Xiankai Li

Peripheral arterial disease, chronic kidney disease, and mortality: The Chinese Ankle Brachial Index Cohort Study

The purpose of this study was to investigate the association between chronic kidney disease (CKD) and peripheral arterial disease (PAD) and examine the combined effect of CKD and PAD on all-cause and cardiovascular disease (CVD) mortality. The Chinese Ankle Brachial Index Cohort consisted of 3732 adults aged 35 years or older enrolled in 2004 and followed-up in 2007. Complete baseline data were compiled on 3610 people which were examined in the final analysis. Mortality surveillance was completed from December 2007 to February 2008. Survival analysis was used to compare the survival rate in different CKD/PAD groups. The relative risks (RR) of death from all-cause and CVD were compared using a Cox regression model. It was found that the prevalence of PAD in patients with and without CKD was 41.9% and 22.3%, respectively (p < 0.001). The survival rate for the CKD and PAD group was significantly lower than that for any single disease, for both all-cause and CVD mortality (log-rank: p < 0.001). In conclusion, CKD is a risk factor for PAD. The combined CKD and PAD patients had the highest risk for all-cause and CVD mortality. Early recognition of risk can be made by taking an ankle-brachial index measurement of PAD; a corresponding laboratory assessment should be used as a measurement of renal function for PAD patients.The purpose of this study was to investigate the association between chronic kidney disease (CKD) and peripheral arterial disease (PAD) and examine the combined effect of CKD and PAD on all-cause and cardiovascular disease (CVD) mortality. The Chinese Ankle Brachial Index Cohort consisted of 3732 adults aged 35 years or older enrolled in 2004 and followed-up in 2007. Complete baseline data were compiled on 3610 people which were examined in the final analysis. Mortality surveillance was completed from December 2007 to February 2008. Survival analysis was used to compare the survival rate in different CKD/PAD groups. The relative risks (RR) of death from all-cause and CVD were compared using a Cox regression model. It was found that the prevalence of PAD in patients with and without CKD was 41.9% and 22.3%, respectively (p < 0.001). The survival rate for the CKD and PAD group was significantly lower than that for any single disease, for both all-cause and CVD mortality (log-rank: p < 0.001). In conclusion, CKD is a risk factor for PAD. The combined CKD and PAD patients had the highest risk for all-cause and CVD mortality. Early recognition of risk can be made by taking an ankle–brachial index measurement of PAD; a corresponding laboratory assessment should be used as a measurement of renal function for PAD patients.

Vinpocetine Attenuates Neointimal Hyperplasia in Diabetic Rat Carotid Arteries after Balloon Injury

Background Diabetes exacerbates abnormal vascular smooth muscle cell (VSMC) accumulation in response to arterial wall injury. Vinpocetine has been shown to improve vascular remolding; however, little is known about the direct effects of vinpocetine on vascular complications mediated by diabetes. The objective of this study was to determine the effects of vinpocetine on hyperglycemia-facilitated neointimal hyperplasia and explore its possible mechanism. Materials and Methods Nondiabetic and diabetic rats were subjected to balloon injury of the carotid artery followed by 3-week treatment with either vinpocetine (10 mg/kg/day) or saline. Morphological analysis and proliferating cell nuclear antigen (PCNA) immunostaining were performed on day 21. Rat VSMCs proliferation was determined with 5-ethynyl-20-deoxyuridine cell proliferation assays. Chemokinesis was monitored with scratch assays, and production of reactive oxygen species (ROS) was assessed using a 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) flow cytometric assay. Apoptosis was detected by annexin V-FITC/PI flow cytometric assay. Cell signaling was assessed by immunblotting. Results Vinpocetine prevented intimal hyperplasia in carotid arteries in both normal (I/M ratio: 93.83 ± 26.45% versus 143.2 ± 38.18%, P<0.05) and diabetic animals (I/M ratio: 120.5 ± 42.55% versus 233.46 ± 33.98%, P<0.05) when compared to saline. The in vitro study demonstrated that vinpocetine significantly inhibited VSMCs proliferation and chemokinesis as well as ROS generation and apoptotic resistance, which was induced by high glucose (HG) treatment. Vinpocetine significantly abolished HG-induced phosphorylation of Akt and JNK1/2 without affecting their total levels. For downstream targets, HG-induced phosphorylation of IκBα was significantly inhibited by vinpocetine. Vinpocetine also attenuated HG-enhanced expression of PCNA, cyclin D1 and Bcl-2. Conclusions Vinpocetine attenuated neointimal formation in diabetic rats and inhibited HG-induced VSMCs proliferation, chemokinesis and apoptotic resistance by preventing ROS activation and affecting MAPK, PI3K/Akt, and NF-κB signaling.

