Sex-Specific Associations of Aldosterone and Renin with Body Composition: A Population-Based Cohort Study.

CONTEXT: Renin-angiotensin-aldosterone system (RAAS) activation is closely linked to obesity; however, the sex-specific associations between RAAS activity and body composition among individuals without obesity are not well understood. OBJECTIVE: To investigate the associations of aldosterone and renin with body composition according to sex in the general population. DESIGN: Population-based cohort study. SETTING: Québec (Canada). PARTICIPANTS: Adults aged 40-69 years enrolled to CARTaGENE between 2009 and 2010 (N=3,687). EXPOSURES: Plasma aldosterone and renin concentrations. MAIN OUTCOME MEASURES: Body composition assessed via anthropometrics (waist circumference and waist-to-hip ratio), bioelectrical impedance (lean body mass, fat mass, and muscle mass), and cardiac magnetic resonance imaging (epicardial and pericardial adipose tissue volumes). RESULTS: The mean (SD) age and body mass index were 55 (8) years and 27.3 (4.8) kg/m2, respectively. Among males, higher aldosterone and renin were associated with increased waist circumference, increased waist-to-hip ratio, increased fat mass, decreased lean body mass, and decreased muscle mass (p<0.05). Aldosterone (p=0.02), but not renin (p=0.43), was associated with increased ectopic cardiac adiposity in males. In contrast, higher renin (p<0.05), but not aldosterone (p≥0.05), was associated with increased waist circumference, increased waist-to-hip ratio, and increased cardiac adiposity in females. Among females, higher renin and aldosterone were associated with increased fat mass (p<0.05) but were not associated with lean body mass or muscle mass (p≥0.05). All aforementioned associations were independent of body weight. CONCLUSIONS: Independent of body weight, increased RAAS activity is associated with unfavorable differences in body composition; however, the strength and pattern of association varies by sex.

Plasma aldosterone concentrations elevation in hypertensive patients: the dual impact on hyperuricemia and gout.

Background: Prior research has highlighted the association between uric acid (UA) and the activation of the renin-angiotensin-aldosterone system (RAAS). However, the specific relationship between aldosterone, the RAAS's end product, and UA-related diseases remains poorly understood. This study aims to clarify the impact of aldosterone on the development and progression of hyperuricemia and gout in hypertensive patients. Methods: Our study involved 34534 hypertensive participants, assessing plasma aldosterone concentration (PAC)'s role in UA-related diseases, mainly hyperuricemia and gout. We applied multiple logistic regression to investigate the impact of PAC and used restricted cubic splines (RCS) for examining the dose-response relationship between PAC and these diseases. To gain deeper insights, we conducted threshold analyses, further clarifying the nature of this relationship. Finally, we undertook subgroup analyses to evaluate PAC's effects across diverse conditions and among different subgroups. Results: Multivariate logistic regression analysis revealed a significant correlation between the occurrence of hyperuricemia and gout and the elevation of PAC levels. Compared to the first quartile (Q1) group, groups Q2, Q3, and Q4 all exhibited a significantly increased risk of occurrence. Moreover, the conducted RCS analysis demonstrated a significant nonlinear dose-response relationship, especially when PAC was greater than 14 ng/dL, with a further increased risk of hyperuricemia and gout. Finally, comprehensive subgroup analyses consistently reinforced these findings. Conclusion: This study demonstrates a close association between elevated PAC levels and the development of UA-related diseases, namely hyperuricemia and gout, in hypertensive patients. Further prospective studies are warranted to confirm and validate this relationship.

Epigenetic Regulation of the Renin-Angiotensin-Aldosterone System in Hypertension.

