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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: 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.)

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.

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.

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.)

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.

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.

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: 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.

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.)

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: The aim of this study was to compare the influence of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on endothelial function and blood pressure in patients with essential hypertension on long-term angiotensin-converting enzyme inhibitor therapy., Method: The study was designed as a prospective, double-blind, randomised, placebo controlled, crossover clinical trial. Twenty patients with essential hypertension were treated with an angiotensin-converting enzyme inhibitor; the control group included 10 healthy subjects. Hypertensive patients received in random order 80 mg of fluvastatin daily or placebo for 6 weeks. The following parameters were assessed at baseline and after each treatment period: serum lipids, flow-mediated vasodilation, activity of von Willebrand factor, concentration of vascular endothelial growth factor, C-reactive protein and 24-hour blood pressure profile., Results: Hypertensive patients did not differ from healthy subjects with respect to age, body mass and biochemical parameters, with the exception of C-reactive protein, which was higher in hypertensive patients ( P =0.02). After statin therapy, low-density lipoprotein cholesterol ( P <0.0001), C-reactive protein ( P =0.03), von Willebrand factor ( P =0.03) and vascular endothelial growth factor ( P <0.01) decreased and flow-mediated vasodilation improved ( P <0.001). Statins had no significant effect on blood pressure., Conclusions: Statins added to angiotensin-converting enzyme inhibitors may improve endothelial function and ameliorate inflammation independently of blood pressure.

Background Hypertension may be associated with renal cellular injury. Cells in distress release extracellular vesicles (EVs), and their numbers in urine may reflect renal injury. Cellular senescence, an irreversible growth arrest in response to a noxious milieu, is characterized by release of proinflammatory cytokines. We hypothesized that EVs released by senescent nephron cells can be identified in urine of patients with hypertension. Methods and Results We recruited patients with essential hypertension (EH) or renovascular hypertension and healthy volunteers (n=14 each). Renal oxygenation was assessed using magnetic resonance imaging and blood samples collected from both renal veins for cytokine-level measurements. EVs isolated from urine samples were characterized by imaging flow cytometry based on specific markers, including p16 (senescence marker), calyxin (podocytes), urate transporter 1 (proximal tubules), uromodulin (ascending limb of Henle's loop), and prominin-2 (distal tubules). Overall percentage of urinary p16+ EVs was elevated in EH and renovascular hypertension patients compared with healthy volunteers and correlated inversely with renal function and directly with renal vein cytokine levels. Urinary levels of p16 + /urate transporter 1 + were elevated in all hypertensive subjects compared with healthy volunteers, whereas p16 + /prominin-2 + levels were elevated only in EH versus healthy volunteers and p16 + /uromodulin + in renovascular hypertension versus EH. Conclusions Levels of p16 + EVs are elevated in urine of hypertensive patients and may reflect increased proximal tubular cellular senescence. In EH, EVs originate also from distal tubules and in renovascular hypertension from Henle's loop. Hence, urinary EVs levels may be useful to identify intrarenal sites of cellular senescence.

This study aimed to investigate the correlation between complement C1q tumor necrosis factor-related protein 1 (CTRP1) and subclinical target organ damage (STOD) in essential hypertension (EH). 720 patients were enrolled in this study, including 360 healthy subjects and 360 patients with EH. The EH group included 183 patients complicated with STOD and 177 patients without STOD. In the STOD group, there were 87 patients with left ventricular hypertrophy (LVH), 32 patients with microalbuminuria (MAU), and 58 patients with complication of LVH and MAU. Enzyme-linked immunosorbent assay (ELISA) was used to detect the CTRP1, adiponectin (APN), interleukin-6 (IL-6), and tumor necrosis factor- α (TNF- α ). We found that CTRP1 levels were higher in patients with EH than those in healthy subjects; moreover, the level of CTRP1 of patients in the group complicated with EH and STOD was increased compared with EH patients without STOD. CTRP1 levels in the group complicated with LVH and MAU were significantly higher than those in the LVH group and the MAU group. Furthermore, APN, CTRP1, and IL-6 were three factors that influenced the STOD of EH patients, among which CTRP1 and IL6 were positively related with the complication of hypertension and STOD. In conclusion, CTRP1 levels are increased and associated with the STOD (heart and kidney) in essential hypertension, which can be regarded as a novel biomarker in the prediction of prognosis for patients with essential hypertension., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Zhengjia Su et al.)

