Circulating Plasma Concentrations of ACE2 in Primary Aldosteronism and Cardiovascular Outcomes.

CONTEXT: The plasma concentrations of angiotensin-converting enzyme 2 (pACE2) has been independently associated with cardiovascular diseases. OBJECTIVE: Higher pACE2 concentrations may be found in patients with primary aldosteronism (PA) and might lead to increased cardiovascular events. METHODS: Using an inception observational cohort, we examined pACE2 among 168 incident patients with PA. The expression of ACE2, serine protease 2 (TMPRSS2), and metalloprotease 17 (ADAM17) were assessed in peripheral blood mononuclear cells. RESULTS: Incident PA and essential hypertension (EH) patients had similarly elevated pACE2 (47.04 ± 22.06 vs 46.73 ± 21.06 ng/mL; P = .937). Age was negatively (ß = -2.15; P = .033) and higher serum potassium level (ß = 2.29; P = .024) was positively correlated with higher pACE2 in PA patients. Clinical complete hypertension remission after adrenalectomy (Primary Aldosteronism Surgery Outcome criteria) was achieved in 36 (50%) of 72 surgically treated unilateral PA (uPA) patients. At follow-up, pACE2 decreased in surgically treated patients who had (P < .001) or had no (P = .006) hypertension remission, but the pACE2 attenuation was not statistically significant in uPA (P = .085) and bilateral PA (P = .409) administered with mineralocorticoid receptor antagonist (MRA). Persistently elevated pACE2 (> 23 ng/mL) after targeted treatments was related to all-cause mortality and cardiovascular events among PA patients (hazard ratio = 8.8; P = .04); with a mean follow-up of 3.29 years. TMPRSS2 messenger RNA (mRNA) expression was higher in uPA (P = .018) and EH (P = .038) patients than in normotensive controls; it was also decreased after adrenalectomy (P < .001). CONCLUSION: PA and EH patients had elevated pACE2 and higher expression of TMPRSS2 mRNA compared to those of normotensive population. Persistently elevated pACE2 (> 23 ng/mL) after targeted treatments was associated risk of mortality and incident cardiovascular events.

Cardiovascular events and all-cause mortality in surgically or medically treated primary aldosteronism: A Meta-analysis.

OBJECTIVES: To compare the effect of surgical or medical treatment on the risk of cardiovascular diseases (CVD) and all-cause mortality in patients with established primary aldosteronism (PA). METHODS: We searched PUBMED, MEDLINE and Cochrane Library for the meta-analysis. We included patients who were diagnosed with PA following guideline-supported protocols and received surgery or mineralocorticoid receptor antagonist (MRA)-based medical treatment, and age-sex matched patients with treated essential hypertension (EH). Primary endpoints were CVD incidence and all-cause mortality. RESULTS: Compared with EH, patients with treated PA had a higher risk of CVD [odds ratio (OR) 1.79; 95% confidence interval (CI) 1.39-2.31]. This elevated risk was only observed in patients with medically treated PA [OR 2.11; 95%CI 1.88-2.38] but not in those with surgically treated PA. The risk of all-cause mortality was significantly lower in patients with treated PA [OR 0.86; 95% CI 0.77-0.95] compared to EH. The reduced risk was only observed in patients with surgically treated PA [OR 0.47; 95% CI 0.34-0.66], but not in those with medically treated PA. CONCLUSIONS: Patients with medically treated PA have a higher risk of CVD compared to patients with EH. Surgical treatment of PA reduces the risk of CVD and all-cause mortality in patients with PA.

Factors Associated with Primary Hypertension in Pediatric Patients: An Up-to-Date.

