Essential Hypertension Controls Research Articles

Abstract P325: Additive effect of nighttime blood pressure on left ventricular strain in patients with primary aldosteronism evaluated via cardiac magnetic resonance tissue tracking

Background: Primary aldosteronism (PA) induces left ventricular (LV) remodeling and increases the risk of high nighttime blood pressure (BP), which causes further heart damage. This study aimed to investigate whether nighttime BP aggravates LV deformation dysfunction and to identify independent factors affecting the global peak strain (PS) of LV remodeling in patients with PA compared to patients with essential hypertension (EH). Methods: A total of 280 patients with PA and 280 age- and sex-matched patients with EH who underwent cardiac magnetic resonance examination at the First Affiliated Hospital of Chengdu Medical College were included. According to the results of adrenal computed tomography and/or adrenal venous sampling, there were 154 patients with aldosterone-producing adenoma (APA) and 126 patients with idiopathic hyperaldosteronism (IHA). Twenty-four-hour ambulatory BP monitoring (ABPM), LV function, global strain parameters, and other clinical medical data were compared, and multivariate analysis was performed to identify the independent indicators of the LV PS. Results: No differences in age, sex, body mass index, clinical BP, 24-h mean BP, daytime BP, or duration of hypertension were found between the groups. Nighttime systolic BP (132 ± 17 vs. 126 ± 18 mm Hg, P < 0.05) and diastolic BP (85 ± 11 vs. 80 ±10 mm Hg, P < 0.05) were greater in PA patients than in EH patients. Compared with the EH controls, the PA patients had a lower LV global PS and peak diastolic strain rate (PDSR) in three directions. No significant differences were found in the PS (radial or longitudinal) or PDSR in the three directions between the APA and IHA groups. Furthermore, nighttime BP was an independent predictor of LV global radial, circumferential, and longitudinal PS. Conclusions: High nighttime BP may aggravate LV stiffness in patients with PA, resulting in decreased LV strain and function. Nighttime BP was independently correlated with LV global PS in patients with PA.

Cholecalciferol, serum calcium and left ventricular hypertrophy in essential hypertension.

Objective: To assess the correlation of vitamin cholecalciferol and serum calcium with left ventricular hypertrophy (LVH) in essential hypertension patients presenting at a tertiary care hospital. Study Design: Cross Sectional Comparative study. Setting: Department of Cardiology and Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh. Period: July 2019 to January 2021. Material & Methods: 100 diagnosed LVH+ Essential Hypertenison cases and 100 diagnosed essential hypertension (controls) were selected through non- probability purposive sampling. Echocardiography, serum cholecalciferol, calcium, phosphate, parathyroid hormone (PTH), alkaline phosphatase (ALP), urea and creatinine were measured form sera. Devereux’s formula measured the LV thickness LVH. SPSS ver. 21.0 analyzed the descriptive statistics and compared the variables at 95% Confidence interval (P≤0.05). Results: Serum calcium, phosphate and parathyroid hormone were found elevated in LVH cases compared to control (P=0.0001). Cholecalciferol in LVH cases was low noted as 27.3±7.84 ng/dl compared to 39.5±0.43 ng/dl in controls (P=0.0001). Cholecalciferol in mild, moderate and severe LVH cases was descending order as 30.67±7.84, 24.76±7.72 and 14.96±6.12 mm respectively (P-0.0001). Serum cholecalciferol proves inverse association (r= -0.180) with LVH (p=0.003). Conclusion: The present study reports vitamin cholecalciferol deficiency increases the chances of left ventricular hypertrophy through increased secretion of parathyroid hormone that induces de – novo protein synthesis of ventricular myocardium.

Arterial stiffness assessment in patients with resistant hypertension using pulse wave analysis

Abstract Introduction People living with resistant hypertension (RH) have a higher prevalence of target organ damage, and demonstrate increased risk of cardiovascular (CV) morbidity and mortality. There are distinctive vascular structural and functional changes associated with hypertension. Among these, endothelial dysfunction and increased arterial stiffness are prevalent. Increased aortic augmentation index (AIx) is a non-invasive hemodynamic indicator of systemic arterial stiffness, which has been associated with hypertension; however, there are less data in RH patients. Purpose To test the hypothesis that people living with RH have increased AIx compared to those with controlled essential hypertension (CH) and normotensive controls (NC); and to explore demographic and clinical variables related to AIx. Methods In our observational study, 54 participants: 17 with RH (mean age 60.5±12.4 years), 18 with CH (57.7±12.2 years), and 19 NC (54.7±11.9 years) were recruited. Anthropometric and resting office blood pressure (BP) measurements were obtained. Pulse wave analysis was performed using a commercially available device (Vicorder) to measure central BP, aortic pulse pressure, mean arterial pressure (MAP), aortic augmentation pressure and AIx. Results The study groups were matched for age, sex, ethnicity, height, body surface area and heart rate (P>0.05) (Table 1). Both office and central BP readings were elevated in RH group compared to CH and NC (162/102mmHg vs 126/86mmHg and 118/80mmHg, P<0.001) and (163/83mmHg vs 131/73mmHg and 120/67mmHg, P<0.05). Aortic pulse pressure, MAP and aortic augmentation pressure were significantly increased in patients with RH compared to other groups (P<0.001). AIx was markedly increased in RH compared to CH and NC (31±7% vs 23±8% and 21±9%, P=0.001, respectively). Antihypertensive medications were similar between both hypertensive groups, except for diuretics and beta-blockers which were more prevalent in the RH group (100% vs 28% and 47% vs 6%, P<0.05, respectively). In stepwise regression analysis, elevated AIx was significantly and independently associated with the presence of RH (β=6.4, P=0.005), age (β=.23, P=0.005), female sex (β=6.3, P=0.003) and body mass index (β=.71, P=0.038). Conclusion AIx is increased in RH patients and independently related to the presence of RH, age, female sex and body mass index. Increased arterial stiffness and reduced arterial compliance in patients with RH may play an important role in the progression of serious CV complications seen in these patients. The non-invasive assessment of arterial stiffness indices such as AIx in RH patients may be valuable to provide prognostic and therapeutic insights.Table 1

