Buddy Balloon versus Buddy Wire Technique Regarding Accuracy of Stent Placement during Percutaneous Coronary Intervention.

We aimed to evaluate whether the buddy balloon technique (BBT) is superior to the buddy wire technique (BWT) with regard to the accuracy of stent placement during percutaneous coronary intervention (PCI).We enrolled patients who had been identified with significant stent movement before the stent was dilated at five hospitals and were randomly converted to either the BBT or BWT technique. The primary endpoints were the incidence of technical success and major adverse cardiovascular events (cardiac death, myocardial infarction, target lesion revascularization, and in-stent restenosis) at 2 years of follow-up. The secondary endpoints were the contrast volume used for the procedure and the total procedural time.From August 2018 to July 2019, 66 patients were enrolled, with 33 patients in each group. All patients were successfully followed up to 2 years. At the primary endpoints, compared with patients treated using BWT, those in the BBT group showed significantly better technical success (93.94% versus 39.39%, respectively; P < 0.0001). There was no significant difference in the incidence of major cardiovascular adverse events (6.06% versus 12.12%, respectively; P = 0.392). At the secondary endpoints, the contrast volume used for the procedure was lower with BBT (85.97 ± 22.45 versus 115.00 ± 21.45 mL, respectively; P < 0.0001); similarly, the total procedural time was shorter with BBT (65.94 ± 12.14 versus 74.33 ± 15.36 minutes, respectively; P < 0.0001).BBT could better restrict stent movement and facilitate precise stent deployment, with significant superiority over BWT. In addition, BBT can reduce the procedural time and contrast dose.

Atorvastatin rescues pulmonary artery hypertension via inhibiting the AKT/ERK-dependent PDGF-BB/HIF-1α axis.

BACKGROUND: To explore the role of Atorvastatin in rescuing pulmonary artery hypertension (PAH) via inhibiting the AKT/ERK-dependent PDGF-BB/HIF-1α axis. METHODS: PAH model in rats was established by MCT induction, followed by Atorvastatin intervention. Pulmonary hemodynamic measurement and pulmonary morphological evaluation in rats were conducted. Human pulmonary artery smooth muscle cells (hPASMCs) were subjected to hypoxic exposure or PDGF-BB treatment, followed by Atorvastatin induction. Relative levels of HIF-1α, p-ERK and p-Akt were detected. Viability and apoptosis were respectively determined by cell counting kit-8 (CCK-8) assay and flow cytometry. RESULTS: Atorvastatin protected PAH-induced increases in RVSP and Fulton's index in rats. Meanwhile, it inhibited vascular remodeling following PAH by downregulating HIF-1α and PDGF-BB. Hypoxia or PDGF-BB treatment in hPASMCs resulted in upregulation of p-ERK and p-Akt, and viability increase, which were partially abolished by Atorvastatin intervention. In addition, Atorvastatin triggered apoptosis in hypoxia or PDGF-BB-induced hPASMCs. CONCLUSIONS: Atorvastatin inhibits the activation of HIF-1α and proliferative ability, and triggers apoptosis in hPASMCs exposed to hypoxia or PDGF-BB treatment through inactivating the AKT/ERK pathway.

Efficacy and Safety of Sacubitril/Valsartan Therapy for Acute Decompensated Heart Failure with Reduced Ejection Fraction during the Vulnerable Phase: A Multicenter, Assessor-Blinded, Prospective, Observational, Cohort Study.

BACKGROUND: The 3-month period after hospitalization for acute cardiac failure is a vulnerable phase with the highest risk of mortality and rehospitalization. Safety and efficacy of early initiation of sacubitril/valsartan during the index hospitalization for acute decompensated heart failure (ADHF) is unclear. Therefore, we tested whether sacubitril/valsartan could result in a lower rate of a composite outcome of first hospitalization for heart failure and death from cardiovascular causes compared to inhibition of the renin-angiotensin system alone. METHODS: We enrolled patients hospitalized for ADHF and reduced ejection fraction at 4 sites; patients were divided into a sacubitril/valsartan group or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) group. All patients were followed up for 3 months after discharge. The primary endpoint was outcomes as a composite of death from cardiovascular causes and rehospitalization for heart failure. RESULTS: In total, 251 patients who received sacubitril/valsartan and 251 patients who received ACEIs/ARBs had similar propensity scores and were included and compared. The primary endpoint was reached in 40 patients (15.9%) treated with sacubitril/valsartan and in 59 patients (23.5%) managed by ACEI/ARB (HR, 0.650; 95% CI: 0.435-0.971; p = 0.035). The NYHA class improved in 72.1% of patients in the sacubitril/valsartan group and in 59.8% of patients in the ACEI/ARB group (HR, 1.303; 95% CI: 1.097-1.548, p = 0.004). The key safety outcomes endpoints did not significantly differ. CONCLUSIONS: Among patients hospitalized with ADHF and reduced left ventricular ejection fraction, we observed that sacubitril/valsartan therapy led to reduction in death from cardiovascular causes and rehospitalizations for heart failure when compared to ACEI/ARB therapy alone during the vulnerable phase. Our results support that sacubitril/valsartan may be administered early in the vulnerable phase after ADHF and improves NYHA class.