BACKGROUND: Arterial hypertension in children is considered a common alteration nowadays, mainly because obesity is a growing worldwide problem closely related to increased blood pressure. Childhood hypertension can be classified as primary or secondary, depending on the etiology. Primary or essential hypertension still has its pathophysiology not fully elucidated, and there is no consensus in the literature on most underlying mechanisms. In this review, genetic and environmental factors, including sodium and potassium intake, socioeconomic status, ethnicity, family structure, obesity, sedentary lifestyle, prematurity and low birth weight, prenatal and postnatal exposures are highlighted. OBJECTIVE: The present study aimed to perform an update on primary hypertension in childhood, providing clinicians and researchers an overview of the current state of the literature regarding the influence of genetic and environmental factors. METHODS: This integrative review searched for articles on genetic and environmental factors related to primary hypertension in pediatric patients. The databases evaluated were PubMed and Scopus. RESULTS: The studies have provided insights regarding many genetic and environmental factors, in addition to their association with the pathophysiology of primary hypertension in childhood. Findings corroborated the idea that primary hypertension is a multifactorial disease. Further studies in the pediatric population are needed to elucidate the underlying mechanisms. CONCLUSION: The study of primary hypertension in pediatrics has utmost importance for the adoption of preventive measures and the development of more efficient treatments, therefore reducing childhood morbidity and the incidence of cardiovascular diseases and other health consequences later in life.

Biochemical interaction of salt sensitivity: a key player for the development of essential hypertension.

Worldwide, more than 1 billion people have elevated blood pressure, with up to 45% of adults affected by the disease. In 2016 the global health study report on patients from 67 countries was released in Lancet, which identified hypertension as the world's leading cause for death and disability-adjusted years since 1990. This paper aims to analyze the pathophysiological connection between hemodynamic inflammatory reactions through sodium balance, salt sensitivity, and potential pathophysiological reactions. Besides, we explore how sodium consumption enhances the expression of transient receptor potential channel 3 (TrpC3) mRNA and facilitates the release of calcium inside immune cell groups, together with elevated blood pressure in essential hypertensive patients.

Human essential hypertension: no significant association of polygenic risk scores with antihypertensive drug responses.

Polygenic risk scores (PRSs) for essential hypertension, calculated from > 900 genomic loci, were recently found to explain a significant fraction of hypertension heritability and complications. To investigate whether variation of hypertension PRS also captures variation of antihypertensive drug responsiveness, we calculated two different PRSs for both systolic and diastolic blood pressure: one based on the top 793 independent hypertension-associated single nucleotide polymorphisms and another based on over 1 million genome-wide variants. Using our pharmacogenomic GENRES study comprising four different antihypertensive monotherapies (n ~ 200 for all drugs), we identified a weak, but (after Bonferroni correction) statistically nonsignificant association of higher genome-wide PRSs with weaker response to a diuretic. In addition, we noticed a correlation between high genome-wide PRS and electrocardiographic left ventricular hypertrophy. Finally, using data of the Finnish arm of the LIFE study (n = 346), we found that PRSs for systolic blood pressure were slightly higher in patients with drug-resistant hypertension than in those with drug-controlled hypertension (p = 0.03, not significant after Bonferroni correction). In conclusion, our results indicate that patients with elevated hypertension PRSs may be predisposed to difficult-to-control hypertension and complications thereof. No general association between a high PRS and less efficient drug responsiveness was noticed.

A Role of Inflammation and Immunity in Essential Hypertension-Modeled and Analyzed Using Petri Nets.

Recent studies have shown that the innate and adaptive immune system, together with low-grade inflammation, may play an important role in essential hypertension. In this work, to verify the importance of selected factors for the development of essential hypertension, we created a Petri net-based model and analyzed it. The analysis was based mainly on t-invariants, knockouts of selected fragments of the net and its simulations. The blockade of the renin-angiotensin (RAA) system revealed that the most significant effect on the emergence of essential hypertension has RAA activation. This blockade affects: (1) the formation of angiotensin II, (2) inflammatory process (by influencing C-reactive protein (CRP)), (3) the initiation of blood coagulation, (4) bradykinin generation via the kallikrein-kinin system, (5) activation of lymphocytes in hypertension, (6) the participation of TNF alpha in the activation of the acute phase response, and (7) activation of NADPH oxidase-a key enzyme of oxidative stress. On the other hand, we found that the blockade of the activation of the RAA system may not eliminate hypertension that can occur due to disturbances associated with the osmotically independent binding of Na in the interstitium. Moreover, we revealed that inflammation alone is not enough to trigger primary hypertension, but it can coexist with it. We believe that our research may contribute to a better understanding of the pathology of hypertension. It can help identify potential subprocesses, which blocking will allow better control of essential hypertension.

Early Programming of Adult Systemic Essential Hypertension.