Activation of the renin-angiotensin-aldosterone system (RAAS) plays an important pathophysiological role in hypertension. Increased mRNA levels of the angiotensinogen angiotensin-converting enzyme, angiotensin type 1 receptor gene, Agtr1a, and the aldosterone synthase gene, CYP11B2, have been reported in the heart, blood vessels, and kidneys in salt-sensitive hypertension. However, the mechanism of gene regulation in each component of the RAAS in cardiovascular and renal tissues is unclear. Epigenetic mechanisms, which are important for regulating gene expression, include DNA methylation, histone post-translational modifications, and microRNA (miRNA) regulation. A close association exists between low DNA methylation at CEBP-binding sites and increased AGT expression in visceral adipose tissue and the heart of salt-sensitive hypertensive rats. Several miRNAs influence AGT expression and are associated with cardiovascular diseases. Expression of both ACE and ACE2 genes is regulated by DNA methylation, histone modifications, and miRNAs. Expression of both angiotensinogen and CYP11B2 is reversibly regulated by epigenetic modifications and is related to salt-sensitive hypertension. The mineralocorticoid receptor (MR) exists in cardiovascular and renal tissues, in which many miRNAs influence expression and contribute to the pathogenesis of hypertension. Expression of the 11beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene is also regulated by methylation and miRNAs. Epigenetic regulation of renal and vascular HSD11B2 is an important pathogenetic mechanism for salt-sensitive hypertension.

Assessment of per- and poly-fluoroalkyl substances and physiological biomarkers in aquarium-based bottlenose dolphins and killer whales.

Environmental concerns about per- and polyfluoroalkyl substances (PFAS) are considerably increasing due to their extensive use in commercial and consumer products. PFAS bioaccumulate and biomagnify throughout the food chain, and their toxicity and potential adverse health effects can potentially represent a threat to living organisms. In this study, we described PFAS profiles in the serum of two species of zoo-based bottlenose dolphins (Tursiops truncatus, n = 14 individuals) and killer whales (Orcinus orca, n = 14 individuals) from three locations (California, Florida, and Texas, USA), from 1994 to 2020. Potential physiological effects of PFAS were also explored by measuring different biomarkers (cortisol, corticosterone, aldosterone, TBARS, and hydrogen peroxide) while accounting for individual age, sex, and reproductive stage. All PFAS were detected in at least one of the individuals, considering both species. ΣPFAS reached 496 ng mL-1 in bottlenose dolphins and 230 ng mL-1 in killer whales. In both species, the PFAS with higher mean concentrations were PFOS (108.0-183.0 ng ml-1) and PFNA (14.40-85.50 ng ml-1), which are long-chain compounds. Newborn individuals of both species were also exposed to PFAS, indicating transference via placenta and lactation. Linear mixed model analyses indicated significant correlations between aldosterone, month, year, location, and status; and between hydrogen peroxide, month, year, age, status, ΣPFAS, and Σ short-chain PFAS in killer whales suggesting seasonal variations related to the animal's physiological state (e.g., reproductive cycles, stress responses, weaning events) and increased reactive oxygen species formation due to PFAS exposure. Given our results, other contaminant classes should be investigated in cetaceans as they might have additive and synergistic detrimental effects on these individuals. This study lays the foundation to guide future researchers and highlights the importance of such assessments for animal welfare, and species conservation. Our results may inform management decisions regarding regulations of contaminant thresholds in delphinids.

Glaucoma and the ocular renin-angiotensin-aldosterone system: Update on molecular signalling and treatment perspectives.

Glaucoma, a leading cause of blindness worldwide, encompasses a group of pathological conditions affecting the optic nerve and is characterized by progressive retinal ganglion cell loss, cupping of the optic nerve head, and distinct visual field defects. While elevated intraocular pressure (IOP) is the main risk factor for glaucoma, many patients do not have elevated IOP. Consequently, other risk factors, such as ocular blood flow abnormalities and immunological factors, have been implicated in its pathophysiology. Traditional therapeutic strategies primarily aim to reduce IOP, but there is growing interest in developing novel treatment approaches to improve disease management and reduce the high rates of severe visual impairment. In this context, targeting the ocular renin-angiotensin-aldosterone system (RAAS) has been found as a potential curative strategy. The RAAS contributes to glaucoma development through key effectors such as prorenin, angiotensin II, and aldosterone. Recent evidence has highlighted the potential of using RAAS modulators to combat glaucoma, yielding encouraging results. Our study aims to explore the molecular pathways linking the ocular RAAS and glaucoma, summarizing recent advances that elucidate the role of the RAAS in triggering oxidative stress, inflammation, and remodelling in the pathogenesis of glaucoma. Additionally, we will present emerging therapeutic approaches that utilize RAAS modulators and antioxidants to slow the progression of glaucoma.