Background: Bone morphogenetic protein9 (BMP9) has been reported to have a role in vascular development. However, there is still a lack of information regarding the association between circulating BMP9 levels and cardiovascular disease in humans. The goal of this study is to measure circulating BMP9 concentrations in patients with essential hypertension (HTN), coronary heart disease (CHD) and HTN + CHD, and evaluates the relationship between circulating BMP9 and these cardiovascular diseases., Methods: A total of 417 individuals were recruited for this cross-sectional study from June 2015 to December 2017. These subjects were screened for HTN and CHD. Circulating BMP9 concentrations were measured by ELISA., Results: Circulating BMP9 concentrations were significantly low in HTN, CHD and HTN + CHD individuals relative to those of the healthy individuals. Circulating BMP9 correlated negatively with SBP, FIns and HOMA- IR in HTN patients and correlated negatively with FBG and 2 h-BG in CHD patients. In both HTN and CHD patients, circulating BMP9 correlated negatively with BMI, WHR, FAT%, BP and TG. Multivariate logistic regression analysis showed that circulating BMP9 levels were associated with HTN, HTN + CHD and CHD. Individuals with low quartile of circulating BMP9 had a significantly high risk of HTN or/and CHD as compared with those in high quartile., Conclusions: BMP9 is likely to be a biomarker for cardiovascular disease in humans, and it may play a role in the progression of cardiovascular disease., Trial Registration: ChiCTR-OPC-14005324 .

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.

Microparticles are a distinctive group of small vesicles, without nucleus, which are involved as significant modulators in several physiological and pathophysiological mechanisms. Plasma microparticles from various cellular lines have been subject of research. Data suggest that they are key players in development and manifestation of cardiovascular diseases and their presence, in high levels, is associated with chronic inflammation, endothelial damage and thrombosis. The strong correlation of microparticle levels with several outcomes in cardiovascular diseases has led to their utilization as biomarkers. Despite the limited clinical application at present, their significance emerges, mainly because their detection and enumeration methods are improving. This review article summarizes the evidence derived from research, related with the genesis and the function of microparticles in the presence of various cardiovascular risk factors and conditions. The current data provide a substrate for several theories of how microparticles influence various cellular mechanisms by transferring biological information.

Background: Essential hypertension can cause many kinds of cardiovascular diseases. The pathogenesis of essential hypertension is very complex, and the mechanism is still unclear. The microRNAs have been identified as novel biomarkers for pre-diagnosis and prognosis of hypertension. However, the kinds of microRNAs that can be used as specific biomarkers for hypertension are unknown., Methods and Results: Plasma samples were isolated from Uyghur subjects with essential hypertension and the healthy individuals. Microarray was used to identify differentially expressed microRNAs. The microarray data were clustered and annotated with online software. The target genes of differentially expressed microRNAs were also analyzed. The microarray results were further verified by quantitative real-time PCR. We identified 257 microRNAs that were differentially expressed between patients with essential hypertension and the healthy individuals. These microRNAs had a total of 6580 target genes. The 47 microRNAs that had target genes, including 24 up-regulated and 23 down-regulated microRNAs, were further screened out to construct a reference set of potential microRNA biomarkers. Most of the 47 microRNAs were located at chromosome 19 (40 microRNAs) and chromosome 1 (45 microRNAs). Their target genes were mainly enriched in metal ion binding, transcription regulation, cell adhesion and junction, indicating that these candidate microRNAs may regulate mineral ion binding and cell communication process of essential hypertension. The quantitative real-time PCR results of miR-198 and miR-1183 (which were the two most significantly up-regulated microRNAs by microarray), and, miR-30e-5p and miR-144-3p (which were the two most significantly down-regulated microRNAs by microarray) were consistent with the microarray results., Conclusions: A reference set of potential microRNA biomarkers that may be involved in essential hypertension is constructed. Our study may provide experimental evidence for further studying the mechanism of essential hypertension.

Objective: Various hematological blood count parameters, including the neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV), were analyzed to assess differences in patients with renovascular (RVH) and essential hypertension (EH)., Methods: A propensity score analysis was performed to match 51 patients with RVH and 173 patients with EH. After matching, 49 pairs of patients were compared., Results: Before matching, patients with RVH had significantly higher NLR values [1.35 (range: 1.14-1.76) vs. 1.05 (range: 0.81-1.3); p<0.001] and MPV [8.7 fL (range: 8.3-9.5 fL) vs. 8.4 fL (range: 7.3-9.2 fL; p=0.002]. After propensity score matching was performed (49 vs 49 patients), age, sex, atherosclerosis risk factors, frequency of atherosclerosis, and the medications used were similar between groups. The NLR was significantly greater in patients with RVH [1.00 (range: 0.76-1.40) vs 1.35 (range: 1.15-1.75; p<0.001]. The MPV did not differ significantly between groups. The NLR was the only parameter independently associated with RVH in a multivariate logistic regression [odds ratio: 5.563, 95% confidence interval (CI): 2.089-14.814; p≤0.001]. Receiver operating characteristic curve analysis results indicated that NLR >1.16 predicted RVH with a sensitivity of 72% and a specificity of 60% [area under curve: 0.724, 95% CI: 0.624-0.823; p≤0.001]., Conclusion: The results of the present study demonstrated that NLR, which is a simple, clinical parameter of inflammation, was elevated in patients with RVH.

