Low Plasma Aldosterone Concentration Research Articles

Associations between thyroid function, thyroid diseases, and primary aldosteronism.

Previous studies focusing on primary aldosteronism (PA) and thyroid diseases were controversial. Hence, this study aimed to examine associations between thyroid function, thyroid diseases, and PA and its subtypes. This was a cross-sectional study, which enrolled 1023 patients with PA and 6138 patients with essential hypertension (EH) admitted to Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from August 2011 to June 2022. All patients with PA were accurately classified into aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) by adrenal vein sampling (AVS). Multivariate logistic regression analysis was used to assess the relationship of thyroid function, thyroid nodules, and PA and its subtypes. A total of 7161 patients (327 APA and 696 IHA, and 6138 EH) were included with a mean age of 48.20 ± 8.83 years. PA patients and PA subtypes showed lower FT4, FT3, TT4, TT3, and prevalence of positive TPOAb, meanwhile higher prevalence of thyroid nodules than EH patients (PA: 56.10%, IHA: 56.90%, APA: 54.80%, and EH: 48.90%, respectively). PA (adjusted OR: 1.290, 95% CI: 1.035-1.607, P = .02) and its subtype (IHA) (adjusted OR: 1.316, 95% CI: 1.005-1.724, P = .04) were significantly associated with thyroid nodules. Compared to patients with lower plasma aldosterone concentration (PAC) levels (<12 ng/dL), patients with PAC levels ≥ 12 ng/dL presented a higher prevalence of thyroid nodules. PA patients had lower thyroid function and higher prevalence of thyroid nodules compared to EH patients. Therefore, the screening of thyroid function and thyroid nodules may be indispensable for PA patients.

Screening for Primary Aldosteronism by Mass Spectrometry Versus Immunoassay Measurements of Aldosterone: A Prospective Within-Patient Study.

Measurements of aldosterone by mass spectrometry are more accurate and less prone to interferences than immunoassay measurements, and may produce a more accurate aldosterone:renin ratio (ARR) when screening for primary aldosteronism (PA). Differences in diagnostic performance of the ARR using mass spectrometry vs immunoassay measurements of aldosterone were examined in 710 patients screened for PA. PA was confirmed in 153 patients and excluded in 451 others. Disease classifications were not achieved in 106 patients. Areas under receiver-operating characteristic curves (AUROC) and other measures were used to compare diagnostic performance. Mass spectrometry-based measurements yielded lower plasma aldosterone concentrations than immunoassay measurements. For the ARR based on immunoassay measurements of aldosterone, AUROCs were slightly lower (P = 0.018) than those using mass spectrometry measurements (0.895 vs 0.906). The cutoff for the ARR to reach a sensitivity of 95% was 30 and 21.5 pmol/mU by respective immunoassay and mass spectrometry-based measurements, which corresponded to specificities of 57% for both. With data restricted to patients with unilateral PA, diagnostic sensitivities of 94% with specificities >81% could be achieved at cutoffs of 68 and 52 pmol/mU for respective immunoassay and mass spectrometry measurements. Mass spectrometry-based measurements of aldosterone for the ARR provide no clear diagnostic advantage over immunoassay-based measurements. Both approaches offer limited diagnostic accuracy for the ARR as a screening test. One solution is to employ the higher cutoffs to triage patients likely to have unilateral PA for further tests and possible adrenalectomy, while using the lower cutoffs to identify others for targeted medical therapy.German Clinical Trials Register ID: DRKS00017084.

Hyporeninemic hypoaldosteronism in RMND1-related mitochondrial disease

BackgroundRMND1 is a nuclear gene needed for proper function of mitochondria. A pathogenic gene will cause multiple oxidative phosphorylation defects. A renal phenotype consisting of hyponatremia, hyperkalemia, and acidosis is frequently reported, previously considered to be due to aldosterone insensitivity.MethodsClinical features and pathophysiology of three patients will be reported. DNA of these patients was subjected to exome screening.ResultsIn the first family, one pathogenic heterozygous and one highly probable heterozygous mutation were detected. In the second family, a homozygous pathogenic mutation was present. The electrolyte disbalance was not due to aldosterone insensitivity but to low plasma aldosterone concentration, a consequence of low plasma renin activity. This disbalance can be treated. In all three patients, the kidney function declined. In the first family, both children suffered from an unexplained arterial thrombosis with dire consequences.ConclusionsHyporeninemic hypoaldosteronism is the mechanism causing the electrolyte disbalance reported in patients with RMND1 mutations, and can be treated.

High plasma aldosterone concentration is associated with worse 24-h ambulatory blood pressure profile in patients with primary aldosteronism.