MRNA Expression Profiles and Molecular Biomarkers Involved in Inflammatory Response for Essential Hypertension in Kazakh Population From Xinjiang

Abstract Background To identify hypertensive inflammation-related mRNA in peripheral blood mononuclear cells (PBMCs) from patients with essential hypertension (EH) of Kazakh Chinese population in Xinjiang, and offer theoretical foundation for further understanding the immune mechanisms that contribute to EH in Kazakh and provide specific molecular biomarkers for clinical diagnosis and targeted-specific treatments of this disorder. Methods Thirty Kazakh patients with EH and 30 age-matched healthy Kazakh people were divided into EH group and control group. After performing blood pressure measurement and determination of serum lipids and blood glucose, total RNA was isolated from PBMCs of hypertensive Kazakh patients and healthy Kazakh subjects, and differentially expressed mRNA in 6 randomly selected samples from each group were identified with human lncRNA/mRNA V4.0 microarray. Gene set enrichment analysis (GSEA), disease process, the Gene Ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of differentially expressed mRNA were carried out using R language and ClusterProfiler software package. Reverse transcription quantitative real-time PCR (qRT-PCR) was used to validate the differential expression pattern of inflammation-related genes in the mRNA microarray data and results of bioinformatics analysis. Results The average blood pressure was significantly higher in the EH group than those in the control group (P < 0.01), while there was no statistical significance for the levels of serum lipids and blood glucose between the 2 groups. Compared with healthy Kazakh controls, a total of 522 mRNA were significantly differentially expressed from PBMCs of hypertensive Kazakh patients with fold change of ≥1.5 and P value <5% in expression. Among them, 411 were upregulated and 111 were downregulated. GO enrichment analysis of upregulated mRNA identified numerous inflammation-related biological processes and molecular functions. Many of these processes and molecular function were mainly involved in immune response-regulating signaling pathway, immune response-activating signal transduction, antigen binding, immunoglobulin receptor binding and peptide antigen binding, etc. GSEA and KEGG pathway analysis for the upregulated mRNA indicated several positively enriched gene sets and pathways related to inflammatory response, such as focal adhesion, cell adhesion molecules, chemokine signaling pathway, leukocyte transendothelial migration, cytokine–cytokine receptor interaction, and B-cell receptor signaling pathway. qRT-PCR validation results of 14 mRNA related to inflammatory response were consistent with the microarray data. Conclusions This is the first study to identify gene expression profile involved in hypertensive inflammation in Kazakh Chinese population in Xinjiang with EH, and not only provides specific molecular biomarkers for predicting and diagnosing progression of EH, but also will provide targeted-specific treatments of this disorder in Kazakh Chinese population in Xinjiang.