Background: This pathophysiological study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes the vasodilator and anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), contributes to conduit artery endothelial dysfunction in type 2 diabetes., Methods and Results: Radial artery endothelium-dependent flow-mediated dilatation in response to hand skin heating was reduced in essential hypertensive patients (n = 9) and type 2 diabetic subjects with (n = 19) or without hypertension (n = 10) compared to healthy subjects (n = 36), taking into consideration cardiovascular risk factors, flow stimulus and endothelium-independent dilatation to glyceryl trinitrate. Diabetic patients but not non-diabetic hypertensive subjects displayed elevated whole blood reactive oxygen species levels and loss of NO release during heating, assessed by measuring local plasma nitrite variation. Moreover, plasma levels of EET regioisomers increased during heating in healthy subjects, did not change in hypertensive patients and decreased in diabetic patients. Correlation analysis showed in the overall population that the less NO and EETs bioavailability increases during heating, the more flow-mediated dilatation is reduced. The expression and activity of sEH, measured in isolated peripheral blood mononuclear cells, was elevated in diabetic but not hypertensive patients, leading to increased EETs conversion to DHETs. Finally, hyperglycemic and hyperinsulinemic euglycemic clamps induced a decrease in flow-mediated dilatation in healthy subjects and this was associated with an altered EETs release during heating., Conclusions: These results demonstrate that an increased EETs degradation by sEH and altered NO bioavailability are associated with conduit artery endothelial dysfunction in type 2 diabetic patients independently from their hypertensive status. The hyperinsulinemic and hyperglycemic state in these patients may contribute to these alterations. Trial registration NCT02311075. Registered December 8, 2014.

Introduction: Hypertension is regarded as a condition of mild inflammation and endothelial imbalance. The aim of the study was to evaluate serum concentrations of biomarkers of inflammation and endothelial function: tumour necrosis factor alpha (TNF-α), endothelin-1 (ET-1), and N-terminal fragment of pro-atrial natriuretic peptide (NTpro-ANP) in hypertensive and normotensive children., Material and Methods: We studied 63 children aged 13.56 ± 3.73 years, divided into two groups: a group with primary hypertension (n = 50) and a group with renal hypertension (n = 13). The control group consisted of 34 normotensive children aged 12.76 ± 3.96 years. Biomarkers were measured with ELISA tests., Results: ET-1 levels were significantly higher in primary hypertension (9.93 ± 1.73 pg/ml) and renal hypertension (10.77 ± 1.50 pg/ml) in comparison to controls (4.03 ± 0.97 pg/ml), (p < 0.001, p < 0.001, respectively). NT-pro ANP concentrations in primary hypertension (71.03 ± 10.02 pg/ml), and renal hypertension (84.78 ± 6.44 pg/ml) were significantly higher than in the control group (29.62 ± 5.56 pg/ml) (p < 0.001, p < 0.001, respectively). TNF-α concentrations in primary hypertension (8.36 ± 1.60 pg/ml) and renal hypertension (7.35 ± 0.93 pg/ml) significantly exceeded concentrations in controls (4.49 ± 0.93 pg/ml), (p < 0.001, p < 0.001, respectively). ET-1 and NT-pro ANP concentrations in renal hypertension significantly exceeded those in primary hypertension (p = 0.049, p < 0.001, respectively) while TNF-α levels in renal hypertension were significantly lower than in primary hypertension (p = 0.046)., Conclusions: The results of our study show that ET-1, NT-pro ANP, and TNF-a concentrations are increased in hypertension in children. Our investigation indicates significant importance of inflammation and endothelial involvement in hypertension in youth.

