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To explore the relationship between serum folic acid (FA) or Vitamin B12 (VB12) and elevated BP in children and adolescents. Both a nested case control and a cohort study were designed to explore the relationship between serum folic acid (FA) or Vitamin B12 (VB12) and elevated blood pressure (BP). All the included participants were from primary school. A total of 326 subjects (116:210) in nested case control were from an established cohort. And 270 participants without hypertension at baseline and followed in 2019 in cohort. FA and VB12 levels were lower in the elevated BP group than in the control group, and homocysteine level was higher than that in the control group. In the elevated BP group, overweight/obese children had lower FA than overweight/obese children in the normal BP group. FA was positively correlated with high-density lipoprotein (HDL) and Apo lipoprotein A (APOA), but negatively correlated with triglyceride (TG). FA was significantly correlated with elevated BP in children and adolescents (β = -0.353, P = 0.032), after adjusting VB12, and homocysteine (HCY), and the interaction effect of FA*HCY was significant. Both systolic and diastolic BP levels were statistically lower in the FA high exposure group than in the FA low exposure group in the cohort study. This study found that FA and vitamin B12 deficiency in childhood was correlated with elevated BP levels, which may affect BP by regulating lipid levels, and confirmed the importance of maintaining high levels of FA and vitamin B12 in childhood either by diet or supplementation., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The Institutional Review Board at the Children’s Hospital of Chongqing Medical University gave its approval for the study. Informed consent to participate in this study was provided by all of the children and their parents/guardians. Consent for publication: All authors critically reviewed and approved the publication of the final paper., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage., Methods: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected., Results: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD ( p  < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants ( p  < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 ( p  = 0.001) and decreased CFH ( p  < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 ( p  = 0.034), elevated AP50 ( p  < 0.001), decreased CFH ( p  < 0.001), increased age ( p  = 0.011) and increased BMI ( p  = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 ( p  = 0.017), elevated AP50 ( p  = 0.023), decreased CFH ( p  = 0.005) and increased age ( p  = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants., Conclusion: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.

Background: Elevated soluble stimulating factor 2 (sST2) level is observed in cardiovascular diseases, such as heart failure and acute coronary syndrome, which reflects myocardial fibrosis and hypertrophy, indicating adverse clinical outcomes. However, the association between sST2 and hypertensive heart disease are less understood. This study aimed to determine the relationship of sST2 with left ventricular hypertrophy (LVH) and geometric remodeling in essential hypertension (EH)., Methods: We enrolled 483 patients (aged 18-80 years; 51.35% female). sST2 measurements and echocardiographic analyses were performed., Results: Stepwise multiple linear regression analysis showed significant associations among sST2, left ventricular (LV) mass, and LV mass index. The prevalence of LVH and concentric hypertrophy (CH) increased with higher sST2 grade levels (P for trend < 0.05). Logistic regression analysis suggested that the highest tertile of sST2 was significantly associated with increased LVH risk, compared with the lowest tertile (multivariate-adjusted odds ratio [OR] of highest group: 6.61; P < 0.001). Similar results were observed in the left ventricular geometric remodeling; the highest tertile of sST2 was significantly associated with increased CH risk (multivariate-adjusted OR of highest group: 5.80; P < 0.001). The receiver operating characteristic analysis results revealed that sST2 had potential predictive value for LVH (area under the curve [AUC]: 0.752, 95% confidence interval [CI]: 0.704-0.800) and CH (AUC: 0.750, 95% CI: 0.699-0.802) in patients with EH., Conclusions: High sST2 level is strongly related to LVH and CH in patients with EH and can be used as a biomarker for the diagnosis and risk assessment of hypertensive heart disease., Clinical Trials Registration: Trial Number ChiCTR2400082764., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Background: The triglyceride-glucose (TyG) index is regarded as an independent predictor of cardiovascular disease consequences and a reliable surrogate measure of insulin resistance (IR). However, the correlation analysis between triglyceride glucose index and heart failure with preserved ejection fraction in patients with essential hypertension remains unknown., Methods: A single-center, retrospective study was conducted with patients diagnosed with essential hypertension at the First Affiliated Hospital of Xinjiang Medical University, from December 2018 to September 2020. Participants were selected based on specific inclusion and exclusion criteria, with their clinical data and laboratory tests collected. The study employed Spearman's correlation analysis, logistic regression models, restricted cubic spline plots, and receiver operating characteristic (ROC) curves to investigate the relationships between the TyG index and HFpEF., Results: Out of 1,602 enrolled hypertensive patients, 992 were included in the analysis after applying exclusion criteria. Patients were categorized into tertiles based on the TyG index, which showed that patients in the highest tertile had characteristics associated with a higher risk of HFpEF, including age, body mass index (BMI), systolic blood pressure (SBP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and left ventricular mass index (LVMI). A significant, independent association between the TyG index and HFpEF was confirmed, with an odds ratio (OR) of 5.127 (95% CI [3.894-6.856]). Furthermore, an S-shaped nonlinear relationship was observed between the TyG index and the incidence of HFpEF (nonlinear p < 0.001). TyG index (AUC: 0.824, 95% CI [0.795-0.854]), NT-proBNP (AUC: 0.840, 95% CI [0.816-0.864]), and LVMI (AUC: 0.847, 95% CI [0.820-0.875]) showed good predictive ability for HFpEF. In addition, the TyG+LVMI combination demonstrated the strongest predictive ability (AUC: 0.907, 95% CI [0.887-0.927])., Conclusion: The study underscores a significant association between IR, as indicated by the TyG index, and the development of HFpEF in hypertensive patients. It highlights the critical role of metabolic dysfunction in the pathophysiology of HFpEF, advocating for a broader perspective on cardiovascular risk management., Competing Interests: The authors declare that they have no competing interests., (© 2024 Shan et al.)

The exact cause of essential hypertension remains unclear. There is evidence to suggest that the development of essential hypertension is causally related to serum calcium levels. This study was designed to assess the status of serum calcium level in patients with essential hypertension and compared with healthy control. The research study was cross-sectional observational in nature. This study was done at the Department of Physiology in Sylhet MAG Osmani Medical College, Sylhet, Bangladesh. The duration of the research period was one year. All the known case of hypertension and newly diagnosed hypertensive patients were selected and compared with age-sex matched apparently healthy individual. Age below 18 years, pregnant women and patients taking supplementary calcium therapy were excluded from this study. Blood pressure was measured by auscultatory method; aneroid sphygmomanometer and standard stethoscope were used. Automated chemistry analyzer Vitrose-350, USA was used to estimate serum calcium level. Standard operating procedure strictly followed. There were 62 hypertensive (both known case of hypertension and newly diagnosed cases) were selected in hypertensive group (Group A) and 62 age-sex matched apparently healthy individuals were selected in normotensive group (Group B). The mean age of hypertensive and normotensive subjects was not statistically significant (p=0.814). There were 27(43.5%) male and 35(56.5%) female in hypertensive group, 32(51.8%) male and 30(48.4%) female in normotensive group. The distribution was statistically not significant (p=0.472). The mean value of the systolic blood pressure (SBP) was 146.45±5.82 mm Hg and the mean value of the diastolic blood pressure (DBP) was 92.90±7.66 mm Hg in hypertensive group. The mean value of the SBP was 112.74±6.88 mm Hg and the mean value of the DBP was 74.52±5.33 mm Hg of the normotensive group. The difference in mean blood pressure (BP) between the two groups was highly significant (p<0.001). The mean value of the serum calcium level was 8.59±0.55 mg/dl in hypertensive group and 9.12±0.93 mg/dl in normotensive group, which was statistically significant (p <0.001) between two groups. Serum calcium was significantly lower in hypertensive group than normotensive group. There was a negative correlation of the serum calcium level with both systolic and diastolic blood pressure.

