Association of serum uric acid levels with cardiovascular and all-cause mortality in hypertensive patients in China: a cohort study.

PURPOSE: The present study aimed to assess the association of elevated serum uric acid (SUA) and hypouricemia with all-cause mortality and cardiovascular mortality in Chinese hypertensive patients. METHODS: In the present prospective cohort, 9325 hypertensive patients from Dongguan, China were enrolled from 2014 to 2018 for analysis. Participants were categorised by quintiles of SUA. The HRs and 95% CIs for the association between SUA, all-cause and cardiovascular mortality were evaluated using the multivariate Cox regression model. After adjusting for multiple confounders, restricted cubic spline analysis was conducted to demonstrate the shape of relationship. RESULTS: After a median follow-up of 4.18 years for 9325 participants, there were 409 (4.4%) and 151 (1.6%) reported cases of all-cause and cardiovascular mortality, respectively. By using the third quintile of SUA (6.68 mg/dL to <7.55 mg/dL for men, 5.63 mg/dL to <6.42 mg/dL for women) as reference, the highest quintiles of SUA were associated with an elevated risk of all cause (HR: 1.34, 95% CI 1.00 to 1.80) in the crude model, but the association was not significant after adjusting for multiple comparisons. The association between low SUA and mortality and the dose-response analysis on the non-linearity of SUA-mortality relationship were not statistically significant. CONCLUSIONS: Although the association between SUA levels, all-cause and cardiovascular disease mortality did not appear to be significant among Chinese hypertensive patients, the findings might be confounded by their medical conditions. Further studies are needed to verify the optimal SUA levels for hypertensive patients.

The association of blood lipid parameters variability with ischemic stroke in hypertensive patients.

BACKGROUND AND AIMS: The relationship between lipid variability and stroke among patients with hypertension were inconclusive. We aimed to investigate the association of lipid variability with ischemic stroke in hypertensive patients. METHODS AND RESULTS: This retrospective cohort study included 4995 individuals with hypertension between 2013 and 2015, and recorded their status of ischemic stroke until the end of 2018. The variability in total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured using the standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM) and average absolute difference between successive values (ASV). Multivariate Cox proportional hazards models with hazard ratios (HRs) and 95% confidence interval (CI) were performed. There were 110 cases of ischemic stroke during a median follow up of 4.2 years. The multivariable adjusted HRs and 95% CIs comparing the highest versus the lowest quartiles of SD of TC, LDL-C, HDL-C and TG were 4.429 (95% CI: 2.292, 8.560), 2.140 (95% CI: 1.264, 3.621), 1.368 (95% CI: 0.793, 2.359) and 1.421 (95% CI: 0.800, 2.525), respectively. High variability in TC and LDL-C were associated with a higher risk for ischemic stroke. Similarly, the results were consistent when calculating variability of TC and LDL-C using CV, ASV and VIM, and in various subgroup analyses. CONCLUSION: Higher variability of TC and LDL-C associated with the risk of ischemic stroke among hypertensive patients. These findings suggest reducing variability of lipid parameters may decrease adverse outcomes.

Relationship between body mass index and ischaemic stroke in Chinese elderly hypertensive patients.

BACKGROUND: Despite obesity being a major risk factor for ischaemic stroke (IS), the association between body mass index (BMI) and IS in patients with hypertension remains uncertain. OBJECTIVE: To assess the association between BMI and IS among elderly hypertensive patients in China. METHODS AND RESULTS: We recruited 3500 hypertensive patients aged ≥60 between 1 January 2010 and 31 December 2011 in China and ascertained their stroke status until December 2016. Multivariate Cox regression was used to evaluate the association between BMI and IS with interaction tests for exposure and covariates. A total of 3315 subjects (mean age 71.41±7.20 years, 44.5% were men) were included for data analysis. During an average follow-up period of 5.5 years, there were 206 onset cases (6.21%) of IS. When BMI was treated as a continuous variable, it was positively associated with the incidence of new onset IS (HR=1.14; 95% CI: 1.05 to 1.34; p=0.005) after adjusting for potential confounders. Meanwhile, when BMI was treated as a categorical variable, the highest category (≥28 kg/m2) was strongly associated with an increased risk for IS compared with normal BMI category (18.5 to 24 kg/m2) (HR=1.36, 95% CI: 1.09 to 1.80; p<0.001) in the fully adjusted model. Subgroup and interaction analysis also demonstrated that BMI independently associated with IS among males, smokers, alcohol drinkers, diabetic patients, people with uncontrolled blood pressure, decreased estimated glomerular filtration rate and those aged ≥70 years. CONCLUSION: BMI was significantly associated with IS and was an independent risk of IS in Chinese elderly hypertensive patients.

