bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPATIAL VARIABILITY IN THE PREVALENCE OF HYPERTENSION: A CANADIAN PERSPECTIVE
Authors: Leroux Denis , Cloutier Lyne 
Published: June 2023

Objective:
Despite significant improvements in hypertension treatment, high blood pressure (HBP) still affects 22.6% of Canadians (Hypertension Canada, 2016). However, disparities associated with risk factors like, age, sex, and lifestyle can impact global prevalence in population. It is also a well-known fact that prevalence varies geographically. Thus, spatial location can give us a different perspective of hypertension in population. Reliable information about trends in hypertension rate is needed at regional scale to support the development of health programs. Geographic information systems (GIS) can provide that information by detecting spatial clusters of high or low HTN rate at health regions scale. The objectives of the study were to identify health regions with significantly high or low HTN rate using geostatistics and compare evolution from 2005 to 2019. It also seeks out to identify their populations’ characteristics using statistical analysis. Canadian Community Health Survey (2005, 2015 & 2019) data were used for the analysis.

Design and method:
For the analysis, we used Canadian Community Health Survey from 2005, 2015 and 2019. The 130,000 respondents representing the whole population are located according to health regions and data can be analyzed using a GIS. Using age and gender as subgroups criteria creation, we applied spatial autocorrelation analysis and Getis-Ord hot analysis to identify geographically contiguous health regions with high or low HTN rates. We then extracted the records in CCHS database for all respondents living in these regions for supplemental statistical analysis.

Results:
HTN is still a problem in Canada. This is especially true for people aged 65 and older although 72.9% considered themselves in good health. Increase in HTN rate is spread all over Canada, although some regions showed a rate decrease. Getis-ord analysis located regions with low HTN rates while regions with high rates were also located. Cluster of health regions with high HTN rates shows more diabetes and more obese people even though 38.4% declared being in good health.

Conclusions:
Hypertension is still a major problem in Canada. Age and gender are still significant risk factors. Geographical variations in HTN rate are presents at health regions scale.
RELATION OF METABOLIC PROFILE WITH DIFFERENT TYPES OF CAROTID LESIONS IN HYPERTENSIVE PATIENTS
Authors: Kadanina Kseniia , Bragina Anna , Druzhinina Natalia , Mohammadi Leila , Shakhmagomedov Rustam , Tyulin Maxim , Kartashov Ioann , Podzolkov Valeriy 
Published: June 2023

Objective:
The aim of our study was to identify the relations of lipid profile and uric acid (UA) with the types of carotid artery lesions (CL) in hypertensive patients.

Design and method:
67 hypertensive patients (35 men and 32 women) were examined (median age 51[45;55], hypertension duration was 3[2;5]). The subjects underwent duplex scanning of the carotid arteries (Samsung HS50, 2021). Metabolic profile included total cholesterol(TC), low density lipoproteins(LDL), high density lipoproteins(HDL), triglycerides(TG), and uric acid(UA). The results of the study were processed by the program Statistica 10.0.