Cardiovascular diseases are being included in the study of developmental origins of health and disease (DOHaD) and essential systemic hypertension has also been added to this field. Epigenetic modifications are one of the main mechanisms leading to early programming of disease. Different environmental factors occurring during critical windows in the early stages of life may leave epigenetic cues, which may be involved in the programming of hypertension when individuals reach adulthood. Such environmental factors include pre-term birth, low weight at birth, altered programming of different organs such as the blood vessels and the kidney, and living in disadvantageous conditions in the programming of hypertension. Mechanisms behind these factors that impact on the programming include undernutrition, oxidative stress, inflammation, emotional stress, and changes in the microbiota. These factors and their underlying causes acting at the vascular level will be discussed in this paper. We also explore the establishment of epigenetic cues that may lead to hypertension at the vascular level such as DNA methylation, histone modifications (methylation and acetylation), and the role of microRNAs in the endothelial cells and blood vessel smooth muscle which participate in hypertension. Since epigenetic changes are reversible, the knowledge of this type of markers could be useful in the field of prevention, diagnosis or epigenetic drugs as a therapeutic approach to hypertension.

Sex-specific role of CYP24A1 rs2762939 in the risk of essential hypertension based on the serum vitamin D and total renin concentrations.

CYP24A1, Vitamin D 24-hydroxylase catabolizes 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D to 24-hydroxylated vitamin D products. It is widely known that low Vitamin D can lead to increased renal renin and angiotensin II production, consequently elevating blood pressure or development of essential hypertension (EH). We have conducted an investigation on hypertensives and controls to evaluate the association of the gene variant, CYP24A1 rs2762939 and 25(OH)D in an Indian population with EH. On gender-based stratification, with multivariate logistic analysis after adjustment for covariates, the CYP24A1 rs2762939 CC variant showed a higher risk of EH in males (aOR = 3.141, CI 1.164-8.478, P = .024) while females illustrated an inverse association with EH (aOR = 0.398, CI 0.172-0.092, P = .031). The 25(OH)D levels among the three genotypes of hypertensives substantiate these results. Our results clearly suggest that gender, CYP24A1 rs2762939, and Vitamin D status may play a significant role in disease susceptibility towards EH in Indian population.

Nicardipine for the Treatment of Neonatal Hypertension During Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is one of the primary reasons systemic hypertension is experienced in hospitalized neonates. Commonly used antihypertensive agents have resulted in significant adverse effects in neonatal and pediatric populations. Nicardipine is a desirable option because of its rapid and titratable antihypertensive properties and low incidence of adverse effects. However, data for use in neonatal ECMO are limited. We conducted a retrospective review of patients less than 44 weeks post-menstrual age who received a nicardipine infusion for first-line treatment of systemic hypertension while on ECMO at our institution between 2010 and 2016. Systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressures were evaluated for 48-h after nicardipine initiation. Eight neonates received a nicardipine infusion while on ECMO during the study period. Nicardipine was initiated at a mean dose of 0.52 ( ± 0.22) mcg/kg/min and titrated to a maximum dose of 1.1 ( ± 0.85) mcg/kg/min. The median duration of nicardipine use was 51 (range 4-227) hours. Significant decreases in SBP, DBP, and MAP occurred within one hour of initiation of nicardipine and were sustained through the majority of the 48-h evaluation period. No patients experienced hypotension. Prospective studies are warranted to evaluate the optimal dose, safety, and efficacy of nicardipine in neonates who require ECMO.

The relationship between Plasma Markers and Essential Hypertension in Middle-aged and Elderly Chinese Population: A Community Based Cross-sectional Study.

Plasma markers have been continuously advocated as pointers to estimate the long-term risk of cardiovascular disease in the general population. We examined the relationship between plasma high-sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy), high-sensitivity cardiac troponin T (hs-cTnT), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 25-Hydroxyvitamin D (25OHD), glycosylated hemoglobin A1c (HbA1c), and serum uric acid (SUA) levels and hypertension in middle and old aged population. A total of 2624 Chinese (62.02 ± 5.73 years old) were recruited into a population-based, cross-sectional study. Plasma hs-CRP, Hcy, HbA1c, and SUA levels were significantly higher in the hypertension group compared with control in the entire population and men (P = 0.05 for all). We observed a positive association between the highest quartiles of Hcy, NT-proBNP, HBA1c concentrations, and the prevalence of hypertension, OR (95% CI) = 1.48 (1.16-1.90), 1.62 (1.27-2.07) and 1.94 (1.49-2.52), respectively. The multivariable-adjusted OR of hypertension for the fourth versus the first quartile of homocysteine were 2.00 and 1.39 in men and women, respectively. In conclusion, our study found an independent and robust association between elevated Hcy, NT-ProBNP, and HBA1c levels and prevalence of hypertension in the middle-aged and elderly Chinese population. A follow-up study is necessary to endorse the observed association.