Objective: Non-dipper hypertension (HT) confers greater risk compared with dipper HT. Growth differentiation factor 15 (GDF-15) recently emerged as a novel and independent marker of cardiovascular disease, both in diagnostic and prognostic scopes. Our aim was to evaluate the relationship of circadian blood pressure (BP) pattern with serum GDF-15 level in newly diagnosed HT patients without left ventricular hypertrophy., Subjects and Methods: Newly diagnosed non-dipper (n = 66) and dipper (n = 60) HT patients were selected according to 24-h ambulatory BP monitoring (ABPM). The controls comprised healthy normotensive subjects (n = 31). Data was collected through physical examination, laboratory analysis, ABPM, and echocardiography. GDF-15 was measured using ELISA., Results: Greater GDF-15 level was found in the non-dippers compared with the dippers and the controls (557.53 ± 91.7, 513.79 ± 62.86, and 494.44 ± 79.30 ng/L, respectively, p < 0.001). In bivariate linear correlation analysis, GDF-15 correlated positively with glomerular filtration rate (r = 0.180, p =0.030), total cholesterol (r = 0.170, p = 0.038), septal E/E' ratio (r = 0.344, p = 0.001), lateral E/E' ratio (r = 0.366, p < 0.001), nighttime systolic BP (r = 0.166, p = 0.046), and nighttime diastolic BP (r = 0.188, p = 0.024); however, it correlated negatively with septal and lateral E' velocities (r = 0.268, p = 0.005 and r = 0.236, p = 0.013, respectively). Furthermore, GDF-15 level and nighttime diastolic BP remained independently associated with non-dipper HT. In ROC analysis, optimal cutoff value for GDF-15 was 524.6 ng/L with 56.7% sensitivity and 72.4% specificity (AUC: 0.676, 95% CI: 0.580-0.772, p < 0.05)., Conclusion: Our results showed GDF-15 upregulation in the non-dipper HT group. GDF-15 and nighttime diastolic BP were independently associated with the non-dipping pattern. This study may suggest possible utilization of GDF-15 in the prediction of non-dipper HT., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

This study was conducted to explore interactions in the association of the kininogen (KNG1) Ile197Met polymorphism and gender with plasma concentrations of irbesartan in Chinese patients with essential hypertension. A total of 1100 subjects with essential hypertension received a daily oral dose of 150 mg irbesartan for twenty-eight consecutive days. High-performance liquid chromatography-fluorescence (HPLC) was used to detect plasma irbesartan concentrations on day 28. The KNG1 Ile197Met gene polymorphism was determined using high-throughput TaqMan technology. The frequency distribution of KNG1 Ile197Met genotype conformed to the Hardy-Weinberg equilibrium. After 28 days of treatment, patients with the GG genotype had significantly lower irbesartan concentrations (P = 0.033) compared to homozygous TT genotype carriers. After stratifying by gender, male G allele carriers had significantly lower irbesartan concentrations (GG, P = 0.015; TG, P = 0.015, respectively) relative to TT genotype after adjusting for age, region, body mass index (BMI), smoking, and alcohol consumption. However, there was no significant difference in female subjects. A further test for a multiplicative interaction between the KNG1 Ile197Met polymorphism and gender in association with ln-plasma irbesartan concentrations in a multiple linear regression model was also significant (P for interaction = 0.033). This is the first study to suggest that gender may influence the association of the Ile197Met variant of KNG1 with ln-plasma irbesartan concentration. This finding may indicate that the interaction of gender and the KNG1 Ile197Met gene polymorphism can influence plasma trough irbesartan concentrations, which may contribute to a better development of personalized hypertensive treatment in Chinese patients.

Background: Essential arterial hypertension (EAH) in adolescents represents a social burden. The endothelium is involved in the pathogenesis of EAH. Imbalance of key vasoactive factors - namely nitric oxide (NO) and endothelin-1 (ET-1) - is observed, and serotonin (5-HT) release is also impaired. The relationship between the factors and high blood pressure (BP) has been established mainly in preclinical studies and in the adult age. The aim of the present manuscript is to establish the association between plasma ET-1, serum NO and 5-HT, platelet 5-HT levels and BP in male adolescents, analyzing their concentrations in controls, prehypertensive and hypertensive children. Consequently, we want to evaluate ET-1, NO and 5-HT levels as preclinical biomarkers of EAH., Methods: Outpatient adolescents, examined at Children's Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan, were recruited between 26th of May and 25th of September 2016. Predictor variables identified were plasma ET-1, serum NO and 5-HT levels and were evaluated in serum and platelets of case and control groups., Results: Plasma ET-1 and serum 5-HT concentrations in prehypertensive and hypertensive children were higher than in controls, with hypertensive adolescents showing higher levels of both factors compared with prehypertensive adolescents. Platelet 5-HT levels were lower in prehypertensive and hypertensive children compared with controls, while serum NO levels were higher in prehypertensive children than in hypertensive children., Conclusion: Measurable ET-1, NO and 5-HT are related to BP in adolescents and may serve as diagnostic biomarkers of EAH. Furthermore, they could help to better define prehypertensive and hypertensive children., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The CYP17A1 gene, which encodes17α-hydroxylase and 17,20-lyase, has been identified as a common hypertension susceptibility locus in a European population. However, the association between CYP17A1 polymorphisms and hypertension is unclear in the Chinese population as well as in the role of serum 25(OH) D levels. Six single nucleotide polymorphisms (SNPs) in CYP17A1 were genotyped in two stages in a Han Chinese population, and the serum 25(OH) D levels were measured. Analysis in stage 1 showed that the rs1004467 minor G-allele and rs11191548 minor C-allele in CYP17A1 were significantly associated with a decreased risk of hypertension and higher serum 25(OH) D levels (all P < 0.05). The larger sample in stage 2 also showed that a mutation in rs11191548 was significantly associated with a decreased risk of hypertension (adjusted OR = 0.707, 95% CI: 0.553-0.904, P = 0.006). The rs11191548 minor C-allele was associated with higher serum 25(OH) D levels in hypertensive subjects (βadj ± SEM = 0.094 ± 0.949, P = 0.003) and controls (βadj ± SEM = 0.128 ± 1.025, P < 0.001). In conclusion, the rs11191548 CYP17A1 gene mutation was associated with hypertension and the serum 25(OH) D levels in Han Chinese.