Objectives: To determine the independent effect of high-sensitivity C-reactive protein (hs-CRP) and the combined effects of hs-CRP and other traditional risk factors on microalbuminuria in hypertensive patients during the 3-year follow-up period., Methods and Results: Baseline hs-CRP levels and other risk factors were measured in 280 adults in 2007. In the third year of examination, 199 patients (mean age 62.5 ± 9.5, men 59.3%) were approached for the measurement of microalbuminuria. The subjects were classified into two groups by the median of baseline hs-CRP. Compared to the patients with baseline hs-CRP below the median group ( n  = 99, 50%), the group with baseline hs-CRP above the median ( n  = 100, 50%) had higher urinary albumin-to-creatinine ratio (ACR) ( P  = 0.007) at the end of follow-up period. ACR at the end of follow-up period was significantly correlated with baseline diabetes ( β  = 0.342; P  < 0.001), baseline SBP ( β  = 0.148; P  = 0.02), and baseline log-transformed hs-CRP ( β  = 0.169; P  = 0.01), while adversely correlated with baseline estimated glomerular filtration rate (eGFR) ( β  = -0.163; P  = 0.02) in multivariate stepwise linear analysis. In addition, ACR change during follow-up period was significantly correlated with baseline diabetes ( β  = 0.359; P  < 0.001) and baseline log-transformed hs-CRP ( β  = 0.190; P  = 0.004) in multivariate stepwise linear analysis. The combined effects of baseline hs-CRP and conventional risk factors, such as male sex, diabetes, smoking status, hyperlipidemia, hyperuricemia, and mildly reduced eGFR had a greater risk for microalbuminuria progression. There was no difference in eGFR changes during the follow-up period between two groups., Conclusion: Our findings offer a new piece of evidence on the predictive value of baseline hs-CRP for microalbuminuria progression in essential hypertensive patients, and highlight those who combined with traditional cardiovascular risk factors had a greater risk for developing microalbuminuria., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: 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., Design and Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Homocysteine (Hcy) is a sulphur-containing nonessential amino acid derived from the intermediate metabolites of methionine. Methionine is obtained from dietary proteins, such as poultry, meat, eggs, seafood, and dairy products. Abnormalities in Hcy metabolic pathways, deficiencies in dietary methionine, folate, and vitamins B12, B6, and B2 and genetic defects, polymorphisms, or mutations in Hcy metabolism-related enzymes may lead to an increase in plasma Hcy levels. Generally, a plasma Hcy level higher than 10 or 15 μmol/L has been defined as hyperhomocysteinemia (HHcy). An individual with essential hypertension complicated with HHcy is considered to have H-type hypertension (HTH). Currently, HHcy is considered a novel independent risk factor for various cardiovascular diseases. To provide a useful reference for clinicians, the research progress on Hcy, HHcy, and HTH in recent years was systematically reviewed here, with a focus on the source and metabolic pathways of Hcy, plasma Hcy levels and influencing factors, detection methods for plasma Hcy levels, relationship between Hcy concentration and hypertension, pathogenesis of HTH, cardiovascular complications of HTH, and treatment of HTH., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We aimed to investigate the association between hemoglobin A1c (HbA1c) and left atrial (LA) stiffness in patients with hypertension and to explore the mediating effect of the neutrophil/lymphocyte ratio (NLR) on this association., Methods: Essential hypertensive patients (n = 292) aged 18-83 years were enrolled and divided into two groups based on the LA stiffness index (LASI): Group I (LASI ≤ 0.32, n = 146) and Group II (LASI > 0.32, n = 146). The LASI was defined as the ratio of early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') to LA reservoir strain. Multivariate linear regression analysis was performed to determine the independent predictors of the LASI., Results: Age, BMI, SBP, HbA1c, CRP, and NLR were significantly greater in Group II than in Group I (P < 0.05). Additionally, Group II had a greater LA volume index (LAVI), left ventricular mass index (LVMI), and early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') and lower LA reservoir, conduit, and booster pump strains than Group I (P < 0.001). Univariate and multivariate linear regression models revealed that age, SBP, HbA1c, and the NLR were independently associated with the LASI. Further mediation analysis was performed to determine the mediating effect of the NLR on the association between HbA1c and the LASI and revealed that the NLR had a mediating role only in overweight hypertensive patients, and the proportion of the mediating effect was 21.9%., Conclusions: The NLR was independently correlated with the LASI and played a mediating role in the relationship between HbA1c and the LASI in overweight hypertensive patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Introduction: Hyperuricaemia is common in essential hypertension with varying results in different populations. This study sought to ascertain the association between serum uric acid levels and essential hypertension in Hospital Universiti Sains Malaysia (HUSM)., Materials and Methods: A case-control study design involving 132 subjects (88 subjects of hypertension patients for case group and 44 subjects for control group) aged 18 to 40 years old of both genders was conducted at HUSM primary care clinic and physician clinic from May 2020 to May 2021. Blood samples were collected from each of the case and control subjects and analysed for serum uric acid, urea, creatinine, total cholesterol, triglycerides, LDL and HDL on chemical analyser Architect c8000. The data were analysed by using SPSS Statistics 26.0 version., Results: The proportion of subjects with hyperuricaemia in the case group was 48.9%. A significant difference in the uric acid levels between the case group (390.64±92.65μmol/L) and control group (352.09±86.07μmol/L), (p<0.05) was observed. There was no significant difference in the serum uric acid mean ± SD based on the duration of hypertension (<5 years and ≥5 years), (p=0.331) and stages of hypertension (p>0.05). In case group, significant correlations were established between uric acid and triglycerides (r=0.255, p<0.05), uric acid and HDL (r= -0.223, p<0.05), uric acid and urea (r=0.299, p<0.05), uric acid and creatinine (r=0.486, p<0.01). No correlation among uric acid and total cholesterol levels (p>0.05), uric acid and LDL (p>0.05). Serum uric acid was a vital variable in developing hypertension (p<0.05) but not when adapted for age and body mass index (BMI) (p>0.05)., Conclusion: Serum uric acid was significantly elevated in essential hypertension. The significant associations were established between uric acid and triglycerides, HDL, urea and creatinine in essential hypertension. Serum uric acid was a vital variable to develop hypertension, but the association was weakened by other co-founders as age and BMI. A large-scale population-based study is required to truly conclude the association between serum uric acid levels and essential hypertension in our population.

Background: Cortistatin (CST), an endogenous bioactive polypeptide, has been acknowledged for its protective effect against several cardiovascular diseases, but its relationship with hypertension remains unclear. Therefore, we aimed to investigate changes in plasma CST in hypertensive patients and further analyze correlations with blood pressure, metabolic parameters and left ventricular structure and function., Methods: In this hospital-based study, basic information and plasma samples for evaluating clinically relevant indicators such as total cholesterol (TC), triglycerides (TGs), fasting blood glucose (FGB), serum creatinine (Scr) and CST were collected from 81 essential hypertension patients and 75 normotensive subjects. Plasma CST levels were examined by enzyme-linked immunosorbent assay (ELISA)., Results: Compared with normotensive subjects, plasma CST was significantly lower in hypertensive patients. Plasma CST levels in hypertensive patients without blood pressure control was significantly lower than those of hypertensive patients with blood pressure control. Plasma CST levels were significantly negatively correlated with SBP and serum creatinine (Scr) in the overall population. Furthermore, multivariate logistic regression analysis showed that the OR of CST for hypertension was 0.64 using the unadjusted model, and there was still statistical significance using the four-adjusted model., Conclusions: The circulating concentration of CST was significantly lower in hypertensive patients and was higher after blood pressure control, suggesting that CST may be a new endogenous protective target for hypertension., Competing Interests: Competing interests The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sirtuin 7 (SIRT7), as a nicotinamide adenine dinucleotide-dependent protein/histone deacetylase, has been implicated in the pathogenesis of cardiovascular diseases. However, whether SIRT7 is related to hypertension remains largely unclear. Thus, this study aims to explore the effects and correlation between SIRT7 and hypertension., Methods: A total of 72 patients with essential hypertension and 82 controls with non-hypertension were recruited at Beijing Tongren Hospital Affiliated with Capital Medical University from July 2022 to June 2023. Plasma SIRT7 expression was measured using enzyme-linked immunosorbent assay analysis. Clinical baseline characteristics, laboratory measurements, echocardiographic data, and medical therapy were collected., Results: Plasma levels of SIRT7 were lower in hypertensive patients compared with non-hypertensive patients [0.97 (0.58-1.30) vs. 1.24 (0.99-1.46) ng/mL, P < 0.001, respectively]. Furthermore, compared with the low SIRT7 group, there were lower levels of systolic blood pressure, hyperlipidemia, and the ultrasonic electrocardiogram parameters left ventricular end-diastolic diameter and left atrial in diastole in the high SIRT7 group (P < 0.05, respectively). More importantly, multivariate logistic regression analyses indicated that plasma SIRT7 was a predictor of hypertension [OR: 0.06, 95 % CI (0.02-0.19), P < 0.001]. Receiver operating characteristics curve analysis revealed that the optimal cutoff value for plasma SIRT7 levels in detecting hypertension was determined as 0.85 ng/mL with a sensitivity of 73.6 % and a specificity of 89.0 %. The area under the curve for SIRT7 was 0.821 (95 % CI, 0.751-0.878; P < 0.001)., Conclusion: Plasma levels of SIRT7 are decreased in patients with essential hypertension, implying its potential as a biomarker for diagnosing essential hypertension.., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: Aim: The main aim of the present paper is to investigate allele frequencies of rs1799983 polymorphism eNOS genes and to determine association between rs1799983 polymorphism of eNOS gene and essential hypertension in Iraqi hypertensive patients., Patients and Methods: Materials and Methods: Data obtained at the Al-Diwaniyah teaching hospital in Iraq by researchers from the Department of Pharmacology and Therapeutics in the College of Medicine at University of Al-Qadisiyah from July 2022 to July 2023. All participants (aged 20 to 70) had been taking valsartan 160 mg once day for essential hypertension for at least two weeks before to the study. There were a total of 90 participants, 37 males and 53 women. Initial investigations of hypertension have indicated that the angiotensinogen gene has a substantial impact in susceptibility to essential hypertension through observational cross sectional descriptive single center study., Results: Results: Indicate, in patients with essential hypertension, that the "AGT gene A>G (rs699) and C>T(rs5051)" have high angiotensinogen level, and there is no signif i cant association between these two (rs699, rs5051) and responsiveness to valsartan (P >0.05)., Conclusion: Conclusions: Result showed the most common allele for rs699 was G allele (67%) while the most frequent genotype was AG (49%) and regarding rs5051 the most frequent allele was C (54%) while the most frequent genotype was CT (46%). In this study we demonstrate the lack of signif i cant association between two these polymorphisms and clinical response to valsartan (P >0.05).