Nox4 and soluble epoxide hydrolase synergistically mediate homocysteine-induced inflammation in vascular smooth muscle cells.

BACKGROUND: Hyperhomocysteinemia leads to a vascular smooth muscle cell (VSMC) inflammatory response. Meanwhile, Nox4 dependent reactive oxygen species (ROS) signaling and soluble epoxide hydrolase (sEH)/epoxyeicosatrienoic acids (EETs) are both involved in vascular inflammation. Herein, we hypothesized that Nox4 and soluble epoxide hydrolase cross regulated during homocysteine-induced VSMC inflammation. METHODS AND RESULTS: In cultured VSMCs, the expression of the inflammatory factors VCAM1 and ICAM1 was measured by real-time PCR and Western blotting, while supernatant MCP1 was measured by ELISA. Upon VSMC stimulation with 50 µΜ homocysteine, we observed the VCAM1 and ICAM1 mRNA levels were increased by 1.15 and 1.0 folds, respectively. The MCP1 levels in the supernatant of cultured VSMCs treated with 100 µΜ increased to 1.76 folds. As expected, homocysteine induced Nox4 expression and Nox4-dependent ROS generation. The sEH expression was also upregulated in the presence of homocysteine in a dose-dependent manner. Furthermore, we knocked down Nox4 with siRNA. Knockdown of Nox4 decreased ROS generation and homocysteine-induced sEH expression. Overexpression of Nox4 with an adenovirus stimulated sEH expression. Similarly, knockdown or chemical inhibition of sEH blunted the upregulation of Nox4 by homocysteine. In vivo, in homocysteine-fed mice, concomitant upregulation of Nox4 and sEH was associated with increased VCAM1 and ICAM1 expression in the aortic wall. CONCLUSIONS: The inflammatory response induced by homocysteine in VSMCs was accompanied by Nox4 and sEH upregulation. Nox4 and soluble epoxide hydrolase synergistically contribute to homocysteine-induced inflammation.

Association between Low Free Triiodothyronine Levels and Poor Prognosis in Patients with Acute ST-Elevation Myocardial Infarction.

BACKGROUND: Low free triiodothyronine (fT3) levels are generally associated with poor prognosis in patients with heart diseases, but this is controversial and there is a lack of data about ST-elevation myocardial infarction (STEMI) in Chinese patients. OBJECTIVE: To assess the association between fT3 levels and the prognosis of patients with STEMI. METHODS: This was a prospective observational study of 699 consecutive patients with STEMI treated at the Xinqiao Hospital between January 1, 2013, and December 31, 2014. The patients were divided into the low fT3 (fT3 < 3.1 pmol/L; n = 179, 27.5%) and normal fT3 (fT3 ≥ 3.1 pmol/L; n = 473, 72.5%) groups according to fT3 levels at admission. Patients were followed up at 1, 3, 6, and 12 months for all-cause death and major adverse cardiac events (MACE). RESULTS: During the 1-year follow-up, there were 70 all-cause deaths (39.1%) in the low fT3 group and 40 (8.5%) in the normal fT3 group (P < 0.001). MACE occurred in 105 patients (58.7%) in the low fT3 group and 74 (15.6%) in the normal fT3 group (P < 0.001). Multivariate Cox proportional hazards regression analysis indicated that fT3 levels were independently associated with 30-day and 1-year all-cause death [30-day: hazard ratio (HR) = 0.702, 95% confidence interval (95% CI): 0.501-0.983, P = 0.04; 1-year: HR = 0.557, 95% CI: 0.411-0.755, P < 0.001] and MACE (30-day: HR = 0.719, 95% CI: 0.528-0.979, P = 0.036; 1-year: HR = 0.557, 95% CI: 0.445-0.698, P < 0.001). CONCLUSION: Low fT3 levels were strongly associated with poor prognosis in patients with STEMI. Measurement of fT3 levels may be a valuable and simple way to identify high-risk STEMI patients.