Background: The present study sought to explore the relationship of common cardiovascular disease risk factors and noncoding RNAs with essential hypertension (EH)., Methods: A total of 402 EH patients and 402 gender- and age-frequency matched healthy controls were enrolled in this study. Each participant received a questionnaire survey, physical examination and laboratory tests. Quantitative real-time polymerase chain reaction (qPCR) was performed to assess relative expression levels of six noncoding RNAs (NR&#95;027032, NR&#95;034083, NR&#95;104181, miR-126, miR-143 and miR-145) in peripheral blood leucocytes. Multiple logistic regression analysis was used to estimate the risk of having EH between hypertensive and non-hypertensive patients., Results: Analysis showed that participants with anxiety, high body mass index, abdominal obesity and family history of hypertension had higher risk for EH, whereas those with bland diet and occupational physical activities had lower risk for EH. qPCR assays showed that NR&#95;027032 (P = 0.015) and NR&#95;034083 (P = 0.004) were significantly reduced in EH patients compared with controls, whereas NR&#95;104181 (P = 0.007), miR-143 (P = 0.005) and miR-145 (P = 0.015) were significantly elevated. After controlling the cardiovascular risk factors, multivariate analysis showed that lower expression levels of NR&#95;034083 and higher expression levels of NR&#95;104181 and miR-143 were risk factors for EH., Conclusions: EH is a result of environmental and epigenetic factors. Strikingly, NR&#95;034083, NR&#95;104181 and miR-143 may be correlated with the risk for EH development; therefore, epigenetic markers could be used to measure hypertension levels to help elucidate the pathogenesis of EH.

The diagnosis of primary aldosteronism typically requires at least one confirmatory test. The fludrocortisone suppression test is generally accepted as a reliable confirmatory test, but it is cumbersome. Evidence from accuracy studies of the saline infusion test (SIT) and the captopril challenge test (CCT) has provided conflicting results. This prospective study aimed to evaluate the diagnostic accuracy of the SIT and CCT using fludrocortisone suppression test as the reference standard. One hundred thirty-five patients diagnosed with primary aldosteronism and 101 patients diagnosed with essential hypertension who completed the 3 confirmatory tests were included for the diagnostic accuracy analysis. The areas under the receiver-operator characteristics curves of the CCT and SIT were 0.96 (95% confidence interval [CI], 0.92-0.98) and 0.96 (95% CI, 0.92-0.98), respectively, using post-test plasma aldosterone concentration (PAC) for diagnosis. However, the areas under the receiver-operator characteristics curves of the CCT decreased to 0.71 (95% CI, 0.65-0.77) when the PAC suppression percentage was used to diagnose primary aldosteronism. The optimal cutoff of PAC post-CCT was set at 11 ng/dL, resulting in a sensitivity of 0.90 (95% CI, 0.84-0.95) and a specificity of 0.90 (95% CI, 0.83-0.95), which were not significantly different from those of SIT (with PAC post-SIT set at 8 ng/dL, sensitivity: 0.85 [95% CI, 0.78-0.91], P =0.192; specificity: 0.92 [95% CI, 0.85-0.97], P =0.551). In conclusion, both CCT and SIT are accurate alternatives to the more complex fludrocortisone suppression test. Because CCT is safe and much easier to perform, it may serve as a more feasible alternative. When interpreting the results of CCT, PAC post-CCT is highly recommended., (© 2017 American Heart Association, Inc.)