Objective: The present study aims to investigate the relationship between vitamin D deficiency and renin-angiotensin-aldosterone levels in patients with essential hypertension., Methods: The present study observed two groups of patients from Urumqi, Xinjiang, China, from April 2017 to March 2018. There were two subject groups: the hypertension group (80 patients with essential hypertension selected by random cluster sampling) and the control group (76 healthy adults). The 25-hydroxyvitamin D (25(OH)D or vitamin D) levels were measured through electrolytes; fasting blood glucose, blood lipids, and other biochemical indicators were detected using immune chemiluminescence; and plasma renin activity and angiotensin II concentrations were detected with radio-immunity., Results: Comparison between the hypertension group and control group showed statistically significant differences in the systolic pressure and levels of 25(OH)D, renin, and triglycerides ( P < 0.05). The correlation analysis showed that 25(OH)D was negatively correlated with renin ( r  = -0.185; P =0.021) and positively correlated with systolic pressure ( r  = -0.105; P =0.035). There were no statistically significant differences in diastolic pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides between the two groups., Conclusions: The results of the present study show that vitamin D deficiency is common in Urumqi, Xinjiang, China and vitamin D levels are negatively correlated with renin levels. Vitamin D plays an important role in regulating blood pressure by affecting renin levels through the renin-angiotensin-aldosterone system., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Lu Han et al.)

Vascular dysfunction and hyperlipidemia are essential risk factors contributing to essential hypertension (EH). The plasmacytoma variant translocation 1 (PVT1) is involved in modulating angiogenesis in tumor tissues and plays an important role in fat differentiation in the progress of obesity. Therefore, we selected two tagSNPs of PVT1 (rs10956390 and rs80177647) to investigate whether they are contributing to the risk of hypertension in Chinese patients. In total, 524 adult patients with EH and 439 matched healthy controls were enrolled for two central of China. Results . PVT1 rs10956390 and rs80177647 polymorphisms were genotyped by using TaqMan assay. PVT1 rs10956390 TT genotype was associated with a decreased risk of EH (OR = 0.561, 95% CI = 0.372-0.846, P = 0.006), while rs80177647 TA genotype was associated with an increased risk (OR = 2.236, 95% CI = 1.515-3.301, P < 0.001). Rs10956390 T allele was associated with lower triglyceride levels in the plasma both from healthy and EH donors. What is more, there is an association between rs10956390 polymorphism and HDL-C level, as well as LDL-C. Conclusion . PVT1 rs10956390 and rs80177647 polymorphisms may contribute to the risk of EH in Chinese population by regulating blood lipid levels., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Rong Li et al.)

Innate immunity and chronic inflammation are involved in atherosclerosis and atherothrombosis, leading to target organ damage in essential hypertension (EH). However, the role of neutrophils in EH is still elusive. We investigated the association between angiotensin II (Ang II) and neutrophil extracellular traps (NETs) in pathogenesis of EH. Plasma samples, kidney biopsies, and surgical specimens of abdominal aortic aneurysms (AAAs) from patients with EH were used. Cell-based assays, NETs/human aortic endothelial cell cocultures, and in situ studies were performed. Increased plasma levels of NETs and tissue factor (TF) activity were detected in untreated, newly diagnosed patients with EH. Stimulation of control neutrophils with plasma from patients with untreated EH generated TF-enriched NETs promoting endothelial collagen production. Ang II induced NETosis in vitro via an ROS/peptidylarginine deiminase type 4 and autophagy-dependent pathway. Circulating NETs and thrombin generation levels were reduced substantially in patients with EH starting treatment with Ang II receptor blockers, whereas their plasma was unable to trigger procoagulant NETs. Moreover, TF-bearing NETotic neutrophils/remnants accumulated in sites of interstitial renal fibrosis and in the subendothelial layer of AAAs. These data reveal the important pathogenic role of an Ang II/ROS/NET/TF axis in EH, linking thromboinflammation with endothelial dysfunction and fibrosis.

Background: Essential hypertension is a condition characterized by a rise in blood pressure of undetermined cause, includes 90% of all hypertensive cases and is a highly important public health challenge with major modifiable cause of morbidity and mortality. Uric acids disorders in particular hyperuricemia are significant problems in essential hypertensive patients and can cause substantial morbidity and mortality. Determination of uric acid disorders may play a major role in the management and early aversion of complications in hypertensive patient. Therefore, this study aimed to determine uric acid disorders and associated factors among essential hypertensive adults in the outpatient department at Wolkite University specialized Hospital, Southern Ethiopia from November 1 to February 30, 2021., Methods and Materials: An institional based cross sectional study was conducted on 270 essential hypertensive adults on follow-up in outpatient department from November 1 to February 30, 2021. Structured questionnaires through face to face interviews and participants' medical records were used to collect information on determinants related with uric acid disorders. The blood specimen was collected and level of serum uric acid, blood sugar and lipid profile was measured using standard principles and procedures with an ABX Pentra 400 automated chemistry analyzer. Bivariate and multivariate logistic regression analyses were done to identify factors associated with hyperuricemia. The p-value was set at <0.05 with a 95% confidence interval of the adjusted odds ratio., Results: A total of 270 adult essential hypertensive patients were participated in the study, among those 196(27.4%) of study participants were hyperuricemic with 95%CI (21.9, 33.3). Being alcoholic [(AOR: 15.68, 95% CI: (5.93, 21.41)], taking antihypertensive medication [(AOR: 11.56, 95% CI: (3.94, 23.80)], BMI > = 30 [(AOR: 4.89, 95% CI: (1.46, 25.5)] and being centrally obese [(AOR: 6.87, 95% CI: (2.53, 18.63)] were factors significantly associated with hyperuricemia., Conclusion: In this study, the high burden of hyperuricemia (27.4%) was observed in essential hypertensive patients with follow-up in outpatient department. Taking alcohol and antihypertensive medication, being overweight and centrally obese were identified factors of uric acid disorders. The finding of this study should be taken into consideration to implement preventive interventions on identified predictors in hypertensive patients. Taking fruit and vegetable, and promoting physical exercise and determinations of serum uric acid level in adult essential hypertensive patients was recommended to minimize the emergence of hyperuricemia., Competing Interests: The authors have declared that no competing interests exist.