Results:
All patients were divided into 4 groups according to on the type of CL: group 1 (n = 39) without pathological carotid tortuosity(PCAT) and atherosclerotic plaques(AP); group 2 (n = 11) with PCAT, but without AP; group 3 (n = 11) with AP<70% stenosis and without PCAT, and group 4 (n = 6), with both PCAT and AP<70% stenosis. The groups did not differ significantly in gender and age (p>0.05). Group 1 had TC level of 5.1[4.5;6.4]mmol/L, LDL of 2.3[2.05;2.8]mmol/L, HDL of 1.3[1.06;1.57]mmol/L, TG 1.2[0.7;1.6]mmol/L. The medians of the lipid profile in group 1 were not statistically different from those in group 2: TC - 4.85[4.5;7.69]mmol/l, LDL- 2.34[2.03;5.05]mmol/L, HDL- 1.38[1.3;1.6]mmol/L, TG- 1.1[0.9;1.23], p>0.05. Group 3, when compared with groups 1 and 2, had the highest levels of TC - 6.7[5.87;6.8]mmol/L (p = 0.001), LDL - 2.97[2.9;3.8]mmol/L (p = 0.0005), HDL - 1.5[0.6;1.64]mmol/L (p>0.05), and TG 1.9[1.8;2.35]mmol/L (p = 0.002), but did not significantly differed from those in group 4 (p>0.05), where median of TC was 6.32[6.02;6.7]mmol/L, LDL 3.5[2.89;3.28]mmol/L, HDL 0.69[0.6;1.64]mmol/L, and TG 2.1[2.01;2.85]mmol/L, p<0.05 when compared with groups 1 and 2. Median UA levels in group 1 (254 [212;310]mmol/L) was significantly lower (p = 0.011), when compared with patients in groups 2, 3, and 4 (311[301;395], 302[286;407], and 325[305;346], mmol/L, accordingly). There were correlations between the presence of PCAT+AP and levels of TC (r = 0.37; p<0.05), LDL (r = 0.53; p<0.05), TG (r = 0.47; p<0.05), presence of dyslipidemia (r = 0.44; p<0.05), and UA level (r = 0.4; p<0.05).

Conclusions:
We have demonstrated a relation of metabolic markers (TC, LDL, and UA) not only with atherosclerotic carotid lesion, but also with pathological carotid tortuosity in hypertensive patients.
ASSOCIATION BETWEEN OBESITY STATUS CHANGE AND HYPERTENSION ONSET: A COMMUNITY-BASED LONGITUDINAL COHORT STUDY IN NORTH CHINA
Authors: Zhao Xiaolei , Zhang Xinmin , Cai Qiujing , Wang Chenglong , Zhou Yi , Tian Tao , Zhou Xianliang , Zhang Yuqing , Liu Lisheng , Zhang Weiguo , Hu Aihua 
Published: June 2023

Objective:
Our study aimed to investigate the association between obesity status change and hypertension onset based on a longitudinal community-based cohort study in north China.

Design and method:
A total of 2618 individuals free of hypertension at baseline were collected from the longitudinal cohort study from 2011 to 2019. The correlation between the obesity status change and the hypertension onset was analyzed by inter groups differences analysis, an adjusted Cox regression model, and Kaplan-Meier survival analysis. Furthermore, the forest plot was used to visualize the subgroups analysis results including age, gender, and the differences of BMI and blood pressure between the baseline and the follow-up.

Results:
Over nearly 7 years follow-up, a total of 811 (31%) were found to develop future hypertension. The new-onset hypertension was mostly observed in participants who were keeping obese all the time (P for trend < 0.01). In the fully adjusted Cox regression model, keeping obese all the time would result in a 30.10% elevated risk of hypertension. The Kaplan-Meier survival analysis revealed the change in obesity status as an important feature to predict the occurrence of hypertension. What's more, we found the female gender and age over 60 years old were the important risks for people with different degree of BMI to have future hypertension.

Conclusions:
This study suggested maintaining obesity status was significantly associated with the risk of hypertension onset among Chinese adults based on a community-based longitudinal cohort. Even if people delivered weight loss after obesity, their hypertension level could not return to normal in a short time.
RIOCIGUAT-INDUCED DOWNREGULATION OF GENES RESPONSIBLE FOR SODIUM TRANSPORT THROUGH THE ALVEOLAR EPITHELIUM IN THE MONOCROTALINE MODEL OF PULMONARY HYPERTENSION
Authors: Lelková Katarína , Velasova Eva , Kmecova Zuzana , Veteskova Jana , Pivackova Lenka Bies , Doka Gabriel , Babal Pavel , Klimas Jan , Krenek Peter 
Published: June 2023

Objective:
Pleural effusions (PLEF) in patients with pulmonary arterial hypertension (PAH) co-diagnosed with isolated right-sided heart failure (RHF) have been reported to be associated with increased mortality. We hypothesized that alterations of transporters responsible for alveolar fluid clearance contributes to fluid accumulation in lungs and secondary formation of PLEF. This was examined in a model of PAH including administration of riociguat (RIO) that as a stimulator of sGC may be responsible for cGMP-dependent inhibition of epithelial sodium channel (ENaC) and might affect alveolar epithelial sodium transport.

