Essential Hypertension Group Research Articles

No effect of anti‐hypertensive treatment during the metaboreflex in patients with essential hypertension

In healthy subjects (HS), when the muscle metaboreflex (MM) is activated, the target mean blood pressure (MBP) is reached thanks to cardiac output (CO) increments, whilst systemic vascular resistance (SVR) plays a minor role 1. Differently, in essential hypertension (EHT) hemodynamics during the MM has been often reported to be dys‐regulated, with exaggerated SVR response (i.e. arteriolar vasoconstriction) and reduced CO 2. We tested the hypothesis that standard anti‐hypertensive treatment could improve this abnormal hemodynamics. 20 patients in pharmacological treatment for EHT (10 females; age 54.5±10.4 yrs, time since diagnosis 8.5±6.9 yrs) participated in this study together with a control group of 20 age‐matched HS. At baseline (BAS), they underwent randomly assigned the following protocol to study the MM activity: 1) post‐exercise muscle ischemia (PEMI), and 2) control exercise recovery CER) test. Exercise was dynamic handgrip performed at 30% of the maximum previously assessed. The EHT group performed again the test at least 7 days later (interval 7–15 days) after pharmacological wash‐out (WHT). Response to the MM for each cardiovascular parameter was assessed as PEMI minus CER level. Hemodynamic variables were evaluated by impedance cardiography. Results demonstrated that in EHT, SVR response did not change at the BAS and at the WHT (338.0±452.7 vs. 371.8±465.3 dynes•s‐1•cm‐5 at BAS and at WHT respectively). Moreover, EHT showed higher SVR response than HS (20.9±399.6 dynes•s‐1•cm‐5, p<0.05 vs. both the BAS and the WHT test). However, the MBP response was similar between groups and conditions. Likewise CO was not different between groups. It was concluded that the anti‐hypertensive treatment was not able to counteract the arteriolar vasoconstriction and the increased SVR response experienced by ETH patients during the MM. Further study is warranted to better understand what causes the hemodynamic abnormalities of EHT patients during the MM activation.Support or Funding InformationThis study was supported by the University of Cagliari and the Italian Ministry of Scientific Research.

Взаимосвязи между форменными элементами крови, половыми гормонами и системой ПОЛ у женщин с эссенциальной гипертонией