Objective: Although aortic dissection occurs predominantly in men, its association with androgens is unknown. The aim of this study was to evaluate the androgen levels in Chinese male patients with uncomplicated, acute type B aortic dissection., Study Design: Cross-sectional study., Materials and Methods: A total of 192 age-matched male patients with uncomplicated, acute type B aortic dissection or essential hypertension were recruited between 2016 and 2018. The demographic and clinical data were analyzed., Results: Male patients with uncomplicated, acute type B aortic dissection had lower serum total testosterone and free testosterone than male patients with essential hypertension (7.6 ± 3.7 nmol/L vs. 10.9 ± 3.8 nmol/L, P < 0.001; 36.0 ± 19.8 pmol/L vs. 56.4 ± 19.2 pmol/L, P < 0.001). Lower free testosterone level was significantly associated with uncomplicated, acute type B aortic dissection (univariate odds ratio 0.948, P < 0.001; multivariate odds ratio = 0.966, P = 0.002). No statistical difference was observed for free testosterone between younger patient groups (aged < 51 years; aged 51-60 years) and older patient groups (aged 61-70 years; aged >70 years) with uncomplicated, acute type B aortic dissection (33.7 ± 19.8 pmol/L vs. 38.5 ± 19.8 pmol/L, P = 0.239)., Conclusions: Lower free testosterone was independently associated with uncomplicated, acute type B aortic dissection in the Chinese male population with hypertension. Additional studies are needed to clarify whether earlier onset in Chinese patients with aortic dissection is associated with androgen deficiency., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Enhanced platelet activation has been reported in patients with essential hypertension and heart failure. The possible contribution of platelet-derived thromboxane (TX)A 2 in their pathophysiology remains unclear. We investigated the systemic TXA 2 biosynthesis in vivo and gene expression of its receptor TP in 22 essential hypertension patients and a mouse model of salt-sensitive hypertension. The contribution of platelet TXA 2 biosynthesis on enhanced blood pressure (BP) and overload-induced cardiac fibrosis was explored in mice by treating with low-dose Aspirin, resulting in selective inhibition of platelet cyclooxygenase (COX)-1-dependent TXA 2 generation. In essential hypertensive patients, systemic biosynthesis of TXA 2 [assessed by measuring its urinary metabolites (TXM) reflecting predominant platelet source] was enhanced together with higher gene expression of circulating leukocyte TP and TGF-β, vs. normotensive controls. Similarly, in hypertensive mice with prostacyclin (PGI 2 ) receptor (IP) deletion (IPKO) fed with a high-salt diet, enhanced urinary TXM, and left ventricular TP overexpression were detected vs. normotensive wildtype (WT) mice. Increased cardiac collagen deposition and profibrotic gene expression (including TGF-β) was found. Low-dose Aspirin administration caused a selective inhibition of platelet TXA 2 biosynthesis and mitigated enhanced blood pressure, cardiac fibrosis, and left ventricular profibrotic gene expression in IPKO but not WT mice. Moreover, the number of myofibroblasts and extravasated platelets in the heart was reduced. In cocultures of human platelets and myofibroblasts, platelet TXA 2 induced profibrotic gene expression, including TGF-β1. In conclusion, our results support tailoring low-dose Aspirin treatment in hypertensive patients with unconstrained TXA 2 /TP pathway to reduce blood pressure and prevent early cardiac fibrosis., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Sympathetic nervous system (SNS) over-activity is associated with essential hypertension. Renal sympathetic denervation (RDN) possibly lowers office- and ambulatory blood pressure (BP) in patients with treatment-resistant hypertension (TRH). We aimed to assess the effect of RDN compared to drug adjustment on SNS activity among patients with TRH by measuring plasma catecholamines and heart rate variability (HRV) during stress tests., Materials and Methods: Patients with TRH were randomised to RDN ( n  = 9) or Drug Adjustment (DA) ( n  = 10). We measured continuous HRV and beat-to-beat-BP using FinaPres® and obtained plasma catecholamines during standardised orthostatic- and cold-pressor stress tests (CPT) before- and six months after randomisation., Results: CPT revealed no differences between groups at baseline in peak adrenaline concentration (69.3 pg/mL in the DA group vs. 70.0 pg/mL in the RDN group, p  = 0.38) or adrenaline reactivity (Δ23.1 pg/mL in the DA group vs. Δ29.3 pg/mL in the RDN group, p  = 0.40). After six months, adrenaline concentrations were statistically different between groups after one minute (66.9 pg/mL in the DA group vs. 55.3 pg/mL in the RDN group, p  = 0.03), and six minutes (62.4 pg/mL in the DA group vs. 50.1 pg/mL in the RDN group, p  = 0.03). There was a tendency of reduction in adrenaline reactivity after six months in the RDN group (Δ26.3 pg/mL at baseline vs. Δ12.8 pg/ml after six months, p  = 0.08), while it increased in the DA group (Δ13.6 pg/mL at baseline vs. Δ19.9 pg/mL after six months, p  = 0.53). We also found a difference in the Low Frequency band at baseline following the CPT (667µs 2 in the DA group vs. 1628µs 2 in the RDN group, p  = 0.03) with a clear tendency of reduction in the RDN group to 743µs 2 after six months ( p  = 0.07), compared to no change in the DA group (1052µs 2, p  = 0.39)., Conclusion: Our data suggest that RDN reduces SNS activity after six months. This finding warrants investigation in a larger study. Clinical Trial Number registered at www.clinicaltrials.gov: NCT01673516.

Purpose : Vitamin D deficiency is known that associated with hypertension. Microalbuminuria (MAU) is associated with increased cardiovascular morbidity and mortality. This study aimed to evaluate the relationship between 25-hydroxyvitamin D (25(OH)D) and MAU in newly diagnosed essential hypertension (NDEH) patients. Methods: A total of 116 patients with a diagnosis of NDEH were enrolled in the study. The diagnosis of hypertension was based on ABPM. Patients were divided into 2 groups according to 25(OH)D levels: Group 1: (25(OH)D)>20 ng/mL was defined as Vitamin D sufficiently (VDS), while Group 2: (25(OH)D)<20 ng/mL was defined Vitamin D deficiently (VDD). The relationship between 25(OH)D and MAU was analyzed. The results were analyzed using the SPSS program version 21. Results: The mean age of the patients was 58.4 ± 14.7 years and 60 (51.7%) of them were female. The prevalence of MAU was 18.9% and Vitamin D deficiency was 61.2% in NDEH. Linear regression analysis showed that 25(OH)D was independently related to MAU [β 0.643, 95% confidence interval 1.173-1.631, p = .011]. Besides, male gender, C-reactive protein, non-dipper hypertension, and diastolic blood pressure were independent risk factors associated with MAU in the multivariate analysis ( p < .05). Conclusion: Vitamin D deficiency is highly prevalent in NDEH patients. This study showed that the level of microalbuminuria was significantly higher in patients with 25(OH)D deficiency compared to patients with normal 25(OH)D levels. Vitamin D deficiency is independently related to microalbuminuria in NDEH.

Abstract: Accumulating evidence indicates that heat shock proteins (HSPs) may represent a suitable biomarker to predict atrial fibrillation (AF). We investigated the relation of circulating serum HSP70 (sHSP70) with inflammatory cytokines and recurrence of symptomatic recent onset AF (ROAF). We enrolled 90 patients with ROAF (the duration from onset of symptoms ≤24 hours) and 30 controls. Patients received amiodarone for cardioversion and rhythm control. The association of serum HSP70, serum interleukin-2 (sIL-2), and serum interleukin-4 (sIL-4) with the presence of cardioversion and AF recurrence within a year was investigated. Toll-like receptor 4 (TLR4) signaling dependence for IL-2 and IL-4 induction in response to stimulation with HSP70 was tested in rat aortic vascular smooth muscle cell cultures. Patients had higher sHSP70 and sIL-2 and lower sIL-4 compared with controls. Serum HSP70 was independently associated with ROAF (P = 0.005) and correlated with sIL-2 (r = 0.494, P < 0.001) and sIL-4 (r = -0.550, P < 0.001). By 48 hours, 71 of the 90 patients were cardioverted, with noncardioverted patients having higher sHSP70 and sIL-2 and lower sIL-4, which were the only independent factors associated with cardioversion. AF recurred in 38 of the 71 cardioverted patients in 1 year. A cutoff value of sHSP70 ≥0.65 ng/mL and sIL-2 ≥0.21 pg/mL was the only independent factor associated with AF recurrence (hazard ratio: 3.311, 95% confidence interval: 1.503-7.293, P = 0.003 and hazard ratio: 3.144, 95% confidence interval: 1.341-7.374, P = 0.008, respectively). The exposure of smooth muscle cell to HSP70 in vitro increased the expression of IL-2 (5×) and IL-4 (1.5×) through TLR4-dependent and receptor-independent mechanisms. In conclusion, sHSP70 and sIL-2 might constitute a prognostic tool for determining the cardioversion and recurrence likelihood in ROAF., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Essential hypertension (EH) is one of the most important public health problems worldwide. However, the pathogenesis of EH is unclear and early diagnostic methods are lacking. Metabolomics demonstrates great potential for biomarker discovery and the mechanistic exploration of metabolic diseases., Data Synthesis: This review included human and animal metabolomics studies related to EH in the PubMed and Web of Science databases between February 1996 and May 2020. The study designs, EH standards, and reported metabolic biomarkers were systematically examined and compared. The pathway analysis was conducted through the online software MetaboAnalyst 4.0. Twenty-two human studies and fifteen animal studies were included in this systematic review. There were many frequently reported biomarkers with consistent trends (e.g., pyruvate, lactic acid, valine, and tryptophan) in human and animal studies, and thus had potential as biomarkers of EH. In addition, several shared metabolic pathways, including alanine, aspartate, and glutamate metabolism, aminoacyl-tRNA biosynthesis, and arginine biosynthesis, were identified in human and animal metabolomics studies. These biomarkers and pathways, closely related to insulin resistance, the inflammatory state, and impaired nitric oxide production, were demonstrated to contribute to EH development., Conclusions: This study summarized valuable metabolic biomarkers and pathways that could offer opportunities for the early diagnosis or prediction of EH and the discovery of the metabolic mechanisms of EH., Competing Interests: Declaration of competing interest The authors state that there are no conflicts of interests., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Introduction: Studies have shown that primary aldosteronism (PA) has a higher risk of cardiovascular events than essential hypertension (EH). Endothelial dysfunction is an independent predictor of cardiovascular events. Whether PA and EH differ in the endothelial dysfunction is uncertain. Our study was designed to investigate the levels of biomarkers of endothelial dysfunction (Asymmetric dimethylarginine, ADMA; E-selectin, and Plasminogen activator inhibitor-1, PAI-1) and assess the microvascular endothelial function in patients with PA and EH, respectively., Methods: The biomarkers of endothelial dysfunction were measured by enzyme-linked immunosorbent assay (ELISA). Microvascular endothelial function was evaluated by Pulse amplitude tonometry (PAT)., Results: Thirty-one subjects with EH and 36 subjects with PA including 22 with aldosterone-producing adenoma (APA) and 14 with idiopathic hyperaldosteronism (IHA) were enrolled in our study. The ADMA levels among the three groups were different (APA 47.83 (27.50, 87.74) ng/ml vs EH 25.08 (22.44, 39.79) ng/ml vs IHA 26.00 (22.23, 33.75) ng/ml; p  = 0.04), however, when the APA group was compared with EH and IHA group, there was no statistical significance (47.83 (27.50, 87.74) ng/ml vs 25.08 (22.44, 39.79) ng/ml for EH, p  = 0.11; 47.83 (27.50, 87.74) ng/ml vs IHA 26.00 (33.75) ng/ml, p  = 0.07). The results of ADMA levels are presented as Median (p25, p75). Whereas, levels of PAI-1 and E-selectin, microvascular endothelial function were not significantly different between PA and EH subjects., Conclusions: Our study shows no significant differences between PA and EH in terms of biomarkers of endothelial dysfunction and microvascular endothelial function. The microvascular endothelial function of PA and EH patients is comparable.