Design and method:
Wistar rats were injected with monocrotaline (MCT; 60 mg/kg, s.c.) or vehicle (CON). 2 weeks after MCT administration, RIO treatment (10 mg/kg/d, p.o.) was started (CON+RIO, MCT+RIO). MCT groups were subdivided: MCT4W - sacrificed 4 weeks after MCT application and prematurely terminated MCT (ptMCT) - sacrificed after PAH deterioration. Expressions of ENaC alpha, beta, gama subunits, Na-K-Cl cotransporter (NKCC1), sodium-glucose linked transporter (SGLT1), sodium-coupled neutral amino acid transporters (SNAT2, SNAT5), aquaporin 3 (AQP3) were determined by RT-qPCR in lungs. Lung samples were subjected to histological analysis.

Results:
Increased lung weight was observed in MCT4W (2.331g vs.CON, p<0.05) and ptMCT (2.778g, vs.MCT4W, p<0.05). Similar situation was observed in RIO treated groups, however, more profound compared to MCT4W (ptMCT+RIO = 3.086g, p<0.05). Expression of ENaC, SNAT5 was decreased in ptMCT and ptMCT+RIO. Expression of NKCC1 decreased in ptMCT+RIO (by 30%) and simultaneously expression of SNAT2 in MCT4W+RIO, ptMCT+RIO (by 58%), both p<0.05 vs.CON, without any changes in MCT4W and ptMCT. 15-fold increase in AQP3 expression was observed in ptMCT, ptMCT+RIO (p<0.05 vs.CON). The presence of fluid in alveoli was observed in MCT4W and ptMCT with incidence of PLEF 20% and 30% respectively (ns). Incidence of PLEF in MCT4W+RIO and ptMCT+RIO was 22% and 44% (p<0.05), however, with interstitial swelling present.

Conclusions:
Downregulation of ENaC in MCT-induced PAH may represent a predisposing factor for alveolar fluid clearance impairment contributing to accumulation of fluid in lungs manifested as lung weight increase. Incidence of PLEF is probably related to lung weight increase. Riociguat rather worsened the incidence of PLEF and downregulation of ENaC.
CARDIORENAL DYSFUNCTION IN MICE SUBMITTED TO AORTIC STENOSIS AND TREATED WITH SODIUM OXALATE
Authors: Silva Amanda , Marques Juliana , Nascimento Bruno , Souza Leandro , Silva Maikon , Benetti Acaris , Irigoyen Maria Claudia 
Published: June 2023

Objective:
The transverse aortic constriction (TAC) model mimics cardiac hypertrophy (CH) caused by hypertension. The model of kidney injury by consumption of soluble sodium oxalate (SO) in the feed also mimics lesions similar to hypertension. Our objective is to test the hypothesis that mice submitted to TAC and gavage with SO will represent an effective model of cardiorenal dysfunction.

Design and method:
Forty male C57BL mice were randomized into 4 groups: sham-operated animals that received gavage for 15 days with water or sodium oxalate (SO) and animals that received TAC and gavage also for 15 days with water or SO. In the fourth and eighth weeks, an echocardiogram was evaluated. Metabolic cage, direct hemodynamic recording, and histological analysis were performed in the eighth week. Data were analyzed using 1-2 way ANOVA followed by Bonferroni's posthoc, considering significant differences for p<0.05.