У женщин, больных гипертонической болезнью, существуют тесные корреляционные взаимосвязи между различными форменными элементами крови и уровнем артериального давления, показателями деятельности сердца, тестами, характеризующими состояние гемодинамики, тромбодинамики и коагуляционной активности крови. Цель исследования - изучение роли различных форменных элементов крови и их соотношения в регуляции уровня эстрогена, прогестерона и пролактина, ТБК-активных продуктов и антиоксидантной активности у больных гипертонической болезнью. Методика. Исследования проведены на 72 больных гипертонической болезнью, контрольную группу составили 12 женщин с нормальным артериальным давлением. Больные были разделены на 2 группы: в 1-ю группу вошли 37 пациенток с гипертонической болезнью II стадии, находящиеся на гипотензивной терапии, 2-ю - составили 35 женщин с гипертонией II стадии, которые кроме медикаментозного лечения, регулярно проходили курсы кинезотерапии на протяжении 2-3 лет. Результаты. Методом корреляционного анализа установлено, что у здоровых женщин и больных гипертонической болезнью, изучаемые взаимосвязи могут носить как однонаправленный, так и разнонаправленный характер. У здоровых женщин обнаруживается прямая связь между количеством лимфоцитов и уровнем прогестерона и обратная - с уровнем пролактина. Прямая связь также выявлена между индексом нейтрофилы/базофилы и прогестероном. При гипертонии у больных 1-й группы обнаруживается прямая связь между количеством эритроцитов и прогестероном, числом эозинофилов и пролактином; индекса лимфоциты/эозинофилы с эстрадиолом; индексов нейтрофилы/моноциты, нейтрофилы/базофилы и лимфоциты/базофилы с прогестероном. Отрицательная корреляция выявляется между индексами нейтрофилы/лимфоциты и нейтрофилы/эозинофилы с пролактином. У больных 2-й группы обнаружены прямые корреляционные связи между абсолютным количеством лейкоцитов, нейтрофилов и эозинофилов и отрицательная связь индекса эритроциты/лейкоциты с пролактином. При оценке корреляционных взаимосвязей показателей крови с показателями активности оксидантно/антиоксидантной системы показано, что у здоровых женщин существуют положительные связи между числом моноцитов с содержанием ТБК-продуктов и активностью антиоксидантной системы; эозинофилов с активностью антиоксидантной системы; индекса лейкоциты/тромбоциты с уровнем ТБК-продуктов. При гипертонической болезни в группе без кинезотерапии (1-я группа) выявлена отрицательная взаимосвязь между общим числом эритроцитов и показателями активности антиоксидантной системы. Заключение. Практически все форменные элементы крови и различные их взаимоотношения у здоровых и больных гипертонической болезнью играют существенную роль в регуляции уровня эстрадиола, прогестерона, пролактина и состояния системы перекисного окисления липидов - антиоксидантная активность. Close correlations exist between different blood cells (BC), blood pressure, heart function, results of hemodynamics tests, thrombodynamics, and blood coagulation in women with hypertension. Aim. The study addressed the role of different BCs and their combinations in regulation of estrogen, progesterone, prolactin, TBA-reactive substances (TBARS), and antioxidant activity (AOA) in hypertensive patients. Methods. The study included 12 healthy women (control) and 72 patients with essential hypertension (EH). Patients with EH were divided into two groups; the first group (EH-1) consisted of 37 women with stage II EH receiving an antihypertensive therapy and the second group (EH-2) consisted of 35 women who, in addition to the drug therapy, yearly underwent 3-4 courses of kinesitherapy for 2-3 year on a regular basis. Results. Both in healthy women and patients of the EH-1 and EH-2 groups, the studied relationships were either positive or negative. In healthy women, LYM positively correlated with progesterone and inversely correlated with prolactin, and the NEU/BAS ratio positively correlated with progesterone. In patients of the EH-1 group, there were positive correlations of RBC with progesterone; EOS with prolactin; and LYM/EOS with estradiol; and NEU/MON, NEU/BAS, and LYM/BAS with progesterone. The NEU/LYM and NEU/EOS ratios inversely correlated with prolactin. In patients of the EH-2 group, there were positive correlations of WBC, NEU, and EOS with prolactin and inverse correlations of the RBC/WBC ratio with prolactin. Evaluation of correlations between blood indexes and the oxidant/antioxidant system showed that in healthy women, there were positive correlations of the MON count with TBARS and AOA; EOS with AOA; and the WBC/PLT ratio with TBARS. Patients of the EH-1 group showed a negative correlation of the total RBC count with AOA. Conclusion. In both healthy subjects and EH groups, almost all BCs and their relationships play a significant role in regulation of estradiol, progesterone, prolactin, and the lipid peroxidation/AOA system.

Retinol-binding protein 4 is closely correlated to blood pressure level and E/A in untreated essential hypertension patients.

Hypertension, a common chronic disease, is a leading cause of death and other cardiovascular diseases. Recent studies show that an inflammatory factor named retinol binding protein 4 (RBP4) was increased with cardiovascular diseases. However, the relationship between RBP4 and hypertension in patients remains unclear. The study cohort was composed of patients with essential hypertension (EH) and healthy control (HC) subjects from the Second Affiliated Hospital of Nanjing Medical University [2017-2019]. The levels of RBP4 and echocardiography were compared in the current study. Statistical differences between two groups were analyzed using unpaired Student's t-tests and the correlation between the two variables adopts Pearson correlation analysis. SPSS 23.0 was used for all statistical analysis. Analysis of patient plasma samples revealed that RBP4 in EH group was greater than HC group (P<0.05). The area under the ROC curve was 0.717. Specificity and sensitivity were 80.4% and 60.8%, respectively. RBP4 had positive correlation with left ventricular systolic diameter (LVDs), interventricular septal thickness (IVS) and left ventricular posterior wall thickness (LVPW), negative correlation with left ventricular shortening fraction (FS) and ejection fraction (EF) (P<0.05), and no correlation with left ventricular end-diastolic diameter (LVDd) (P>0.05). RBP4 was closely related with E/A, evaluation method of left ventricular diastolic function, in patients with EH. RBP4 levels are closely correlated with blood pressure (BP) levels and might be involved in the regulation of left ventricular diastolic function in patients with EH.