VEGF promotes endothelial progenitor cell differentiation and vascular repair through connexin 43.

BACKGROUND: Endothelial progenitor cell (EPC) differentiation is considered crucial for vascular repair. Vascular endothelial growth factor (VEGF) induces EPC differentiation, but the underlying mechanism of this phenomenon remains unclear. Connexin 43 (Cx43) is reported to be involved in the regulation of stem cell differentiation. Therefore, we sought to determine whether Cx43 is involved in VEGF-induced EPC differentiation and vascular repair. METHODS: Rat spleen-derived EPCs were cultured and treated with various concentrations of VEGF (0, 10, or 50 ng/mL), and the relationship between EPC differentiation and Cx43 expression was evaluated. Thereafter, fluorescence redistribution after photobleaching was performed to assess the relationship between adjacent EPC differentiation and Cx43-induced gap junction intercellular communication (GJIC). After carotid artery injury, EPCs pretreated with VEGF were injected into the tail veins, and the effects of Cx43 on vascular repair were evaluated. RESULTS: EPCs cultured with VEGF exhibited accelerated differentiation and increased expression of Cx43. However, inhibition of Cx43 expression using short interfering RNA (siRNA) attenuated EPC GJIC and consequent EPC differentiation. VEGF-pretreated EPC transplantation promoted EPC homing and reendothelialization, and inhibited neointimal formation. These effects were attenuated by siRNA inhibition of Cx43. CONCLUSIONS: Our results from in vivo and in vitro experiments indicated that VEGF promotes EPC differentiation and vascular repair through Cx43.

Fibroblast growth factor 23 as a predictor of cardiovascular and all-cause mortality in prospective studies.

BACKGROUND AND AIMS: The prognostic value of fibroblast growth factor 23 (FGF23) for mortality remains controversial. We performed a meta-analysis of cohort studies to examine the controversial relationship between FGF23 and mortality. METHODS: PubMed, EMBASE, the Cochrane Library databases and reference bibliographies were searched through September 2016 to identify prospective cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) for FGF23 and mortality. A random effects model was used to pool the risk estimates. A dose-response analysis of the risk for all-cause mortality associated with FGF23 was conducted using the generalized least squares trend estimation method. RESULTS: Nineteen prospective cohort studies were eligible for inclusion in this meta-analysis, of which 16 reported all-cause mortality and 9 reported cardiovascular mortality. During the follow-up periods ranging from 1 to 18.6 years, 5606 deaths occurred among 22,805 participants and 2458 cardiovascular deaths occurred among 28,845 participants. Elevated FGF23 was associated with an increased risk of all-cause mortality (RR 1.68; 95% CI 1.48-1.92) and cardiovascular mortality (RR 1.68; 95% CI 1.38-2.04) with moderate heterogeneity. These associations were not markedly modified by the geographic location, follow-up length, patient predisposition, FGF23 measurement or study quality. A sensitivity analysis yielded a similar effect on the pooled risk estimate. Evidence of a nonlinear relationship between FGF23 and all-cause mortality was observed in the dose-response analysis, with the risk gradually increasing as FGF23 increased. CONCLUSIONS: This meta-analysis showed that individuals with increased plasma FGF23 levels might suffer a higher risk of all-cause mortality and cardiovascular mortality.

Overexpression of Jagged1 Ameliorates Aged Rat-Derived Endothelial Progenitor Cell Functions and Improves Its Transfusion Efficiency for Rat Balloon-Induced Arterial Injury.