Association between pulse pressure and ischaemic stroke in elderly patients with hypertension.

BACKGROUND: The association between pulse pressure (PP) and the risk of first ischaemic stroke (IS) is inconsistent. Therefore, we evaluated the association between PP and the risk of first IS among elderly hypertensive population in China. METHODS: This was a retrospective cohort study. Patients with hypertension and aged ≥60 years were recruited. Multivariate Cox regression was performed to evaluate the association between PP and the risk of IS. We further stratified the regression models into subgroups and test for interaction to assess whether the associations were modified by other covariates. RESULTS: A total of 3315 patients with hypertension (44.49% male; mean age 71.41±7.20 years) were included, and 206 cases of IS occurred with a median follow-up of 5.5 years. The results showed that per SD mm Hg increment in PP was associated with a 17% (95% CI 1.05 to 1.40, p=0.0172) increased risk of IS. Moreover, the HR of IS for the highest quartile of PP was 1.46 (95% CI 1.18 to 1.73, p=0.0011, p for trend <0.001) comparing with the lowest quartile of PP. Subgroup analysis showed that population aged ≥70 years, male, patients with smoking or drinking habit, diabetes at baseline, being overweight, with uncontrolled blood pressure or did not take antihypertensive drugs have a higher risk for IS. CONCLUSIONS: We found that PP was significantly associated with IS and was an independent risk factor for IS.

Relationship between triglyceride levels and ischaemic stroke in elderly hypertensive patients.

BACKGROUND: Although hyperlipidaemia was a well-known risk factor for ischaemic stroke, the association between triglyceride and first ischaemic stroke remains uncertain. OBJECTIVES: The present study attempted to explore the relationship between triglyceride and first ischaemic stroke in a Chinese community elderly patients with hypertension. METHODS AND RESULTS: This was a retrospective cohort study. We enrolled 3249 consecutive elderly patients with hypertension from a community in China between January 2010 and December 2011. Patients were divided into four groups based on the quartiles of triglyceride. Multivariate Cox regression analysis, subgroup and interaction test were performed to evaluate the relationship between triglyceride and first ischaemic stroke. There were a total of 3249 participants including 1455 male and 1794 female, with a mean age of 71.36±7.18 years. At an average follow-up of 5.5 years, 205 patients were identified to have first ischaemic stroke. After adjustment for potential confounders, using the lowest quartiles of triglyceride as the reference, multivariable HR (95% CI) for first ischaemic stroke increased in parallel with the quartiles of triglyceride (HRs were 1.56 (95% CI 1.07 to 2.51), 1.74 (95% CI 1.07 to 2.84) and 1.85 (95% CI 1.05 to 2.89)) from the second to the fourth quartiles, respectively (p=0.002 for trend). Subgroup and interaction analysis showed that there was no interactive effect on triglyceride and first ischaemic stroke. CONCLUSION: Triglyceride was an independent risk factor for first ischaemic stroke among Chinese elderly patients with hypertension.

Relationship between diastolic blood pressure and the first ischaemic stroke in elderly patients with hypertension.