Results:
The TAC+SO group showed increased serum urea (SHAM:37.85±3 vs. TAC+SO:49.9±2.6mg/dL, p = 0.02) and, compared to the SHAM+SO group, a decrease in water consumption and water balance. The TAC+SO group had the highest systolic (SHAM:122.4±5.2 vs. TAC+SO:160±5.2mmHg, p<0.01), diastolic (SHAM:78.9±5.4 vs. TAC+SO:105±5mmHg, p<0.01) and mean pressure (SHAM:100.6±5 vs. TAC+SO:132±4.8mmHg, p<0.01) values. Compared to the SHAM+SO and the SHAM, TAC+SO showed increased double product (DP) (SHAM:64.6 ± 4.7 vs. SHAM+SO:62.7±3.3 vs. TAC+SO:96.6±5.2, p<0.01). The TAC group had the highest weight of corrected ventricles (SHAM:6.73 ± 0.1 vs.TAC:10±0.6mg/mm, p<0.01), and the TAC+SO group had the highest pulmonary congestion index. The SHAM+SO group showed increased autonomic modulation and HR variability, while the TAC+SO group showed an important reduction. TAC animals had the highest mean BP variability. The reflex tachycardia of the TAC, SHAM+SO and TAC+SO groups was very reduced, and only the TAC+SO group had a reduction in the alpha index.

Conclusions:
TAC surgery caused CH, reduction in reflex tachycardia, and changes in autonomic modulation. Gavage with SO for 15 days promoted primary renal injury, and separately it was able to increase autonomic modulation. TAC surgery associated with SO gavage caused greater cardiac and renal dysfunction.
THE ASSOCIATION BETWEEN PURINE AND PYRIMIDINE INHIBITORS AND THE RISK OF HYPERTENSION: SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Alosaimi Hani , Maffia Pasquale , Padmanabhan Sandosh , Guzik Tomasz 
Published: June 2023

Objective:
To compare the effects of various purine and pyrimidine inhibitors in drug format on the risk of hypertension.

Design and method:
Various meta-analyses and systematic reviews of randomised-control trials (RCTs) were identified using a selection of relevant electronic databases, including MEDLINE Ovid, EMBASE Ovid and CENTRAL. These documents were then all assessed to extrapolate current approaches towards analysis of the effects of purine and pyrimidine inhibitors in adult patients with respect to hypertension.

Results:
The search as described yielded data for 27 trials, featuring a total of 8,907 participants, across three relevant medications: Azathioprine, Mycophenolate Mofetil (MMF), and Leflunomide.
Purine and pyrimidine inhibitors were compared to placebos in five studies, which included 1,748 patients, and to other active drugs in 22 studies, which thus included 7,159 patients.
A total of 50 (4.1%) and 16 (3%) events occurred for purine and pyrimidine inhibitors and the placebo groups, respectively. The risk of hypertension was higher among the purine and pyrimidine inhibitor groups than the placebo groups, although the resulting risk ratio was not statistically significant (RR = 1.37, 95% CI 0.78; 2.44, P = 0.28).
A total of 696 and 971 events occurred in purine and pyrimidine inhibitor and the active drug groups, respectively. The risk of hypertension was significantly lower in the purine and pyrimidine inhibitor groups than in those featuring other active drugs (RR = 0.8, 95% CI 0.65; 0.99, P = 0.04), thus favouring the use of purine and pyrimidine inhibitors. Studies by Gheith and Becker contributed to 10.7% and 10.8% of the meta-analysis weight, respectively. Substantial heterogeneity was thus observed between studies (I2 = 77%, P < 0.00001).

