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.

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.

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.

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.

The relationship between soluble CD40 ligand level and atherosclerosis in white-coat hypertension.

This study was designed to examine the distribution of plasma soluble CD40 ligand (sCD40L), and its relationship with carotid intima-media thickness (CIMT) in healthy controls and subjects with white-coat hypertension (WCH) or hypertension (HT). Thirty-five patients with HT, 35 patients with WCH, and 35 healthy controls were enrolled. The normal group (CIMT < 0.9 mm), subclinical atherosclerosis group (0.9 mm ≤ CIMT < 1.2 mm) and atherosclerosis group (CIMT ≥ 1.2 mm) were grouped based on the value of CIMT. The highest level of sCD40L was observed in HT group, followed by WCH group and healthy controls. The level of sCD40L was significantly increased in atherosclerosis group compared with subclinical atherosclerosis group and healthy controls. In the WCH group, sCD40L level was significantly and positively correlated with CIMT and systolic blood pressure. Multiple logistic regression indicated that sCD40L was a risk factor for increased CIMT (odds ratio, 1.504; 95% confidence interval, 1.054-1.956, P < 0.001). The data provided evidence that sCD40L levels in subjects with WCH and HT were significantly and consistently higher than those in healthy controls. SCD40L may represent a potential non-invasive atherosclerosis marker in WCH patients.

Effects of glucagon-like peptide-1 on advanced glycation endproduct-induced aortic endothelial dysfunction in streptozotocin-induced diabetic rats: possible roles of Rho kinase- and AMP kinase-mediated nuclear factor κB signaling pathways.

Interaction between advanced glycation endproducts (AGEs) and receptor for AGEs (RAGE) as well as downstream pathways leads to vascular endothelial dysfunction in diabetes. Glucagon-like peptide-1 (GLP-1) has been reported to attenuate endothelial dysfunction in the models of atherosclerosis. However, whether GLP-1 exerts protective effects on aortic endothelium in diabetic animal model and the underlying mechanisms are still not well defined. Experimental diabetes was induced through administration with combination of high-fat diet and intraperitoneal injection of streptozotocin. Rats were randomly divided into four groups, including controls, diabetes, diabetes + sitagliptin (30 mg/kg/day), diabetes + exenatide (3 µg/kg/12 h). Eventually, endothelial damage, markers of inflammation and oxidative stress, were measured. After 12 weeks administration, diabetic rats received sitagliptin and exenatide showed significant elevation of serum NO level and reduction of ET-1 as well as inflammatory cytokines levels. Moreover, sitagliptin and exenatide significantly inhibited aortic oxidative stress level and improved aortic endothelial function in diabetic rats. Importantly, these drugs inhibited the protein expression level in AGE/RAGE-induced RhoA/ROCK/NF-κB/IκBα signaling pathways and activated AMPK in diabetic aorta. Finally, the target proteins of p-eNOS, iNOS, and ET-1, which reflect endothelial function, were also changed by these drugs. Our present study indicates that sitagliptin and exenatide administrations can improve endothelial function in diabetic aorta. Of note, RAGE/RhoA/ROCK and AMPK mediated NF-κB signaling pathways may be the intervention targets of these drugs to protect aortic endothelium.

Effects of guideline-based hypertension management in rural areas of Guangdong Province.

BACKGROUND: Despite the improvement in the health care industry, the rates of undetected, untreated, and uncontrolled hypertension (HTN) are still very high, especially in rural areas of China. The aim of this study was to investigate the efficacy and efficiency of a guideline-based HTN management (novel therapy) in population of rural areas of Guangdong Province. METHODS: Totally, 3113 patients with essential HTN in a rural area of Guangdong Province were enrolled and assigned to two groups, named traditional (n = 372) and novel therapeutic (n = 2741) groups, respectively. Patients in the traditional group were treated routinely, and patients in the novel group were treated in a novel model characterized by regular educational programs for hypertensive populations, close monitoring of blood pressure in combination with finely tuned antihypertensive medications, strict implementation of lifestyle modification and improving medical knowledge and skill of local medical staff efficiently. After 2 years of follow-up, primary endpoints including magnitude of systolic and diastolic blood pressures (SBP and DBP) decrease, treated and controlled rates, as well as secondary endpoints, were evaluated in both groups. RESULTS: Initially, the treated rate was significantly higher in traditional group than that of novel group (71.15% vs. 64.99%, P < 0.05), while the controlled rates were comparable and insignificant difference between baseline BP in both groups (31.07% vs. 26.88%, P > 0.05). Four variables were significantly different, namely smoking rate, daily vegetable consumption (VC), and serum levels of low-density lipoprotein-cholesterol and fasting blood glucose between these two groups. After 2 years of follow-up, decreases in SBP and DBP were more prominent in the novel group (P < 0.001). Treated and controlled rates in both groups were both increased. Nevertheless, in comparison to the traditional group, controlled rate increased more significantly in the novel group (64.31% vs. 37.85%, P < 0.001). Variables indicating lifestyle modification such as high sodium consumption, percentages of alcohol abuse, daily VC were profoundly improved in the novel group. CONCLUSIONS: The guideline-based HTN management implemented in the current study was beneficial for HTN control in rural areas of Guangdong Province.

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.