Characteristics of abdominal fat distribution in patients with primary aldosteronism

Objective To compare the abdominal fat distribution in patients with primary aldosteronism (PA) and essential hypertension (EH), and to analyze the correlation between abdominal fat area and indexes such as glycolipid metabolism and insulin resistance. Methods Forty-five PA and 55 EH patients were collected from inpatients in the First Affiliated Hospital of Zhengzhou University for suspicious secondary hypertension, from September 2016 to February 2019. All patients received quantitative computed tomography to measure the total abdominal fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) when receiving adrenal CT detection. Visceral obesity was defined as VFA≥130 cm2. The percentage of visceral fat area in total abdominal fat area (V%=VFA/TFA), the ratio of visceral fat area to subcutaneous fat area (V/S=VFA/SFA) and the percentage of visceral obesity were calculated. Results TFA and VFA in EH group were higher than those in PA group matched by age, gender, and body mass index (BMI, all P<0.01), and there were no statistically significant differences in SFA, V%, V/S, and the percentage of visceral obesity between the two groups. In PA group, TFA and VFA were positively correlated with homeostasis model assessment of insulin resistance index (P<0.01), TFA was positively correlated with triglycerides (TG) and low density lipoprotein-cholesterol, while SFA was positively correlated with TG (all P<0.05). Conclusion Compared with EH patients matched by age, gender, and BMI, TFA and VFA in PA patients are lower. Abdominal fat area is associated with insulin resistance and blood lipids in PA patients, while VFA exerts a greater effect on insulin resistance than that of TFA and SFA. Key words: Primary aldosteronism; Abdominal fat area; Insulin resistance; Quantitative computed tomography

Vessel wall stiffness parameters and left ventricle remodeling in patients receiving renal replacement therapy

Aim. To perform a comparative assessment of vessel wall stiffness parameters and left ventricle (LV) remodeling in groups of patients with arterial hypertension (AH) receiving renal replacement therapy (RRT) and patients with hypertensive heart disease. Material and methods. One hundred fifty eight people were examined: 32 patients on program hemodialysis (PG), 37 — after kidney transplantation (KT), 69 — with essential hypertension and 20 healthy volunteers. All patients underwent 24-hour blood pressure (BP) monitoring with an assessment of the parameters of daily vessel wall stiffness, aortic pressure and Mand B-mode echocardiography. Results. In groups of patients with PG and after KT, the central and peripheral blood pressure did not differ significantly. When comparing with the group of essential hypertension in RRT patients, with similar values of office systolic and diastolic BP, higher average values of peripheral and central BP were determined. An increase in the values of the pulse wave velocity in the aorta of more than 10 m/s was observed only in RRT patient groups. In all groups of patients with AH, BP and vessel wall Conclusion. Patients receiving RRT have higher values of the average daily pulse wave velocity in the aorta, central BP and a longer period of an increase in the pulse wave velocity in the aorta during the day, higher vessel wall stiffness values, and less pronounced LV spherification than in patients with hypertensive heart disease and comparable values of office BP.

The Association between a 24-Hour Blood Pressure Pattern and Circadian Change in Plasma Aldosterone Concentration for Patients with Aldosterone-Producing Adenoma.

The absence of nocturnal blood pressure (BP) decline is associated with hypertensive complications. Data regarding circadian BP patterns in patients with aldosterone-producing adenoma (APA) are limited and equivocal. We evaluated the circadian BP profile in patients with APA and its relationship with the circadian aldosterone rhythm. BP in patients with APA and in those with essential hypertension (EH) were assessed through in-hospital 24-h ambulatory blood pressure monitoring. Over a 24-h in-hospital period, plasma aldosterone levels taken at midnight, 0400, 0800, 1200, 1600, and 2000 h were measured. To evaluate a correlation between BP and hormone rhythm, we included 27 patients with APA (APA group) and 27 patients with EH (EH group). Both groups had similar age, sex ratio, body mass index, duration of hypertension, family history of hypertension, and lipid profiles. The day-night BP differences in both patient groups were similar, whether expressed as absolute values or percentages. The proportions of patients with dipping BP profiles were also comparable (APA group, 5 of 27; EH group, 7 of 27; χ2 = 0.429; P = 0.513). At each time point, APA group plasma aldosterone concentrations (PACs) were higher than those of the EH group. A circadian change in relation to PAC was observed in both groups. A correlation between PAC and BP was statistically nonsignificant in most study patients in either group. Our data indicated that the circadian BP pattern was not associated with a change in PAC levels in patients with APA.