BACKGROUND: It is uncertain how diastolic blood pressure (DBP) may associate with ischaemic stroke in elder patients with hypertension. We aimed to explore this relationship in a Chinese community. METHODS: A total of 3315 participants aged ≥60 years with essential hypertension were enrolled between January 2010 and December 2011, and being followed up until 31 December 2016. DBP levels were categorised into five groups (<60, 60-70, 70-80, 80-90 and ≥90 mm Hg), using 70-80 mm Hg as referent. We performed Cox regression analysis and subgroup analyses to evaluate the relationship between DBP and the incidence of ischaemic stroke. RESULTS: Among the 3315 participants, 44.49% were men and they were 71.4 years old on average. During a median follow-up period of 5.5 years, there were 206 onset cases of ischaemic stroke. The HRs for the first ischaemic stroke in the fully adjusted model were 1.32 (95% CI 0.73 to 2.40) for DBP <70 mm Hg, 1.50 (95% CI 1.13 to 2.73) for DBP between 80 and 89.9 mm Hg and 2.31 (95% CI 1.14 to 4.68) for DBP ≥90 mm Hg compared with DBP between 70 and 79.9 mm Hg (p=0.020 for trend). Subgroup and interaction analysis showed no significant findings. CONCLUSIONS: DBP had a non-linear association with the risk of ischaemic stroke among Chinese elderly patients with hypertension. DBP between 70 and 80 mm Hg may be an appropriate indicator for a lower stroke risk.

Association of Serum Omentin-1 Concentrations with the Presence of Atrial Fibrillation.

BACKGROUND Omentin-1 is one of the adipokines associated with obesity, diabetes, and coronary heart disease development. We determined to investigate whether serum omentin-1 concentrations were correlated with the presence of atrial fibrillation (AF). MATERIAL AND METHODS Serum omentin-1 concentrations were examined in a cross-sectional population that included 220 patients with AF (70 with paroxysmal AF, 78 with persistent AF, and 72 with permanent AF) and 115 healthy controls. RESULTS Reduced serum omentin-1 concentrations were found in AF patients compared to the controls. In addition, patients with permanent AF had lower serum omentin-1 concentrations compared to patients with persistent AF and patients with paroxysmal AF. Significantly decreased serum omentin-1 concentrations were observed in persistent AF patients compared to paroxysmal AF patients. Spearman correlation analysis suggested that serum omentin-1 concentrations were negatively correlated with left atrial diameter in AF patients. CONCLUSIONS Serum omentin-1 concentrations were correlated with the presence of AF and atrial remolding.

Community-based interventions in hypertensive patients: a comparison of three health education strategies.

BACKGROUND: Community-based health education programs may be helpful in improving health outcomes in patients with chronic illnesses. This study aimed to evaluate community-based health education strategies in the management of hypertensive patients with low socioeconomic status in Dongguan City, China. METHODS: This was a randomized, non-blinded trial involving 360 hypertensive patients enrolled in the community health service centre of Liaobu Town, Dongguan City, China. Participants were randomized to receive one of the three community-based health education programs over 2 years: self-learning reading (Group 1), monthly regular didactic lecture (Group 2), monthly interactive education workshop (Group 3). Outcomes included the changes in the proportion of subjects with normalized blood pressure (BP), hypertension-related knowledge score, adherence to antihypertensive treatment, lifestyle, body mass index and serum lipids. RESULTS: After the 2-y intervention, the proportion of subjects with normalized BP increased significantly in Group 2 (from 41.2% to 63.2%, p<0.001), and increased more substantially in Group 3 (from 40.2% to 86.3%, p<0.001), but did not change significantly in Group 1. Improvements in hypertension-related knowledge score, adherence to regular use of medications, appropriate salt intake and regular physical activity were progressively greater from group 1 to group 2 to group 3. Group 3 had the largest reductions in body mass index and serum LDL cholesterol levels. CONCLUSION: Interactive education workshops may be the most effective strategy in community-based health promotion education programs for hypertensive patients in improving patients' knowledge on hypertension and alleviating clinical risk factors for preventing hypertension-related complications.