Patients with primary aldosteronism (PA) have a higher risk of cardiovascular disease (CVD) than essential hypertension due to underlying hyperaldosteronism. However, the association between high plasma aldosterone concentrations (PACs) and diurnal blood pressure (BP) variation has not been fully elucidated. Because abnormal ambulatory blood pressure monitoring (ABPM) profiles are associated with increased CVD risk, we investigated the association between PACs and the ABPM profile in 36 patients with PA diagnosed by confirmatory tests who underwent adrenal venous sampling (AVS). The clinical parameters were measured during hospitalization for AVS. The dietary salt intake of hospitalized patients was controlled at 6 g/day. During AVS, blood samples were collected from the inferior vena cava before and 1 h after adrenocorticotropic hormone (ACTH) stimulation to measure the PACs. The post-stimulation PAC had a significant negative correlation with nocturnal BP dipping rates (R = -0.387, p = 0.020), whereas pre-stimulation PAC did not (R = -0.217, p = 0.204). The nocturnal BP dipping rates were significantly lower in the high PAC group (PAC higher than the median) than low PAC group (PAC lower than the median) (p = 0.009). Multiple regression analysis revealed that high PAC was an independent factor contributing to low nocturnal BP dipping rates (β = -0.316, p = 0.038). In conclusion, in patients with PA, hyperaldosteronism is associated with nocturnal hypertension, which is an important risk factor for CVD. Additionally, ACTH stimulation may improve the sensitivity of PACs as a clinical indicator of nocturnal hypertension.

PS-BPC08-1: VALIDATION OF PRIMARY ALDOSTERONISM DIAGNOSIS DURING THE TRANSITIONAL PERIOD OF ALDOSTERONE ASSAY AND GUIDELINE CHANGES IN JAPAN

Objectives and Methods: In Japan, the plasma aldosterone concentration (PAC) measurement method was changed from RIA to CLEIA method in April 2021. From then until August 2021, when the 2021 clinical practice guidelines for the diagnosis and management of primary aldosteronism (PA) were published, we diagnosed PA using the RIA-converted PAC value (conversion formula from CLEIA (X) to RIA (Y): Y = 1.174X + 42.3) and the conventional positive decision criteria of the screening and confirmatory tests in PA diagnosis. The new criteria were then used to re-determine and confirm the agreement. Results: PAC(CLEIA) and renin activity (PRA) or active renin concentration (ARC) were measured simultaneously for PA screening at our hospital from April to August 2021 in 122 patients (135 measurements in total). PAC values (CLEIA) were less than 4 pg/mL in 21 measurements (16%). This value was converted to PAC(RIA) at 47 pg/mL based on the formula. (i) PA screening tests: 10% of the measurements were found to be ‘not excluded’ by the conventional criteria and negative by the new criteria. This was due to the fact that the calculated PAC(RIA) values were higher than they should be when the conversion formula to RIA was applied to cases with low PAC(CLEIA) values, resulting in higher estimated ARR values (PAC(RIA)/PRA or PAC(RIA)/ARC ratio). (ii) PA confirmatory tests: In the captopril challenge test, one case was found to be positive by the conventional criteria and negative by the new criteria due to the same reason as that on point (i). In the saline infusion test, PAC(CLEIA) of 12–15 pg/mL was determined to be less than PAC(RIA) 60 pg/mL by the conversion formula, which was deemed negative by the conventional criteria but borderline by the new criteria. (iii) PA diagnosis using the confirmatory tests: In one case, the diagnosis did not match the positive (borderline) classification based on the new criteria, although the patient was deemed negative by the conventional criteria. This was due to discrepancies of the saline infusion test results. Conclusion: During the transition period of PA diagnosis from the RIA to CLEIA method, it was necessary to review the data and retest the patients according to their symptoms because of possible inconsistencies between the new and conventional criteria-based diagnostic results. PA diagnosis and treatment should be judged comprehensively on a case-by-case basis, without relying entirely on the values of the criteria.