Conclusions:
The final outcomes indicated that the initial hypothesis of this meta-analysis, that purine and pyrimidine meta-analysis do not cause any additional risk of hypertension as compared to the placebo group could not be rejected. Additionally, a reduction in levels of risk as compared to other active drugs emerged that may require further analysis.
THE CHANGES OF LIPIDS` METABOLISM IN PATIENTS WITH ARTERIAL HYPERTENSION DEPENDING ON THE VITAMIN D RECEPTOR GENE (VDR, RS2228570) POLYMORPHISM
Authors: Repchuk Yuliia , Sydorchuk Larysa , Biletsky Semen , Petrynych Oksana , Kasantseva Tetiana , Ivashchuk Serge , Semianiv Marianna , Sokolenko Alina , Voroniuk Kseniia , Yarynych Yuliia , Dzhuryak Valentyna 
Published: June 2023

Objective:
The aim of the study was to analyze lipids` changes in patients with essential arterial hypertension (EAH) depending on the vitamin D receptor gene (VDR, rs2228570) polymorphism.

Design and method:
The study involved 100 patients suffering from EAH with target-organ damaging, moderate, high, or very high cardiovascular risk. Among them were 79.0% (79) women and 21.0% (21) men, the average age was 59.87±8.02 yo. The control group involved 60 practically healthy persons, matched by age and gender distribution. All enrolled/screened patients signed the Informed Consent to participate in the research. The VDR gene (rs2228570) polymorphism was studied by a real-time polymerase chain reaction (RT-PCR) method. Lipids’ profile in serum was studied by total cholesterol (TC), high- and low-density cholesterol levels(HDL-C, LDL-C), triglycerides (TG) concentration, and atherogenic index (AI).

Results:
The levels of TC and LDL-C in AA-genotype carriers of the control group exceeded those of GG-genotype carriers by 13.85% (PGG = 0.044) and 22.59% (PGG = 0.045), and the content of HDL-C, on the contrary, was lower - by 16 .56% (PGG = 0.048). The analysis of the lipid profile, taking into account the gender distribution, showed a higher concentration of TC, due to LDL-C, in hypertensive women with AA-genotype than in those with the G-allele: according to the TC- by 7.61-14.07% (RAA<0.03), for LDL-C - by 12.78-17.39% (RAA<0.02), respectively. On the other hand, men with EAH carrying the AA-genotype, on the contrary, had lower levels of TC and LDL-C than those with the G-allele: for TC - by 20.24% (PAA = 0.02), for LDL-C - by 30.20% and 24.45% (PAA<0.04), respectively. In practically healthy carriers of the A-allele of the VDR gene (rs2228570), especially the AA-genotype, the concentrations of TC and LDL-C were within the reference values, but exceeded that in GG-genotype carriers: for TC - by 13.85% (PGG = 0.044), LDL-C - by 22.59% (PGG = 0.045), and the content of HDL-C, on the contrary, was lower - by 16.56% (PGG = 0.048).

Conclusions:
Thus, the polymorphic site of the VDR gene (rs2228570) is associated with an increased LDL-C in practically healthy individuals, according to the analysis of variance (ANOVA) (F = 4.61; p = 0.014).
DO GENES AFFECT METABOLIC AND HORMONAL PARAMETERS IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION?
Authors: Repchuk Yuliia , Sydorchuk Larysa , Biletsky Semen , Petrynych Oksana , Kasantseva Tetiana , Ivashchuk Serge , Semianiv Marianna , Sokolenko Alina , Voroniuk Kseniia , Yarynych Yuliia , Dzhuryak Valentyna 
Published: June 2023

Objective:
The aim of the study was to analyze metabolic and hormonal parameters changes in patients with essential arterial hypertension (EAH) depending on the vitamin D receptor gene (VDR, rs2228570) polymorphism.

Design and method:
The study involved 100 patients suffering from EAH with target-organ damaging, moderate, high or very high cardiovascular risk. Among them were 79.0% (79) women and 21.0% (21) men, an average age was 59.87±8.02 yo. The control group involved 60 practically healthy persons, matched by age and gender distribution. All enrolled/screened patients signed the Informed Consent to participate in the research. The VDR gene (rs2228570) polymorphism was studied by a real-time polymerase chain reaction (RT-PCR) method. The intact parathyroid hormone (intact PTH) and vitamin 25 (OH) D levels in blood serum were determined by chemiluminescence immunoassay (MAGLUMI).