Association of the ENPP1 K121Q polymorphism with susceptibility to type 2 diabetes in different populations: evidence based on 40 studies.

The K121Q gene polymorphism of ectoenzyme nucleotide pyrophosphate phosphodiesterase 1(ENPP1) has been widely investigated, however, results have been somewhat conflicting. The aim of this meta-analysis was to establish a precise estimation of the association between ENPP1 gene polymorphisms and type 2 diabetes (T2D). A literature search in PubMed, Embase, Cochrane Library and China Biology Medicine (CBM) databases was conducted on publications published prior to November 21(st), 2013. The combined odds ratio (OR) with 95% confidence intervals (95% CI) was calculated to estimate the strength of the association using a random-effects/fixed-effects model. Statistical analyses were performed using the STATA 11.0 software. For the overall population, there was a significant association between ENPP1 gene polymorphisms and T2D when comparing the Q allele versus K allele (OR = 1.29, 95% CI 1.16-1.44, p = 0.000). Considering diverse ethnic groups, effect sizes were consistent for patients of Caucasian and Asian descent (OR = 1.20, 95% CI = 1.08-1.33 and OR = 1.47, 95% CI = 1.15-1.89, respectively); however, effect size was not consistent for those of African descent. Under other models of inheritance, significant associations were also observed. Sensitivity analyses did not leading to differing he results. In summary, the Q allele of the ENPP1 K121Q gene may contribute to the susceptibility for T2D in Caucasians and Asians.

[Glycosylated hemoglobin A1c for the diagnosis of diabetes mellitus: a meta-analysis].

OBJECTIVE: To assess the diagnostic value of glycosylated hemoglobin A1c (HbA1c) ≥ 6.5% for diabetes in Chinese adults with oral glucose tolerance test (OGTT) as the reference standard. METHODS: Major databases were searched to get all diagnostic tests with HbA1c ≥ 6.5% for diabetes in Chinese adults. QUADAS items were used to evaluate the quality of the eligible studies. Meta-disc software was used to perform comprehensive quantitative assessment for all included studies and summary ROC (SROC) curve were drawn. RESULTS: A total of 11 studies were included. The outcomes of the diagnostic value with HbA1c ≥ 6.5% were as the following: pooled sensitivity 0.62 (95%CI: 0.60 - 0.64), pooled specificity 0.96 (95%CI: 0.95 - 0.96), diagnostic odds ratio (DOR) 40.25 (95%CI: 20.79 - 77.95) and AUCSROC 0.7702 (sx = 0.0636). CONCLUSIONS: The diagnostic specificity is pretty high for the diagnostic test with HbA1c ≥ 6.5%, while sensitivity is low. Combination of HbA1c and glucose tests is needed to reduce the missed diagnosis rate.

Control status of ambulatory blood pressure and its relationship with arterial stiffness in the China nationwide registry of treated hypertensive patients: the REACTION-ABP study.

The control rate of ambulatory blood pressure (BP) is unclear in Chinese hypertensive patients, and whether it would be associated with the ambulatory arterial stiffness indices is also unknown. From June 2018 until December 2022, 4408 treated hypertensive patients (52.8% men, average age 58.2 years) from 77 hospitals in China were registered. Ambulatory BPs were measured with validated monitors and analyzed with a web-based standardized Shuoyun system ( www.shuoyun.com.cn ). The BP control rate was the highest in the office (65.7%), moderate in the daytime (45.0%), low in the morning (34.1%), and the lowest in the nighttime (27.6%, P < 0.001). Only 21.0% had their 24 h BP perfectly controlled. The stepwise regression analyses identified that the factors associated with an imperfect 24 h BP control included male sex, smoking and drinking habits, a higher body mass index, serum total cholesterol and triglycerides, and the use of several specific types of antihypertensive drugs. After adjustment for the above-mentioned factors, the 24 h pulse pressure (PP) and its components, the elastic and stiffening PPs, were all significantly associated with an uncontrolled office and ambulatory BP status with the standardized odds ratios ranging from 1.09 to 4.68 (P < 0.05). The ambulatory arterial stiffness index (AASI) was only associated with an uncontrolled nighttime and 24 h BP status. In conclusion, the control rates of 24 h ambulatory BP, especially that in the nighttime and morning time windows, were low in Chinese hypertensive patients, which might be associated with arterial stiffness in addition to other common risk factors.