PS-C34-2: CORRELATION BETWEEN SERUM URIC ACID AND RENIN - ANGIOTENSIN - ALDOSTERONE SYSTEM IN COLLEGE STUDENTS

Objective: To study the correlation between serum uric acid (SUA) and renin-angiotensin-aldosterone(RAAS) in college students. Design and method: A total of 228 college students (age 20.44 ± 2.09 years, male 108 cases) without cardiovascular complications and any treatment were enrolled by random sampling method. The whole study population was divided into three groups according to the SUA level(umol/L) from low to high: Q1 (139∼325), Q2(326∼396), Q3 (398∼670). The participants were divided into SUA-tertiles according to sex-specific cut-off values of SUA: q1 (males 240∼370, females 139∼279), q2 (males 375∼458, females 280∼343), q3 (males 461∼670, females 345∼641). We investigated the relationship among SUA, plasma renin concentration(PRC) and plasma aldosterone concentration(PAC). Results: In this study, the numbers of SUA tertile groups were 8 (10.5%), 40 (52.6%) and 60 (78.9%) in males. Compared with females, men have higher SUA [410.5 (358.5–487.0) VS 315 (265.0–367.5), P &lt; 0.001] and lower PAC[29.95 (19.03–53.33) VS 46.80 (26.93–82.48), P &lt; 0.001], PRC [23.06(16.93–30.22) VS 22.92 (17.56–29.70) pg/ml, P = 0.941] was not significantly different. PAC in Q1 and Q3 was different (P = 0.001). PRC in male group q1 and q3 was different (P = 0.017). There was no statistical difference in RAAS among the three groups in female population. There was a negative correlation between SUA and PAC in the general population (P &lt; 0.05), and a negative correlation between SUA and PRC and PAC in males (P &lt; 0.05). After adjusting confounding factors, there was still a negative correlation between SUA and PRC in males (R = -0.209, P = 0.041). The model was constructed with uric acid triquartile as dependent variable, including gender, SBP, DBP, BMI, BaPWV, fasting blood glucose, blood lipids (triglyceride, HDL-C, LDL-C, except total cholesterol due to collinearity), eGFR, PRC, Ang2, PAC and other independent variables. Multivariate Logistic regression analysis showed that with the first quartile of uric acid as the control group, there were significant differences in renin concentration in causing different quartile uric acid levels. For every 1pg/ml increase of renin concentration in males, the possibility of developing high-quartile uric acid was 0.931 times higher than that of low-quartile uric acid. Conclusions: SUA was negatively correlated with PRC in college students, but not with PAC.

AW-APSH-2: “MINERALOCORTICOID RECEPTOR (MR)-ASSOCIATED HYPERTENSION” IN “GREEDY ORGAN HYPOTHESIS”

Spironolactone has been used for more than 60 years. Eplerenone is MR-specific MRB and esaxerenone possesses non-steroidal structure with high affinity and specificity to MR and exhibits long half-life. We conducted a double-blind phase III study of esaxerenone compared with eplerenone in patients with essential hypertension in 2020. Esaxerenone 2.5 mg elicited comparable hypotensive effect to eplerenone 50 mg and 5 mg exhibited significantly stronger effect than 2.5 mg. We also investigated the efficacy of dosage-escalation of esaxerenone added to a RAS inhibitor in hypertensive patients with type 2 diabetes (DM) (HbA1c:6.8%) and albuminuria (212 mg/gCr). 5 mg esaxerenone induced 20/8mmHg blood pressure reduction and reduced albumin excretion significantly. Interestingly, in these studies, esaxerenone exerted similar hypotensive action in the patients with RAS inhibitors, compared to the groups without them. This observation indicates that MR can be activated being independent of renin-angiotensin-aldosterone system. In 2012, we proposed the concept of “MR-associated hypertension”, hypertension caused by over-activation of MR with wide range of plasma aldosterone level. Primary aldosteronism is the typical example of MR-associated hypertension, but even in low plasma aldosterone concentration state, such as obesity, DM, CKD, MR can be over-activated. There are several postulated mechanisms of over-activation of MR. Increased expression of MR, increased sensitivity of MR and MR protein stabilization. We are interested in the activation of MR by salt and sugar themselves. We focus on MR expressed in the intestine for sodium absorption. Administration of DOCA and high salt induced up-regulation of epithelial sodium channel, ENaC, the target molecule of MR. And intestine specific knock-out of MR mice exhibited blunted increase of blood pressure by DOCA and high salt loading. We also demonstrated that high sugar induces MR protein stabilization by PKC activation, O-GlcNac modification or EGFR-ERK activation. More recently, in relation to excessive salt and sugar intake and occurrence of non-communicable diseases (NCDs), including hypertension, we have proposed “Greedy Organ Hypothesis”. Excessive intake of salt and sugar are sensed by the kidney and the intestines, and these organs up-regulate SGLT, sodium-glucose co-transporters and come to absorb salt and sugar greedily. Excessive salt intake through SGLT2 makes the kidney greedy to induce hypertension/CKD. Excessive food intake through SGLT1 make the intestines greedy to induce obesity/DM. Furthermore, there is “crossing” relationships between “greedy organs” and NCDs. Greedy kidney and intestines over-activate MR and induce MR-associated hypertension. Therefore, MRB are effective to alleviate Greedy Organs and to suppress NCDs.

Prediction of long-term biochemical cure in patients with unilateral primary hyperaldosteronism treated surgically based on the early post-operative plasma aldosterone value.