Objective: Saline infusion testing (SIT) for confirmation of primary aldosteronism (PA) is based on impaired aldosterone suppression in PA compared to essential hypertension (EH). In the past, aldosterone was quantified using immunoassays (IA). Liquid chromatography tandem mass spectrometry (LC-MS/MS) is increasingly used in clinical routine. We aimed at a method-specific aldosterone threshold for the diagnosis of PA during SIT and explored the diagnostic utility of steroid panel analysis., Design: Retrospective cohort study of 187 paired SIT samples (2009-2018). Diagnosis of PA (n = 103) and EH (n = 84) was established based on clinical routine workup without using LC-MS/MS values., Setting: Tertiary care center., Methods: LC-MS/MS using a commercial steroid panel. Receiver operator characteristics analysis was used to determine method-specific cut-offs using a positive predictive value (PPV) of 90% as criterion., Results: Aldosterone measured by IA was on average 31 ng/L higher than with LC-MS/MS. The cut-offs for PA confirmation were 54 ng/L for IA (sensitivity: 95%, 95% CI: 89.0-98.4; specificity: 87%, 95% CI: 77.8-93.3; area under the curve (AUC): 0.955, 95% CI: 0.924-0.986; PPV: 90%, 95% CI: 83.7-93.9) and 69 ng/L for LC-MS/MS (79%, 95% CI: 69.5-86.1; 89%, 95% CI: 80.6-95.0; 0.902, 95% CI: 0.857-0.947; 90%, 95% CI: 82.8-94.4). Other steroids did not improve SIT., Conclusions: Aldosterone quantification with LC-MS/MS and IA yields comparable SIT-cut-offs. Lower AUC for LC-MS/MS is likely due to the spectrum of disease in PA and previous decision making based on IA results. Until data of a prospective trial with clinical endpoints are available, the suggested cut-off can be used in clinical routine.

Hypertension is a common chronic disease in middle-aged and elderly people and is an important risk factor for many cardiovascular diseases. Its pathogenesis remains unclear. Epidemiological studies have found that the loss of telomere length in peripheral blood cells can increase the risk of coronary heart disease, myocardial infarction, and other diseases. However, a correlation between loss of telomere length and hypertension has not been established. In this study, we aimed to explore the association between telomere length and the risk of essential hypertension (EH) in Chinese coal miners. A case-control study was performed with 215 EH patients and 222 healthy controls in a large coal mining group located in North China. Face-to-face interviews were conducted by trained staff with the necessary medical knowledge. Relative telomere length (RTL) was measured by a quantitative real-time PCR assay using DNA extracted from peripheral blood. In the control group, the age-adjusted RTL was statistically significantly lower in miners performing hard physical labour compared with nonphysical labour ( P = 0.043). A significantly shorter age-adjusted RTL was found in the control group of participants who consumed alcohol regularly compared with those who do not consume alcohol ( P = 0.024). Age-adjusted RTL was negatively correlated with body mass index (BMI) and alcohol consumption. Hypertension was also found to be significantly correlated with factors such as age, BMI, alcohol consumption, smoking, and tea consumption. Our results suggest that RTL is associated with hypertension in coal miners., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 Sheng-nan Yu et al.)

Epidemiological studies have documented a high incidence of diabetes in hypertensive patients.Insulin resistance is defined as a less than expected biologic response to a given concentration of the hormone and plays a pivotal role in the pathogenesis of diabetes. However, over the last decades, it became evident that insulin resistance is not merely a metabolic abnormality, but is a complex and multifaceted syndrome that can also affect blood pressure homeostasis. The dysregulation of neuro-humoral and neuro-immune systems is involved in the pathophysiology of both insulin resistance and hypertension. These mechanisms induce a chronic low grade of inflammation that interferes with insulin signalling transduction. Molecular abnormalities associated with insulin resistance include the defects of insulin receptor structure, number, binding affinity, and/or signalling capacity. For instance, hyperglycaemia impairs insulin signalling through the generation of reactive oxygen species, which abrogate insulin-induced tyrosine autophosphorylation of the insulin receptor. Additional mechanisms have been described as responsible for the inhibition of insulin signalling, including proteasome-mediated degradation of insulin receptor substrate 1/2, phosphatase-mediated dephosphorylation and kinase-mediated serine/threonine phosphorylation of both insulin receptor and insulin receptor substrates. Insulin resistance plays a key role also in the pathogenesis and progression of hypertension-induced target organ damage, like left ventricular hypertrophy, atherosclerosis and chronic kidney disease. Altogether these abnormalities significantly contribute to the increase the risk of developing type 2 diabetes.

Objective: The aim of this study was to investigate the correlation between microRNA-136 levels and biochemical markers of renin-angiotensin-aldosterone system (RAAS) in patients with essential hypertension (EH)., Patients and Methods: The subjects were divided into EH group (n=110) and healthy control group (n=110). MicroRNA-136 expression, angiotensin-converting enzyme (ACE) activity, and expression of renin (RA) and angiotensin II (Ang II), and aldosterone (ALD) in peripheral blood serum were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), equine glycylglycine glycine method, magnetic particle chemistry, and radioimmunoassay, respectively. In addition, the correlation between microRNA-136 and RAAS biochemical markers was estimated by Pearson linear regression. Meanwhile, ROC curve analysis was carried out to evaluate the potential of microRNA-136 for the diagnosis of EH. Follow-up data were recorded for assessing the influence of microRNA-136 on the prognosis in patients with EH., Results: It was found that microRNA-136 expression was remarkably elevated in peripheral blood serum of patients with EH, and the expression levels of biochemical markers of RASS, such as ACE, RA, Ang II, and ALD were also found higher than those in healthy controls. Meanwhile, a significant positive correlation was confirmed between microRNA-136 level and ACE activity, RA, Ang II, as well as ALD levels in patients with EH. In addition, the area under the ROC curve (AUC) was calculated as 0.8662, with a sensitivity of 82.73% and a specificity of 80.91%. After two-months medication intervention, patients with EH expressing a high level of microRNA-136 had better therapeutic efficacy than those with a low level., Conclusions: In peripheral blood serum, microRNA-136 expression was dramatically negatively correlated with biochemical markers of RASS. High level of microRNA-136 predicts a good prognosis in patients with EH following medication. Therefore, microRNA-136 can be used as a potential biomarker for the diagnosis of EH.

Iron overload has been recently shown to be associated with a hyperadrenergic state in genetic hemochromatosis. Whether this is also the case in essential hypertension, characterized by sympathetic activation and frequently by body iron overload, is unknown. In 17 healthy normotensive controls (age 52.3±3.2 years, mean±SE), in 21 age-matched patients with hypertension with iron overload (HT+), defined by serum ferritin levels, and in 28 hypertensives without this condition, we measured efferent postganglionic muscle sympathetic nerve traffic (microneurography), heart rate and blood pressure variability (power spectral analysis), serum ferritin, and metabolic variables. Muscle sympathetic nerve traffic was significantly ( P <0.02 at least) greater in HT+ than in patients with hypertension without iron overload and normotensive subjects both when expressed as bursts incidence over time (41.8±1.4 versus 31.5±1.4 and 23.6±0.9 bursts/min) and as bursts corrected for heart rate (55.3±1.8 versus 42.3±1.2 and 31.7±1.2 bursts/100 heartbeats). In HT+, low-frequency systolic blood pressure variability was significantly reduced. In HT+, but not in the other 2 groups, muscle sympathetic nerve traffic was significantly related to serum ferritin ( r =0.51, P <0.03), transferrin saturation ( r =0.47, P <0.03), and hepatic iron load ( r =0.76, P <0.0001, magnetic resonance imaging), as well as to homeostatic model assessment index values ( r =0.46, P <0.05). These data provide the first evidence that in HT+ elevated serum ferritin is associated with a hyperadrenergic state of greater magnitude than the one seen in patients with hypertension without iron overload. They also show that the potentiation of the sympathetic activation detected in HT+ is related to elevated serum ferritin and to the associated metabolic alterations, possibly participating in the increased cardiovascular risk characterizing iron overload.