PD03-01 FGF-23 PRODUCTION COUPLING WITH ALDOSTERONE AND PREDICTING CLINICAL OUTCOMES IN PRIMARY ALDOSTERONISM

You have accessJournal of UrologyCME1 Apr 2023PD03-01 FGF-23 PRODUCTION COUPLING WITH ALDOSTERONE AND PREDICTING CLINICAL OUTCOMES IN PRIMARY ALDOSTERONISM Jeff Chueh, Shuo-Meng Wang, VinCent Wu, and Kang-Yung Peng Jeff ChuehJeff Chueh More articles by this author , Shuo-Meng WangShuo-Meng Wang More articles by this author , VinCent WuVinCent Wu More articles by this author , and Kang-Yung PengKang-Yung Peng More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003220.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Higher fibroblast growth factor-23 (FGF-23) levels are associated with activating renin-angiotensin-aldosterone system (RAAS), more volume overload, and hypertension. The roles of FGF-23 in primary aldosteronism (PA) haven't been studied. METHODS: Unilateral PA (uPA) patients who underwent adrenalectomy were enrolled and followed for their clinical outcomes from Aug 15 to Jan 19. The FGF-23 expression in a rat osteoblast-like cell culture was evaluated after the addition of aldosterone. RESULTS: A total of 121 uPA patients & 69 matched essential hypertension (EH) controls were enrolled. The log [carboxyl-terminal FGF-23 (cFGF-23)] level was higher in uPA patients (p=0.001).] In Cox proportional hazard model, the preoperative Log [plasma cFGF-23]>1.98 was a risk factor for either all-cause mortality and cardiovascular or kidney events (HR, 4.01, p=0.038). Plasma cFGF-23 levels were increased in a nonlinear manner re: plasma aldosterone concentration (PAC). Log [plasma cFGF-23]>1.75 independently predicted post-op remission of hypertension (odds ratio (OR), 3.8, p=0.004). The plasma total FGF-23 level was significantly higher in PA patients (p<0.001), and it was significantly reduced post-op (p<0.001). When osteoblast-like UMR-106 cells were cultured with aldosterone, the cFGF-23 concentration in the culture medium was elevated (p=0.028), but it was abrogated after family with sequence similarity 20, member C (FAM20c) short hairpin RNA was added (p= 0.659). Docking experiments showed that aldosterone may bind to the potential drug binding pocket of FAM20c (Pdb: 5YH3; Figure 1A, B). CONCLUSIONS: Compared with EH controls, uPA patients had higher cFGF-23 levels--associated with a higher risk of cardiovascular composite outcomes, though such higher cFGF-23 levels predicted hypertension remission after adrenalectomy. Their total FGF-23 levels were significantly attenuated after adrenalectomy. An increase in cFGF-23 production among the uPA patients was secondary to increased cleavage of intact FGF-23 evidenced by higher FAM20c activity modulated by aldosterone. Source of Funding: Taiwan (NSC 101-2314-B-002-132-MY3, NSC100-2314-B-002-119, NSC 101-2314-B-002-085-MY3, MOST 104-2314-B-002 -125 -MY3; 111-2314-B-002-232-MY3) and NTUH 100-N1776, 101-M1953, 102-S2097 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e74 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jeff Chueh More articles by this author Shuo-Meng Wang More articles by this author VinCent Wu More articles by this author Kang-Yung Peng More articles by this author Expand All Advertisement PDF downloadLoading ...

Essential Hypertension and Oxidative Stress: Novel Future Perspectives.

Among cardiovascular diseases, hypertension is one of the main risk factors predisposing to fatal complications. Oxidative stress and chronic inflammation have been identified as potentially responsible for the development of endothelial damage and vascular stiffness, two of the primum movens of hypertension and cardiovascular diseases. Based on these data, we conducted an open-label randomized study, first, to evaluate the endothelial damage and vascular stiffness in hypertense patients; second, to test the effect of supplementation with a physiological antioxidant (melatonin 1 mg/day for 1 year) in patients with essential hypertension vs. hypertensive controls. Twenty-three patients of either gender were enrolled and randomized 1:1 in two groups (control and supplemented group). The plasmatic total antioxidant capacity (as a marker of oxidative stress), blood pressure, arterial stiffness, and peripheral endothelial function were evaluated at the beginning of the study and after 1 year in both groups. Our results showed that arterial stiffness improved significantly (p = 0.022) in supplemented patients. The endothelial function increased too, even if not significantly (p = 0.688), after 1 year of melatonin administration. Moreover, the supplemented group showed a significative reduction in TAC levels (p = 0.041) correlated with the improvement of arterial stiffness. These data suggest that melatonin may play an important role in reducing the serum levels of TAC and, consequently, in improving arterial stiffness.

Inflammatory cytokines induce neutrophil extracellular traps interaction with activated platelets and endothelial cells exacerbate coagulation in moderate and severe essential hypertension.

Essential hypertension (EH) patients suffer from paradoxically thrombotic rather than haemorrhagic, although the exact mechanism remains elusive. Our aim is to explore whether and how neutrophil extracellular traps (NETs) play the procoagulant role in EH patients, as well as evaluated whether the NET releasing were triggered by inflammatory cytokines. The concentration of plasma NETs components were detected by ELISA. The morphology of cells and NETs formation were analysed using immunofluorescence. Procoagulant activity was analysed by clotting time, purified coagulation complex and fibrin generation assays. Phosphatidylserine (PS) exposure on endothelial cells (ECs) was analysed with flow cytometry. Moderate to severe EH patients plasma NETs levels were significantly higher compared to mild EH patients or controls. Furthermore, inflammatory cytokines can induce NETs generation, depleting these patients plasma inflammatory cytokines led to a reduction in NET releasing. NETs from moderate to severe EH patients neutrophils led to significantly decreased clotting time (CT), increased potency to generate thrombin and fibrin (all P < 0.05). These procoagulant effects were markedly attenuated by approximately 70% using DNase I. Additionally, high concentrations NETs exerted a strong cytotoxic effect on ECs, conferring them a procoagulant phenotype. Our study reveals that EH drives a systemic inflammatory environment, which, in turn, drives neutrophils to prime and NET releasing, and found a link between hypercoagulability and NETs levels in moderate to severe EH patients. Therefore, anti-inflammatory combined with block the generation of NETs may represent a new therapeutic target for preventing thrombosis in EH patients.