In 2017, the Primary Aldosteronism Surgical Outcome (PASO) investigators proposed consensus criteria for clinical and biochemical outcomes. However, 6 to 12 months need to pass in order to assess for the outcome in patients who have undergone surgery for the management of primary hyperaldosteronism. This study aims to evaluate the post-operative biochemical and clinical outcomes of primary aldosteronism (PA) on the basis of the laboratory findings obtained within 10 days after surgery. We retrospectively studied 59 consecutive patients with unilateral PA who underwent adrenalectomy and were assessed for plasma aldosterone concentration (PAC) and plasma renin activity both at the initial assessment (1-10 days after surgery) and the final assessment (6-12 months after surgery). When comparing the complete biochemical success group (n = 51) and the partial or absent biochemical success group (n = 8), the median post-operative PAC at the initial assessment was significantly greater in the partial or absent biochemical success group (12.7 ng/dL; interquartile range [IQR], 10.6-14.5) than that in the complete biochemical success group (6.3 ng/dL; IQR, 5.0-7.9) (p < 0.001), while no significant differences were observed in other factors. The receiver operating characteristic curves of post-operative PAC at the initial assessment, which was used to predict biochemical outcomes, indicated that 8.1 ng/dL is the optimal PAC cut-off for biochemical success (sensitivity, 76.5%; specificity, 100%). Low post-operative PAC at the initial assessment may predict the biochemical cure of PA.

Characteristics and Outcomes in Primary Aldosteronism Patients Harboring Glucocorticoid-Remediable Aldosteronism.

The clinical characteristics and surgical prognosis of glucocorticoid-remediable aldosteronism (GRA, also known as familial hyperaldosteronism type 1, FH-I) have not been widely studied. Using data from the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry retrospectively, we describe the associated clinical factors for GRA and clinical predictors of surgical outcomes among identified GRA patients. We found 79 GRA-positive (51.2 ± 13.8 years; women 39 (49.4%)) and 114 GRA-negative primary aldosteronism (PA) patients matched with age, gender, and body mass index. Lower plasma aldosterone concentrations (PACs) and aldosterone-renin ratios were found among GRA-positive individuals. Multivariable logistic regression demonstrated that a PAC ≤ 40 ng/dL could predict concealed GRA individuals (OR 0.523, p = 0.037). Low serum potassium (OR 0.285, p = 0.008), but not the presence of GRA, was associated with hypertension-remission. Of note, PRA (OR 11.645, p = 0.045) and hypokalemia (OR 0.133, p = 0.048) were associated with hypertension-remission in GRA patients. Unilateral primary aldosteronism patients harboring concomitant GRA were not associated with inferior hypertension-remission after an adrenalectomy. Low serum potassium and high PRA were positively associated with hypertension-remission in GRA patients.

Association of the ratio of visceral-to-subcutaneous fat volume with renal function among patients with primary aldosteronism

Patients with primary aldosteronism have a higher risk of chronic kidney disease. Visceral fat tissue is hypothesized to stimulate the adrenal glands to overproduce aldosterone, and aldosterone promotes visceral fat tissue to produce inflammatory cytokines. However, it is unclear whether the volume of accumulated visceral fat tissue is associated with renal impairment among patients with hyperaldosteronism. We conducted a single-center cross-sectional study to assess the association between the estimated glomerular filtration rate and the ratio of the visceral-to-subcutaneous fat volume calculated by computed tomography. One hundred eighty patients with primary aldosteronism were enrolled. The mean ± SD age was 52.7 ± 11.0 years, and 60.0% were women. The ratio of visceral-to-subcutaneous fat volume was highly correlated with the estimated glomerular filtration rate (r = 0.49, p < 0.001). In multiple linear regression models, the ratio of visceral-to-subcutaneous fat tissue volume was significantly associated with the estimated glomerular filtration rate (estimates: −4.56 mL/min/1.73 m² per 1-SD), and there was an interaction effect between the plasma aldosterone concentration and the ratio of visceral-to-subcutaneous fat volume (p < 0.05). The group with a higher plasma aldosterone concentration exhibited a steeper decline in eGFR than the lower plasma aldosterone concentration group when the ratio increased. The ratio of visceral-to-subcutaneous fat tissue volume was an independent risk factor for renal dysfunction. This association increased in the presence of a high plasma aldosterone concentration. Clinicians should pay attention to the ratio of visceral-to-subcutaneous fat tissue volume and encourage primary aldosteronism patients to improve their lifestyle in addition to treating renin-aldosterone activity.

Should Adrenal Venous Sampling Be Performed in PA Patients Without Apparent Adrenal Tumors?