Objective: In order to search for metabolic biomarkers of antihypertensive drug responsiveness, we measured >600 biochemicals in plasma samples of subjects participating in the GENRES Study. Hypertensive men received in a double-blind rotational fashion amlodipine, bisoprolol, hydrochlorothiazide and losartan, each as a monotherapy for one month, with intervening one-month placebo cycles., Methods: Metabolomic analysis was carried out using ultra high performance liquid chromatography-tandem mass spectrometry. Full metabolomic signatures (the drug cycles and the mean of the 3 placebo cycles) became available in 38 to 42 patients for each drug. Blood pressure was monitored by 24-h recordings., Results: Amlodipine (P values down to 0.002), bisoprolol (P values down to 2 x 10-5) and losartan (P values down to 2 x 10-4) consistently decreased the circulating levels of long-chain acylcarnitines. Bisoprolol tended to decrease (P values down to 0.002) the levels of several medium- and long-chain fatty acids. Hydrochlorothiazide administration was associated with an increase of plasma uric acid level (P = 5 x 10-4) and urea cycle metabolites. Decreases of both systolic (P = 0.06) and diastolic (P = 0.04) blood pressure after amlodipine administration tended to associate with a decrease of plasma hexadecanedioate, a dicarboxylic fatty acid recently linked to blood pressure regulation., Conclusions: Although this systematic metabolomics study failed to identify circulating metabolites convincingly predicting favorable antihypertensive response to four different drug classes, it provided accumulating evidence linking fatty acid metabolism to human hypertension.

This study aimed to test the effects of xuezhikang, a cholestin extract that contains statin-like components, on arterial stiffness in patients with essential hypertension. One hundred hypertensive patients from the Chinese PLA General Hospital were randomly allocated to receive xuezhikang (1200 mg/day, orally) or placebo (same capsules containing only pharmaceutical excipients). Physical examination outcomes, lipid profile, high sensitivity C-reactive protein (hs-CRP) levels, matrix metalloproteinases-9 (MMP-9) levels, and arterial outcomes, including stiffness parameter (β), pressure-strain elasticity modulus (Ep), arterial compliance (AC), augmentation index (AI), and one-point pulse wave velocity (PWVβ) were obtained at baseline and after 6 months of the intervention. Xuezhikang significantly reduced β (8.4±3.1 vs 6.8±2.1, P=0.007), Ep (122.8±43.9 vs 100.7±33.2, P=0.009), PWVβ (6.7±1.2 vs 6.1±1.0, P=0.013), low-density lipoprotein cholesterol (3.4±0.6 vs 2.9±0.5, P=0.001), hs-CRP [2.1 (0.4-10.0) vs 1.4 (0.3-4.1), P=0.020], and MMP-9 (17.2±2.4 vs 12.7±3.8, P <0.001) compared to baseline. The placebo had no effect on these parameters. The changes of PWVβ in the xuezhikang group was significantly associated with the changes of hs-CRP and MMP-9 (r=0.144, P=0.043; r=0.278, P=0.030, respectively) but not with lipid profile changes. Our research showed xuezhikang can improve the parameters of arterial stiffness in hypertensive patients, and its effect was independent of lipid lowering.

Background: Atherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance., Methods: A total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 (Lp-PLA2) in each group were detected, and the related risk factors were also statistically analyzed., Results: Fibrinogen (Fbg) was the most significant independent risk factor in acute coronary syndrome (ACS) group (odds ratio [OR]: 22.242, 95% confidence interval [CI]: 6.458-76.609, P< 0.001) with the largest absolute value of the standardized partial regression coefficient B' (b': 1.079). Lp-PLA2 was the most significant independent risk factor in stroke group (OR: 13.699, 95% CI: 5.236-35.837, P< 0.001) with b' = 0.708. Uric acid (UA) was the most significant independent risk factor in renal damage group (OR: 15.307, 95% CI: 4.022-58.250, P< 0.001) with b' = 1.026., Conclusions: Fbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence of ACS, ischemic stroke, and renal damage in EH patients, respectively.

Despite the easy and reliable methods of blood pressure measurement, the screening of essential hypertension (EH) is usually ignored due to delayed onset of symptoms. A probe into the biochemical changes in hypertension would serve as a welcome asset to provide insight into the mechanistic aspects of EH. Filtered serum samples from 64 EH patients and 59 healthy controls (HC) were analysed using 800 MHz nuclear magnetic resonance (NMR) spectroscopy. Application of principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) following receiver operating characteristic (ROC) curve of NMR data reveals significantly perturbed metabolites: alanine, arginine, methionine, pyruvate, adenine, and uracil. This set of metabolites correctly classified 99% of cases from HC and also showed excellent correlation in both isolated elevated diastolic blood pressure (DBP) cases and combined elevated systolic-diastolic blood pressure cases. Proton NMR metabolomics of EH may prove helpful in defining associated biomarkers and serve as an alternate diagnostic tool with judicious clinical assessment.