PROFILING CIRCULATING EXTRACELLULAR VESICLE SURFACE ANTIGENS IN PRIMARY ALDOSTERONISM

Objective: Primary aldosteronism (PA) is characterized by an inappropriate secretion of aldosterone. Chronic aldosterone excess exerts detrimental effects on cardiovascular system, including endothelial dysfunction and vascular inflammation. Circulating extracellular vesicles (EVs) are central players in the crosstalk between endothelium and inflammatory cells, and they may be involved in the development of organ damage in patients with PA. The aim of the present study was to assess the potential role of EVs in aldosterone-related vascular injury by evaluating a panel of 37 EV surface antigens through an innovative flow cytometry multiplex bead-based platform. Design and method: Serum EVs were isolated by immuno-capture from 32 patients with PA, 29 patients with essential hypertension (EH) and from 22 normotensive (NT) controls. EVs were characterized by nanoparticle tracking analysis, transmission electron microscopy, western blotting, and flow cytometry. Results: EV concentration was higher and diameter lower in patients with PA compared to patients with EH and NT controls and the number of particles decreased after unilateral adrenalectomy. Nineteen EV surface antigens were differentially expressed in patients with PA compared to patients with EH or NT controls, including markers from activated platelets, endothelial and immune/inflammatory cells. Supervised learning was used to combine the expression levels of EV surface markers in a specific molecular signature which discriminated patients with PA from controls (EH and NT), whereas after specific treatment the profile became similar to EH. Stimulation of human endothelial cells with PA patient-derived EVs, but not with EVs from EH, resulted in the overexpression of 5 selected genes (AKT1, CALR, CSNK2A1, FN1, and PIK3R1), previously identified by bioinformatics analysis as potential targets of differentially expressed EV antigens. Notably, the effect was specifically dependent on EV surface antigens, since it was abolished by removal of EV membrane associated proteins. The overexpression of CALR and FN1 was confirmed also at protein level. Conclusions: Our data suggest that EVs represent biomarkers of vascular inflammation and endothelial dysfunction in patients with PA, and also potential biovectors contributing to endothelial dysfunction, vascular inflammation, and accelerated organ damage by multiple signalling processes.

Long-term mortality and cardiovascular events in patients with unilateral primary aldosteronism after targeted treatments.

Long-term outcomes (especially mortality and/or major cardiovascular events (MACE)) of the unilateral primary aldosteronism (uPA) patients who underwent medical or surgery-targeted treatment, relative to those with essential hypertension (EH), have been scarcely reported. Using the prospectively designed observational Taiwan Primary Aldosteronism Investigation cohort, we identified 858 uPA cases among 1220 primary aldosteronism patients and another 1210 EH controls. Operated uPA patients were grouped via their 1-year post-therapy statuses. Primary Aldosteronism Surgical Outcome clinical complete success (hypertension remission) was achieved in 272 (49.9%) of 545 surgically treated uPA patients. After follow-up for 6.3 ± 4.0 years, both hypertension-remissive (hazard ratio (HR): 0.54; P < 0.001) and not-cured (HR: 0.61; P < 0.001) uPA patients showed a lower risk of all-cause mortality than that of EH controls; whereas the not-cured group had a higher risk of incident MACE (sub-hazard ratio (sHR), 1.41; P = 0.037) but similar atrial fibrillation (Af) and congestive heart failure (CHF). Mineralocorticoid receptor antagonist (MRA)-treated uPA patients had higher risks of MACE (sHR: 1.38; P = 0.033), Af (sHR:1.62, P = 0.049), and CHF (sHR: 1.44; P = 0.048) than those of EH controls, with mortality as a competing risk. Using inverse probability of treatment-weighted matching and counting adrenalectomy as a time-varying factor, treatment with adrenalectomy was associated with lower risks of all-cause mortality (HR: 0.57; P = 0.035), MACE (HR: 0.67; P = 0.037), and CHF (HR: 0.49; P = 0.005) compared to those of MRA therapy. Adrenalectomy, independent of post-surgical hypertension remission, was associated with lower all-cause mortality of uPA patients, compared to that of EH patients. We further documented a more beneficial effect of adrenalectomy over MRA treatment on long-term mortality, MACE, and CHF in uPA patients.

Assessment of skin microcirculation in primary aldosteronism: impaired microvascular responses compared to essential hypertensives and normotensives.