Diagnostic Accuracy of Aldosterone and Renin Measurement by Chemiluminescence for Screening of Patients with Primary Aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine arterial hypertension, and the suggested screening test for case detection is the aldosterone-to-renin ratio (ARR) or aldosterone-to-direct renin ratio (ADRR) based on radio-immunoassay (RIA) and chemiluminescence assay (CLIA), respectively. The objective of our study was to evaluate the reliability of CLIA for aldosterone and renin measurement and the diagnostic performance of ADRR. A prospective cohort of 1110 patients referred to a single laboratory medicine center underwent measurement of aldosterone and direct renin concentration (DRC) by CLIA and measurement of aldosterone and plasma renin activity (PRA) by RIA. Of 1110 patients, 640 obtained a final diagnosis of hypertension, and 90 of these patients were diagnosed with PA. Overall, between-method correlation was highly significant for aldosterone concentrations (R = 0.945, p < 0.001) and less strong but significant for DRC/PRA (R = 0.422, p < 0.001). Among hypertensive patients, in PA cases, the areas under the receiver operator characteristics (ROC) curves were 0.928 (95% confidence interval 0.904-0.954) for ADRR and 0.943 (95% confidence interval 0.920-0.966) for ARR and were comparable and not significantly different. The highest accuracy was obtained with an ADRR cut-off of 25 (ng/L)/(mIU/L), displaying a sensitivity of 91% and a specificity of 85%. The chemiluminescence assay for aldosterone and DRC is a reliable method for PA diagnosis compared to the classical RIA method.

Post-acute CoVid-19 syndrome (PACS) linked cardiovascular symptoms.

Officials have marked the end of the CoVid-19 pandemic, yet we continue to learn more about the SARS-CoV2 virus itself and its lasting multidimensional effects after acute infection. Long COVID, or the post-acute CoViD-19 syndrome (PACS), manifests as a wide range of prolonged physical, mental, and emotional symptoms over at least 1 to 12 months after SARS-CoV2 infection. Here, we describe certain pervasive clinical consequences of PACS on the cardiovascular system, and insight on the potentially improved prognoses in heart failure patients.

Primary aldosteronism and hypokalemia-induced rhabdomyolysis in a patient with aldosterone-producing adenoma: A case report and literature review.

Many cases of primary aldosteronism (PA) in patients who developed hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for aldosterone-producing adenoma (APA) have been reported; however, the immunohistopathological and molecular features remain unknown. We herein report the case of a 28-year-old woman with PA who presented with hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for unilateral APA. An immunohistochemical analysis revealed that most adenoma cells were positive for steroidogenic enzymes, including CYP11B2. A genetic analysis revealed a somatic mutation in the KCNJ5. These findings suggest a strong aldosterone production capacity in our patient's adenoma, which was presumably related to her severe hyperaldosteronism and the resultant hypokalemia-induced rhabdomyolysis.

Adrenal Pathologies.

Adrenal pathologies have variable clinical presentations and primary care providers should be aware of common and serious adrenal disorders. All adrenal masses require evaluation for malignancy, whether primary or metastatic, and all masses require evaluation for inappropriate hormonal secretion. In the event of adrenal insufficiency, the etiology of cortisol inadequacy must be identified and appropriately treated to prevent life-threatening complications.