IntroductionSome aldosterone-producing micro-adenomas cannot be detected through image inspection. Therefore, adrenal venous sampling (AVS) is often performed, even in primary aldosteronism (PA) patients who have no apparent adrenal tumors (ATs) on imaging. In most of these cases, however, the PA is bilateral.ObjectiveTo clarify the clinical need for AVS in PA patients without apparent ATs, taking into consideration the rates of adrenalectomy.MethodsThis is a retrospective cross-sectional study assessing 1586 PA patients without apparent ATs in the multicenter Japan PA study (JPAS). We analyzed which parameters could be used to distinguish unilateral PA patients without apparent ATs from bilateral patients. We also analyzed the prevalences of adrenalectomy in unilateral PA patients.ResultsThe unilateral subtype without an apparent AT was diagnosed in 200 (12.6%) of 1586 PA patients. Being young and female with a short hypertension duration, normokalemia, low creatinine level, low plasma aldosterone concentration, and low aldosterone-to-renin ratio (ARR) was significantly more common in bilateral than unilateral PA patients. If PA patients without apparent ATs were female and normokalemic with a low ARR (<560 pg/ml per ng/ml/h), the rate of unilateral PA was only 5 (1.1%) out of 444. Moreover, 77 (38.5%) of the 200 did not receive adrenalectomy, despite being diagnosed with the unilateral subtype based on AVS.ConclusionThe low prevalence of the unilateral subtype in PA patients without apparent ATs suggests AVS is not indicated for all of these patients. AVS could be skipped in female normokalemic PA patients without apparent ATs if their ARRs are not high. However, AVS should be considered for male hypokalemic PA patients with high ARRs because the rates of the unilateral subtype are high in these patients.

Analysis of the Relationships between Multiple Endocrine Hormones and Return of Spontaneous Circulation (ROSC) in Cardiac Arrest Patients: Possible Association of the Serum Free T4 Level with ROSC.

Background Endocrine hormones are closely associated with homeostasis, so it is important to clarify hormone secretion dynamics in shock. Few reports, however, have examined the dynamics of endogenous hormone secretion relative to prognosis in cardiac arrest patients. Therefore, to clarify the roles of endocrine hormones in out-of-hospital cardiac arrest (OHCA) patients, the concentrations of anterior pituitary, thyroid, and adrenocortical hormones were measured, and their associations with return of spontaneous circulation (ROSC) were examined. Methods The subjects were OHCA patients transported to our Emergency Department. In addition to conventional clinical laboratory tests, the following were measured: serum TSH, serum free T3, serum free T4 (F-T4), plasma ACTH, serum cortisol, serum GH, serum IGF-1, plasma aldosterone concentration (PAC), and plasma renin activity. The primary endpoint was the presence or absence of ROSC, and the secondary endpoint was 24-hour survival. Results A total of 29 patients, 17 in the ROSC group and 12 in the non-ROSC group, were studied. There were associations between ROSC and low serum potassium, high F-T4, low cortisol, and low PAC on bivariate analyses. There were associations between ROSC and serum potassium, F-T4, and GH using the step-wise method. On multiple logistic regression analysis, a relationship between ROSC and high serum F-T4 level was identified by both methods. There were also associations between 24-hour survival and both low serum potassium and elevated blood glucose levels. Conclusions The present findings suggest a possible relationship between the serum F-T4 level and ROSC in OHCA patients. A higher serum F-T4 level might cause an increase in the β-adrenergic response in cardiomyocytes and increased responsiveness to catecholamines and was possibly associated with ROSC.

Apparent mineralocorticoid excess caused by novel compound heterozygous mutations in HSD11B2

Abstract Background Apparent mineralocorticoid excess (AME) is a rare autosomal recessive genetic disorder caused by a mutation in the 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2). AME is characterized by early-onset and severe hypertension, hypokalemia, and metabolic alkalosis. Purpose This study aimed to study the molecular genetics, clinical presentation, biochemical parameters, and treatment in the proband with AME from a non-consanguineous Chinese family. Methods Genomic DNA was recovered from peripheral blood leukocytes from nine subjects in this family. Next-generation sequencing and Sanger sequencing were performed to identify the HSD11B2 variants. In silico and genotype-phenotype correlations analyses were used to predict pathogenicity of candidate variants. A tailored therapy was performed for identified mutations carriers. Results Genetic analysis identified novel compound heterozygous HSD11B2 mutations (c.343-348del/c.1099-1101del) in the proband. In silico analysis predicted these HSD11B2 mutations were deleterious. The structural change and predicted consequences owing to the compound mutations have been modeled. The same compound mutations were not found in any other family members, 100 hypertensives, or 100 healthy controls. The proband had typical manifestations of AME, including early-onset and severe hypertension, hypokalemia, low plasma aldosterone concentration, hypokalemic alkalosis and nephrolithiasis. The probands' blood pressure and serum potassium level had returned to normal after treatmennt with dexamethasone (1.5 mg/day) and spirolactone (40 mg/day) for three months. Conclusions We conclude that this novel compound mutations are responsible for AME in the proband. These genetic and clinical data expand the genetic spectrum of HSD11B2 and demonstrate the pathogenic effects of identified mutations and genotype-phenotype correlations. It is emphasized that genetic diagnosis and specific treatment play an important role in patients with AME. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Key Research and Development Program of China; PUMC Youth Fund and the Fundamental Research Funds for the Central Universities