BACKGROUND: Endothelial progenitor cell (EPC) has significant age-dependent alterations in properties, but the role of Jagged1 in aging-induced decline of EPC functions remains unclear. METHODS: 2- and 20-month old healthy male Sprague-Dawley rats were used in present study. Jagged1 gene transfection was performed in EPC isolated from aged (AEPC) and young rats (YEPC), respectively. Experiments were divided into 4 groups: (1) pIRES2-EGFP (PE) group, (2) PE-combined N-[N-(3, 5-difluoro-phenacetyl)-1- alany1]-S-phenyglycine t-butyl ester (DAPT) (PE + D) group, (3) pIRES2 EGFP-Jagged1 (PEJ) group, and (4) PEJ combined DAPT (PEJ + D) group. Notch molecules were detected by real-time quantitative polymerase chain reaction or Western blotting. CD34, CD133, CD45, and KDR markers were detected by flow cytometry. EPC migration and proliferation were detected with a modified Boyden chamber and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, respectively; the tube formation ability was assayed by in vitro angiogenesis kit; EPC transfusion after Jagged1 gene transfection was performed in rat carotid artery injury models. RESULTS: Jagged1 gene transfection effectively activates notch-signaling pathway. Compared with PE groups, overexpression of Jagged1 significantly promoted AEPC functions including proliferation, migration, the tube formation ability, and cell differentiation, these effects could be reasonably diminished by DAPT. In vivo study demonstrated that Jagged1 overexpressing also significantly promoted AEPC homing to the vascular injury sites and decreases the neointima formation after vascular injury. CONCLUSIONS: Overexpression of Jagged1 ameliorates aged rat-derived EPC functions and increases its transfusion efficiency for balloon-induced rat arterial injury.

The association between periodontal disease and the risk of myocardial infarction: a pooled analysis of observational studies.

BACKGROUND: Several meta-analyses have indicated that periodontal disease (PD) are related to cardiovascular diseases (CVDs). However, the association between PD and myocardial infarction (MI) remains controversial. Here we aimed to assess the association between PD and MI by meta-analysis of observational studies. METHODS: PubMed, EMBASE and the Cochrane Library were searched through July, 2016. Observational studies including cohort, cross-sectional and case-control studies reporting odds ratio (OR) or relative risk (RR) with 95% confidence intervals (CIs) were included in the analysis. Either fixed or random-effects model were applied to evaluate the pooled risk estimates. Sensitivity and subgroup analyses were also carried out to identify the sources of heterogeneity. Publication bias was assessed by the Begg's, Egger's test and funnel plot. RESULTS: We included 22 observational studies with 4 cohort, 6 cross-sectional and 12 case-control studies, including 129,630 participants. Patients with PD have increased risk of MI (OR 2.02; 95% CI 1.59-2.57). Substantial heterogeneity in risk estimates was revealed. Subgroup analyses showed that the higher risk of MI in PD patients exists in both cross-sectional studies (OR 1.71; 95% CI 1.07-2.73) and case-control studies (OR 2.93; 95% CI 1.95-4.39), and marginally in cohort studies (OR 1.18; 95% CI 0.98-1.42). Further, subgroup meta-analyses by location, PD exposure, participant number, and study quality showed that PD was significantly associated with elevated risk of MI. CONCLUSION: Our meta-analysis suggested that PD is associated with increased risk of future MI. However, the causative relation between PD and MI remains not established based on the pooled estimates from observational studies and more studies are warranted.

N-terminal pro-brain natriuretic peptide and cardiovascular or all-cause mortality in the general population: A meta-analysis.

The prognostic role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the general population remains controversial. We conducted this meta-analysis to investigate the association between baseline NT-proBNP concentrations and cardiovascular or all-cause mortality in the general population. PubMed and Embase databases were systematically searched from their inception to August 2016. Prospective observational studies that investigated the association between baseline NT-proBNP concentrations and cardiovascular or all-cause mortality in the general population were eligible. A summary of the hazard ratio (HR) and 95% confidence interval (CI) of mortality were calculated by the highest versus the lowest category of NT-proBNP concentrations. Eleven studies with a total of 25,715 individuals were included. Compared individuals in the highest with those in the lowest category of NT-proBNP, the pooled HR was 2.44 (95% CI 2.11-2.83) for all-cause mortality, 3.77 (95% CI 2.85-5.00) for cardiovascular mortality, and 2.35 (95% CI 1.45-3.82) for coronary heart disease mortality, respectively. Subgroup analyses indicated that the effects of NT-proBNP on the risk of cardiovascular mortality (RR 2.27) and all-cause mortality (RR 3.00) appeared to be slightly lower among men. Elevated NT-proBNP concentrations appeared to be independently associated with increased risk of cardiovascular and all-cause mortality in the general population.

Irisin Increased the Number and Improved the Function of Endothelial Progenitor Cells in Diabetes Mellitus Mice.