Primary aldosteronism (PA) is associated with considerably higher cardiovascular risk and increased prevalence of organ damage compared to essential hypertension (EH). Laser speckle contrast imaging (LSCI) has emerged as a novel non-invasive tool to assess of skin microcirculation. Our aim was to evaluate skin microvascular function (SMF) using LSCI coupled with post-occlusive reactive hyperemia (PORH) in a group of PA patients (PAs) compared to patients with EH (EHs) and normotensive controls (NTs). We enrolled PAs, age- and gender-matched with EHs and NTs. All participants underwent SMF assessment by LSCI with PORH. We enrolled 109 participants including 29 PAs, 47 EHs, and 33 NTs. SMF was significantly impaired in PAs, including peak time (p < 0.001) and base to peak flux (p < 0.001) compared to NTs and EHs. Among PAs, plasma aldosterone showed a positive correlation with occlusion flux (p = 0.005). Our study shows for the first time that PAs present impaired SMF as assessed with LSCI coupled with PORH, not only compared to NTs but also compared to EHs with similar blood pressure profile. Further studies are needed to investigate the clinical impact of such alterations in terms of pathophysiology and cardiovascular risk prediction.

Left ventricular global longitudinal strain in secondary hypertension: A meta-analysis of echocardiographic studies

AimInformation on systolic dysfunction, as assessed by left ventricular (LV) mechanics in secondary hypertension is still largely limited. We performed a systematic meta- analysis of 2D/3D speckle tracking studies in order to provide an updated comprehensive information on this topic. MethodsThe PubMed, OVID-MEDLINE, and Cochrane library databases were analysed to search for articles published from the inception up to March 31st 2021. Studies were identified by using MeSH terms and crossing the following search items: “myocardial strain” “left ventricular mechanics”, “speckle tracking echocardiography”, “systolic dysfunction”, “hypertensive heart disease”, “left ventricular hypertrophy”, “secondary hypertension”, “primary aldosteronism”, “pheochromocytoma”, “Cushing disease”, “renal artery stenosis”. ResultsOn the whole, 515 patients with secondary hypertension (169 pheochromocytoma, 165 primary aldosteronism, 144 renal artery stenosis and 37 Cushing's syndrome) and 601 essential hypertensive patients from 11 studies were considered. Pooled ejection fraction (EF) was similar in essential hypertensive controls and in patients with secondary hypertension (SMD 0.12±0.06, CI: 0.001/0.25, p=0.05). Of note, EF was higher in patients with pheochromocytoma than in essential hypertensives (0.50±0.11, CI: 0.27/0.73, p<0.001). In contrast, pooled GLS was impaired in patients with secondary hypertension compared to their essential hypertensive counterparts (SMD 0.83±0.26, CI: 0.32/1.30, p< 0.001). ConclusionsThe present meta-analysis adds a new piece of evidence by showing that GLS performs better than EF in identifying systolic dysfunction in the setting of secondary hypertension. In particular, this is true in patients with pheochromocytoma in whom conventional EF suggests a normal or even super-normal systolic function.

Characterization of Circulating Extracellular Vesicle Surface Antigens in Patients With Primary Aldosteronism.

[Figure: see text].

Time-Varying Risk of Atrial Fibrillation in Patient With Medically and Surgically Treated Primary Aldosteronism: A Nationwide Cohort Study

Evidence of increased cardiovascular risk, especially atrial fibrillation, has been accumulating among patients with primary aldosteronism (PA), but there is still limited information about long-term prognosis related to different treatment strategy. The aim of this study was not only to investigate the incidence of atrial fibrillation, but also to evaluate their time-dependent changes after adrenalectomy (surgery group) or mineralocorticoid receptor antagonists (drug group) for patients with PA compared to those with essential hypertension (EH). From a nationwide cohort in Korea (2003–2017), PA were individually matched for sex, age (±10 years), and index year in a 1:5 ratio with EH. The primary end point was the time-varying risk of new-onset atrial fibrillation (NOAF) among PA according to treatment mode compared to EH. The secondary end points were the risks of major adverse cardiovascular events (composite of non-fatal myocardial infarction, non-fatal stroke, and death from cardiovascular causes), hospitalization for heart failure, and all-cause mortality. Cox proportional-hazards analysis or time-dependent Cox analysis based on the Schoenfeld residuals testing were performed. We enrolled 1,418 PA patients (755 in PA surgery group and 663 in PA drug group), and matched theses with 7,090 EH controls with a median of 5 years. The risk of incident NOAF was statistically higher in patients with PA (both surgery and drug groups) within the three years after diagnosis (adjusted hazard ratio, 3.02; p<0.001), whereas there was no statistically significance after the three years compared to EH (adjusted hazard ratio, 0.50; p=0.053). Patients in the PA drug group had higher risk of non-fatal stroke during the total followed up period (adjusted hazard ratio, 1.53, p=0.031), although the PA surgery group didn’t. In contrast, patients with PA had no statistically significant difference in risks for other secondary cardiovascular outcomes. In conclusion, this propensity cohort study of adults with PA demonstrated the changeable risk of NOAF over time possibly due to the residual effect of inappropriate aldosterone levels. These findings can provide clinically relevant guidance in the monitoring the cardiovascular complications, especially NOAF and non-fatal stroke, even after treatment among patients with PA. Acknowledgements: This study was supported by Collaborative Research Project of Korean Endocrine Society and National Health Insurance Sharing Service (NHIS-2019-4-005). We also thank Minheui Yu and Doori Cho, the members of the SENTINEL (Severance ENdocrinology daTa scIeNcE pLatform) team for technical assistance in searching and summarizing the relevant literature (4-2018-1215).