Circulating CTRP1 Levels Are Increased and Associated with the STOD in Essential Hypertension in Chinese Patients.

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.

Cardiovascular risk in primary aldosteronism: A systematic review and meta-analysis.

Aim:This study aimed to evaluate whether the increased cardiovascular risk and the incidence of cerebrovascular (CCV) events in hypertensive patients were related to primary aldosteronism (PA).Methods:The PubMed, EmBase, and the Cochrane Central Register of Controlled Trials were searched to evaluate the risk of CCV in PA patients and compared to essential hypertension (EH) patients. The mean differences (MD) and the risk ratios (RR) were calculated to assess the risk of main outcomes, such as stroke, coronary artery disease, left ventricular hypertrophy (LVH), levels of systolic blood pressure (SBP), diastolic blood pressure (DBP), blood glucose, and urinary potassium.Results:We identified 31 individual studies including 4546 patients in PA group and 52,284 patients in EH group. Our results revealed that PA was significantly associated with increased risk of stroke (RR=2.03, 95% CI = 1.71–2.39, Pheterogeneity = .331, I2 = 12.7%), coronary artery disease (RR = 1.67, 95% CI = 1.23–2.25, Pheterogeneity = .043, I2 = 48.3%), and LVH (RR = 1.54, 95% CI = 1.29–1.83, Pheterogeneity = .004, I2 = 62.6%) when compared with those in the EH group. Moreover, PA group had significantly increased levels of SBP (WMD = 4.14, 95% CI = 2.60–5.68, Pheterogeneity < .001, I2 = 84.3%), DBP (WMD = 2.65, 95% CI = 1.83–3.47, Pheterogeneity < .001, I2 = 77.7%), and urinary potassium (SMD = 0.04, 95% CI = -0.03–0.11, Pheterogeneity = .827, I2 = 0%) when compared to EH group. However, no significant difference was observed in the levels of blood glucose between the groups.Conclusions:These findings suggested that PA significantly increased the risk of cardiac and cerebrovascular complications. In addition, patients with PA might benefit from a periodic assessment of CCV risk.

KLHL3 single-nucleotide polymorphism is associated with essential hypertension in Chinese Han population.

Hypertension, including secondary and essential hypertension (EH) variants, is a multifactorial disease, affecting more than one billion people worldwide. Secondary hypertension results from mutations in the putative gene KLHL3 (Kelch-like protein 3); however, it has not been reported whether the KLHL3 gene polymorphisms are associated with EH. Here, we investigated the association between KLHL3 (rs2301708 and rs7444370) polymorphisms and EH in the Chinese Han population.This case–control study included 522 subjects—260 patients with EH and 262 normotensive controls matched for age, gender, body mass index (BMI), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), and levels of Na+, K+, and Cl−. The distribution of functional rs2301708 and rs7444370 polymorphisms within the KLHL3 gene was assessed through polymerase chain reaction (PCR) and restriction-fragment length polymorphism (RFLP).There was no significant difference in allelic and genotypic frequencies of KLHL3 rs2301708 between the EH and normotensive groups; however, the rs7444370 T allele and CT genotype in females was significantly associated with a protective effect against EH (P = .001, P = .002; P = .019, P = .052), and the haplotype CT of rs2301708 and rs7444370 among females in the EH group was less than in the normotensive group (P = .000; P = .007).The KLHL3 rs7444370 variant could be a protective factor in the pathogenesis of females’ EH.