MicroRNAs (miRs) are key posttranscriptional regulators of gene expression in all eukaryotic cells and have a vital role in the evolution of hypertension and cardiovascular remodelling and, therefore, have emerged as potential biomarkers for cardiovascular disease. We assessed 240 participants, including 60 healthy volunteers with normal carotid intima-media thickness (nCIMT), 60 healthy volunteers with increased CIMT (iCIMT), 60 hypertensive patients with nCIMT and 60 hypertensive patients with iCIMT. All patients underwent measurements of CIMT, carotid-femoral pulse wave velocity (cfPWV) and ambulatory blood pressure (BP) monitoring. Plasma miR-92a expression was quantified by real-time reverse transcription PCR. Correlations between miR-92a expression and BP parameters, CIMT and cfPWV were assessed using the Spearman correlation coefficient. We observed the lowest miR-92a expression (24.59±1.30 vs 27.76±2.13 vs 29.29±1.89 vs 33.76±2.08; P<0.001) in healthy controls with nCIMT, followed by healthy controls with iCIMT, then hypertensive patients with nCIMT and the highest expression in hypertensive patients with iCIMT. Additionally, MiR-92a levels showed a significant positive correlation with 24-h mean systolic BP (r=0.807, P<0.001), 24-h mean diastolic BP (r=0.649, P<0.001), 24-h mean pulse pressure (PP) (r=0.697, P<0.001), 24-h daytime PP (r=0.654, P<0.001), 24-h nighttime PP (r=0.573, P<0.001), CIMT (r=0.571, P<0.001) and cfPWV (r=0.601, P<0.001). Our data present significant evidence that circulating miR-92a represents a potential noninvasive atherosclerosis marker in essential hypertensive patients.

Essential hypertension (EH) is a risk factor for some severe diseases. This study aimed to screen out serum special proteins and seek interaction between them, which would provide new therapeutic targets and elucidate the comprehensive pathophysiological mechanism for EH. Patients with EH (Group A, n = 47) and healthy controls (HC) (Group B, n = 47) were recruited in this study. Serums from the two groups were analyzed with isobaric tags for relative and absolute quantitation coupled two-dimensional liquid chromatography followed by electrospray ionization-tandem mass spectrometry technique, while the candidate special proteins were verified with ELISA and western blot. A total of 404 proteins were identified, of which 30 proteins were upregulated (>1.2-fold, p < 0.05) and 81 proteins were downregulated (<0.833-fold, p < 0.05) compared with HC group. With GO, KEGG analysis, and literature retrieval, 4 proteins, cathepsin G, transforming growth factor beta-1, hyaluronidase-1, and kininogen-1, were found jointly involved in the renin-angiotensin-aldosterone system and kallikrein-kinin system. The profiles of these 4 candidate proteins were confirmed with ELISA and western blot. The concentration variation of these 4 proteins could better predict the occurrence and illustrate the pathophysiological mechanism of EH. And their discovery may help pave the way for exploring new therapies of EH.

The aim of the study was the assessment of the impact of supplementation with folic acid on the concentration of homocysteine, total cholesterol (TC), HDL- and LDL-cholesterol, triglycerides (TG), apoprotein AI (apoAI) and apoprotein B (apoB) in patients suffering from primary hypertension. The examined group comprised 42 patients suffering from primary hypertension. All examined patients underwent laboratory tests as follows: concentration of homocysteine, folic acid, TC, LDL-cholesterol, HDL-cholesterol, TG, apoAI and apoB. All patients were orally administered with 15 mg of folic acid per day for 45 d. After this period, all laboratory tests were repeated. Homocysteine concentration was measured by the FPIA method, concentrations of apoAI and apoB were measured by the nephelometric method, and other parameters with routine methods. After administration of 15 mg of folic acid to patients with primary hypertension, a considerable decrease in the concentration of homocysteine was observed in parallel with a substantive growth of HDL-cholesterol, as well as apoprotein AI concentrations and a reduction of the apoprotein B concentration. Results of statistical analysis indicated a significant correlation between the decline in homocysteine concentration and the increase in HDL-cholesterol concentration, as well as between the increase of folic acid concentration and the increase in apoAI concentration in patients following the intake of folic acid. The drop in homocysteine concentration through the supplementation with folic acid can cause quantitative changes in the lipid and lipoprotein parameters which, in consequence, may lead to the mitigation of risk concerning the development of atherosclerosis.