Long-Term Mortality and Cardiac Outcomes in Patients With Clinical Aldosterone Producing Adenomas After Target Treatments

Background: Long-term outcomes (especially mortality and/or major cardiovascular events [MACE]) of the clinical aldosterone producing adenoma (cAPA) patients who underwent medical targeted therapy or adrenalectomy, relative to those with essential hypertension (EH), have been scarcely reported. Methods: Using an inception observational cohort, we examined the longitudinal outcomes for all cAPA patients diagnosed throughout 2003-2017. We identified 858 cAPA cases among 1220 primary aldosteronism (PA) patients and another 1210 EH controls. cAPA patients underwent unilateral adrenalectomy or mineralocorticoid receptor antagonist (MRA) therapy as opposed to standard medical treatment for EH. Operated cAPA patients were grouped via their 1-year post-therapy statuses according to the Primary Aldosteronism Surgical Outcome (PASO) criteria. Long term all-cause mortality was the primary outcome. Secondary outcomes were incident MACE, atrial fibrillation (Af) or congestive heart failure (CHF) after the PA confirmatory diagnosis. Findings: 272 (49.9%) of the 545 surgically-treated cAPA patients achieved PASO clinical complete success (hypertension-remission without medications). After a follow-up of 6.3±4.0 years, both hypertension-remissive (HR, 0.54, p 27 ng/dL after adrenalectomy or plasma renin activity < 0.6 ng/mL/hr after MRA treatment could be associated with higher risks of mortality or MACE. Interpretation: Adrenalectomy, independent of post-surgical hypertension-remission, was associated with lower all-cause mortality of cAPA patients. However, post-adrenalectomy non-cured hypertension and/or MRA therapy in cAPA patients could still have higher MACE risk than that of the EH controls. We further documented a more beneficial effect of adrenalectomy over MRA treatment on long-term mortality, MACE, and CHF in cAPA patients. Trial Registration: NCT00917345 Funding Statement: This study was supported by Taiwan National Science Council (grants NSC 101- 2314-B-002-132-MY3, NSC100-2314-B-002-119, NSC 101-2314-B-002-085-MY3, MOST 104- 2314-B-002 -125 -MY3) and NTUH 100-N1776, 101-M1953, 102-S2097. Declaration of Interests: No competing interest was declared. No financial conflict of interest exists. Ethics Approval Statement: Ethical approval (approval number: 201801049RIND, NCT00917345) was obtained from the institutional review board of the National Taiwan University Hospital.

Association of Cytochrome P450 2C9*3 and Angiotensin II Receptor 1 (1166A>C) Gene Polymorphisms With the Antihypertensive Effect of Irbesartan.

To analyze whether the cytochrome P450 enzyme 2C9*3 (CYP2C9*3) and angiotensin II receptor 1 (AGTR1) (1166A>C) gene polymorphisms are associated with the risk of essential hypertension (EH) and the antihypertensive effect of irbesartan. A total of 2,057 EH patients and 286 healthy controls were enrolled for genotyping in which 598 EH patients were given irbesartan 150 mg/day for 4 weeks. Blood pressure of all subjects were determined before and at the end of 4-week treatment. There was no significant difference in genotype frequencies of CYP2C9*3 and AGTR1 (1166A>C) between EH and control groups. Subjects with *1*3/*3*3 genotypes of the CYP2C9*3 gene had larger systolic and diastolic blood pressure reductions (34.9 ± 15.5 vs. 29.3 ± 10.2 mm Hg and 22.8 ± 9.0 vs. 19.6 ± 8.5 mm Hg, respectively) compared with the *1*1 genotype. For AGTR1 (1166A>C) polymorphisms, although there was no significant difference among AC, CC, and AA genotypes, male subjects with AC/CC genotypes had larger systolic and diastolic blood pressure reductions (32.3 ± 1.3 vs. 29.3 ± 0.5 mm Hg and 21.6 ± 0.8 vs. 19.4 ± 0.1 mm Hg, respectively, P < 0.05) in response to irbesartan treatment compared with the AA genotype. Polymorphisms of CYP2C9*3 and AGTR1 (1166A>C) are not significantly different between EH and healthy controls. Male subjects with AC and CC genotypes of AGTR1 (1166A>C) show better antihypertensive effect of irbesartan than the AA genotype.

Insulin sensitivity and pancreatic β-cell function in patients with primary aldosteronism.