Polymorphism M55V in gene encoding small ubiquitin-like modifier 4 (SUMO4) protein associates with susceptibility to type 1 (and type 2) diabetes.

BACKGROUND: The association between small ubiquitin-like modifier 4 (SUMO4) gene polymorphism and type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) has been investigated in several studies. We conducted a meta-analysis to evaluate the association of SUMO4 gene polymorphism with T1DM and T2DM susceptibility. METHODS: A meta-analysis was performed on the published studies before August 2011. The association of SUMO4 M55V polymorphism with T1DM and T2DM was evaluated. Meta-analysis was performed for genotypes AA versus GG, AA versus AG, AA versus AG + GG and A allele versus G allele in a fixed/random effect model. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association. RESULTS: Sixteen case-control studies including 9190 cases and 10 456 healthy controls were included. T1DM patients were divided into Asian and Caucasian subgroup. We detected a significant association of SUMO4 M55V polymorphism with T1DM in Asian population (A versus G: OR = 0.79, 95%CI = 0.72-0.86, p = 0.000) and a significant association of SUMO4 M55V polymorphism with T1DM in Caucasian population (A versus G: OR = 0.84, 95%CI = 0.73-0.97, p = 0.007). Included T2DM patients were all Asian. Meanwhile, a significant association of SUMO4 M55V polymorphism with T2DM was also found (A versus G: OR = 0.86, 95%CI = 0.79-0.94, p = 0.001). CONCLUSIONS: Our study demonstrates significant associations of SUMO4 M55V polymorphism with T1DM in Asian and Caucasian population and with T2DM in Asian population.

Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with polycystic ovary syndrome: a meta-analysis.

The association between Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma (PPAR) and polycystic ovary syndrome (PCOS) has been investigated in several studies, whereas results were often incompatible. We conducted a meta-analysis to evaluate the association of Pro12Ala polymorphism in PPAR with PCOS susceptibility. A meta-analysis was performed on the published studies before November, 2011. Meta-analysis was performed for genotypes CG versus CC, CG+GG versus CC and G allele versus C allele in a fixed effect model. The combined odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to estimate the strength of the association. A total of 13 studies including 1,598 cases and 1,881 controls were enrolled. Ultimately, sensitivity analysis demonstrated that, in total, there was no significant association between Pro12Ala polymorphism and PCOS in the contrast of G allele versus C allele OR = 0.84 (95 % CI 0.69-1.04) and in Europeans, no significant association in the comparison of G allele versus C allele (OR = 0.84, 95 % CI 0.67-1.06) was also indicated. In summary, according to the results of our meta-analysis, strictly, the Pro12Ala polymorphism did not significantly associate with PCOS, though the protective trend of G allele existed.

Relationship Between Change in Serum Uric Acid and Ischemic Stroke in Chinese Hypertensive Patients.

