterized by the autonomous hypersecretion of aldosterone. Sporadic PA and 3 familial forms (familial hyperaldosteronism types I, II, and III) have been described.1 Sporadic PA accounts for >90% of all cases and is caused by either an aldosterone-producing adenoma (APA), which can be surgically removed, or bilateral adrenal hyperplasia, which is treatable with mineralocorticoid receptor antagonists.Somatic APA mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K + channel 4, GIRK4 (also called the inward rectifier K + channel, Kir3.4), were first identified by Choi et al. 2 Subsequently, Boulkroun et al 3 determined a 34% prevalence of KCNJ5 mutations in a large European cohort of 380 APA. Intriguingly, the KCNJ5 mutations were markedly more prevalent in women, 3 and this predominance was confirmed by successive studies. 4,5 To date, 5 different KCNJ5 mutations causing sporadic PA have been identified, the majority of which are Abstract-Aldosterone-producing adenomas (APAs) cause a sporadic form of primary aldosteronism and somatic mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K + channel 4, GIRK4, account for ≈40% of APAs. Additional somatic APA mutations were identified recently in 2 other genes, ATP1A1 and ATP2B3, encoding Na + /K + -ATPase 1 and Ca 2+ -ATPase 3, respectively, at a combined prevalence of 6.8%. We have screened 112 APAs for mutations in known hotspots for genetic alterations associated with primary aldosteronism. Somatic mutations in ATP1A1, ATP2B3, and KCNJ5 were present in 6.3%, 0.9%, and 39.3% of APAs, respectively, and included 2 novel mutations (Na