Steroidomics-Based Screening for Primary Aldosteronism: Impact of antihypertensive Drugs.

BACKGROUND: Diagnosis of primary aldosteronism (PA) is complicated by the need to withdraw antihypertensive medications that interfere with test results, particularly renin. This study examined whether machine learning-based steroid-probability scores offer a renin measurement-independent approach for testing less prone to interference than the aldosterone-to-renin ratio (ARR). METHODS: This prospective multicenter cohort study involved the use of plasma steroidomics and the ARR in 839 patients tested for PA, including 190 with and 578 without PA (71 indeterminate). Receiver operating characteristic curves for steroid-probability scores and the ARR were examined with and without interfering medications. Impacts of individual medications on plasma aldosterone, 18-oxocortisol, 18-hydroxycortisol, steroid-probability scores, renin, and ARRs were examined by multivariable and paired analyses in patients with and without PA. RESULTS: Receiver operating characteristic curves indicated a significant impact of interfering antihypertensive medications on the diagnostic performance of the ARR and minimal impact on steroid-probability scores. Mineralocorticoid receptor antagonists increased plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol in patients without PA and resulted in false-positive test results for steroid-probability scores and false-negative results for the ARR. Diuretics increased aldosterone, 18-oxocortisol, and steroid-probability scores in patients without PA, whereas angiotensin-converting enzyme inhibitors decreased aldosterone, steroid-probability scores, and ARRs. Beta-adrenoceptor blockers, dihydropyridine calcium channel blockers, and angiotensin receptor blockers had negligible impact on mineralocorticoids and steroid-probability scores. CONCLUSIONS: Among antihypertensive drugs that impact plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol, mineralocorticoid receptor antagonists stood out as a cause of false-positive results for derived steroid-probability scores. Other antihypertensives have minimal or no impact, an advantage for use of steroid-probability scores over the ARR when those medications cannot be withdrawn. REGISTRATION: URL: https://drks.de/; Unique identifier: DRKS00017084.

Combining Bibliometric Analysis to Uncover the Detrimental and Protective Roles of Various Dendritic Cell Types in Cardiovascular Arterial Diseases.

Immune cell dysregulation is increasingly recognized as a pivotal pathological factor in cardiovascular disease. Over the past decade, a surge of research has focused on the role of immune cells such as dendritic cells (DCs), T cells, macrophages, and neutrophils in cardiovascular diseases, findings that are frequently featured in leading cardiology journals. This review provides a comprehensive synthesis of the roles that DCs play in common and potentially fatal arterial diseases, including hypertension, coronary artery atherosclerosis, acute coronary syndrome, pulmonary arterial hypertension, aortic aneurysm, aortic dissection, and vasculitis. Combining with bibliometric analysis, this review delves into the critical mechanisms by which DCs contribute to these diseases and reveals the shared mechanisms across diverse diseases. This review also offers new advances in clinical treatment strategies involving DCs.

Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions.

Aprotinin is a broad-spectrum inhibitor of human proteases that has been approved for the treatment of bleeding in single coronary artery bypass surgery because of its potent antifibrinolytic actions. Following the outbreak of the COVID-19 pandemic, there was an urgent need to find new antiviral drugs. Aprotinin is a good candidate for therapeutic repositioning as a broad-spectrum antiviral drug and for treating the symptomatic processes that characterise viral respiratory diseases, including COVID-19. This is due to its strong pharmacological ability to inhibit a plethora of host proteases used by respiratory viruses in their infective mechanisms. The proteases allow the cleavage and conformational change of proteins that make up their viral capsid, and thus enable them to anchor themselves by recognition of their target in the epithelial cell. In addition, the activation of these proteases initiates the inflammatory process that triggers the infection. The attraction of the drug is not only its pharmacodynamic characteristics but also the possibility of administration by the inhalation route, avoiding unwanted systemic effects. This, together with the low cost of treatment (≈2 Euro/dose), makes it a good candidate to reach countries with lower economic means. In this article, we will discuss the pharmacodynamic, pharmacokinetic, and toxicological characteristics of aprotinin administered by the inhalation route; analyse the main advances in our knowledge of this medication; and the future directions that should be taken in research in order to reposition this medication in therapeutics.