Background: Limited studies focused on the association between serum uric acid (SUA) change with ischemic stroke, and their results remain controversial. The present study aimed to investigate the relationship between change in SUA with ischemic stroke among hypertensive patients. Method: This was a retrospective cohort study. We recruited adult hypertensive patients who had two consecutive measurements of SUA levels from 2013 to 2014 and reported no history of stroke. Change in SUA was assessed as SUA concentration measured in 2014 minus SUA concentration in 2013. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan-Meier analysis and log-rank test were performed to quantify the difference in cumulative event rate. Additionally, subgroup analysis and interaction tests were conducted to investigate heterogeneity. Results: A total of 4,628 hypertensive patients were included, and 93 cases of ischemic stroke occurred during the mean follow-up time of 3.14 years. Participants were categorized into three groups according to their SUA change tertiles [low (SUA decrease substantially): <-32.6 µmol/L; middle (SUA stable): ≥-32.6 µmol/L, <40.2 µmol/L; high (SUA increase substantially): ≥40.2 µmol/L]. In the fully adjusted model, setting the SUA stable group as reference, participants in the SUA increase substantially group had a significantly elevated risk of ischemic stroke [HR (95% CI), 1.76 (1.01, 3.06), P = 0.0451], but for the SUA decrease substantially group, the hazard effect was insignificant [HR (95% CI), 1.31 (0.75, 2.28), P = 0.3353]. Age played an interactive role in the relationship between SUA change and ischemic stroke. Younger participants (age < 65 years) tended to have a higher risk of ischemic stroke when SUA increase substantially. Conclusion: SUA increase substantially was significantly correlated with an elevated risk of ischemic stroke among patients with hypertension.

The Relationship Between Fasting Blood Glucose Levels and First Ischemic Stroke in Elderly Hypertensive Patients.

OBJECTIVE: The relationship between fasting blood glucose and first ischemic stroke in older adults was unclear, so we explored this association among older patients with hypertension in China. METHODS: We recruited hypertensive participants with 60 or more of age. Fasting blood glucose concentrations were categorized into quartiles. Hazard ratio (HR) and 95% confidence interval (CI) for ischemic stroke were estimated using multivariate Cox regression analysis and subgroup analysis. RESULTS: A total of 3310 (1474 (44.53%) male) patients with mean age of 71.41±7.20 years were included. During the mean follow-up period of 5.5 years, 206 cases of ischemic stroke occurred. After adjusting for potential confounding variables, multivariate adjusted HRs for each standard deviation increment of fasting blood glucose, the risk of ischemic stroke increased by 11% (95% CI: 1.03, 1.21; P= 0.008). In addition, when using the lowest group (Q1) as reference, the multivariate adjusted HRs for first ischemic stroke were 1.76 (95% CI: 1.08, 2.86; P=0.023), 1.73 (95% CI: 1.06, 2.81; P=0.027) and 2.42 (95% CI: 1.49, 3.93; P<0.001) (P for trend<0.001). Subgroup analysis revealed that the association between fasting blood glucose and the risk of ischemic stroke was higher in male (HR: 1.22 vs 1.10), those with uncontrolled hypertension (HR: 1.22 vs 1.10), subjects with diabetes (HR: 1.19 vs 1.10), overweight (HR: 1.19 vs 1.09), smoking habits (HR: 1.33 vs 1.13) and those whose eGFR< 90 (HR: 1.16 vs 1.09). CONCLUSION: Fasting blood glucose was an independent risk factor for the first ischemic stroke among older adults with hypertension. Managing fasting blood glucose may be beneficial for participants with diabetes, poorly controlled blood pressure, had smoking habits, being overweight, and with reduced renal function.

A nonlinear relationship between low-density-lipoprotein cholesterol levels and atrial fibrillation among patients with hypertension in China.

BACKGROUND: The association between low-density-lipoprotein cholesterol (LDL-C) and atrial fibrillation (AF) in hypertensive population remains controversial. Therefore, we explored the relationship between LDL-C and AF among patients with hypertension in a Chinese community. METHODS: This is a retrospective cross-sectional study that enrolled 7808 hypertensive patients between January 2013 and December 2013 in Guangdong, China. AF was diagnosed by 12-lead electrocardiogram (ECG) or self-reported status. LDL-C value were categorized by quartiles. Univariate and multivariate logistic regression were performed to examine the relation between LDL-C and AF. LDL-C values were expressed in continuous (every 1 mg/dL increment) or categorical variables in each regression model. RESULTS: Among 7,808 (47.1% man, with mean age 62.3 years) participants, 78 AF cases were identified. In multivariate logistic regression, when LDL-C was presented as continuous variable, it was inversely associated with the occurrence of new onset AF (OR =0.99, 95% CI: 0.98, 1.00; P=0.018). Meanwhile, when LDL-C was presented as categorical variable, the negative association between LDL-C and AF was attenuated after adjusting for confounders. Adjusted restricted cubic spline demonstrated a non-linear correlation between LDL-C and AF. CONCLUSIONS: Lower levels of LDL-C was associated with increased incidence of AF in a Chinese community hypertensive population.