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., (Copyright © 2020 Zhang, Gao, Guo, Feng, Tang, Yan, Wang, Cheng and Liu.)

The recent European Society of Cardiology/European Society of Hypertension hypertension guidelines identify resting heart rate (HR) values >80 bpm as predictors of cardiovascular risk, with the unproven assumption that this might reflect the presence of a sympathetic overdrive. In the present study, we tested this hypothesis throughout the use of direct and indirect sympathetic markers. In 193 untreated moderate essential hypertensives aged 50.4±0.6 years (mean±SEM), we measured clinic and ambulatory blood pressure and corresponding HR, venous plasma norepinephrine (high performance liquid chromatography), and muscle sympathetic nerve traffic (microneurography). We then subdivided the study population into 2 groups according to HR < or >80 bpm. Eighty-four patients displayed resting HR >80 bpm, which was this cutoff value in the remaining 109 patients, the 2 groups showing superimposable age, and sex distribution. Clinic and ambulatory blood pressure were similar in the 2 groups, whereas left ventricular mass index was significantly greater in the group with HR >80 bpm. Muscle sympathetic nerve traffic values were also significantly greater in this latter group (72.77±0.9 versus vs 36.83±1.3 bursts/min, P <0.0001); this being the case also for norepinephrine (293.0±8.7 versus 254.1±8.9 pg/mL, P <0.002). In the whole population, there was a significant direct relationship between muscle sympathetic nerve traffic, norepinephrine, left ventricular mass index, and HR values. Similar results were obtained when 24-hour HR values were analyzed. Thus patients with hypertension displaying HR >80 bpm are characterized by a marked sympathetic overdrive, particularly when direct adrenergic markers are used. This finding suggests that cardiac and peripheral sympathetic activation are involved in the increased cardiovascular risk detected in this group of patients.

Endothelial Nitric Oxide Synthase (eNOS) is an indispensable regulator of blood pressure through producing Nitric Oxide (NO). There is some evidence to suggest that eNOS gene polymorphisms are associated with Essential Hypertension (EHT). In this study, the potential association between eNOS 4a/4b, A922G, G894T, T786C gene polymorphisms and EHT as individual risk factors and as haplotypes are examined in the southern population of Iran (Bandar-Abbas). In this study, 200 EHT patients and 200 normotensive subjects which were matched for age and sex were included. Genotyping was performed by either utilizing Polymerase Chain Reaction (PCR) or PCR followed by Restriction Fragment length Polymorphism (RFLP) method. Our results demonstrated statistically significant associations between T786C, G894T, and 4a/4a and EHT (p < 0.05); however, A922G had no significant association with EHT (p > 0.05). Haplotype analysis also suggested that - 786C/- 922A/4a, - 786C/- 922A/4b and - 786C/- 922G/4a haplotypes were more frequent in EHT group than control group, hypothesizing a positive association with EHT. The present study has identified that the eNOS genetic variations are associated with EHT in southern population of Iran (Bandar-Abbas). These findings also suggested that a number of haplotypes of eNOS gene may be a driving factor for EHT susceptibility in respected population.

Objectives : The association between serum uric acid (SUA) and ischemic stroke is still inconsistent across population. This study aimed to examine the association between SUA and ischemic stroke in essential hypertension patients. Methods : This retrospective study recruited participants from September 2011 to December 2012, in the Liao-bu community, Guangdong Province, China, and followed them until 31 December 2016. Participants were divided into quartiles based on SUA concentrations. Hazard ratio (HR) and confidence intervals (CIs) was estimated from Cox proportional hazards models, and propensity score analysis, Kaplan-Meier survival curves and receiver operating characteristic (ROC) curve were performed to evaluate the relationship between SUA and the risk of ischemic stroke. Results : A total of 5473 eligible hypertensive subjects were enrolled in this study, 2666 (48.71%) of them were males with an average age of 62.02 ± 13.76 years. A total of 155 (2.83%) ischemic stroke occurred after the mean follow-up period of 4.5 years. After adjusting for potential confounders, comparing with the lowest quartiles of SUA, multivariable HR (95%CI) for ischemic stroke for participants with SUA at the second, third and fourth quartiles were 1.13 (95%CI: 1.10, 1.81), 1.39 (95%CI: 1.18, 1.89), and 1.64 (95%CI: 1.19, 1.95), respectively (P < 0.0001 for trend). Elevated SUA was positively associated with ischemic stroke (HR = 1.41, 95%CI: 1.16, 1.84; P < 0.01) and the propensity scores analysis (HR = 1.45, 95%CI: 1.17, 1.90; P < 0.01) showed the similar results. Gender subgroup analysis showed SUA was an independent risk of ischemic stroke in female (HR = 1.35, 95%CI: 1.11, 1.81, P = 0.002) and male (HR = 1.53, 95%CI: 1.14, 1.92, P < 0.001). ROC curve demonstrated that SUA yielded an AUC of 0.7476 (95%CI: 0.7098, 0.7855, P < 0.001) for predictive of ischemic stroke. Conclusions : SUA was an independent risk factor for ischemic stroke, and also have a good predictive value ischemic stroke among hypertensive patients in Chinese community.

Background: To investigate the relationships of plasma renin, angiotensin, and aldosterone levels to blood pressure variability and target organ damage in children with essential hypertension., Methods: A case-control study was conducted on 132 children diagnosed with essential hypertension (103 males and 29 females with the mean age of 11.8 ± 2.4 years). The plasma RAAS levels were measured using the enhanced chemiluminescence method, the ambulatory blood pressure was monitored for 24 h, and then the average real variability (ARV) was calculated. Data on indicators were used for assessing cardiac and renal damages. The correlations of plasma renin, angiotensin, and aldosterone (RAAS) levels to blood pressure variability (BPV) and target organ damage (TOD) were studied. A comparison between the groups was conducted using SPSS 20., Results: Among the 132 children, 55 cases had target organ damage. The 24-h ARV and the daytime ARV of the systolic blood pressure of the high angiotensin II (AT II) group was significantly higher than that of the normal AT II group (t = 2.175, P = 0.031; t = 2.672, P = 0.009). Plasma AT II and aldosterone levels were significantly associated with the left ventricular mass index (r = 0.329, P = 0.0001; r = 0.175, P = 0.045). Linear regression analysis showed that AT II [β ± s.e. = 0.025 ± 0.006, 95% CI (0.013-0.038), P = 0.0001] and aldosterone [β ± s.e. = 0.021 ± 0.007, 95% CI (0.008-0.034), P = 0.002] were risk factors for LVH., Conclusions: The AT II level in children with essential hypertension affected the variability of the 24-h and the daytime SBP. Plasma AT II and aldosterone levels were associated with cardiac damage. Results from this study indicated that AT II and aldosterone are risk factors for LVH in childhood hypertension and are of great significance for improving the clinical prognosis of pediatric patients with hypertension.

MicroRNAs are key molecules involved in the regulation of endothelial function. They are important risk factors and biomarkers for the development of hypertension related to endothelial dysfunction. However, the gene expression patterns associated with hypertension development related to endothelial dysfunction have not been fully elucidated. We conducted a case-control study of 65 patients with essential hypertension (EH) and 61 controls without EH. Plasma levels of miR-122 and its target protein high-affinity cationic amino acid transporter 1 (CAT-1) were measured by qRT-PCR and ELISA, respectively. miR-122 expression in plasma of patients with EH was significantly higher than that of the control group (p = 0.001), while CAT-1 expression in patients with EH was significantly lower than that in the control group (p = 0.018). miR-122 expression in plasma of young patients with EH was significantly higher than that in young people without EH (p = 0.0004), and CAT-1 expression in plasma of young patients with EH was also significantly lower than that of the control group (p = 0.002). CAT-1 expression in the plasma of young participants was significantly higher than that of individuals aged ≥40 years (p = 0.003), whereas miR-122 expression was significantly lower (p = 0.001). We showed that among patients with EH, the high expression of miR-122 contributed to endothelial dysfunction by suppressing the expression of the CAT-1 protein, which led to a decrease in CAT-1 expression in plasma. Therefore, high expression of miR-122 appears to be a risk factor for endothelial dysfunction in EH, especially in younger patients.