Tetrandrine inhibits aldosterone synthesis by covalently targeting CYP11A1 to attenuate hypertension.

Introduction: Tetrandrine (Tet) is the main pharmacological component of Stephania tetrandra S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive properties. Unraveling the specific targets and mechanisms of Tet involved in inducing diuresis and mitigating hypertension can provide valuable insights into its therapeutic effects. This study aimed to explore the diuretic and antihypertensive targets and mechanisms of Tet using chemical biology coupled with activity analyses in vivo and in vitro. Methods: The diuretic effects of Tet were evaluated using a water-loaded mouse model. The direct target proteins for the diuretic and antihypertensive effects of Tet were determined using chemical biology. Furthermore, the molecular mechanism of Tet binding to target proteins was analyzed using a multidisciplinary approach based on the structure and function of the proteins. Finally, the effects of the Tet-targeted protein on downstream signaling pathways and blood pressure were evaluated in hypertensive model rats. Results: Tet exhibited significant antihypertensive and potassium-preserving diuretic effects. The mechanism underlying these effects involves the modulation of the enzyme activity by covalent binding of Tet to Cys423 of CYP11A1. This interaction alters the stability of heme within CYP11A1, subsequently impeding electron transfer and inhibiting aldosterone biosynthesis. Discussion: This study not only revealed the mechanism of the diuretic and antihypertensive effects of Tet but also discovered a novel covalent inhibitor of CYP11A1. These findings contribute significantly to our understanding of the therapeutic potential of Tet and provide a foundation for future research in the development of targeted treatments for hypertension.

Intra- and postoperative relative angiotensin II deficiency in patients undergoing elective major abdominal surgery.

Introduction: The classical axis of the renin-angiotensin system (RAS) makes an important contribution to blood pressure regulation under general anesthesia via the vasopressor angiotensin II (Ang II). As part of the alternative RAS, angiotensin-converting enzyme 2 (ACE2) modulates the pro-inflammatory and fibrotic effects of Ang II by processing it into the organ-protective Ang 1-7, which is cleaved to Ang 1-5 by ACE. Although the levels of ACE2 may be associated with postoperative complications, alternative RAS metabolites have never been studied perioperatively. This study was designed to investigate the perioperative kinetics and balance of both RAS axes around major abdominal surgery. Methods: In this observational cohort study, 35 patients undergoing elective major abdominal surgery were included. Blood sampling was performed before and after induction of anesthesia, at 1 h after skin incision, at the end of surgery, and on postoperative days (POD) 1, 3, and 7. The equilibrium concentrations of Ang I-IV, Ang 1-7, and Ang 1-5 in plasma were quantified using mass spectrometry. The plasma protein levels of ACE and ACE2 were measured with ELISA. Results: Surgery caused a rapid, transient, and primarily renin-dependent activation of both RAS axes that returned to baseline on POD 1, followed by suppression. After induction, the Ang II/Ang I ratio persistently decreased, while the ACE levels started to increase on POD 1 (all p < 0.01 versus before anesthesia). Conversely, the ACE2 levels increased on POD 3 and 7 (both p < 0.001 versus before anesthesia), when the median Ang 1-7 concentrations were unquantifiably low. Discussion: The postoperative elevation of ACE2 may prolong the decrease of the Ang II/Ang I ratio through the increased processing of Ang II. Further clarification of the intraoperative factors leading to relative Ang II deficiency and the sources of postoperatively elevated ACE2 is warranted.

Comparing ARR Versus Suppressed PRA as Screening Tests for Primary Aldosteronism.