Association of liver enzymes levels with fasting plasma glucose levels in Southern China: a cross-sectional study.

OBJECTIVE: According to several studies, liver enzymes levels are associated with fasting plasma glucose (FPG) levels. However, the association stratified by body mass index (BMI) remains to be elucidated, especially in Southern China. Therefore, the aim of this study was to investigate the correlation between liver enzymes levels and FPG levels stratified by BMI in Southern China. DESIGN: Cross-sectional study. PARTICIPANTS AND SETTING: 3056 individuals participated in real-time interviews and blood tests in Southern China. Participants were divided into three groups (underweight, normal weight and overweight or obesity) based on BMI cut-offs. MAIN OUTCOME MEASURED: Partial correlation analysis was performed to investigate the relationship between FPG levels and liver tests. Multivariate logistic regression analyses were applied to calculate the adjusted ORs for FPG levels based on liver enzymes levels. RESULTS: There was no association between liver enzymes and FPG either in the underweight group or in the normal weight group; however, a significant correlation was observed in the overweight or obesity group (alanine transaminase (ALT), p<0.01; aspartate aminotransferase (AST), p<0.05). After adjusting for confounding factors, the highest tertiles of ALT still remained significantly positively related to FPG levels in the overweight or obesity group, with an OR of 2.205 (95% CI 1.442 to 3.371) for the 5.56≤FPG<7.00 mmol/L vs the FPG<5.56 mmol/L group and with an OR of 2.297 (95% CI 1.017 to 5.187) for the FPG≥7.00 mmol/L vs the FPG<5.56 mmol/L group, but this correlation was not found for AST. CONCLUSIONS: The association of liver enzymes levels with FPG levels differed based on different BMI cut-offs. ALT levels were significantly positively associated with FPG levels in the overweight or obesity group, but not in the other two groups; AST levels were not associated with FPG levels in any group.

Glucagon-like peptide-1 attenuates endothelial barrier injury in diabetes via cAMP/PKA mediated down-regulation of MLC phosphorylation.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) showed protective effects on endothelium-dependent dilatation. Since endothelial barrier dysfunction also plays a pivotal role in atherosclerosis, this study was designed to investigate the effects of GLP-1 on endothelial barrier function in diabetic aortic endothelium and explore the underlying mechanism. METHODS: For in vivo studies, diabetic rats were established and subjected to 12- and 24-week treatment of exenatide. The morphological changes of aortic endothelium were observed with transmission electron microscope. A permeability assay of aortic endothelium was performed using the surface biotinylation technique. Protein expression was detected by immunohistochemical analysis and Western blots. For in vitro studies, human umbilical vein endothelial cells (HUVECs) were cultured in medium enriched with advanced glycation end products (AGEs) or AGEs plus GLP-1 and other reagents. The integrity of endothelium was evaluated by endothelial monolayer permeability assay and transendothelial resistance. The in vitro expressions of relevant proteins in signaling pathways were also detected by immunofluorescence and Western blots. RESULTS: In vivo, the enhanced aortic endothelial permeability in diabetic aortas were attenuated by exenatide treatment. Additionally, myosin light chain (MLC) phosphorylation, related to actomyosin contractility, and activation of its upstream targets in diabetic aorta were inhibited after administration of exenatide. In vitro, the endothelial monolayer permeability and the assembly of stress fibers were reduced by GLP-1 intervention under diabetic condition. Meanwhile, AGE-induced MLC phosphorylation mediating ECs contractility was inhibited by GLP-1. Furthermore, GLP-1 down-regulated the upstream targets of MLC phosphorylation, including RAGE, Rho/ROCK and MAPK signaling pathways. Intriguingly, the effects of GLP-1 elicited on ECs contractility and barrier function in diabetes were blunted by inhibition of GLP-1R, cAMP or PKA and stimulation of Rho/ROCK and MAPK signaling pathways. CONCLUSION: The findings of this study suggest that the stabilizing effect of GLP-1 on the endothelial barrier and contraction of AGE-treated ECs is caused by GLP-1R/cAMP/PKA activation and the subsequent inactivation of RAGE/Rho/ROCK as well as MAPK signaling pathways.