SUN-366 The Optimal Cutoff Value for Basal Plasma Aldosterone Concentration Suspected as Primary Aldosteronism Distributed According to Aldosterone-Renin Ratio and Confirmatory Tests Response

Aldosterone/renin ratio (ARR) >200 [(pg/mL)/(ng/mL/hr)] is a widely accepted threshold to screen for primary aldosteronism (PA) (1). Because using ARR as a sole index leads to excessive inclusion of cases with low renin essential hypertension, it may be desirable to combine ARR with a minimum plasma aldosterone concentration (PAC) value to increase diagnostic accuracy, but currently there is no consensus on the minimum PAC value. Therefore, we carried out a single-center, retrospective study to investigate optimal PAC cutoff to be used with ARR >200. The subjects were 385 individuals (240 female and 145 male) with ARR >200 who underwent PA screening tests between 2010 and 2015. They were diagnosed according to the Japan Endocrine Society guideline (2) with either PA or essential hypertension (EH). The optimal cutoff value for baseline PAC that best distinguished between PA and EH was calculated. Of the 385 subjects, 297 were diagnosed with PA and 88 with EH. Of 194 PA patients who underwent adrenal venous sampling, 141 exhibited aldosterone hypersecretion from both adrenal glands, and 53 were diagnosed with aldosterone-producing adenoma (APA) on the basis of adrenalectomy. There was no difference between the PA (n = 194) and EH (n = 88) groups in terms of age, body mass index, or glucose and lipid profiles. Receiver operating characteristic curve analysis found that the optimal baseline PAC for distinguishing between PA and EH was 171 pg/mL, which provided a sensitivity of 0.75 and a specificity of 0.65 (area under the curve 0.718 and 95% confidence interval 0.656-0.780). Baseline PAC was ≥171 pg/mL for all 53 subjects with APA (minimum 171 pg/mL, maximum 943 pg/mL, and median 341 pg/mL), and if the cutoff value for baseline PAC is set at 171 pg/mL, it is unlikely that significant cases of APA will be overlooked in PA screening using ARR >200. Combining PAC ≥171 pg/mL with ARR >200 increases diagnostic accuracy for PA without compromising APA detection. Reference: (1)Hiramatsu et al., Arch Intern Med. 1981 Nov;141(12):1589-93. (2) Nishikawa et al., Endocr J. 2011;58(9):711-21.

The Relationship Between Serum Endocan Level and Aortic Elastic Properties in Patients With Newly Diagnosed Essential Hypertension

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.

Emotional disorders in patients with controlled hypertension

To conduct a comprehensive examination of patients with controlled hypertension, including assessment of the functional state of the cardiovascular system, vegetative and psycho-emotional status. The study involved 80 patients (51 men, 29 women) divided into 2 groups: 60 patients with essential hypertension (EH) without concomitant severe pathology and normal blood pressure during the preceding 3 months (group 1) and 20 healthy patients without EH (group 2). Anthropometric parameters (height, weight, body mass index), parameters of central hemodynamic (heart rate, systolic and diastolic blood pressure), vegetative status (vegetative Kerdo index), mental and emotional status (SCL-90R, Leonhard questionnaire, HADS, SF-36, MPQ) were assessed. There were significant differences in the psycho-emotional status between patients with hypertension and patients with normal blood pressure. Significant correlations between anthropometric indicators, the state of the autonomic nervous system and psycho-emotional status of patients with hypertension were shown.

Association of ACE2 genetic polymorphisms withhypertension-related target organ damages in south Xinjiang