Epigenetic modification: a regulatory mechanism in essential hypertension.

Essential hypertension (EH) is a multifactorial disease of the cardiovascular system that is influenced by the interplay of genetic, epigenetic, and environmental factors. The molecular dynamics underlying EH etiopathogenesis is unknown; however, earlier studies have revealed EH-associated genetic variants. Nevertheless, this finding alone is not sufficient to explain the variability in blood pressure, suggesting that other risk factors are involved, such as epigenetic modifications. Therefore, this review highlights the potential contribution of well-defined epigenetic mechanisms in EH, specifically, DNA methylation, post-translational histone modifications, and microRNAs. We further emphasize global and gene-specific DNA methylation as one of the most well-studied hallmarks among all epigenetic modifications in EH. In addition, post-translational histone modifications, such as methylation, acetylation, and phosphorylation, are described as important epigenetic markers associated with EH. Finally, we discuss microRNAs that affect blood pressure by regulating master genes such as those implicated in the renin-angiotensin-aldosterone system. These epigenetic modifications, which appear to contribute to various cardiovascular diseases, including EH, may be a promising research area for the development of novel future strategies for EH prevention and therapeutics.

PTH Modulation by Aldosterone and Angiotensin II is Blunted in Hyperaldosteronism and Rescued by Adrenalectomy.

CONTEXT: Accumulating evidence suggests a link between adrenocortical zona glomerulosa and parathyroid gland through mechanisms that remain unexplored. OBJECTIVES: To test the hypothesis that in vivo angiotensin II blockade affects PTH secretion in patients with hypertension and that aldosterone and angiotensim II directly stimulate PTH secretion ex vivo. DESIGN AND SETTING: We investigated the changes of serum PTH levels induced by oral captopril (50 mg) administration in patients with primary essential hypertension (EH) and with primary aldosteronism (PA) caused by bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenoma (APA), the latter before and after adrenalectomy. We also exposed primary cultures of human parathyroid cells from patients with primary hyperparathyroidism to angiotensin II (10-7 M) and/or aldosterone (10-7 M). RESULTS: Captopril lowered PTH levels (in nanograms per liter) both in patients with EH (n = 63; 25.9 ± 8.3 baseline vs 24.4 ± 8.0 postcaptopril, P < 0.0001) and in patients with APA after adrenalectomy (n = 27; 26.3 ± 11.6 vs 24.0 ± 9.7 P = 0.021). However, it was ineffective in patients with full-blown PA caused by APA and BAH. In primary culture of human parathyroid cells, both aldosterone (P < 0.001) and angiotensin II (P = 0.002) markedly increased PTH secretion from baseline, by acting through mineralocorticoid receptor and angiotensin type 1 receptor, as these effects were abolished by canrenone and irbesartan, respectively. CONCLUSION: These results collectively suggest an implication of the renin-angiotensin-aldosterone system in PTH regulation in humans, at least in PTH-secreting cells obtained from parathyroid tumors. Moreover, they further support the concept that mild hyperparathyroidism is a feature of human PA that is correctable with adrenalectomy.

[The role of «Youth and aging proteins¼ in essential hypertension pathogenesis.]