BACKGROUND: In many practices, the screening for primary aldosteronism relies on a single-blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to establish an aldosterone-to-renin ratio (ARR). ARR levels vary between expert centers and repeated assays in the same individual, emphasizing the potential variability of this screening approach. A suppressed PRA to <1 ng/mL per h has been proposed as an alternative test to the ARR. METHODS: We compared 2 potential screening approaches to identify probable primary aldosteronism (ARR≥30 or ARR≥20 versus PRA suppressed below 1 ng/mL per h) in a cohort of 94 829 paired PRA and PAC samples submitted by clinicians to evaluate the presence of primary aldosteronism. RESULTS: Of 94 829 patients, 20.3% tested positive based on ARR≥20 (95% CI, 20.0%-20.5%), 13.9% based on ARR≥30 (95% CI, 13.6%-14.1%), versus 45.9% based on suppressed PRA (<1 ng/mL per minute [95% CI, 45.5%-46.2%]). In the PRA group, a range of aldosterone levels was observed: 5.5% had PAC >15 ng/dL, 25.2% had PAC 5 to 15 ng/dL, and 15.2% had PAC <5 ng/dL, compared with 6%, 12.7%, and 1.6% in the ARR≥20 group and 4.7%, 8.5%, and 0.7% in the ARR≥30 group. CONCLUSIONS: In this cohort of individuals being screened for primary aldosteronism, substantially more individuals were identified using criteria focused on suppression of renin activity compared with using the aldosterone renin ratio as a screening tool.

Increased adrenocortical activity in patients with vasovagal syncope.

OBJECTIVE: Syncope is a transient loss of consciousness resulting from cerebral hypoperfusion. Vasovagal syncope (VVS) is a form of orthostatic intolerance (OI). Its clinical signs such as dizziness and hypotension may mimic symptoms of adrenal insufficiency. The objective of this study was to evaluate the adrenal gland function in patients with vasovagal syncope after stimulation with synthetic adrenocorticotropic hormone (ACTH). DESIGN: Case-control study on patients with VVS and healthy controls. METHODS: The study involved 42 participants, including 27 patients diagnosed with VVS using the head-up tilt test and 15 healthy individuals with no history of syncope or any orthostatic symptoms. Serum cortisol and aldosterone concentrations were measured under basal conditions and at 30 and 60 min after intramuscular ACTH stimulation. RESULTS: Patients with VVS had significantly higher cortisol levels at baseline (441 ± 143 vs. 331 ± 84.7 nmol/L, p = 0.01), at 30 min (802 ± 143 vs. 686 ± 105 nmol/L, p = 0.01) and at 60 min (931 ± 141 nmol/L vs. 793 ± 147 nmol/L, p = 0.001) after ACTH administration (Synacthen 250 µg). Plasma aldosterone increased after ACTH stimulation, but did not show significant differences among groups. Furthermore, there was also no significant correlation between cortisol levels and blood pressure or heart rate. CONCLUSION: Patients diagnosed with VVS have higher cortisol levels both at baseline and after ACTH stimulation. This finding indicates that individuals with VVS have higher adrenocortical activity potentially as a response to the orthostatic stress induced by syncope, which acts as a stressful stimulus on the autonomic nervous system.

Elderly men are underscreened for primary aldosteronism even in Hypertension Excellence Centre.