The dysfunction of endothelial progenitor cells (EPCs) was found to be associated with vascular complications in diabetes mellitus (DM) patients. Previous studies found that regular exercise could improve the function of EPCs in DM patients, but the underling mechanism was unclear. Irisin, a newly identified myokine, was induced by exercise and has been demonstrated to mediate some of the positive effects of exercise. In this study, we hypothesize that irisin may have direct effects on EPC function in DM mice. These data showed for the first time that irisin increased the number of EPCs in peripheral blood of DM mice and improved the function of EPCs derived from DM mice bone marrow. The mechanism for the effect of irisin is related to the PI3K/Akt/eNOS pathway. Furthermore, irisin was demonstrated to improve endothelial repair in DM mice that received EPC transplants after carotid artery injury. The results of this study indicate a novel effect of irisin in regulating the number and function of EPCs via the PI3K/Akt/eNOS pathway, suggesting a potential for the administration of exogenous irisin as a succedaneum to improve EPC function in diabetic patients who fail to achieve such improvements through regular exercise.

The ubiquitin-activating enzyme E1 as a novel therapeutic target for the treatment of restenosis.

AIMS: The ubiquitin-activating enzyme E1 (UBA1, E1), the apex of the ubiquitin proteasome pathway, plays a critical role in protein degradation and in pathological processes. Whether UBA1 participates the development of vascular restenosis remains unknown. This study aims to determine the role of UBA1 in the development of balloon injury induced neointimal formation. METHODS AND RESULTS: Immunostaining and western blots were used to examine the expression of the ubiquitinated protein in the injured carotid after angioplasty. Higher levels of ubiquitinated protein were observed in the neointima. Local delivery of potent chemical UBA1 inhibitor PYR-41 (100 µM) and UBA1 shRNA lentivirus both resulted in a substantial decrease in intimal hyperplasia at 2 weeks and 4 weeks after balloon injury. UBA1 inhibition also reduced Ki-67 positive cell percentage and inflammatory response in the carotid artery wall. We further determined that in vitro UBA1 inhibition was able to ameliorate TNF-α-induced nuclear factor-kappa B (NF-κB) activation by reducing IκB degradation in vascular smooth muscle cells (VSMCs). UBA1 inhibition also led to the accumulation of short-lived proteins such as p53, p21 and c-jun, which may account for the UBA1 inhibition-induced cell cycle delay. Thus, VSMCs proliferation was blocked. CONCLUSIONS: UBA1 inhibition effectively suppresses neointimal thickening through its anti-proliferative and anti-inflammatory effects. Our results provide further evidence that the ubiquitin-proteasome system is a potential new target for the prevention of vascular restenosis.

Protective effect of a polysaccharide from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial injury in rats.

In this study, we investigated the cardioprotective effect of one purified polysaccharide (SMP1) from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. ISO-treated rats showed severe myocardial damage and high lipid peroxidation level, as well as decreased endogenous myocardial antioxidant function. Pretreatment with SMP1 (100 and 400mg/kg) for 30 days significantly increased the body weight, decreased the heart weight, attenuated the serum levels of creatine kinase (CK), creatine phospokinase-MB (CK-MB), dehydrogenase (LDH), alkaline phosphate (ALP), aspartate transaminase (AST), alanine transaminase (ALT), total cholesterol, triglyceride, and LDL-cholesterol (LDL-C), along with the increased concentration of HDL-cholesterol (HDL-C). In addition, SMP1 also enhanced myocardial superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities and elevated myocardial reduced glutathione (GSH) level, along with a decrease in thiobarbituric acid reactive substances (TBARS) concentration. Collectively, our results indicated that long-term oral administration of SMP1 offered significant protection against the damage induced by ISO in rat heart through enhancement of endogenous antioxidants and antihyperlipidemic activity.

Glycogen synthase kinase 3ß inhibition enhanced proliferation, migration and functional re-endothelialization of endothelial progenitor cells in hypercholesterolemia microenvironment.

