BACKGROUND: 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.
METHODS: Population-based cohort study.
METHODS: Québec (Canada).
METHODS: Adults aged 40-69 years enrolled to CARTaGENE between 2009 and 2010 (N=3,687).
METHODS: Plasma aldosterone and renin concentrations.
METHODS: 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

暂无摘要。

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.

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.

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.

BACKGROUND: Syndrome of apparent mineralocorticoid excess (AME) is characterized by excessive MR stimulation despite low levels of aldosterone. 11Beta-hydroxysteroid dehydrogenase-2 (11βDSH-2) inactivates cortisol to cortisone, preventing cortisol-induced MR activation. Genetic defects in 11βDSH-2 cause AME through accumulation of cortisol in the distal nephron, leading to MR activation induced hypertension, hypokalemia and metabolic alkalosis. Acquired AME can occur due to the ingestion of glycyrrhizic acid, found in licorice root, which inhibits 11βDSH-2 and has additional effects on cortisol homeostasis through inhibition of 11βDSH-1.
METHODS: We present a case of acquired AME with a hyperadrenergic symptoms induced by ingestion of Advanced Liver Support, a nutritional supplement produced by Advanced BioNutritionals(R), in a 65-year-old Caucasian female who presented with accelerated hypertension, hypokalemia, metabolic alkalosis and adrenergic symptoms. Cessation of the licorice-containing supplement resulted in complete resolution of the patient\'s hypertension, symptoms and abnormal lab values. To our knowledge this is the first reported case of AME from this supplement, and the first to describe accompanying hyperadrenergic symptoms.
CONCLUSIONS: Glycyrrhizic acid is increasingly being found in unregulated nutritional supplements and has the potential to induce a reversable syndrome of AME. Acquired AME should be suspected in individuals who present with hypertension along with hypokalemia, metabolic alkalosis and low plasma renin and serum aldosterone levels.

Apparent resistant hypertension (aTRH) is a significant public health issue. Once low adherence to antihypertensive treatment has been ruled out and true resistant hypertension is diagnosed, aldosterone-direct-renin-ratio (ADRR) aids in the screening of an aldosterone-producing adenoma (APA) and primary aldosteronism (PA). Once PA and other secondary causes have been ruled out, the values of aldosterone and renin allow patients to be classified into phenotypes such as low renin hypertension (LRH), Liddle\'s-like (LLph), and primary hyperaldosteronism (PAph). These classifications could aid in the treatment decision-making process. However, optimal cut-off points for these classifications remain uncertain. This study aims to assess the prevalence of these phenotypes and the behavior of different cut-offs of the ADRR in an Afro-Colombian population with apparent resistant hypertension, as well to describe their sodium consumption. Afro-descendant individuals 18 years of age or older, diagnosed with resistant hypertension and attending to a primary care center in Colombia were recruited as volunteers. As part of the study, their plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured. The phenotypes were categorized into three groups based on multiple cut-off points from different authors: low renin and low aldosterone phenotype (LLph), low renin and high aldosterone phenotype (PAph), and high renin and high aldosterone phenotype, referred to as the renal phenotype (Rph). The prevalence of ADRR values exceeding the cut-off and phenotypes were calculated. A linear regression model was derived to assess the effect of sodium consumption with PAC, PRC and ADRR. A total of 88 patients with aTRH were included. Adherence to at least 3 antihypertensive medications was 62.5%. The median age was 56 years (IQR 48-60), 44% were female, and 20% had diabetes. The study found that the prevalence of ADRR values exceeding the cut-off ranged from 4.5 to 23%, while low-renin hypertension (LRH) varied from 15 to 74%, Rph was found in approximately 30 to 34% of patients, PAph in 30 to 51%, and the LLph in 15 to 41%, respectively, depending on the specific cut-off value by different authors. Notably, sodium consumption was associated with lower aldosterone (β - 0.15, 95% CI [- 0.27, - 0.03]) and renin concentrations (β - 0.75, 95% CI [- 1.5, - 0.02]), but ADRR showed no significant association with sodium consumption. There were no significant differences in prevalences between the groups taking < 3 vs ≥ 3 antihypertensive medications. Altered aldosterone-direct-renin-ratio, low renin hypertension, Liddle\'s-like, and primary hyperaldosteronism are prevalent phenotypes in patients within Afro-Colombian patients with apparent treatment-Resistant hypertension.

UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: URL: https://drks.de/; Unique identifier: DRKS00017084.

BACKGROUND: Extracellular calcium critically regulates physiologic aldosterone production. Moreover, abnormal calcium flux and signaling are involved in the pathogenesis of the majority of primary aldosteronism cases.
METHODS: We investigated the influence of the saline suppression test (SST) on calcium homeostasis in prospectively recruited participants (n = 86).
RESULTS: During SST, 100% of participants had decreases in serum calcium, with 48% developing frank hypocalcemia. Serum calcium declined from 2.30 ± 0.08 mmol/L to 2.13 ± 0.08 mmol/L (P < .001) with parallel increases in parathyroid hormone from 6.06 ± 2.39 pmol/L to 8.13 ± 2.42 pmol/L (P < .001). In contrast, serum potassium and bicarbonate did not change, whereas eGFR increased and serum glucose decreased (P < .001). Lower body surface area (translating to greater effective circulating volume expansion during SST) was associated with greater reductions in (β = .33, P = .001), and absolutely lower, serum calcium levels (β = .25, P = .001). When evaluating clinically-relevant diagnostic thresholds, participants with post-SST aldosterone levels <138 pmol/L had lower post-SST calcium and 25-hydroxyvitamin D levels (P < .05), and higher post-SST parathyroid hormone levels (P < .05) compared with those with post-SST aldosterone levels >277 pmol/L.
CONCLUSIONS: SST uniformly decreases serum calcium, which is likely to be due to the combination of variable dilution, increased renal clearance, and vitamin D status. These acute reductions in bioavailable calcium are associated with lower post-SST aldosterone. Given the critical role of extracellular calcium in regulating aldosterone production, these findings warrant renewed inquiry into the validity of SST interpretations for excluding primary aldosteronism.