Purpose The Endocrine Society (ES) guidelines recommend screening for primary aldosteronism (PA) in high risk hypertensive patients presenting with at least one of seven criteria (resistant HTN, hypokalaemia, adrenal nodule, etc.) Although guidelines are clear and screening is simple, compliance rates among clinicians are extremely low. This results in underdiagnosis of early disease, leading to cadiovasculaer complications and the extra-burden of advanced chronic kidney disease. We aimed to evaluate the screening rates in our Nephrology and Hypertension clinics, as an example of a dedicated Hypertension Excellence Centre. Materials and methods Data on adult hypertensive patients was retrieved from January 2018 to December 2020. Included in the study were hypertensive patients who had at least one of the ES criteria for PA screening. Of all suitable patients, we compared those who were screened for PA to patients who were not screened. Univariate and multivariate cox regression analyses were used for comparison between groups. Results Of 661 patients with HTN, 218 patients (33%) met the ES guidelines for PA screening. Forty-six of them (21.1%) were referred for screening. Advanced age and male gender were associated with lower screening referral rates. Odds ratio for age was 0.945 for every year (95% CI 0.915 - 0.975). There was a trend towards decreased referral rate in advanced kidney disease. Conclusions A 21% screening rate, suggests that many cases of PA are likely missed, more often in older patients. We therefore advocate for PA screening of all hypertensive patients, especially elderly patients with CKD, in whom clinicians' awareness is low but the absolute risk is high.

Aldosterone is a hormone secreted from the adrenal gland.Oversecretion of aldosterone (Primary Aldosteronism [PA]) causes salt retention, urinary loss of potassium and difficult to control hypertension.Both hypertension and hyperaldosteronism act synergistically and cause, over time, severe cardiac, vascular and renal damage.Different guidelines support doctors' decision-making algorithm, suggesting who should be evaluated for aldosterone hypersecretion.Our study demonstrates that even in an expert hypertension centre, many candidates for screening are missed. Elderly men are specifically underscreened.Since PA is not as rare as once thought, and can have a devastating impact on patients' health, we suggest screening all hypertensive patients for autonomous hypersecretion of aldosterone.

Genetic testing for primary aldosteronism in SPAIN: Results from the SPAIN-ALDO Registry and review of the literature.

PURPOSE: To determine the rate of genetic testing for familial hyperaldosteronism (FH) in the SPAIN-ALDO Registry and to describe the clinical characteristics of patients with FH. In addition, a literature review of reports of FH cases was performed. METHODS: A retrospective multicenter study of primary aldosteronism (PA) in patients followed in 35 Spanish tertiary hospitals (SPAIN-ALDO Registry). RESULTS: Twenty-five of the 855 patients (3%) with PA included in the registry underwent genetic testing for FH, with complete results available in only 24 patients. However, we found that there were 57 patients who met the criteria for performing a genetic study of PA. Only 8 out of these 57 patients were genetically tested (14.0%), while the reasons to perform a genetic study in the remaining 9 genetically studied cases were quite heterogeneous. A positive result for FH was found only in one case for FH type III (KCNJ5 pathogenic variant). A systematic review of the literature was performed and identified a total of 25 articles reporting 246 patients with FH type I; 12 articles reporting 72 patients with FH type II; 14 articles reporting 29 cases of FH type III and 3 articles reporting 12 patients with FH type IV. CONCLUSION: The genetic study of familial hyperaldosteronism is often scarce in real-world clinical practice, as 86% of patients with criteria to undergo genetic study were not evaluated in our cohort. Nevertheless, FH is an uncommon cause of PA, representing only 0.2% of cases in the SPAIN-ALDO Registry, although its prevalence may be as high as 4% among suspected cases might be studied.

Updates on the Renin-Angiotensin-Aldosterone System and the Cardiovascular Continuum.

The cardiovascular continuum describes how several cardiovascular risk factors contribute to the development of atherothrombosis, ischemic heart disease, and peripheral arteriopathy, leading to cardiac and renal failure and ultimately death. Due to its multiple valences, the renin-angiotensin-aldosterone system plays an important role in all stages of the cardiovascular continuum, starting from a cluster of cardiovascular risk factors, and continuing with the development of atherosclerosis thorough various mechanisms, and culminating with heart failure. Therefore, this article aims to analyze how certain components of the renin-angiotensin-aldosterone system (converting enzymes, angiotensin, angiotensin receptors, and aldosterone) are involved in the underlying pathophysiology of the cardiovascular continuum and the possible arrest of its progression.