This Month in Anesthesiology

This Month in Anesthesiology

Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency

BackgroundIn short bowel syndrome, epithelial surface loss results in impaired nutrient absorption and may lead to intestinal insufficiency or intestinal failure. Nucleotide oligomerization domain 2 (Nod2) dysfunction predisposes to the development of intestinal failure after intestinal resection and is associated with intestinal barrier defects. Epithelial barrier function is crucial for intestinal absorption and for intestinal adaptation in the short bowel situation.AimsThe aim of the study was to characterize the effects of the GLP-2 analogue Teduglutide in the small intestine in the presence and absence of Nod2 in a mouse model of short bowel syndrome.MethodsMice underwent 40% ICR and were thereafter treated with Teduglutide versus vehicle injections. Survival, body weight, stool water, and sodium content and plasma aldosterone concentrations were determined. Intestinal and kidney tissue was examined with light and fluorescence microscopy, Ussing chamber studies and quantitative PCR in wild type and transgenic mice.ResultsTeduglutide reduced intestinal failure incidence in Nod2 k.o. mice. In wt mice, Teduglutide attenuated intestinal insufficiency as indicated by reduced body weight loss and lower plasma aldosterone concentrations, lower stool water content, and lower stool sodium losses. Teduglutide treatment was associated with enhanced epithelial paracellular pore function and enhanced claudin-10 expression in tight junctions in the villus tips, where it colocalized with sodium–glucose cotransporter 1 (SGLT-1), which mediates Na-coupled glucose transport.ConclusionsIn the SBS situation, Teduglutide not only maximizes small intestinal mucosal hypertrophy but also partially restores small intestinal epithelial function through an altered distribution of claudin-10, facilitating sodium recirculation for Na-coupled glucose transport and water absorption.

High Fib4 index in patients with suspected NASH is associated with elevation of chymase-dependent angiotensin II-forming activity in circulating mononuclear leucocytes.

Fatal hepatic disease is closely related to non-alcoholic fatty liver disease, especially non-alcoholic steatohepatitis (NASH). NASH is associated with cardiovascular events because it develops on the background of lifestyle-related diseases. Chymase-dependent angiotensin II-forming activity (dAIIFA) in circulating mononuclear leucocytes (CML) is a marker of local angiotensin II production and inflammation. This study investigated the association between CML chymase dAIIFA and NASH. Cardiovascular outpatients were recruited and the Fib4 index (F4I) was calculated. Patients with an F4I > 2.67 were classified into the high F4I group and these patients were strongly suspected to have NASH, while patients with an F4I < 1.30 were classified into the low F4I group. Patient background factors were compared between these groups. CML chymase dAIIFA was measured by ELISA using Nma/Dnp-modified angiotensin I. Among 499 patients, 16% were classified into the high F4I group. Compared with the low F4I group, the high F4I group had a significantly higher age, pancytopenia, more frequent diabetes mellitus, lower diastolic blood pressure, lower estimated glomerular filtration rate, higher brain natriuretic peptide, lower plasma aldosterone concentration, higher total AIIFA, higher CML chymase dAIIFA, and higher pulse wave velocity. Contrary to expectations, the body mass index, triglycerides, and low-density lipoprotein cholesterol were relatively low in the high F4I group. Many cardiovascular outpatients have a high F4I and can probably be categorized as NASH. The high F4I patients had few features of metabolic syndrome and were suspected to have elevated tissue chymase dAIIFA contributing to inflammation in the liver as well as in cardiovascular organs.

Impact of obesity on the association of active renin and plasma aldosterone concentrations, and aldosterone-to-renin ratio with preeclampsia.