The Gender Differences in Baseline Characteristics and Statin Intervention Among Outpatients with Coronary Heart Disease in China: The China Cholesterol Education Program

The China Cholesterol Education Program (CCEP) aimed to investigate the baseline characteristics of outpatients with coronary heart disease (CHD) according to gender, especially lipid levels, statin intervention, and rates of achieving their goal low‐density lipoprotein cholesterol (LDL‐C) level.

KCNE1 rs1805127 polymorphism increases the risk of atrial fibrillation: a meta-analysis of 10 studies.

Background Atrial fibrillation (AF) is one of the most common types of arrhythmia in humans. Recently, many studies have investigated the relationship between human atrial fibrillation and the single nucleotide polymorphism (SNP) of rs1805127 (A>G) in KCNE1 gene, but the results were still inconsistent and inconclusive. Method Electronic databases and bibliographies of retrieved studies were searched. We performed a meta-analysis of ten case-control studies, including 2099 cases and 2252 controls, to evaluate the association of rs1805127 polymorphism (A>G) with the risk of AF. Random-effects model was used when the heterogeneity was obvious; otherwise, fixed-effects model was applied. Meta-regression was performed to examine potential source of heterogeneity. Eggers test and Beggs test were used to detect publication biases. Results The results showed a significantly increased risk of AF in homozygote comparison (GG vs. AA:OR = 1.899, 95%CI: 1.568, 2.300; Pheterogeneity = 0.217), heterozygote comparison (GA vs. AA:OR = 1.436, 95% CI:1.190, 1.732; Pheterogeneity = 0.739), dominant model(GA /GG vs. AA: OR = 1.624, 95%CI: 1.361, 1.938; Pheterogeneity = 0.778) and recessive model (GG vs. GA/AA: OR = 1.394, 95%CI:1.152, 1.686; Pheterogeneity = 0.03). Meta-regression revealed that the sample size and the types of AF were the source of the heterogeneity. Conclusion The rs1805127 polymorphism (A>G) of KCNE1 is associated with an increased risk of AF, which suggests the rs1805217 polymorphism of KCNE1 gene may play an important role in the pathogenesis of AF.

Combined effects of smoking and peripheral arterial disease on all-cause and cardiovascular disease mortality in a Chinese male cohort

OBJECTIVE Smoking is a major risk factor for peripheral arterial disease (PAD), and PAD is associated with all-cause and cardiovascular disease (CVD) mortality. The objective of this study was to determine the combined effects of smoking and PAD on all-cause and CVD mortality. METHODS A total of 1979 males 35 years of age or older were enrolled from eight university-affiliated hospitals in Beijing and Shanghai in 2004, with both smoking status and PAD diagnosis obtained, 1712 of them had complete follow-up data. Mortality data were obtained from all participants between December 2007 and February 2008. Cox proportional hazards models were used to evaluate relative risks (RRs) of all-cause mortality and CVD mortality among different groups. RESULTS At baseline, the average age of participants was 66.98-years-old (SD = 11.57), prevalence of PAD was 24.0% and 65.4% smoked cigarettes. During the 3-year follow-up, all-cause cumulative mortality rates were 27.9% (PAD/smoker), 26.3% (PAD/nonsmoker), 14.1% (no PAD/smoker), and 14.4% (no PAD/nonsmoker) (P < .001), and CVD cumulative mortality rates were 17.8%, 14.9%, 8.1%, and 7.3%, respectively (P < .001). Compared with the no PAD/nonsmoker subjects, adjusted RR from all-cause mortality in the groups of both PAD/smoker, PAD/nonsmoker, and no PAD/smoker were 1.88 (95% confidence interval [CI], 1.34-2.64), 1.37 (95% CI, 0.85-2.23), and 1.08 (95% CI, 0.79-1.49), respectively. The adjusted RR from CVD mortality was 2.12 (95% CI, 1.37-3.28), 1.55 (95% CI, 0.84-2.86), and 1.13 (95% CI, 0.74-1.71), respectively. CONCLUSION PAD is a major determinant of mortality. Smoking did not contribute to mortality in this study. Further research is needed.