Essential hypertension (EH) is a principal contributing factor inworldwide cardiovascular disease mortality. Although interventions that minimizeenvironmental risk factors for EH are associated with reduced cardiovasculardisease, such approaches are limited for individuals with high genetic EH risk. Inthis study, we investigated possible associations between ACE2 polymorphisms andhypertension-related target organ damages in south Xinjiang, China. Four hundred andtwo hypertensive patients were enrolled as study participants in an EH group, and233 normotensive individuals were enrolled as control subjects. Participants wererecruited from the south Xinjiang region. Fourteen ACE2 polymorphisms were genotypedby matrix-assisted laser desorption ionization time-of-flight mass spectrometry.Risk genotypes of rs2074192 (TT+CT, OR = 1.72, 95% CI: 1.17–2.53), rs2106809 (TT,OR = 1.71, 95% CI: 1.13–2.58), rs4240157 (CC+CT, OR = 1.99, 95% CI: 1.17–3.41),rs4646155 (TT+CT, OR = 1.94, 95% CI: 1.06–3.54), rs4646188 (TT+CT, OR = 3.25, 95%CI: 1.95–5.41), rs4830542 (CC+CT, OR = 1.88, 95% CI: 1.10–3.23), and rs879922(CC+CG, OR = 4.86, 95% CI: 2.74–8.64) were associated with EH. Hypertensive patientscarrying the control genotype of rs2074192 (CC, OR = 2.37, 95% CI: 1.28–4.39) wereassociated with CAS ≥50%, while those carrying a high-EH-risk genotype of rs4240157(OR = 2.62, 95% CI: 1.24–5.54), rs4646155 (OR = 2.44, 95% CI: 1.16–5.10), orrs4830542 (CC+CT, OR = 2.20, 95% CI: 1.03–4.69) were associated with atrialfibrillation (AF), larger left atrial diameter, and higher levels ofrenin–angiotensin–aldosterone system (RAAS) activation (renin and angiotensin I/II).In conclusion, the ACE2 variant rs2074192 was associated with EH and EH with CAS≥50%, while 3 ACE2 variants (rs4240157, rs4646155, and rs4830542) were associatedwith EH- and hypertension-related AF and left atrial remodeling in south Xinjiang,China.

Risk of severe erectile dysfunction in primary hyperaldosteronism: A population-based propensity score matching cohort study

An elevated plasma aldosterone level has been reported as an independent risk factor for severe erectile dysfunction in men. The aim of this study was to explore whether primary hyperaldosteronism patients experience erectile dysfunction after targeted treatment. We conducted a population-based cohort study of men with newly identified primary hyperaldosteronism/aldosterone-producing adenoma from January 1, 1997, to December 31, 2009. Men with essential hypertension and normotension were matched to the primary hyperaldosteronism group according to propensity score matching. We identified 1,067 men with primary hyperaldosteronism (mean age, 46.7 ± 12.8 years) and matched them with the same number of men with essential hypertension or normotension. During the mean follow-up interval of 5.4 years, the incident rates of total erectile dysfunction were 5.7, 3.9, and 3.1 per 1,000 person-years for the primary hyperaldosteronism, essential hypertension, and normotension groups, respectively. Men with primary hyperaldosteronism exhibited a higher risk of erectile dysfunction compared with men with normotension (competing risks hazard ratio, 1.83), and no difference was seen in comparison with men who have essential hypertension. After adrenalectomy, men who have primary hyperaldosteronism had a higher risk of exhibiting severe erectile dysfunction compared with men who have essential hypertension (competing risks hazard ratio, 2.44) or normotension (competing risks hazard ratio, 2.90). Men with primary hyperaldosteronism reported a higher incidence of severe erectile dysfunction than normotension controls despite targeted treatment. The risk of severe erectile dysfunction increased after men who have primary hyperaldosteronism underwent adrenalectomy. This result raises the possibility of severe erectile dysfunction after adrenalectomy and calls for a prospective large-scale study of men who have aldosterone-producing adenoma regarding their erectile function both before and after adrenalectomy.

Serine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension.

Serine hydroxymethyltransferase 1 (SHMT1) is an enzyme involved in folic acid metabolism and is known to contribute to the development of hypertension. We evaluated the relationship between SHMT1 promoter methylation and essential hypertension (EH). Quantitative methylation-specific polymerase chain reaction was used to measure the SHMT1 promoter methylation level in 241 EH patients and 288 age- and gender-matched healthy individuals. The diagnostic value of SHMT1 promoter hypermethylation was analyzed using a receiver operating characteristic (ROC) curve. The Gene Expression Omnibus (GEO) database and dual-luciferase reporter assay were used to validate our findings. Compared with the control group, significant differences in SHMT1 promoter methylation were found in both EH and hyperhomocysteinemia groups (P<0.001 and P=0.029, respectively). The area under the curve of the diagnosis of SHMT1 promoter hypermethylation for EH was 0.808, with a sensitivity and specificity of 73.9% and 77.8%, respectively. The risk of SHMT1 promoter hypermethylation was significantly higher in the >65-year group than in the ≤65-year group (odds ratio=3.925; 95% confidence interval=2.141-7.196). In addition, GEO database analysis showed that 5-aza-deoxycytidine increased gene expression in several carotid endothelial cell lines. A dual-luciferase reporter assay revealed that the target sequence in the SHMT1 promoter upregulated gene expression. Our findings indicate that SHMT1 promoter hypermethylation increases the risk of EH and may be a promising biomarker for EH.