Essential hypertension (EG) is an age-associated disease. Often EG of elderly patients haven't good way of treatment. Thus, the search of new target molecules for EG therapy is an actual goal of gerontology and molecular medicine. It was shown, that during EG concentrations of GDF11 «youth protein¼ decreased in 3,3 times and GDF15, JAM-A/1, CCL11 «aging proteins¼ increased in 1,4-2,4 times. EG patients have abnormal microcirculation processes. It was shown as decreasing in 1,3 and 1,7 times of hemodynamic HI1 and H1-H3 indexes. EG patients have negative correlation of GDF15 concentration with arterial pressure. EG patients have no correlation of JAM-A/1 concentration with arterial pressure. Normal is positive correlation with GDF15, JAM-A/1 concentration with arterial pressure. GDF15 blood level during EG have positive correlation with HI1-HI3 and negative correlation with NEUR_HI2 and MAYER_HI3 indexes. It can show on pathogenesis mechanisms of endothelial and smooth muscles function of vessels tissues. We suppose, that the regulation of GDF11, GDF15, JAM-A/1, CCL11 «youth and aging proteins¼ can be target object of EG therapy.

Postulating the major environmental condition resulting in the expression of essential hypertension and its associated cardiovascular diseases: Dietary imprudence in daily selection of foods in respect of their potassium and sodium content resulting in oxidative stress-induced dysfunction of the vascular endothelium, vascular smooth muscle, and perivascular tissues.

We hypothesize that the major environmental determinant of the expression of essential hypertension in America and other Westernized countries is dietary imprudence in respect of the consumption of daily combinations of foods containing suboptimal amounts of potassium and blood pressure-lowering phytochemicals, and supraphysiological amounts of sodium. We offer as premise that Americans on average consume suboptimal amounts of potassium and blood pressure-lowering phytochemicals, and physiologically excessive amounts of sodium, and that such dietary imprudence leads to essential hypertension through oxidative stress-induced vascular endothelial and smooth muscle dysfunction. Such dysfunctions restrict nitric oxide bioavailability, impairing endothelial cell-mediated relaxation of the underlying vascular smooth muscle, initiating and maintaining inappropriately increased peripheral and renal vascular resistance. The biochemical steps from oxidative stress to vascular endothelial dysfunction and its pernicious cardiovascular consequences are well established and generally accepted. The unique aspect of our hypothesis resides in the contention that Americans' habitual consumption of foods resulting in suboptimal dietary intake of potassium and supraphysiological intake of sodium result in oxidative stress, the degree of which, we suggest, will correlate with the degree of deviation of potassium and sodium intake from optimal. Because suboptimal intakes of potassium reflect suboptimal intakes of fruits and vegetables, associated contributors to oxidative stress include suboptimal intakes of magnesium, nitrate, polyphenols, carotenoids, and other phytochemical antioxidants for which fruits and vegetables contain abundant amounts. Currently Americans consume potassium-to-sodium in molar ratios of less than or close to 1.0 and the Institute of Medicine (IOM) recommends a molar ratio of 1.2. Ancestral diets to which we are physiologically adapted range from molar ratios of 5.0 to 10.0 or higher. Accordingly, we suggest that the average American is usually afflicted with oxidative stress-induced vascular endothelial dysfunction, and therefore the standards for normal blood pressure and pre-hypertension often reflect a degree of clinically significant hypertension. In this article, we provide support for those contentions, and indicate the findings that the hypothesis predicts.

Increased prevalence of essential hypertension in areas previously exposed to fallout due to nuclear weapons testing at the Semipalatinsk Test Site, Kazakhstan.

This study examines the association between environmental radiation exposure and essential hypertension in a series of investigated geographical districts adjacent to the Semipalatinsk nuclear test site in Kazakhstan. The sample consists of 2000 volunteers participants in screening examinations in three administrative districts close to the nuclear test site, which was carried out as part of the Government Programs on Environmental Health Hazard. The cross-sectional study compares prevalence ratios in a population sample with long-term exposure in the low and intermediate dose range. Age-adjusted odds ratios for hypertension were found significantly increased with higher exposure groups. After accounting for main cardiovascular risk factors into the model and stratifying by gender, the prevalence odds ratios for radiation remained significantly increased, with a significant dose-response effect observed for some but not all subgroups. The results support existing evidence of cardiovascular health effects of radiation exposure and of persisting environmental health issues that require attention in both epidemiological surveys and healthcare provision.

Relationship between obstructive sleep apnoea syndrome and essential hypertension: a dose-response meta-analysis.