MicroRNA (miR)-202-3p has attracted a great deal of attention in the fields of oncology, gynecology, and metabolic disorders. However, its role in cardiovascular diseases remains to be clarified. We previously found that disruption of miR-202-3p mediated regulation of expression of soluble (s)ST2, a decoy receptor for interleukin (IL)-33, promotes essential hypertension (EH). In the present study, we first measured miR-202-3p expression levels in the blood of 182 EH cases and 159 healthy controls using TaqMan assays. miR-202-3p levels were shown to be significantly higher in EH cases than controls (fold change = 3.58, P<0.001). Logistic regression analysis revealed that higher miR-202-3p expression was associated with an increased occurrence of EH (adjusted odds ratio (OR): 1.57; 95% confidence interval (CI), 1.36-1.82; P<0.001). Addition of miR-202-3p to traditional risk factors showed an additive prediction value for EH. Further functional experiments indicated that miR-202-3p could be induced by angiotensin II (Ang II) and inhibited by Ang II-triggered soluble ST2 (sST2) expression in a negative feedback manner. Moreover, blood miR-202-3p levels were negatively correlated with sST2 expression in vivo. Our study shows that blood miR-202-3p levels were significantly associated with the occurrence of EH. These findings indicate that miR-202-3p exerts a protective role against EH by antagonizing the induction of sST2 by Ang II., (© 2020 The Author(s).)

Purpose: To explore the association between the sympathetic system activity and myocardial hypertrophy in patients with essential hypertension., Methods: A total of 84 essential hypertension inpatients were recruited from China-Japan Friendship Hospital between January 2019 and September 2019. Activity of sympathetic system was quantified by plasma metanephrines (MNs) levels. All subjects received an echocardiographic test., Results: The interventricular septum thickness (diastolic), left ventricular mass and left ventricular mass index increased significantly with plasma MNs quartiles, and plasma MNs were positively and significantly correlated with early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity., Conclusions: In patients with essential hypertension, high level of plasma MNs associates with left ventricular hypertrophy and impaired diastolic function.

Background: The relationship between circulating regulatory T-cell (Tregs) subset distribution and hypertension severity in children with primary hypertension is not known. We aimed to find out if target organ damage (TOD) in children with primary hypertension is related to defects in Tregs distribution reflected by their phenotype characteristics., Methods: The study constituted 33 nontreated hypertensive children and 35 sex-matched and age-matched controls. Using multicolor flow cytometry technique, we assessed a distribution of the total Tregs (CD4CD25CD127) and their subsets (CD45RA-naive Tregs, CD45RA memory/activated Tregs, CD45RACD31 recent thymic emigrants Tregs and mature naive CD45RACD31 Tregs) in the whole blood., Results: Hypertensive children showed decreased percentage of the total Tregs, the CD45RA-naive Tregs, the total CD31 Tregs and the recent thymic emigrants Tregs but elevation of the CD45RA memory/activated Treg and mature naive CD45RACD31 Tregs. Decreased frequency of the total Tregs, naive Tregs and CD31-bearing Treg cell subsets (CD31 total Tregs, CD45RACD31 recent thymic emigrants Tregs) negatively correlated to TOD markers, arterial stiffness and blood pressure elevation. In contrast, increased percentage of memory Tregs and CD31 Tregs subsets positively correlated to organ damage markers, arterial stiffness and blood pressure values. These changes were independent of BMI, age, sex and hsCRP., Conclusion: Both diagnosis of hypertension, TOD and arterial stiffness in hypertensive children were associated with decreased population of total CD4 Tregs, limited output of recent thymic emigrants Tregs, and increased pool of activated/memory Tregs. Hypertension was an independent predictor of the circulating Treg subsets distribution irrespective of hsCRP.

Background: Glutathione S-transferases play a key role in the detoxification of persistent oxidative stress products which are one of several risks factors that may be associated with many types of disease processes such as cancer, diabetes, and hypertension. In the present study, we characterize the null genotypes of GSTM1 and GSTT1 in order to investigate the association between them and the risk of developing essential hypertension., Methods: We conducted a case-control study in Burkina Faso, including 245 subjects with essential hypertension as case and 269 control subjects with normal blood pressure. Presence of the GSTT1 and GSTM1 was determined using conventional multiplex polymerase chain reaction followed by gel electrophoresis analysis. Biochemical parameters were measured using chemistry analyzer CYANExpert 130., Results: Chi-squared test shows that GSTT1-null (OR = 1.82; p = 0.001) and GSTM1-active/GSTT1-null genotypes (OR = 2.33; p <  0.001) were significantly higher in cases than controls; the differences were not significant for GSTM1-null, GSTM1-null/GSTT1-active and GSTM1-null/GSTT1-null (p > 0.05). Multinomial logistic regression revealed that age ≥ 50 years, central obesity, family history of hypertension, obesity, alcohol intake and GSTT1 deletion were in decreasing order independent risk factors for essential hypertension. Analysis by gender, BMI and alcohol showed that association of GSTT1-null with risk of essential hypertension seems to be significant when BMI < 30 Kg/m 2 , in non-smokers and in alcohol users (all OR ≥ 1.77; p ≤ 0.008). Concerning GSTT1, GSTM1 and cardiovascular risk markers levels in hypertensive group, we found that subjects with GSTT1-null genotype had higher waist circumference and higher HDL cholesterol level than those with GSTT1-active (all p <  0.005), subjects with GSTM1-null genotype had lower triglyceride than those with GSTM1-active (p = 0.02) and subjects with the double deletion GSTM1-null/GSTT1-null had higher body mass index, higher waist circumference and higher HDL cholesterol than those with GSTM1-active/GSTT1-active genotype (all p = 0.01)., Conclusion: Our results confirm that GSTT1-null genotype is significantly associated with risk of developing essential hypertension in Burkinabe, especially when BMI < 30 Kg/m 2 , in non-smokers and in alcohol users, and it showed that the double deletion GSTM1-null/GSTT1-null genotypes may influence body lipids repartition.

We investigated changes in blood pressure (BP) and metabolic adverse effects, especially elevation of uric acid (UA), after treatment with a thiazide-like diuretic (TD) in patients with essential hypertension. Furthermore, the role of genetic factors in the elevation of UA by TD was assessed by a 500 K SNP DNA microarray. The subjects included 126 hypertensive patients (57 women and 69 men, mean age 59 ± 12 years) who registered for the GEANE (Gene Evaluation for ANtihypertensive Effects) study. After one month of the nontreatment period, TD, indapamide, angiotensin II receptor antagonist valsartan, and Ca channel blocker amlodipine were administered to all patients for 3 months each in a randomized crossover manner. BP, renal function, serum UA level, and electrolytes were measured at baseline and at the end of each treatment period. Single nucleotide polymorphisms (SNPs) associated with UA elevation after treatment with indapamide were investigated by a genome-wide association study (GWAS). Indapamide significantly decreased both office and home BP levels. Treatment with indapamide also significantly reduced the estimated glomerular filtration rate and serum potassium and increased serum UA. Patients whose UA level increased more than 1 mg/dl showed significantly higher baseline office SBP and plasma glucose and showed greater decline in renal function compared with those who showed less UA increase (<1 mg/dl). Some SNPs strongly associated with an increase in UA after treatment with indapamide were identified. This study is the first report on SNPs associated with UA elevation after TD treatment. This information may be useful for the prevention of adverse effects after treatment with TD.

Background: The prognostic value of serum uric acid (SUA) for incident acute coronary syndrome (ACS) in hypertensive subjects is uncertain. Therefore, the present study examined the association between SUA and incident ACS in a large cohort of Chinese hypertensive adults., Methods: This was a retrospective cohort study, which enrolled 5473 Chinese community-dwelling hypertensive patients from 1 January 2012 to 31 December 2012. Study outcomes were ACS events, and patients were followed until 31 December 2016. Cox regression analyses were conducted to determine adjusted HRs and 95% CIs for baseline SUA tertiles (low, middle and high group) and for men and women separately., Results: A total of 5473 participants were included in the analysis (median follow-up was 4.5 years). Participants were divided into tertiles based on SUA levels. During follow-up, 9 (0.49%), 14 (0.77%) and 25 (1.37%) patients developed ACS in the lowest, middle and highest tertiles, respectively. When compared with the lowest tertile of SUA, the highest tertile of SUA was associated with ACS risk in all subjects and in men and women separately (HR: 2.62, 95% CI 1.14 to 7.01, p=0.0233; 2.15, 95% CI 1.08 to 6.04, p=0.021, and 3.49, 95% CI 1.25 to 7.74, p=0.017, respectively)., Conclusions: Higher SUA levels were independently associated with an elevated risk of ACS incidence. The relationship between SUA levels and ACS in hypertensive patients was J-shaped., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2019. Published by Elsevier Inc.)