To evaluate the association of active renin concentration (ARC), plasma aldosterone concentration (PAC) and aldosterone-to-renin ratio (ARR) with the risk of preeclampsia (PE), in particular according to the status of obesity. This retrospective case-control study involved 90 women with PE (mean gestation 35.6 ± 3.6 weeks) and 90 age-matched control women with uncomplicated pregnancies (mean gestation 38.5 ± 2.5 weeks). ARC and PAC were measured by radioimmunoassay; ARR calculated as PAC to ARC ratio. PE cases were stratified into 5 percentiles groups, and analyzed in multivariate logistic regression. Women with PE had significantly lower median ARC and PAC than control women, which were confirmed by percentiles analysis. Spearman correlation demonstrated negative correlation of ARC with body mass index, systolic/diastolic blood pressure. PAC correlated negatively with systolic/diastolic blood pressure, but positively with baby weight, ARC and ARR. On the other hand, ARR positively correlated with BMI and PAC, but negatively with ARC. Lower PAC was associated with PE, irrespective of body weight, while ARC levels were significantly lower in non-obese PE cases vs. control women. ARR was not significantly different between PE cases and control women, when stratified according to obesity. Low ARC and PAC in third trimester are more strongly associated with preeclampsia respectively in non-obese and obese women.

Clinical Implications

HomeHypertensionVol. 71, No. 3Clinical Implications Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBClinical Implications Originally published1 Mar 2018https://doi.org/10.1161/HYPERTENSIONAHA.118.10860Hypertension. 2018;71:367Cardiovascular Disease in Primary Aldosteronism (p 530)Download figureDownload PowerPointAldosterone causes organ damage in animal models, and the prevalence of cardiovascular disease (CVD) among patients with primary aldosteronism (PA) is reportedly high. There have been several clinical studies examining the factors associated with CVD in these people; but the results are controversial. In some studies, the prevalence of CVD was distributed nearly equally across the spectrum of plasma aldosterone or serum potassium levels, whereas other studies reported that hypokalemic patients with PA had an elevated rate of CVD. Of the 2582 patients with PA studied in this study, the prevalence of CVD was higher than in age-, gender-, and blood pressure-matched patients with essential hypertension. Hypokalemia (≤3.5 mEq/L) and the unilateral subtype was associated with significantly higher adjusted odds ratios for CVD. Although plasma aldosterone concentration (PAC) was not linearly related to the adjusted odds ratios for CVD, patients with high PAC (≥125 pg/mL) had significantly higher adjusted odds ratios for CVD than patients with lower PAC (<125 pg/mL). Our result suggests PA patients with PACs higher than the upper limit of normal as well as with hypokalemia or unilateral subtype are at higher risk of developing CVD and, therefore, have a greater need for PA-specific treatment. In contrast, PA patients with normokalemia, the bilateral subtype, and PACs lower than the upper limit of normal are at lower risk of CVD and may not need immediate PA-specific treatment.Left Ventricular Function and Cognitive Impairment (p 429)Download figureDownload PowerPointA growing literature is revealing connections between cardiovascular disease and cognitive impairment/dementia. However, the relationships between subclinical cardiac dysfunction and cognitive performance is not been well established in the general population. In this issue of Hypertension, we investigated longitudinally cardiac magnetic resonance measures of left ventricular structure and function in relation to cognitive performance and incident dementia in a large multiethnic population free of cardiovascular disease at baseline. A total of 4999 participants with cardiac magnetic resonance images at baseline were followed for a median of 12 years. Left ventricular hypertrophy and remodeling were strongly associated with lower cognitive function and a higher risk of future hospitalization with dementia. Additionally, lower left ventricular sphericity (increased conicity) was associated with increased risk of future dementia. These associations were independent of demographic confounders, cardiovascular risk factors, and cardiovascular events. Measures of left ventricular function were not associated with risk of future dementia or cognitive function. This study provides 2 avenues of important insight into the link between cardiac and cerebral involvement in dementia. First, cardiac structural and functional abnormalities may be useful in the identification of individuals at risk of future cognitive impairment. Second, these data suggest that potential common pathophysiological mechanisms could underlie both cardiovascular and cerebrovascular structural remodeling (eg, microvascular disease) leading or contributing to cardiac concentric remodeling and vascular dementia.VEGF Inhibitor–Induced Hypertension and Renal NO (p 473)Download figureDownload PowerPointVEGF (vascular endothelial growth factor) is critically involved in tumor angiogenesis and is therefore an important target in the pharmacological treatment of many cancer diseases. Clinical use of VEGF inhibitors is associated with a preeclampsia-like syndrome characterized by rapid development of hypertension and proteinuria and has revealed an important role of VEGF in blood pressure regulation. The underlying mechanisms of VEGF inhibitor–induced hypertension are only partly understood but may include decreased systemic nitrogen oxide (NO) and increased plasma endothelin-1. Pazopanib is one of the recommended first line treatments in advanced renal cell carcinoma patients and in a prospective, single center observational study in a cohort of pazopanib-treated patients, significant hypertension developed during the first 4 weeks of treatment. Hypertension was accompanied by proteinuria, decreased plasma NO metabolites and increased endothelin-1. In addition, results showed decreased urinary excretion of NO metabolites without change in urine endothelin-1 or renal function. The kidneys are important in long-term regulation of blood pressure, and data support a significant role of reduced renal NO bioavailability in VEGF inhibitor–induced hypertension. Sufficient blood pressure control is necessary in this group of patients to prevent impaired treatment options of cancer targeted therapy. Based on mechanistic evidence, long-acting NO donors or cGMP-based drug interventions seem particularly well suited for organ protection and blood pressure reduction. Previous Back to top Next FiguresReferencesRelatedDetails March 2018Vol 71, Issue 3 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.118.10860PMID: 30543472 Originally publishedMarch 1, 2018 PDF download Advertisement