Hypercholesterolemia impairs the quantity and function of endothelial progenitor cell. We hypothesized that glycogen synthase kinase 3ß activity is involved in regulating biological function of endothelial progenitor cells in hypercholesterolemia microenvironment. For study, endothelial progenitor cells derived from apolipoprotein E-deficient mice fed with high-fat diet were used. Glycogen synthase kinase 3ß activity was interfered with glycogen synthase kinase 3ß inhibitor lithium chloride or transduced with replication defective adenovirus vector expressing catalytically inactive glycogen synthase kinase 3ß (GSK3ß-KM). Functions of endothelial progenitor cells, proliferation, migration, secretion and network formation of endothelial progenitor cells were assessed in vitro. The expression of phospho-glycogen synthase kinase 3ß, ß-catenin and cyclinD1 in endothelial progenitor cells was detected by Western blot. The in vivo function re-endothelialization and vasodilation were also analyzed by artery injury model transplanted with glycogen synthase kinase 3ß-inhibited endothelial progenitor cells. We demonstrated that while the proliferation, migration, network formation as well as VEGF and NO secretion were impaired in apolipoprotein E-deficient endothelial progenitor cells, glycogen synthase kinase 3ß inhibition significantly improved all these functions. Apolipoprotein E-deficient endothelial progenitor cells showed decreased phospho-glycogen synthase kinase 3ß, ß-catenin and cyclinD1 expression, whereas these signals were enhanced by glycogen synthase kinase 3ß inhibition and accompanied with ß-catenin nuclear translocation. Our in vivo model showed that glycogen synthase kinase 3ß inhibition remarkably increased re-endothelial and vasodilation. Taken together, our data suggest that inhibition of glycogen synthase kinase 3ß is associated with endothelial progenitor cell biological functions both in vitro and in vivo. It might be an important interference target in hypercholesterolemia microenvironment.

Cardiovascular effects in vitro of a polysaccharide from Salvia miltiorrhiza.

A polysaccharide (SMP1) was isolated from the roots of Salvia miltiorrhiza. This study is designed to investigate whether SMP1 prevents H9c2 cells from hydrogen peroxide (H2O2)-induced apoptosis. The present study showed that exposure of H9c2 cells to 100mM H2O2 for 24h caused a significant increase in cell death and apoptosis, but pretreatment with SMP1 eliminated H2O2-induced apoptotic cell death. Furthermore, pretreatment with SMP1 significantly prevented the mitochondria disruption, cytochrome c release, the rise of the ratio between proapoptotic Bax and antiapoptotic Bcl-2 protein expression, and caspase-3 activation in H9c2 cells upon H2O2 stimulation. Moreover, the decline of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities together with the elevation of malondialdehyde (MDA) in PC12 cells exposed to H2O2 were remarkably reversed to normal levels by pretreatment with SMP1. These results suggest that SMP1 protects H9c2 cells from H2O2-induced apoptosis through inhibition of mitochondrial dysfunction, inactivation of caspase-3 cascade and enhancement of antioxidant capacity.

Laboratory aspirin resistance and the risk of major adverse cardiovascular events in patients with coronary heart disease on confirmed aspirin adherence.

AIM: Previous meta-analyses have demonstrated an increased risk of adverse events in aspirin-resistant patients. In this meta-analysis, we aimed to update clinical evidence regarding the relationship between aspirin resistance and major adverse cardiovascular events (MACEs) in patients with coronary heart disease (CHD) on confirmed aspirin adherence. METHODS: An electronic literature search of PubMed, EMBASE, Web of Science and the Cochrane Library and a hand search of bibliographies through April 2013 were conducted. Studies were included if they prospectively investigated the association between aspirin resistance and the risk of adverse cardiovascular events during follow-up in CHD patients, mentioned confirmed compliance and provided adequate data for a statistical analysis. RESULTS: Nine prospective studies with a total 1,889 CHD patients who were followed for one month to 2.5 years and study sample sizes ranging from 86 to 496 patients were identified. Overall, 622 of the 1,889 CHD patients (33.0%) were classified as being aspirin resistant with confirmed aspirin adherence. The aspirin-resistant patients exhibited a significantly higher risk of adverse events than the aspirin-sensitive patients (odds ratio 2.44, 95% confidence interval 1.81 to 3.30; p＜0.00001). CONCLUSIONS: Among CHD patients, approximately one in three individuals can be diagnosed as aspirin resistant on confirmed aspirin adherence. Patients identified as having laboratory aspirin resistance exhibit a 2.4-fold increased risk of MACE compared with aspirin-sensitive patients.

Optimization of extraction and purification of arctiin from Fructus arctii and its protection against glucose-induced rat aortic endothelial cell injury.

To develop an efficient method for extracting and purifying the active ingredient, arctiin, from Fructus arctii and to investigate the protective effect of arctiin against glucose-induced rat aortic endothelial cell (RAEC) injury was investigated. Using a L9 (34) orthogonal array and two-step column chromatography (with AB-8 macroporous resin) arctiin extraction was optimized using a reflux method with 70% ethanol. The RAECs were then treated with different concentrations of arctiin (1, 10, or 100 µg/ml). The effects of arctiin on cell viability in a high glucose medium, malondialdehyde (MDA) levels, and lactate dehydrogenase were measured using commercially available assays. After extraction, the purity of arctiin reached 95.7%. In rats, arctiin was shown to stimulate the proliferation of RAECs in a high glucose medium in a dose-dependent manner. Exposure of RAECs to high glucose resulted in a significant increase in MDA and release of lactate dehydrogenase. This was accompanied by significant increase in nitric oxide release and expression of antiendothelial nitric oxide synthase. This technique resulted in relatively pure arctiin extraction. Furthermore, the results from this study suggest that arctiin could potentially function as a protector against vascular endothelial cell injury and further investigation is warranted.

Tailored antiplatelet therapy and clinical adverse outcomes.

OBJECTIVE: The clinical evidence regarding the influence of tailored antiplatelet strategy on adverse outcomes has been controversial. The aim of the study was to evaluate the significance of tailored antiplatelet therapy with respect to clinical adverse events in antiplatelet-resistant patients. METHODS: Randomised studies that assess clinical relevance of personalised antiplatelet treatment in antiplatelet-resistant patients were identified through a literature search: PubMed, EMBASE, Web of Science and the Cochrane Library. The primary endpoint was the composite of death from any cause and stent thrombosis. All total clinical adverse events and bleeding complications were evaluated. RESULTS: Data were combined across seven randomised studies comprising 12 048 subjects, of whom 3738 (31.0%) were found to be antiplatelet-resistant. Antiplatelet-resistant patients provided with tailored antiplatelet therapy showed less risk of death or stent thrombosis than those assigned conventional antiplatelet treatment (0.5% vs. 2.2%; OR (95% CI) 0.25 (0.13 to 0.49), p<0.0001). A significant benefit in terms of total adverse event risk reduction was observed during follow-up for tailored vs conventional antiplatelet therapy (5.5% vs. 10.0%; OR (95% CI) 0.40 (0.20 to 0.77), p=0.006). No statistical difference in bleeding complications was observed between these two groups (p=0.08). CONCLUSIONS: In the study, personalised antiplatelet treatment for antiplatelet resistance was found to be associated with less occurrence of death or stent thrombosis and the less risk of total clinical adverse events than conventional treatment, without increasing the risk of bleeding complications.

Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and all-cause mortality: a meta-analysis of prospective studies.

OBJECTIVE: Serum uric acid (SUA) levels have been used to predict cardiovascular and all-cause mortality event, but the data have yielded conflicting results. We investigated whether SUA was an independent predictor for cardiovascular or all-cause mortality with prospective studies by meta-analysis. METHODS: Pubmed and Embase were searched without language restrictions for publications available till April 2013. Only prospective studies on cardiovascular or all-cause mortality related to SUA levels were included. Pooled adjust relative risk (RR) and corresponding 95% confidence intervals (CI) were calculated separately for the highest vs. lowest category or the lowest vs. middle category. RESULTS: For the highest SUA, eleven studies with 172,123 participants were identified and analyzed. Elevated SUA increased risk of all-cause mortality (RR 1.24; 95% CI 1.09-1.42) and cardiovascular mortality (RR 1.37; 95% CI 1.19-1.57). Subgroup analyses showed that elevated SUA significantly increase the risk of all-cause mortality among men (RR 1.23; 95% CI 1.08-1.42), but not in women (RR 1.05; 95% CI 0.79-1.39). Risk of cardiovascular mortality appeared to be more pronounced among women (RR 1.35; 95% CI 1.06-1.72). The association between extremely low SUA and mortality was reported in three studies; we did not perform a pooled analysis because of high degree of heterogeneity in these studies. CONCLUSIONS: Baseline SUA level is an independent predictor for future cardiovascular mortality. Elevated SUA appears to significantly increase the risk of all-cause mortality in men, but not in women. Whether low SUA levels are predictors of mortality is still inconclusive.