Background : Elabela (ELA) is a newly identified endogenous ligand of apelin receptor (APJ) which has been confirmed to be implicated in the pathogenesis of hypertension. Previous experiments have revealed the critical role of ELA in eliciting vasodilation and lowering blood pressure. However, the role of plasma ELA levels in hypertensive patients and its relationship with vascular function have not been investigated. Method : Thirty-one patients with essential hypertension (EH) and 31 age-matched healthy subjects as controls were recruited in the study. Plasma ELA concentration and vascular function parameters including brachial artery flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV) were measured. Results : We observed remarkably lower plasma ELA concentration in hypertensive patients as compared with controls (1.29 ± 0.56 ng/ml vs. 1.79 ± 0.55 ng/ml; P = 0.001). Linear correlation analysis showed that ELA was negatively correlated with systolic blood pressure ( r = -0.388, P = 0.002) and diastolic blood pressure ( r = -0.321, P = 0.011) and positively correlated with FMD ( r = 0.319, P = 0.011). There was no statistically significant relationship between ELA and baPWV ( r = 0.234, P = 0.067). Stepwise multiple linear analysis also identified a close association of plasma ELA levels with endothelial function. Conclusion : The present study demonstrates for the first time that circulating ELA levels are reduced in patients with EH. The fall in endogenous ELA levels may be involved in the pathogenesis of hypertension-related vascular damage.

Introduction: Essential hypertension (EH) is a disease caused by various environmental and genetic factors. Nitric oxide (NO) is important for the functional integrity of the endothelium. It is produced in endothelial cells by endothelial NO synthase (eNOS) that mediates the conversion of the amino acid arginine into NO and citrulline. Asymmetric dimethylarginine (ADMA) acts as an inhibitor of eNOS. In contrast, symmetric dimethylarginine (SDMA) has no direct effect on eNOS but plays an important role competing with arginine for transport across the amino acid transporter. ADMA and SDMA have been found to play a central role in the development of cardiovascular diseases. Serum ADMA levels may serve as a future diagnostic marker and a target of therapy in hypertensive patients in the Sudanese population. This study aimed to investigate the relation between serum arginine, ADMA, and SDMA levels with EH in the Sudanese population., Methods: Patients (n = 260) with established hypertension and controls (n = 144) with normal blood pressure were included in this case-control study. Serum blood samples were analyzed for arginine, ADMA, and SDMA, using high-performance liquid chromatography-tandem mass spectrometry. Other laboratory data were measured using routine methods. Mann-Whitney's U test and χ2 tests were used for continuous and categorical data, respectively. A multivariate logistic regression analysis was conducted to investigate the independent effect of multiple variables on the development of hypertension., Results: Serum arginine levels were significantly lower in the patient group than in the control group (p < 0.001). ADMA and SDMA levels were significantly higher in the patient group than the control group (p < 0.001, p = 0.001, respectively). Multivariate logistic regression analysis showed that only older age, being a male, and arginine levels are independent factors controlling the development of hypertension (p < 0.001, p < 0.001, and p = 0.046, respectively). ADMA and SDMA levels were not independent factors for the development of hypertension., Conclusions: This study demonstrated increased serum levels of ADMA and SDMA and decreased arginine levels in Sudanese patients with EH. Lowering serum ADMA levels or increasing the arginine levels might be a novel therapeutic target in these individuals., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Primary aldosteronism is recognized as the most frequent cause of secondary hypertension, and its screening is expected to become a routine evaluation in most patients with hypertension. The interference of antihypertensive therapies with the aldosterone-to-renin ratio during screening process is a major confounder. Renin-angiotensin-aldosterone system Triple-A analysis is a novel liquid chromatography/tandem mass spectrometry diagnostic assay that allows simultaneous quantification of aldosterone, equilibrium Ang I (angiotensin I), and Equilibrium Ang II in a single sample of serum. We performed a comparative evaluation of the diagnostic performance of the aldosterone-to-Ang II ratio and 5 renin-based diagnostic ratios, differing in methods to determine aldosterone levels and renin activity in a cohort of 110 patients with hypertension (33 patients with confirmed primary aldosteronism and 77 with essential hypertension). All ratios showed comparable areas under the curves ranging between 0.924 and 0.970 without significant differences between each other. The evaluation of the Ang II-to-Ang I ratio revealed persistent drug intake in some patients as cause for suppressed renin-based diagnostic ratios, while aldosterone-to-Ang II ratio remained unaffected. The Youden index optimal cutoff value for the aldosterone-to-Ang II ratio was 6.6 ([pmol/L]/[pmol/L]) with a sensitivity of 90% and a specificity of 93%, proving noninferiority compared with the aldosterone-to-renin ratio while pointing to the potential for an interference-free application in patients under ACE (angiotensin-converting enzyme) inhibitor therapy. This study shows for the first time the accuracy and reliability of renin-angiotensin-aldosterone system triple-A analysis for the screening of primary aldosteronism that can be applied in clinical routine.

Background: Patients with primary aldosteronism (PA) experience more cardiovascular events compared to patients with essential hypertension (EHT), independent from blood pressure levels. In animals, mineralocorticoid receptor antagonists limit ischaemia-reperfusion (IR) injury by increasing extracellular adenosine formation and adenosine receptor stimulation. Adenosine is an endogenous compound with profound cardiovascular protective effects. Firstly, we hypothesized that patients with PA have lower circulating adenosine levels which might contribute to the observed increased cardiovascular risk. Secondly, we hypothesized that by this mechanism, patients with PA are more susceptible to IR compared to patients with EHT., Design: In our prospective study in 20 patients with PA and 20 patients with EHT, circulating adenosine was measured using a pharmacological blocker solution that halts adenosine metabolism after blood drawing. Brachial artery flow-mediated dilation (FMD) before and after forearm IR was used as a well-established method to study IR injury., Results: Patients with PA had a 33% lower adenosine level compared to patients with EHT (15.3 [13.3-20.4] vs 22.7 [19.4-36.8] nmol/L, respectively, P < .01). The reduction in FMD after IR, however, did not differ between patients with PA and patients with EHT (-1.0 ± 2.9% vs -1.6 ± 1.6%, respectively, P = .52)., Conclusions: As adenosine receptor stimulation induces various powerful protective cardiovascular effects, its lower concentration in patients with PA might be an important novel mechanism that contributes to their increased cardiovascular risk. We suggest that modulation of the adenosine metabolism is an exciting novel pharmacological opportunity to limit cardiovascular risk in patients with PA that needs further exploration., (© 2019 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background and Aims: The adrenal mineralocorticoid system plays a key role in cardiovascular, metabolic and renal damage. This study aimed to assess the relationship between plasma aldosterone concentration (PAC) and some surrogate markers of subclinical atherosclerosis, such as carotid intima-media thickness (cIMT), ankle-brachial index (ABI) and biochemical parameters in patients with essential hypertension., Methods and Results: From January 2014 to December 2017, we consecutively enrolled 804 essential hypertensive patients (407 men and 397 women, mean age 50 ± 14 years) without cardiovascular complications, distinguishing patients in quartiles according to PAC. Compared with the first quartile, the highest PAC quartile was associated with the highest levels of serum uric acid (SUA) (5.3 ± 1.3 vs. 5.0 ± 1.0 mg/dl; P = 0.01), triglycerides (117.5 ± 15.7 vs. 106.8 ± 10.5 mg/dl; P < 0.05), 24-h urinary albumin excretion (UAE) (38.8 ±  vs. 7.6 ± mg/24 h; P < 0.05), cIMT (0.87 ± 0.22 vs. 0.80 ± 0.21 mm; P = 0.001) and increased prevalence of carotid plaques (26 vs. 16%; P < 0.005). Moreover, we found that in patients with PAC more than 150 pg/ml, the ABI was significantly lower than those with PAC < 150 pg/ml (1.01 ± 0.09 vs. 1.10 ± 0.09; P < 0.022). PAC was also found to be an independent predictor of the presence of carotid plaques and pathological ABI (<0.9) in essential hypertensive individuals., Conclusion: Our results revealed that higher PAC values are strongly associated with some metabolic variables, as triglycerides, UAE, cIMT, worse ABI and major prevalence of carotid plaques that, together with elevated blood pressure values, are strictly correlated with higher risk of atherosclerosis and cardiovascular complications.

Endothelial dysfunction plays role in the generation of both essential hypertension (EH) and aortic stiffness. We evaluated the relationship between serum endocan level and aortic elastic properties (AEPs) assessed with the aortic strain, aortic distensibility, and aortic stiffness index by echocardiography. Newly diagnosed EH patients (n = 67) and controls (n = 70) were included in the study. The EH group was subdivided into stage 1 and 2 EH groups. A higher endocan level was found in the EH group, compared to the controls (34.2 ± 13.0 vs 24.1 ± 7.3 ng/mL, respectively, P < .001). All the AEP parameters were worse in the EH group, compared to the controls. Further, endocan levels correlated with aortic distensibility ( r = -0.305, P < .001) and aortic strain ( r = -0.181, P = .038), but not with aortic stiffness index ( r = 0.162, P = .064) in the whole study population. Aortic elastic properties deteriorate and serum endocan level increases in patients with EH. Moreover, serum endocan level shows a correlation with deteriorated AEPs, and hence may a surrogate marker of escalating aortic stiffness in patients with newly diagnosed EH.