The basic social medical insurance is associated with clinical outcomes in the patients with ST-elevation myocardial infarction: a retrospective study from Shanghai, China.

Objective: Several social economic factors play important roles in treatments of ST-elevation myocardial infarction (STEMI) and finally influence the clinical outcomes. The basic social medical insurance (BSMI) is an important economic factor in Chinas medical system. However, the impact of BSMI on clinical outcomes in STEMI patients has not been explored yet. The aim of this study is to investigate whether BSMI is a predictor of clinical outcomes in the patients with STEMI in Shanghai, China. Material and methods: In this retrospective study, 681 STEMI patients from different areas in Shanghai were classified into four groups: new rural cooperative medical scheme (NCMS) group, urban resident basic medical insurance scheme (URBMI) group, urban employee basic medical insurance scheme (UEBMI) group and UNINSURED group, major adverse events (cardiac death, nonfatal reinfarction, clinically driven target lesion revascularization/target vessel revascularization, stroke, heart failure) were regarded as study endpoints to determine whether BSMI was a prognostic factor. Results: During a mean follow-up of 36 months, the incidence of major adverse events was significantly higher in NCMS patients (64; 38.8%) compared with the other groups: URBMI (47; 24.6%); UEBMI (28; 15.6%); UNISURED (40; 27.6%). Similarly, cardiac mortality was also higher in NCMS group (19; 11.5%). A Kaplan-Meier survival analysis revealed significantly lower event-free survival rate for major adverse events (p < 0.001) and cardiac mortality (p = 0.01) in NCMS group. Multivariate Cox regression analysis revealed that BSMI was an important prognostic factor in STEMI patients. Conclusion: These results demonstrate that BSMI is closely associated with the major adverse events-free survival rate at 36-month follow-up in the STEMI patients under the current policies in Shanghai, China.

Factors Associated with Blood Pressure Control in Hypertensive Patients with Coronary Heart Disease: Evidence from the Chinese Cholesterol Education Program

Blood pressure (BP) remains poorly controlled among hypertensive patients with coronary heart disease (CHD) in China. Improvement of its management will require an understanding of the patient characteristics and treatment factors associated with uncontrolled hypertension. A cross-sectional survey of 3,279 patients from 52 centers in China was performed to examine potential barriers to adequate blood pressure control of hypertensive patients with CHD. Uncontrolled hypertension was defined as blood pressure ≥130/or 80 mmHg. Multivariable logistic regression was used to identify factors associated with poor blood pressure control. Mean age of the patients was 65 years, 40% were women, and mean BMI was 25 kg/m2. Mean systolic blood pressure was 136±18 mmHg and mean diastolic blood pressure was 80±11 mmHg. Only 18% of patients had a mean blood pressure <130/80 mmHg during the study period. Multivariate analysis revealed several independent factors of poor blood pressure control: body mass index ≥23 kg/m2, the presence of stable angina pectoris (SAP), family history of diabetes, and use of calcium channel blockers (CCB). Further analysis showed that non-dihydropyridine calcium antagonist was significantly correlated with low BP control rate. Some of these may be amenable to modification. The results of our study suggest that overweight, the presence of SAP and family history of diabetes are important factors for tight BP control in primary care. In addition, non-dihydropyridine calcium channel blockers appear less effective than other therapies in control of blood pressure and should not be the first choice among hypertensive patients with CHD. Further identification of patients at risk of poor BP control can lead to targeted interventions to improve management.

Tesaglitazar ameliorates non-alcoholic fatty liver disease and atherosclerosis development in diabetic low-density lipoprotein receptor-deficient mice.