Plasma Aldosterone Concentration as a Determinant for Statin Use among Middle-Aged Hypertensive Patients for Atherosclerotic Cardiovascular Disease.

The use of statin therapy on the prevention of atherosclerotic cardiovascular disease (ASCVD) is recommended by the American College of Cardiology (ACC) and the American Heart Association (AHA); nevertheless, its validation on primary aldosteronism (PA) patients has not been reported. We investigated the risk of incident ASCVD in middle-aged patients with PA compared with essential hypertension (EH) based on ACC/AHA recommendations. We enrolled 461 PA patients and 553 EH patients. Even though the ratio of metabolic syndrome in each group was similar, the PA group had higher systolic blood pressures, higher low-density lipoprotein levels, higher plasma aldosterone concentration (PAC), lower high-density lipoprotein levels, and higher 10-year ASCVD compared to the EH group. The discriminative power for predicting ASCVD by the recommended statin use from the ACC/AHA guidelines was proper in the PA group (i.e., under the receiver operating characteristic curve (95% confidence interval; 0.94 (0.91–0.96)). The generalized additive model showed patients with PAC higher than 60 ng/dL accompanying the standard timing of the statin use suggested by the ACC/AHA. The ACC/AHA guidelines have good discriminative power in the prediction of middle-aged high-risk hypertensive patients, while PAC identifies those high-risk individuals who may benefit from early statin therapy.

Association of ACE2 polymorphisms with susceptibility to essential hypertension and dyslipidemia in Xinjiang, China

BackgroundCardiovascular benefits by reversing environmental risks factors for essential hypertension (EH) and dyslipidemia could be weaken by high genetic risk. We investigated possible associations between ACE2 polymorphisms and dyslipidemia in patients with EH.MethodsFour hundred and two hypertensive patients were enrolled in an EH group and 233 normotensive individuals were enrolled as control group from the Xinjiang region of China. Fourteen ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry.ResultsParticipants carrying T allele (TT + CT) of rs2074192 (P = 0.006), rs4646155 (P = 0.030) and rs4646188 (P < 0.001), C allele (CT + CT or CC + CG) of rs4240157 (P = 0.012), rs4830542 (P = 0.020) and rs879922 (P < 0.001) and TT genotype of rs2106809 (P = 0.012) were associated with EH. Meanwhile,ACE2 SNPs also exhibited association with dyslipidemia but exhibited obvious heterogeneity. rs1978124 (TT + CT, P = 0.009), rs2106809 (TT, P = 0.045), rs233575 (CC + CT, P = 0.018), rs4646188 (CC, P = 0.011) and rs879922 (CC + CG, P = 0.003) were association with increased LDL-C (≥1.8 mmol/L). rs2106809 (CC + CT, P < 0.001), rs2285666(TT + CT, P = 0.017), rs4646142(CC + CG, P = 0.044), rs4646155(TT + CT, P < 0.001) and rs4646188(TT + CT, P = 0.033) were association with decreased HDL-C (< 1.0 mmol/L). rs2074192 (TT + CT, P = 0.012), rs4240157 (CC + CT, P = 0.027), rs4646156 (AA+AT, P = 0.007), rs4646188 (TT + CT, P = 0.005), rs4830542 (CC + CT, P = 0.047) and rs879922 (CC + CG, P = 0.001) were association with increased TC (≥5.2 mmol/L). rs2106809 (P = 0.034) and rs4646188 (P = 0.013) were associated with hypertriglyceridemia. Further, ischemic stroke was more prevalent with rs4240157 (CC + CT, P = 0.043), rs4646188 (CC + CT, P = 0.013) and rs4830542 (CC + CT, P = 0.037). In addition, rs2048683 and rs6632677 were not association with EH, dyslipidemia and ischemic stroke.ConclusionThe ACE2 rs4646188 variant may be a potential and optimal genetic susceptibility marker for EH, dyslipidemia and its related ischemic stroke.