Primary aldosteronism (PA) is associated with an increased risk for dysglycemia. However, the effects of hyperaldosteronism on insulin sensitivity and β-cell function are unclear. Using a cross-sectional study design, we assessed insulin sensitivity and pancreatic β-cell function from an oral glucose tolerance test (OGTT) in patients from two cohorts: subjects with PA (n = 21) and essential hypertension control (EHC) subjects (n = 22). Age, sex, BMI, and mean arterial pressure adjusted measures of insulin sensitivity and β-cell function were compared between the groups. PA individuals were less insulin sensitive compared to EHC subjects (Quantitative insulin sensitivity check index [QUICKI]: 0.340 ± 0.006 vs. 0.374 ± 0.013, p < 0.001; Matsuda index: 4.14 ± 0.49 vs. 7.87 ± 1.42, p < 0.001; SI: 11.45 ± 4.85 vs. 21.23 ± 6.11 dL/kg/min per μU/mL, p = 0.02). The hepatic insulin resistance index (HIRI) was higher in PA subjects (PA: 5.61 ± 1.01 vs. EHC: 4.13 ± 0.61, p = 0.002). The insulinogenic index (IGI), an index of β-cell function was higher in the PA cohort (PA: 1.49 ± 0.27 vs. 1.11 ± 0.21 μU/mL/mg/dL, p = 0.03). However, the oral disposition index (DI) was similar between the groups (PA: 4.77 ± 0.73 vs. EHC: 5.46 ± 0.85, p = 0.42), which likely accounts for the similar glucose tolerance between the two cohorts, despite lower sensitivity. In summary, insulin sensitivity is significantly lower in PA with an appropriately compensated β-cell function. These results suggest that excess aldosterone and/or other steroids in the context of PA may negatively affect insulin action without adversely impacting β-cell function.

Left Ventricular Remodeling in Patients with Primary Aldosteronism: A Prospective Cardiac Magnetic Resonance Imaging Study.

ObjectiveThis study used cardiac magnetic resonance imaging (MRI) to compare the characteristics of left ventricular remodeling in patients with primary aldosteronism (PA) with those of patients with essential hypertension (EH) and healthy controls (HCs).Materials and MethodsThis prospective study enrolled 35 patients with PA, in addition to 35 age- and sex-matched patients with EH, and 35 age- and sex-matched HCs, all of whom underwent comprehensive clinical and cardiac MRI examinations. The analysis of variance was used to detect the differences in the characteristics of left ventricular remodeling among the three groups. Univariable and multivariable linear regression analyses were used to determine the relationships between left ventricular remodeling and the physiological variables.ResultsThe left ventricular end-diastolic volume index (EDVi) (mean ± standard deviation [SD]: 85.1 ± 13.0 mL/m2 for PA, 75.9 ± 14.3 mL/m2 for EH, and 77.3 ± 12.8 mL/m2 for HC; p = 0.010), left ventricular end-systolic volume index (ESVi) (mean ± SD: 35.2 ± 9.8 mL/m2 for PA, 30.7 ± 8.1 mL/m2 for EH, and 29.5 ± 7.0 mL/m2 for HC; p = 0.013), left ventricular mass index (mean ± SD: 65.8 ± 16.5 g/m2 for PA, 56.9 ± 12.1 g/m2 for EH, and 44.1 ± 8.9 g/m2 for HC; p < 0.001), and native T1 (mean ± SD: 1224 ± 39 ms for PA, 1201 ± 47 ms for EH, and 1200 ± 44 ms for HC; p = 0.041) values were higher in the PA group compared to the EH and HC groups. Multivariable linear regression demonstrated that log (plasma aldosterone-to-renin ratio) was independently correlated with EDVi and ESVi. Plasma aldosterone was independently correlated with native T1.ConclusionPatients with PA showed a greater degree of ventricular hypertrophy and enlargement, as well as myocardial fibrosis, compared to those with EH. Cardiac MRI T1 mapping can detect left ventricular myocardial fibrosis in patients with PA.

Associations Between Metabolic Profiles and Target-Organ Damage in Chinese Individuals With Primary Aldosteronism