MPS 04-05 THE ASSOCIATION BETWEEN PLASMA ALDOSTERONE CONCENTRATION /PLASMA RENIN ACTIVITY AND PULSE PRESSURE IN NEVER-TREATED HYPERTENSIVE PATIENTS; 24 HOURS AMBULATORY BLOOD PRESSURE MONITORING STUDY

Objective: Reduction of vascular compliance leads to an increment of afterload on the heart (as lower arterial compliance is closely related to increased pulse pressure), which in turn leads to left ventricular hypertrophy and diastolic dysfunction. Plasma aldosterone concentration (PAC) are influenced by a number of factors, including potassium and volume status. Design and Method: This study aimed to examine the association the association between PAC/plasma renin activity (ARR) and pulse pressure in Never-Treated Hypertensive Patients. This prospective study included a total of 314 patients (mean age: 52.0 ± 12.2 years; 55.0 % male) with never-treated essential hypertension. We collected the data from 24-hour ambulatory BP, Echocardiography, pulse wave velocity, ankle brachial index, PAC, and plasma renin activity (PRA) from all of the patients. Results: The measured pulse pressure from 24 hours ambulatory BP monitoring was correlated with E/E′ (r = 0.149, P = 0.012) and LA volume index (r = 0.308, P < 0.001). However, there are negative associations between pulse pressure and PAC levels (r = −0.145, P = 0.032). Conclusions: Pulse pressures in never-treated hypertensive patients were closely correlated with diastolic dysfunctions and inversely correlated with PAC. Relative low PAC could be caused by high salt intake and volume overload. Pulse pressure could be a surrogate marker of diastolic dysfunction and volume overload including high salt intake in never treated hypertensives.

Clinical diagnosis and treatment of adrenocortical adenoma in patients aged 60 years or above

To investigate the clinical features of adrenocortical adenoma's diagnosis and treatment in patients aged 60 years or above. A retrospective study was performed with a total of 249 patients aged 60 years or above who suffered from adrenocortical adenoma and treated in Peking Union Medical College Hospital from January 2004 to January 2014.The clinical features, treatments and prognosis of the 249 patients aged 60 years or above were compared with another 249 patients which were randomly selected during the same period aged from 30 to 50 years.t-test or χ(2) test was used to analyze the data between the two groups. Endocrine examinations were performed in all 249 patients aged 60 years or above.There were 144 patients diagnosed as non-functional adrenocortical adenoma, 94 cases as aldosterone-producing adenoma and 11 cases as Cushing adenoma.For the patients aged 60 years or above, the rate of cardio-cerebral vascular incident in non-functional adrenocortical adenoma group was 26.4%(38/144), which was significantly lower than that of the aldosterone-producing adenoma and Cushing adenoma group(54.3%, 57/105)(χ(2)=20.027, P=0.000). There were 91.5%(65/71) of the patients aged 60 years or above who got a relief in low blood potassium symptoms after the operation.Forty-nine point one percent(53/108) of the non-functional adrenocortical adenoma patients aged 60 years or above had a better control of their blood pressure level, while functional adrenocortical adenoma group were 64.0%(48/75) which indicated that the functional adrenocortical adenoma patients have a better control of their blood pressure then the non-functional adrenocortical adenoma patients after the operation(χ(2)=3.987, P=0.046). There were 37.1% of the patients aged 60 years or above whose fasting blood-glucose was higher than 7.1 mmol/L, while the patients aged from 30 to 50 years was 14.1%(χ(2)=22.02, P=0.000). The differences in plasma aldosterone and blood potassium between the patients aged 60 years or above and the patients aged from 30 to 50 years had statistical significance(t=10.48, -2.58; P=0.00, 0.01). Most of the adrenocortical adenoma in patients aged 60 years or above is non-functional adrenocortical adenoma.Among who, patients with aldosterone-producing adenoma tend to have lower plasma aldosterone concentration and higher blood potassium level then the patients aged from 30 to 50 years.The patients aged 60 years or above with functional adrenocortical adenoma are tend to have severe cardio-cerebral vascular incidence.A few of non-functional adrenocortical adenoma patients who combine with hypertension can benefit for the operation.