Previous research has demonstrated that the dual PPARα/γ agonist tesaglitazar reduces atherosclerosis in a mouse model of hyperlipidemia by reducing both lipid content and inflammation in the aorta. However, much of the underlying mechanism of tesaglitazar in non-alcoholic fatty liver disease (NAFLD) remains less clear. The aim of the present study was to determine whether tesaglitazar attenuates NAFLD and atherosclerosis development in diabetic low-density lipoprotein receptor-deficient (LDLr−/−) mice. Female LDLr−/− mice (3 weeks old) were induced by a high-fat diet (HFD) combined with low-dose streptozotocin (STZ) injection to develop an animal model of type 2 diabetes (T2DM). The mice were randomly divided into two groups: diabetic group (untreated diabetic mice, n=15) and tesaglitazar therapeutic group (n=15, 20 μg/kg/day oral treatment for 6 weeks). Fifteen LDLr−/− mice were fed with an HFD as the control group. Tesaglitazar decreased serum glucose and lipid levels compared with the diabetic mice. Tesaglitazar significantly reduced atherosclerotic lesions, lipid accumulation in the liver, macrophage infiltration, and decreased total hepatic cholesterol and triglyceride content compared to the diabetic mice. In addition, tesaglitazar reduced inflammatory markers at both the serum and mRNA levels. Our data suggest that tesaglitazar may be effective in preventing NAFLD and atherosclerosis in a pre-existing diabetic condition by regulating glucose and lipid metabolism, and the inflammatory response.

Optimal Blood Pressure in Patients after Stroke in Rural Areas of China

BACKGROUND The purpose of this study was to investigate the impact of different blood pressure (BP) categories on risk of developing cardiovascular disease (CVD) events and mortality, and to evaluate the optimal range of BP in patients after stroke in rural areas of China. METHODS We performed a post hoc analysis of 1058 patients with a history of stroke or transient ischemic attack from the Northeast China Rural Cardiovascular Health Study. The average follow-up systolic blood pressure (SBP) and diastolic blood pressure (DBP) were categorized into 10-mm Hg increments. The primary outcome was a composite of death due to any cause, nonfatal coronary heart disease, and nonfatal stroke. The secondary outcomes were recurrent stroke, CVD events, CVD mortality, and all-cause mortality. RESULTS The relationship between BP (systolic and diastolic) followed a J- or U-shaped curve with primary and secondary outcomes, with increased event rates at low and high BP values, both unadjusted variables and after adjustment for baseline confounding variables. The event rates were lowest in the SBP of 110-119 and DBP of 80-89 mm Hg. Patients with a BP lower than 110/70 or 140/90 mm Hg or higher had a significantly increased risk of worse outcomes. CONCLUSIONS For stroke survivors, a J- or U-shaped curve association exists between BP and the risk of future CVD events and mortality, with the lowest event rates in the BP range of 110-119 systolic and 80-89 diastolic. SBPs of 110-139 and DBPs of 70-89 are the appropriate range for patients after stroke in rural areas of China.

XAV939 Inhibits Intima Formation by Decreasing Vascular Smooth Muscle Cell Proliferation and Migration Through Blocking Wnt Signaling

Background: Excessive proliferation, migration, and oxidative stress of vascular smooth muscle cells (VSMCs) are key mechanisms involved in intima formation, which is the basic pathological process of in stent restenosis. This study aims at exploring the role of XAV939 in proliferation, migration, and reactive oxygen species (ROS) generation of VSMCs, and hence evaluating its effects on intima formation. Methods: Carotid artery ligation models for C57BL/6 mice were established and gave them different intervention: saline, XAV939, Axin2 overexpression adenovirus, and negative control adenovirus. The intima formation was assayed by intima area and intima/media ratio. To investigate the underlying mechanisms, primary rat VSMCs were cultured and treated with XAV939 and platelet-derived growth factor-BB. EdU, direct cell counting, cell wound–healing assay, and flow cytometry were used to measure proliferation, migration, cell cycle, apoptosis, and ROS generation of VSMCs, respectively. By Western blot, we examined proliferating cell nuclear antigen, Cyclin D1, Cyclin E, p21, &bgr;-actin, JNK, phosphorylated JNK, Axin2 and &bgr;-catenin expression. Immunofluorescence staining and confocal microscopy were conducted to detect translocation of &bgr;-catenin. Results: XAV939 inhibited intima formation, which was exhibited by the loss of intima area and I/M ratio and attenuated proliferation, migration, and ROS generation, as well as promoted cell cycle arrest of VSMCs. Specifically, XAV939 inhibited Wnt pathway. Conclusions: XAV939 attenuates intima formation because of its inhibition of proliferation, migration, and apoptosis of VSMCs through suppression of Wnt signaling pathway.