Microvascular endothelial function is impaired in patients with idiopathic hyperaldosteronism.

The aims were to evaluate the relationship between idiopathic hyperaldosteronism (IHA) and grade of vascular function in the macrovasculature and microvasculature. Vascular function, including reactive hyperemia index (RIH), flow-mediated vasodilation (FMD), and nitroglycerine-induced vasodilation (NID) were evaluated in 52 patients with IHA, 53 patients with aldosterone-producing adenoma (APA), and 52 age-, sex-, and blood pressure-matched patients with essential hypertension (EHT). Log RHI was lower in the IHA and APA groups than in the EHT group (0.54 ± 0.25 and 0.55 ± 0.23 versus 0.79 ± 0.28; P < 0.01, respectively). FMD was lower in the APA group than in the EHT group (3.4 ± 2.1% versus 4.8 ± 2.8%; P = 0.02), whereas there was no significant difference in FMD between the IHA and the APA and EHT groups. NID was lower in the APA group than in the EHT group (10.0 ± 4.5% versus 12.5 ± 5.7%; P = 0.03), whereas there was no significant difference in NID between the IHA, APA, and EHT groups. Multiple regression analysis revealed an association of log RHI with plasma aldosterone concentration (t = -2.24; P = 0.03) and an association of FMD with plasma aldosterone concentration (t = -3.07; P < 0.01). Microvascular endothelial function was impaired in patients with IHA compared with that in patients with EHT.

Identification of essential hypertension biomarkers in human urine by non-targeted metabolomics based on UPLC-Q-TOF/MS

BackgroundIn recent years, using metabolomics technology to study hypertension has made some progress. However, in actual clinical studies, there are few studies on hypertension related metabonomics with human urine as samples. In this study, the urine samples of patients with essential hypertension (EH) were studied by comparing with healthy people to explore the changes of urine metabolites between hypertensive patients and healthy people in order to find potential biomarkers and metabolic pathways. MethodsAn ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology was used to analyze the urine metabolites of 75 cases of essential hypertension group (EH) and 75 cases of healthy control group (HC). ResultsAccording to the PLS-DA pattern recognition analysis, substances with significant differences (P < .05) between the EH group and the HC group were screened out, including 10 potential biomarkers such as L-methionine. The metabolic pathways involved were amino acid metabolism, fatty acid metabolism steroid hormone, biosynthesis and oxidative stress. ConclusionThe non-targeted metabolomics based on UPLC-Q-TOF/MS technology can effectively identify the differential metabolites of potential biomarkers in the urine of essential hypertensive patients and provide a theoretical basis for the treatment of clinical hypertension.

Association of mitofusin 2 methylation and essential hypertension: a case-control study in a Chinese population.

Mitofusin 2 (Mfn2), a gene that negatively regulates the proliferation of vascular smooth muscle cells (VSMCs), is expressed at low levels in the VSMCs of hypertensive patients. DNA methylation can inhibit gene expression. The purpose of this study was to investigate the relationship between Mfn2 methylation and essential hypertension (EH). After bioinformatics analysis, five EH patients and five normal control (NC) subjects were selected for methylation chip screening. Then, bisulfite DNA sequencing was used to analyze the methylation status of differentially methylated fragments of Mfn2 in 40 EH patients and 36 NC subjects. Mfn2 mRNA expression in the blood was detected by RT-qPCR. There were three CpG islands in the full length Mfn2 DNA sequence and some transcription factor binding sites in these regions, including Sp1, Ap2, GATA box, NF-κB, etc. The chip screening showed that only the third CpG island had a significantly high degree of methylation. Subsequent verification experiments found that the EH group had a significantly lower C base rate of methylation than the NC group (2.5% vs. 44.44%, P < 0.0001), but a similar CpG methylation rate (P > 0.05). RT-qPCR detection showed that the level of Mfn2 mRNA expression was significantly lower in the EH group than in the NC group (P = 0.013). Further association analysis showed that the level of Mfn2 methylation was associated with systolic blood pressure and diastolic blood pressure (r = -0.902, r = -0.713, respectively) but not the other indexes. The DNA methylation level of Mfn2 was significantly lower in hypertensive patients than in control subjects, which may be an independent risk factor for EH.