OBJECTIVE: The objective of this study was to summarize the evidence regarding the relationship between obstructive sleep apnoea syndrome (OSAS) and the risk of essential hypertension. METHODS: The study was a dose-response meta-analysis of observational studies. The PubMed, Embase, CNKI, VIP and CBM databases were searched to collect relative studies examining the relationship between OSAS and the risk of essential hypertension. Studies were retrieved from database establishment through September 2016, and new literature published between September 2016 and May 2017 was later supplemented. Linear and non-linear dose-response models were used to assess the relationship between apnoea-hypopnea index (AHI), which was used to reflect the severity of OSAS, and the risk of essential hypertension. Stata 13.0 was used for the meta-analysis. RESULTS: Six prospective cohort studies and one case-control study were included, for a total sample size of 6098. The dose-response meta-analysis showed that a high AHI significantly increased the risk of essential hypertension compared with a low AHI (odds ratio (OR) = 1.77, 95% confidence interval (CI) (1.30, 2.41), p = 0.001). The linear dose-response meta-analysis showed that the risk of essential hypertension increased by 17% for every 10 events/h increase in the AHI (OR = 1.17, 95% CI (1.07, 1.27), p = 0.001), and the results of the non-linear dose-response meta-analysis showed that the risk of essential hypertension increased with increasing AHI value. CONCLUSION: A potential dose-response relationship exists between the severity of OSAS and the risk of essential hypertension. This relationship should be considered when developing prevention measures for essential hypertension.

Sonographic evaluation of renal parameters in individuals with essential hypertension and correlation with normotensives.

BACKGROUND: Hypertension can secondarily involve the kidneys, and renal sonographic parameters can be used to indirectly assess renal function or status. Ultrasound is an inexpensive and safe modality for evaluating the kidneys. The purpose of this study was to sonographically assess renal parameters in patients with essential hypertension to determine the parameters that may indicate increased risk of renal damage. MATERIALS AND METHODS: One hundred and fifty individuals (96 females and 54 males) with essential hypertension attending consultant outpatient clinic in University of Benin Teaching Hospital were evaluated. An equal number of nonhypertensive volunteers comprising of 80 females and 70 males were studied as controls. For individuals and controls, the renal length, width, anteroposterior diameters, renal parenchymal volume, cortical thickness, and echogenicity were assessed. Serum creatinine was also obtained. Statistical Package for the Social Sciences (SPSS version 17.0) was used in data analysis. RESULTS: The mean renal parenchymal volume and cortical thickness were 99.1 ± 25.8 cm3 and 1.0 ± 0.2 cm on the right and 113.8 ± 35.8 cm3 and 1.0 ± 0.2 cm on the left for the hypertensive individuals. The values for the normotensives were 100.5 ± 19.8 cm3 and 1.2 ± 0.2 cm on the right and 118.7 ± 27.4 cm3 and 1.3 ± 0.2 cm on the left. The difference in cortical thickness between the two groups was statistically significant. No significant difference was noted between renal parenchymal volume of the right and left kidneys in the individuals and controls. The variation in cortical echogenicity between the hypertensives and controls was statistically significant; 74.0% and 75.3% of hypertensives and 28.0% and 26.0% of normotensives had increased cortical echogenicity on the right and left kidneys, respectively. The serum creatinine value was significantly higher in the hypertensive group. CONCLUSION: Cortical echogenicity grading was significantly higher among hypertensives than normotensives while renal parenchymal volume and cortical thickness were lower among hypertensives. In the hypertensives and normotensives, renal parenchymal volume, cortical thickness, and renal length were higher in males compared to the females and in the left kidney compared to the right. Hypertension seems to have more effect in the renal cortex than the medulla.

Familial aggregation of first degree relatives of children with essential hypertension.

PURPOSE: Determining familial aggregation is an important first step in narrowing the search for disease-causing genes and hence we determined the familial aggregation of EH among first degree relatives of children with EH. MATERIALS AND METHODS: We prospectively enrolled children with EH along with their first degree relatives from a tertiary pediatric hypertension clinic in a large ambulatory care center. We utilized rigorous methodology for blood pressure (BP) measurements and diagnoses of EH to reduce the heterogeneity in the phenotype. For those enrolled, parental BP status was confirmed by in-clinic direct BP measurements. We also enrolled control children without EH along with their first degree relatives from the same pediatric ambulatory center. RESULTS: In our case-control study of 153 families, the odds of having familial EH was more than 3 times higher among the cases than in controls (OR: 3.63, 95% CI: 1.85-7.12) with 71% of the cases and 41% of the controls reporting familial EH. One parent with EH was seen in 88% of the cases and 52% of the controls (OR: 6.92, 95% CI: 2.68-17.84). The odds of at least one parent (compared to neither) with EH was almost 7-fold higher, and odds of having two parents with EH was 14-fold higher among cases versus controls. The risk of EH did not go back from the first degree relative to the second degree relatives. CONCLUSIONS: We identified familial aggregation with an increased liability of childhood onset EH with parental EH. The risk of childhood onset EH is more than doubled in the presence of EH in both parents versus in a single parent. Prediction for childhood-onset EH is improved by obtaining a family history of EH in the first degree relatives.