Purpose: Patients with primary aldosteronism (PA) have an increased risk of target-organ damage (TOD), but whether metabolic syndrome (MetS) is more prevalent and contributes to TOD in PA patients remains unresolved. We aimed to evaluate the associations between MetS profiles and TOD in Chinese PA individuals.Methods: Metabolic parameters and pre-clinical TOD including left ventricular hypertrophy, estimated glomerular filtration, and microalbuminuria; insulin sensitivity or resistance; and islet β-cell function were assessed by the homeostasis models (HOMA-IR, HOMA-β) and the other surrogate indexes [composite insulin sensitivity index (ISI), modified β-cell function index (MBCI)] determined from the oral glucose tolerance test were compared in PA vs. matched essential hypertension (EH) patients.Results: A total of 109 PA patients and 109 essential hypertension (EH) controls individually matched for sex, age, and office systolic blood pressure and duration of hypertension were studied. The prevalence of MetS and its individual components in PA was significantly lower than in EH [MetS: 28 (25.6%) vs. 54 (49.5%), P < 0.001]. PA patients had a higher composite ISI but a lower HOMA-IR, HOMA-β, and MBCI than EH controls (all P < 0.05). Concerning TOD, PA patients had significantly higher prevalence of microalbuminuria and left ventricular hypertrophy (LVH), and lower levels of estimated glomerular filtration (eGFR) than EH controls (all P < 0.05). On multivariate logistic regression analysis, female gender and elevated plasma aldosterone levels were significantly associated with TOD in PA. However, there were no significant associations between MetS and its individual components and TOD in PA patients.Conclusions: PA patients had a lower MetS prevalence but exhibited more severe TOD than matched EH controls. The study highlights the deleterious effects of aldosterone excess on the development of TOD, whereas MetS or its individual components might be less influential in PA.

Primary aldosteronism: Higher volume load, cardiac output and arterial stiffness than in essential hypertension.

The diagnostics of primary aldosteronism (PA) are usually carried out in patients taking antihypertensive medications. We compared haemodynamics between medicated PA, medicated essential hypertension (EH), never-medicated EH and normotensive controls (n=130 in all groups). The hypertensive groups were matched for age (53years), sex (84 male/46 female) and body mass index (BMI) (30kgm-2 ); normotensive controls had similar sex distribution (age 48years, BMI 27kgm-2 ). Haemodynamics were recorded using whole-body impedance cardiography and radial pulse wave analysis, and the results were adjusted as appropriate. Radial blood pressure recordings were calibrated by brachial blood pressure measurements from the contralateral arm. Radial and aortic systolic and diastolic blood pressure was similar in PA and never-medicated EH, and higher than in medicated EH and normotensive controls (P≤0.001 for all comparisons). Extracellular water balance was~4% higher in PA than in all other groups (P<0.05 for all), whilst cardiac output was~8% higher in PA than in medicated EH (P=0.012). Systemic vascular resistance and augmentation index were similarly increased in PA and both EH groups when compared with controls. Pulse wave velocity was higher in PA and never-medicated EH than in medicated EH and normotensive controls (P≤0.033 for all comparisons). Medicated PA patients presented with corresponding systemic vascular resistance and wave reflection, but higher extracellular water volume, cardiac output and arterial stiffness than medicated EH patients. Whether the systematic evaluation of these features would benefit the clinical diagnostics of PA remains to be studied in future.

Analysis of correlation of community management index of essential hypertension and type 2 diabetes with probability of premature mortality caused by major non-communicable diseases in Zhejiang Province

Objective: To evaluate the correlation of community management index of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases. Methods: From 2016 to 2018, the management of essential hypertension and type 2 diabetes were obtained from annual report of comprehensive prevention and control of chronic diseases in communities of Zhejiang province. The death data of chronic diseases were obtained from Information Management System of Chronic Diseases of Zhejiang province and annual population data were obtained from Public Security Bureau of Zhejiang Province. The management of essential hypertension and type 2 diabetes in communities of Zhejiang Province from 2016 to 2018 was described. The death status of major chronic diseases, including cardiovascular diseases, malignant tumors, diabetes and chronic respiratory diseases, in the same period was also described. Spearman correlation analysis and linear regression model were used to explore the correlation of community management of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases. Results: The number of essential hypertension patients under standardized management, blood pressure control and regular medication increased from 3.127 3, 2.811 5 and 3.569 7 million in 2016 to 3.355 9, 3.151 8 and 4.010 6 million in 2018, respectively. The number of type 2 diabetes patients with standardized management, blood glucose control and regular medication increased from 0.805 5, 0.687 5 and 0.913 4 million in 2016 to 0.912 6, 0.798 7 and 1.064 8 million in 2018, respectively. The standardized mortality rate of chronic diseases decreased from 403.07/100 000 in 2016 to 380.07/100 000 in 2018. The proportion of premature deaths of chronic diseases decreased from 28.39% in 2016 to 26.90% in 2018. The proportion of deaths from major chronic diseases in all chronic diseases decreased from 90.96% in 2016 to 90.69% in 2018.The probability of premature mortality decreased from 10.68% in 2016 to 9.67% in 2018. The spearman correlation analysis showed that the blood pressure control and regular drug use were negatively correlated with the probability of premature death of major chronic diseases (r values were -0.367 and -0.392; P values were 0.035 and 0.024). According to the linear regression model analysis, with increase of 100 000 of essential hypertension control cases or regular medication use cases of type 2 diabetes, the probability of premature death of major chronic diseases decreased by 0.47% (95%CI: 0.39%, 0.54%) or 1.31% (95%CI: 1.12%, 1.50%), respectively. Conclusion: From 2016 to 2018, the community management of essential hypertension and type 2 diabetes was negatively correlated with probability of premature death of major chronic diseases in Zhejiang province.