Objective: To investigate the relationship between the level of serum cystatin C (s-CC) and reverse-dipper blood pressure (BP) pattern., Design: Cross-sectional study., Setting: Single centre., Participants: A total of 718 hypertensive patients were eventually recruited from cardiac clinics between 2012 and 2014 in the Second Affiliated Hospital, Xi'an Jiaotong University. They were diagnosed as essential hypertension according to their casual office records of systolic blood pressure (SBP) and/or diastolic blood pressure (DBP). Patients were excluded if they were <18 or >90 years old, under antihypertensive treatment, night workers, suffering from acute stroke or myocardial infarction within the past 6 months, diagnosed as secondary hypertension, sleep apnoea or other sleep disorders, renal failure, cardiac failure, chronic obstructive pulmonary disease, women during pregnancy or intolerant to the ambulatory BP monitoring (ABPM)., Measurement: The selected patients were evaluated with 24 hours ABPM. Peripheral venous blood samples were collected to evaluate the s-CC levels by ELISA., Methods: The distribution of hypertensive patients with different levels of s-CC among each circadian BP pattern group was analysed using analysis of variance. Multinomial logistic regression analysis was applied to explore the relationship between the relevant variables and ABPM results., Results: S-CC level in reverse-dipper group (1.19±0.53 mg/L) was increased significantly when compared with dipper group (1.06±0.36 mg/L) (p=0.021). In addition, after multinomial logistic regression analysis, s-CC (OR 1.717; 95% CI 1.033 to 2.854; p=0.037) and diabetes (OR 2.313; 95% CI 1.401 to 3.821; p=0.01) were significantly different between the reverse-dipper group and dipper group. On the other hand, the decline rate of nocturnal SBP (r=-0.117; p=0.002) and DBP (r=-0.089; p=0.018) was negatively correlated with the s-CC level., Conclusions: The s-CC level was significantly higher in the reverse-dipper group than the dipper group and that s-CC was associated with the reverse-dipper pattern of BP examined with 24 hour ABPM., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Inflammation has been shown to play a pivotal role in the pathogenesis and development of hypertensive vascular injury. Neopterin is a novel marker of immune activation produced mainly by activated macrophages. Few data are available to show the association between neopterin and vascular function in hypertension. The present study was designed to investigate the relationship between neopterin levels related to arterial stiffness and endothelial function in patients with hypertension, and their changes after blood pressure-lowering treatment. Twenty-four hypertensive patients and 30 age- and gender-matched healthy volunteers were recruited. Plasma neopterin levels were higher in hypertensive patients compared with their counterparts (log-neopterin: 0.77±0.18 versus 0.61±0.16, P=0.003). Increased neopterin levels were correlated with increased brachial-ankle pulse wave velocity (baPWV; control: r=0.659, P<0.001; hypertension: r=0.487, P=0.021), and inversely associated with impaired brachial flow-mediated dilation (FMD; control: r=-0.735, P<0.001; hypertension: r=-0.557, P=0.005). Fifteen hypertensives received 3 months of standard antihypertensive treatment. Three months later, their plasma neopterin levels decreased (log-neopterin: 0.63±0.17 versus 0.50±0.19, P=0.001), whereas arterial elasticity (baPWV: 1764±101 versus 1685±96 cm s(-1), P=0.272) and endothelial function (FMD: 5.92±1.43% versus 7.73±1.31%, P<0.05) were improved. The decline in neopterin levels was linearly correlated with baPWV decrease (r=0.800, P<0.001), FMD improvement (r=0.670, P=0.006) and blood pressure reduction (r=0.548, P=0.042). Our present study demonstrated for the first time that neopterin is closely correlated with vascular dysfunctions, and measurement of plasma neopterin levels might be used as a surrogate biomarker for the clinical evaluation of vascular damage and risk stratification of future atherosclerotic cardiovascular disease in patients with hypertension.

The critical role of metabolic abnormality in hypertension is increasingly recognized, but its biomarkers are not clearly identified. In this study, 47 chemical compounds recorded by literature were employed as target metabolites of essential hypertension (EH). We detected their content in the plasma of EH patients and healthy subjects by using the Multiple Reaction Monitoring-Mass Spectrometry (MRM-MS). After screening the most altered compounds, acupuncture was used to treat patients for 3 months and these plasma metabolites were tested again. The results showed that oleic acid (OA) and myoinositol (MI) were the most important differential metabolites between the hypertensive plasma and the healthy plasma. They were also closely correlated with 24-hour blood pressure and nocturnal dipping. Moreover, plasma OA and MI could be restored to normal levels by acupuncture, accompanying with reduction of 24-hour systolic and diastolic blood pressure [from 145.10 ± 9.28 mm Hg to 140.70 ± 9.59 mm Hg (P < 0.0001), and 88.35 ± 7.92 mm Hg to 85.86 ± 7.95 mm Hg (P = 0.0024), respectively] and improvement of circadian blood pressure rhythm. This study demonstrated that plasma OA and MI were potential hypertension biomarkers and they could be used to preliminarily assess the treating effects such as acupuncture.