Results:
The decreased level of vitamin 25 (OH) D (<30 ng/ml) was found more often in the A-allele carriers of the VDR gene (rs2228570), than in GG-genotype carriers: in the control group - by 36.84% (x2 = 10.32; p = 0.001), in study group - by 42.42% (x2 = 39.27; p<0.001). Hypocalcemia according to the level of ionized blood calcium (Ca2+ <1.12 mmol/l) was registered only in G-allele carriers, both among practically healthy and hypertensive patients. In the control group, GG-genotype carriers had a lower ionized Ca2+ blood level with a compensatory higher concentration of the intact PTH in comparison with A-allele carriers - by 3.42%, 25.19% and 16.03% (p<0.05), respectively. Secondary hyperparathyroidism due to a compensatory increasing of the intact PTH (>65 pg/ml) was found more often in the G-allele carriers of the VDR gene (rs2228570) than in AA-genotype carriers: in control group - by 55.55% (x2 = 11.11; p<0.001), and in the group of patients with EAH - by 62.5% (x2 = 12.5; p<0.001).

Conclusions:
The GG-genotype of the VDR gene (rs2228570) increases the risk of hypocalcemia by more than 6 times [OR = 6.25; 95% CI: 1.05-37.37; p = 0.046], with the lowest probability in carriers of the A-allele [OR = 0.16; 95% CI: 0.03-0.96].
ANGIOTENSIN II REDUCES THE EXPRESSION OF CX43 AND INHIBITS THE C-SRC /MAPK/ERK PATHWAY VIA CX43 IN CARDIOMYOCYTES
Authors: Fan Xin , Chen Xinrong , Yu Jing 
Published: June 2023

Objective:
Hypertension is associated with abnormal renin angiotensin system (RAS). Angiotensin II (AngII), an important substance in RAS, is closely related to cardiomyocyte injury. Connexin43 (Cx43), a key structural protein in cardiomyocyte membrane, takes part in signal transduction and substance transport. Cx43 may cause extracellular interstitial fibrosis. It is known that Cx43 increases collagen I in heart tissue by regulating nuclear factor kappa B and Mechanistic metalloproteinase. However, the relationship between Ang II and Cx43 has been controversial,and how Ang II affects Cx43-related pathway is unclear. Otherwise, the activation and inhibition of the c-SRC /MAPK/ERK pathway may is related to Cx43, but the fact which is the forward is not sure.
Objective:The purpose of this study is to explore whether Ang II affects the expression of Cx43 and inhibits c-Src /MAPK/ERK pathway via Cx43.

Design and method:
First, we given rat cardiomyocytes (H9C2 cells) different concentrations of Ang II (10-5M,10-6M and 10-7M,for 48h), and establish Ang II groups. There is a contral group, which was given normal culture without Ang II. Second,we given H9C2 cells the Gap26,which is the inhibition of Cx43. Proteins of Cx43 and c-SRC /MAPK/ERK pathway from all groups were detected by Western Blot, and mRNA of these proteins were detected by PCR. SPSS was used for statistical analysis to compare the difference between all the groups.

Results:
First, compared with the control group, protein of Cx43, c-SRC, ERK2 and ERK1 were significantly decreased in Ang II group, and when the concentration of Ang II was 10-5M, these proteins were the least. mRNA of Cx43, ERK2 and ERK1 also were cut down after giving Ang II (only 10-5M). Second, the Gap26-intervention group had the lower expression protein and mRNA of Cx43, c-SRC, ERK2 and ERK1.

Conclusions:
We proved that Angiotensin II can reduce the expression of Cx43 and inhibit c-SRC /MAPK/ERK pathway via Cx43 in cardiomyocytes. Based on the role of Cx43 and c-Src /MAPK/ERK pathway, hypertesion may injury the cardiomyocytes via RAS and these pathways.