Inhibition of miR-29b suppresses MAPK signaling pathway through targeting SPRY1 in atherosclerosis.

The treatment of atherosclerosis (AS), a severe condition associated with the pathogenesis of cardiovascular diseases (CVDs), is still not satisfactory worldwide. In this study, we aim to investigate whether protein sprout homologue 1 (SPRY1), a upstream mediator of MAPK signal pathway, is the target of miR-29b in vascular endothelium during the development of AS. ApoE-/- mice model was established, and an inverse correlation was noticed between level of miR-29b and SPRY1 expression in the aortic tissues. Meanwhile, the tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) expression and NADPH oxidase activity were up-regulated in atherosclerotic tissues. In vitro experiments were carried out to investigate the roles of miR-29b in regulating the expression of SPRY1 in cultured human umbilical vein endothelial cells (HUVECs). We found that miR-29b mimic and antagomir could modulate the expression of SPRY1 protein in cultured HUVECs. However, the expression of SPRY1 mRNA showed no statistical difference when treating with miR-29b mimic or antagomir. These indicated that the modulation of SPRY1 induced by miR-29b was at the posttranslational level. Dural luciferase reporter assay was conducted to detect the potential interaction between miR-29b and the 3'UTR of SPRY1, which indicated that SPRY1 was a target of miR-29b. Besides, miR-29b antagomir induced decrease of TNF-α, ROS production and NADPH oxidase activity and down-regulated the expression of p-ERK and p-p38 in the presence of oxLDL. In conclusion, inhibition of miR-29b could attenuate AS by inhibiting the SPRY1/MAPK signaling pathway and inflammation in aorta. In future, treatment options based on miR-29b may be applicable for the treatment of AS.

Melatonin ameliorates myocardial apoptosis by suppressing endoplasmic reticulum stress in rats with long­term diabetic cardiomyopathy.

The effects of melatonin (MLT), which exerts cardioprotective effects against myocardial apoptosis, in long­term diabetic cardiomyopathy are not currently well defined. The present study aimed to investigate how MLT protects the heart through modulating myocardial apoptosis in rats with type 2 diabetes mellitus (DM). In total, 36 rats were randomly divided into three groups, including control (n=12), DM (n=12) and DM + MLT (n=12) groups. The results demonstrated that, in DM rats, a significant increase was observed in the serum fasting blood glucose and lipid levels, in addition to insulin resistance and cardiac dysfunction, which were attenuated in DM rats treated with MLT. Additionally, cellular apoptosis in rats with DM was increased, and the expression of Bcl­2 was downregulated, while levels of Bcl­2­associated X and caspase­3 were upregulated, and these observations were reversed by MLT, as determined by TUNEL and western blot analysis, respectively. As increased endoplasmic reticulum (ER) stress induced by hyperglycemia is reported to be a factor for apoptosis, the present study also determined the expression of proteins associated with ER stress in cardiac tissues following MLT treatment by western blotting. The results further indicated that MLT decreased the expression of ER stress hallmarks, including CCAAT/enhancer­binding protein homologous protein, glucose­regulated protein 78, protein kinase RNA­like endoplasmic reticulum kinase (PERK) and activating transcription factor 6α in cardiac tissues. In conclusion, the results of the present study indicate that MLT may protect heart by ameliorating cardiac ER stress­induced apoptosis in diabetic cardiomyopathy.