Evaluation of the Saline Infusion Test and the Captopril Challenge Test in Chinese Patients With Primary Aldosteronism.

Context: The aim of this study was to determine whether the diagnosis cutoff values associated with the saline infusion test (SIT) and captopril challenge test (CCT) in the Endocrine Society guidelines are applicable to Chinese subjects. Objective and Design: We performed a head-to-head comparison of the SIT and CCT among Chinese subjects with primary aldosteronism (PA) and essential hypertension (EH). Participants and Setting: One hundred sixty-four hypertensive patients were enrolled. Intervention: All participants underwent both the SIT and CCT. Main Outcome Measures: The plasma aldosterone concentration (PAC) and plasma renin activity were measured before and after the SIT and CCT. The degree of PAC decline after CCT was calculated. Results: This study included 115 PA and 49 EH subjects. The prevalence of hypokalemia was 74.8% in the PA group. Supine PACs in the EH and PA groups were 15.1 ± 4.7 mmol/L and 30.4 ± 12.1 mmol/L. Post-SIT PACs were 8.8 ± 1.7 ng/dL and 22.7 ± 10.2 ng/dL in the EH and PA groups. The degree of PAC decline after CCT was 17.7% and 14.2% in the EH and PA groups; post-CCT PACs were 11.7 ± 3.3 ng/dL and 25.9 ± 10.6 ng/dL. PAC values of 11.2 ng/dL and 16.7 ng/dL after the SIT and CCT represented the optimal cutoff values for PA diagnosis. The post-SIT and post-CCT area under the receiver operating characteristic curve values were 0.972 [95% confidence interval (CI) = 0.934 to 0.991] and 0.933 (95% CI = 0.883 to 0.966). Conclusions: Post-SIT and post-CCT PACs, but not the degree of PAC suppression, were both reliable for PA diagnosis. However, the optimal cutoffs were slightly higher in Chinese subjects than those recommended by the Endocrine Society.

IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis.

Aims: An excess of aldosterone results in cardiac remodelling and fibrosis. Interleukin-6 (IL-6) is a key mediator in the fibrotic process; however, the effect of aldosterone on the expression of IL-6 remains unclear. We investigated whether aldosterone induces the expression of IL-6 and thereby contributes to the fibrotic process. Methods and results: In this clinical study, we prospectively enrolled 25 patients with primary aldosteronism (PA) and 26 patients with essential hypertension (EH). The PA patients had higher plasma IL-6 levels, left ventricular mass index, degree of myocardial fibrosis, and more impaired diastolic function than the EH patients. In addition, plasma IL-6 levels were positively correlated with 24-h urinary aldosterone and echocardiographic parameters. In cell studies, we investigated the possible molecular mechanism how aldosterone-induced IL-6 secretion and the further effects of collagen production. Aldosterone significantly induced IL-6 protein and mRNA production in human umbilical vein endothelial cells. Intracellular signalling occurred through the mineralocorticoid receptor/PI3K/Akt/NF-kB pathway. In cardiac fibroblasts, IL-6 trans-signalling played a critical role in aldosterone-induced IL-6-enhanced fibrosis-related factor expression. To further investigate the role of IL-6 trans-signalling in aldosterone-induced cardiac fibrosis, we measured the severity of myocardial fibrosis in aldosterone infusion mice models including an IL-6 chemical inhibitor and Sgp130 Knockin Transgenic Mice. Mice receiving recombinant soluble gp130 and Sgp130 Knockin Transgenic Mice prevented myocardial fibrosis and cardiac hypertrophy by aldosterone infusion. Conclusions: IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis.