The relative and combined ability of stress hyperglycemia ratio and N-terminal pro-B-type natriuretic peptide to predict all-cause mortality in diabetic patients with multivessel coronary artery disease.

BACKGROUND: Stress hyperglycemia ratio (SHR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased mortality risk in diabetic patients with coronary artery disease (CAD). However, the role of these biomarkers in patients with diabetes and multivessel disease (MVD) remains unknown. The present study aimed to assess the relative and combined abilities of these biomarkers to predict all-cause mortality in patients with diabetes and MVD. METHODS: This study included 1148 diabetic patients with MVD who underwent coronary angiography at Tianjin Chest Hospital between January 2016 and December 2016. The patients were divided into four groups according to their SHR (SHR-L and SHR-H) and NT-proBNP (NT-proBNP-L and NT-proBNP-H) levels. The primary outcome was all-cause mortality. Multivariate Cox regression analyses were performed to evaluate the association of SHR and NT-proBNP levels with all-cause mortality. RESULTS: During a mean 4.2 year follow-up, 138 patients died. Multivariate analysis showed that SHR and NT-proBNP were strong independent predictors of all-cause mortality in diabetic patients with MVD (SHR: HR hazard ratio [2.171; 95%CI 1.566-3.008; P < 0.001; NT-proBNP: HR: 1.005; 95%CI 1.001-1.009; P = 0.009). Compared to patients in the first (SHR-L and NT-proBNP-L) group, patients in the fourth (SHR-H and NT-proBNP-H) group had the highest mortality risk (HR: 12.244; 95%CI 5.828-25.721; P < 0.001). The areas under the curve were 0.615(SHR) and 0.699(NT-proBNP) for all-cause mortality. Adding either marker to the original models significantly improved the C-statistic and integrated discrimination improvement values (all P < 0.05). Moreover, combining SHR and NT-proBNP levels into the original model provided maximal prognostic information. CONCLUSIONS: SHR and NT-proBNP independently and jointly predicted all-cause mortality in diabetic patients with MVD, suggesting that strategies to improve risk stratification in these patients should incorporate SHR and NT-porBNP into risk algorithms.

Prognostic performance of multiple biomarkers in patients with acute coronary syndrome without standard cardiovascular risk factors.

Background and aims: Acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRFs) represents a special case of ACS. Multiple biomarkers have been shown to improve risk stratification in patients with ACS. However, the utility of biomarkers for prognostic stratification in patients with ACS without SMuRFs remains uncertain. The aim of the present study was to evaluate the prognostic value of various biomarkers in patents with ACS without SMuRFs. Methods: Data of consecutive patients with ACS without SMuRFs who underwent coronary angiography in Tianjin Chest Hospital between January 2014 and December 2017 were retrospectively collected. The primary outcome was the occurrence of major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, myocardial infarction and stroke. Seven candidate biomarkers analyses were analyzed using models adjusted for established risk factors. Results: During a median 5-year follow-up, 81 of the 621 patients experienced a MACE. After adjustment for important covariates, elevated fibrinogen, D-dimer, N-terminal proB-type natriuretic peptide (NT-proBNP), and lipoprotein (a) [Lp(a)] were found to be individually associated with MACE. However, only D-dimer, NT-proBNP and Lp(a) significantly improved risk reclassification for MACE (all P < 0.05). The multimarker analysis showed that there was a clear increase in the risk of MACE with an increasing number of elevated biomarkers and a higher multimarker score. The adjusted hazard ratio- for MACE (95% confidential intervals) for patients with 4 elevated biomarkers was 6.008 (1.9650-18.367) relative to those without any elevated biomarker-. Adding- the 4 biomarkers or the multimarker score to the basic model significantly improved the C-statistic value, the net reclassification index and the integrated discrimination index (all P < 0.05). Conclusion: Fibrinogen, D-dimer, NT-proBNP and Lp(a) provided valuable prognostic information for MACE when applied to patients with ACS without SMuRFs. The multimarker strategy, which combined multiple biomarkers reflecting different pathophysiological process with traditional risk factors improved the cardiovascular risk stratification.

Association of D-dimer with long-term prognosis in type 2 diabetes mellitus patients with acute coronary syndrome.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (DM) accounts for more and more individuals worldwide. D-dimer has been demonstrated to be associated with cardiovascular diseases. The aim is to study the potential impact of D-dimer on the long-term prognosis of acute coronary syndrome (ACS) in the special population with type 2 DM. METHODS AND RESULTS: A total of 2265 consecutive patients with DM and ACS were eligible in the study. Patients were divided into four groups according to quartiles of D-dimer concentration. Univariate and multivariate Cox regression analysis were conducted to explore the prognostic value of D-dimer for future outcomes. Patients with higher level of D-dimer presented with higher percentage of major adverse cardiovascular events (MACEs) (23.7%), all-cause death (18.3%) and cardiovascular (CV) death (9.4%) in Quartile 4. In multivariate Cox regression analysis, D-dimer was demonstrated to be independently associated with MACEs, all-cause death and CV death. The prognostic value of D-dimer is still significant in subgroups of HbA1C <7% and ≥7%. In Kaplan-Meier analysis, higher D-dimer showed poorer prognosis in MACEs, all-cause death and CV death (all log rank p < 0.001). The area under the curve (AUC) by receiver operating characteristic (ROC) curve analysis is 0.609 for MACEs, 0.708 for all-cause death, 0.747 for CV death (p < 0.001). CONCLUSION: The present study demonstrated the independent predictive value of D-dimer for outcomes in DM patients with ACS. In addition, for the first time, we explored the prognostic value in different glucose control status.

The de Winter electrocardiographic pattern evolves to ST elevation in acute total left main occlusion: A case series.

The de Winter electrocardiographic (ECG) pattern was characterized by upsloping ST-segment depressions, tall and positive symmetrical T waves in precordial leads. This rare ECG pattern was recognized as an indication of proximal left anterior descending artery occlusion. Less commonly, this ECG pattern was reported in association with occlusion of other coronary artery segments. We present three cases of the de Winter pattern associated with acute total left main occlusion. This pattern may evolve to ST elevation within hours of presentation. Widespread upsloping ST-segment depressions from V2 -V6 , centered on V5 were observed in these patients.

Prognostic Significance of Preprocedural N-Terminal Pro-B-Type Natriuretic Peptide Assessment in Diabetic Patients With Multivessel Coronary Disease Undergoing Revascularization.

Background and Aims: The N-terminal pro-B-type natriuretic peptide (NT-proBNP) may predict adverse cardiovascular outcomes in patients with diabetes. However, its prognostic value in patients with multivessel disease (MVD) undergoing coronary revascularization remains unclear. This study aimed to evaluate the prognostic significance of preprocedural NT-proBNP levels in diabetic patients with MVD undergoing coronary revascularization. Methods: A total of 886 consecutive diabetic patients with MVD who underwent coronary revascularization were enrolled in this study. Patients were divided into quartiles according to their pre-procedural NT-proBNP levels. Kaplan-Meier curves and Cox regression analyses were performed to evaluate the risk of cardiovascular events, including all-cause death, cardiovascular death, myocardial infarction (MI), stroke, and major adverse cardiovascular events (MACE), according to the NT-proBNP quartiles. Results: During a median follow-up period of 4.2 years, 111 patients died (with 82 being caused by cardiovascular disease), 133 had MI, 55 suffered from stroke, and 250 experienced MACE. Kaplan-Meier curves demonstrated that NT-proBNP levels were significantly associated with higher incidences of all-cause death, cardiovascular death, MI, and MACE (log-rank test, P < 0.001, respectively). Multivariate Cox regression analysis revealed that NT-proBNP level was an independent predictor of adverse outcomes, including all-cause death (HR, 1.968; 95% CI, 1.377-2.812; P < 0.001), cardiovascular death (HR, 1.940; 95% CI, 1.278-2.945; P = 0.002), MI (HR, 1.722; 95% CI, 1.247-2.380; P = 0.001), and MACE (HR, 1.356; 95% CI, 1.066-1.725; P = 0.013). The role of NT-proBNP in predicting adverse outcomes was similar in patients with stable angina pectoris and acute coronary syndrome. Moreover, preprocedural NT-proBNP alone discriminated against the SYNTAX II score for predicting all-cause death [area under the curve (AUC), 0.662 vs. 0.626, P = 0.269], cardiovascular death (AUC, 0.680 vs. 0.622, P = 0.130), MI (AUC, 0.641 vs. 0.579, P = 0.050), and MACE (AUC, 0.593 vs. 0.559, P = 0.171). The addition of NT-proBNP to the SYNTAX II score showed a significant net reclassification improvement, integrated discrimination improvement, and improved C-statistic (all P < 0.05). Conclusion: NT-proBNP levels were an independent prognostic marker for adverse outcomes in diabetic patients with MVD undergoing coronary revascularization, suggesting that preprocedural NT-proBNP measurement might help in the risk stratification of high-risk patients.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study).

BACKGROUND: The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE. RESULTS: In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group ( P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250). CONCLUSIONS: In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Bivalirudin in patients undergoing percutaneous coronary intervention and independent predictors of postoperative adverse events in these patients: A real world retrospective study.

ABSTRACT: The efficacy and safety of bivalirudin in percutaneous coronary intervention (PCI) has always been a hot topic in perioperative antithrombotic therapy, but there are still some controversies. So studies are needed to provide more evidence, especially the real world study which includes patients excluded from previous RCT studys. Our study aimed to investigate these information and analyze the independent predictors of postoperative adverse events.A retrospective study enrolled 1416 patients underwent PCI in Tianjin Chest Hospital from May 2016 to October 2017. The incidence of stent-thrombosis and net clinical adverse events, including all-cause death, myocardial infarction, stroke, urgent target-vessel revascularization and bleeding, were followed up for 30 days and 1 year. Logistic regression and COX regression were respectively used to analyze independent predictors of bleeding events within 30-days, and independent predictors of Major adverse cardiovascular and cerebrovascular events (MACCE) in patients with stent implantation within 1-year.Seven hundred six patients were treated with bivalirudin while 710 with unfractionated heparin (UFH). The proportions of diabetes, hypertension, anemia, myocardial-infarction history, PCI history, moderate-to-severe renal-impairment, gastrointestinal-bleeding history in the bivalirudin group were significantly higher (P < .05). Women, anemia were independent risk factors for bleeding within 30-days (P < .05). Among 682 patients with stent implantation in bivalirudin group, anemia, Body Mass Index (BMI) >25 kg/m2, KILLIP ≥2, ejection fraction (EF) <45%, eGFR <60 ml/minutes were independent risk factors for MACCE, while Statins, proton pump inhibitor (PPI) were independent protective factors for MACCE with-in 1-year (P < .05).Bivalirudin have good anticoagulant effect and lower bleeding risk during PCI, especially in patients with higher bleeding risk. In patients treated with bivalirudin, female, anemia were independent predictors of bleeding within 30-days, BMI >25 kg/m2, anemia, KILLIP ≥2, EF <45%, eGFR <60 ml/minutes were independent risk factors and Statins, PPI were independent protective factors of MACCE within 1-year.

Triglyceride-glucose index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome.

BACKGROUND: The triglyceride-glucose index (TyG index) has been regarded as a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular outcomes. Whether the TyG index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome (ACS) remains uncertain. The aim of this study was to investigate the prognostic value of the TyG index in patients with diabetes and ACS. METHODS: A total of 2531 consecutive patients with diabetes who underwent coronary angiography for ACS were enrolled in this study. Patients were divided into tertiles according to their TyG index. The primary outcomes included the occurrence of major adverse cardiovascular events (MACEs), defined as all-cause death, non-fatal myocardial infarction and non-fatal stroke. The TyG index was calculated as the ln (fasting triglyceride level [mg/dL] × fasting glucose level [mg/dL]/2). RESULTS: The incidence of MACE increased with TyG index tertiles at a 3-year follow-up. The Kaplan-Meier curves showed significant differences in event-free survival rates among TyG index tertiles (P = 0.005). Multivariate Cox hazards regression analysis revealed that the TyG index was an independent predictor of MACE (95% CI 1.201-1.746; P < 0.001). The optimal TyG index cut-off for predicting MACE was 9.323 (sensitivity 46.0%; specificity 63.6%; area under the curve 0.560; P = 0.001). Furthermore, adding the TyG index to the prognostic model for MACE improved the C-statistic value (P = 0.010), the integrated discrimination improvement value (P = 0.001) and the net reclassification improvement value (P = 0.019). CONCLUSIONS: The TyG index predicts future MACE in patients with diabetes and ACS independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for risk stratification and prognosis in patients with diabetes and ACS.

Long-term treatment effect of a modified jailed-balloon technique for de Winter syndrome: a case report.

Timely recognition of the characteristic electrocardiographic pattern of de Winter syndrome is important for providing immediate reperfusion therapy for acute anterior myocardial infarction. In this case, an electrocardiogram showed 1- to 3-mm upsloping ST-segment depression at the J point in leads V1 to V6, with loss of R wave progression in leads V1 to V4. Urgent angiography showed occlusion of the proximal left anterior descending coronary artery and 70% stenosis in the ostial first diagonal branch (Medina type 1.1.1.). For this bifurcation lesion, we successfully performed a modified jailed-balloon technique to protect the side branch during percutaneous coronary intervention stenting. Thereafter, thrombolysis in myocardial infarction 3 flow was restored in both branches. This modified jailed-balloon technique is safe and effective in stent placement for de Winter syndrome without any loss of side branches.

NEAT1 knockdown suppresses endothelial cell proliferation and induces apoptosis by regulating miR­638/AKT/mTOR signaling in atherosclerosis.

Long non­coding RNAs (lncRNAs) have been validated to mediate the development of atherosclerosis (AS). In the present study, the molecular mechanisms and functions of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in the advancement of human aortic endothelial cells (HAECs) were investigated. The levels of lncRNA­NEAT1 and miR­638 expression in clinical samples and cells were explored via quantitative reverse transcription polymerase chain reaction. Colony formation and CCK­8 assays were performed to determine the proliferative capacity of cells, and the apoptotic capacity of cells was analyzed on the basis of apoptotic cell proportion and caspase­3 activity. Then, the proportion of cells and correlations among phosphoglycerate kinase 1 (PGK1), NEAT1, and miR­638 were determined through RNA immunoprecipitation and luciferase assays and bioinformatics analysis. Moreover, the expression levels of Ki­67, proliferating cell nuclear antigen, PGK1, Bax, Bcl­2, (p)­mTOR, (p)­AKT, and ß­catenin were analyzed via western blot analysis. In the serum of patients with AS and HAECs induced by oxidized low­density lipoprotein (ox­LDL), the expression level of miR­638 was decreased, whereas that of NEAT1 was increased. After ox­LDL therapy, NEAT1 knockdown suppressed HAEC proliferation and stimulated HAEC apoptosis, which could be reversed by the miR­638 inhibitor. NEAT1 inhibited miR­638 expression through direct mutual action. The following mechanical investigations revealed that PGK1 was a miR­638 target, whose expression was increased by NEAT1, a competing endogenous RNA of miR­638. Additionally, the miR­638 inhibitor contributed to proliferation and suppressed apoptosis through the activation of the AKT/mTOR signaling pathway in ox­LDL­induced HAECs. NEAT1 adjusted the AKT/mTOR signaling pathway via miR­638 in ox­LDL­induced HAECs to accelerate their proliferation and impede their apoptosis. This result revealed that NEAT1 may be valuable in the treatment of AS.

A drug-eluting Balloon for the trEatment of coronarY bifurcatiON lesions in the side branch: a prospective multicenter ranDomized (BEYOND) clinical trial in China.

BACKGROUND: Treatment of coronary bifurcation lesions remains challenging; a simple strategy has been preferred as of late, but the disadvantage is ostium stenosis or even occlusion of the side branch (SB). Only a few single-center studies investigating the combination of a drug-eluting stent in the main branch followed by a drug-eluting balloon in the SB have been reported. This prospective, multicenter, randomized study aimed to investigate the safety and efficacy of a paclitaxel-eluting balloon (PEB) compared with regular balloon angioplasty (BA) in the treatment of non-left main coronary artery bifurcation lesions. METHODS: Between December 2014 and November 2015, a total of 222 consecutive patients with bifurcation lesions were enrolled in this study at ten Chinese centers. Patients were randomly allocated at a 1:1 ratio to a PEB group (n = 113) and a BA group (n = 109). The primary efficacy endpoint was angiographic target lesion stenosis at 9 months. Secondary efficacy and safety endpoints included target lesion revascularization, target vessel revascularization, target lesion failure, major adverse cardiac and cerebral events (MACCEs), all-cause death, cardiac death, non-fatal myocardial infarction, and thrombosis in target lesions. The main analyses performed in this clinical trial included case shedding analysis, base-value equilibrium analysis, effectiveness analysis, and safety analysis. SAS version 9.4 was used for the statistical analyses. RESULTS: At the 9-month angiographic follow-up, the difference in the primary efficacy endpoint of target lesion stenosis between the PEB (28.7% ± 18.7%) and BA groups (40.0% ±â€Š19.0%) was -11.3% (95% confidence interval: -16.3% to -6.3%, Psuperiority <0.0001) in the intention-to-treat analysis, and similar results were recorded in the per-protocol analysis, demonstrating the superiority of PEB to BA. Late lumen loss was significantly lower in the PEB group than in the BA group (-0.06 ±â€Š0.32 vs. 0.18 ± 0.34 mm, P < 0.0001). For intention-to-treat, there were no significant differences between PEB and BA in the 9-month percentages of MACCEs (0.9% vs. 3.7%, P = 0.16) or non-fatal myocardial infarctions (0 vs. 0.9%, P = 0.49). There were no clinical events of target lesion revascularization, target vessel revascularization, target lesion failure, all-cause death, cardiac death or target lesion thrombosis in either group. CONCLUSIONS: In de novo non-left main coronary artery bifurcations treated with provisional T stenting, SB dilation with the PEB group demonstrated better angiographic results than treatment with regular BA at the 9-month follow-up in terms of reduced target lesion stenosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02325817; https://clinicaltrials.gov.

Preventive Effects of Nicorandil Against Contrast-Induced Nephropathy in Patients With Moderate Renal Insufficiency Undergoing Percutaneous Coronary Intervention.

We investigated the preventive effect of nicorandil on contrast-induced nephropathy (CIN) in patients with moderate renal insufficiency undergoing percutaneous coronary intervention (PCI). A total of 250 patients with a creatinine clearance (crCl) ≤60 mL/min undergoing PCI were randomly assigned to either a nicorandil group (nicorandil 10 mg 3 times/d and hydration; n = 125) or a control group (hydration only; n = 125). The first end point was the incidence of CIN defined as an increase in serum creatinine (Scr) levels by ≥0.5 mg/dL or ≥25% within 72 hours after exposure to the contrast medium. The secondary end points were (1) changes in Scr, blood urea nitrogen, and crCl and (2) the incidence of major adverse events during hospitalization. The incidence of CIN was 1.6% (2/125) in the nicorandil group and 9.6% (12/125) in the control group (P = .011). There was no obvious difference in the incidence of major adverse events during hospitalization between the nicorandil and the control group (4.0% vs 4.8%, P = 1.000). Multivariate logistic regression analysis showed that nicorandil was a protective factor for CIN (odds ratios = 0.126, 95% confidence interval: -19.996 to -0.932, P = .012). Prophylactic administration of nicorandil may prevent against CIN in patients with moderate renal insufficiency undergoing PCI.

No association between low-dose reserpine use and depression in older hypertensive patient: result of a multicenter, cross-sectional study.

BACKGROUND: Reserpine is currently used by millions of Chinese hypertensive patients, in spite of the continued concern of its depressogenic effect, even when used in low dose. This study aimed to investigate the association between low-dose reserpine use and depression in older Chinese hypertensive patient. METHODS: In this cross-sectional, case-control study, we recruited patient aged 60 years or over who had regularly taken one or two tables of "compound reserpine and triamterene tablets (CRTTs)" for more than one year (reserpine user) from 26 community health centers located in 10 provinces in China. For each patient who took CRTTs, we selected an age (within five years) and sex matched hypertensive patient who had never taken any drugs containing reserpine (non-reserpine user) as control. Depressive symptoms were evaluated using a Chinese depression scale adapted from the Zung Self-Rating Depression Scale. Demographic, clinical data and laboratory examination results within six months were collected. RESULTS: From August 2018 to December 2018, 787 reserpine user and 787 non-reserpine user were recruited. The mean age of all study subjects was 70.3 years, with about equal numbers of males and females. The mean depression score was 40.4 in reserpine users and 40.6 in non-reserpine users (P = 0.7). The majority of study subject had a depression score < 53 (87.6% in reserpine users and 88.2% in non-reserpine users, respectively). There were no significant differences in the prevalence of mild, moderate or severe depression in reserpine users and non-reserpine users. CONCLUSIONS: There is no association between low-dose reserpine use and depression in older hypertensive patient. The role of reserpine in the treatment and control of hypertension should be reconsidered; and further studies, especially randomized, controlled clinical trials to compare efficacy and safety of reserpine and other widely recommended anti-hypertensive agents are needed.

Preventive Effects of Alprostadil Against Contrast-Induced Nephropathy Inpatients With Renal Insufficiency Undergoing Percutaneous Coronary Intervention.

We investigated the preventive effect of alprostadil on contrast-induced nephropathy (CIN) in patients with renal insufficiency undergoing percutaneous coronary intervention (PCI). A total of 300 patients with creatinine clearance (crCl) ≤60 mL/min undergoing PCI were randomly assigned to alprostadil or a control group. The primary end point was the incidence of CIN defined as an increase in serum creatinine (Scr) levels by ≥0.5 mg/dL or≥ 25% after administration of the contrast media within 72 hours. The secondary end points were (1) changes in Scr and crCl within 72 hours and (2) the incidence of major adverse events during hospitalization. The incidence of CIN was 2.7% (4/150) in the alprostadil group, and 8.7% (13/150) in the control group (χ2 = 5.05, P = .043).There was no difference regarding the incidence of major adverse events during hospitalization between the alprostadil group and control groups (2.7% vs 4.0%, P = .750). Multivariate logistic regression analysis showed that alprostadil was an independent protective factor for CIN (odds ratio = 0.136, 95% confidence interval: 0.020-0.944, P = .044). Prophylactic administration of alprostadil may prevent CIN in patients with renal insufficiency undergoing PCI.

AMP-activated protein kinase mediates the effects of lipoprotein-associated phospholipase A2 on endothelial dysfunction in atherosclerosis.

The present study aimed to investigate the effects of lipoprotein-associated phospholipase A2 (Lp-PLA2) on endothelial dysfunction in an in vitro cell model of atherosclerosis, and to determine whether AMP-activated protein kinase (AMPK) mediates the effects of Lp-PLA2 on endothelial dysfunction. A total of 392 patients with coronary artery disease (CAD), including various sub-conditions, were recruited, and the plasma concentrations of Lp-PLA2 were evaluated. In addition, an in vitro model of atherosclerosis was established by exposing human umbilical vein endothelial cells (HUVECs) to oxidized low-density lipoprotein (oxLDL). SB-435495 was used to inhibit Lp-PLA2, and compound C was used to suppress AMPK expression. Lp-PLA2, AMPKα and phosphorylated-AMPKα (T172) expression in HUVECs were evaluated using western blot analysis. The concentrations of nitric oxide (NO), endothelin 1 (ET-1), intercellular adhesion molecule 1 (ICAM-1) and platelet/endothelial cell adhesion molecule 1 (PECAM-1) in cell culture supernatant were determined using commercially available ELISA kits. MTT assays were employed to indicate changes in cell viability. The current study found the plasma Lp-PLA2 levels were elevated in the CAD patients with stable angina pectoris, unstable angina pectoris, acute coronary syndromes and acute myocardial infarction, compared with a healthy control population. In addition, the in vitro results showed that Lp-PLA2 expression levels were elevated in oxLDL-exposed HUVECs. Lp-PLA2 suppression could increase cell viability, induce the production of NO and decrease the secretion of ET-1, in addition to suppressing the expression of cell adhesion molecules, including ICAM-1 and PECAM-1 in oxLDL-exposed HUVECs. The expression of AMPKα and phosphorylated-AMPKα (T172) was regulated by Lp-PLA2, and AMPK suppression was able to reverse the effects of Lp-PLA2 with regard to cell viability, endothelial vasorelaxation capacity and the secretion of adhesion molecules in oxLDL-exposed HUVECs. In conclusion, the present study provides initial evidence that Lp-PLA2 is able to cause endothelial dysfunction in an in vitro model of atherosclerosis, and the effects of Lp-PLA2 on endothelial dysfunction was at least partially a result of the downregulation of AMPKα, thus contributing to the progression of atherosclerosis.

Rosuvastatin postconditioning protects isolated hearts against ischemia-reperfusion injury: The role of radical oxygen species, PI3K-Akt-GSK-3ß pathway, and mitochondrial permeability transition pore.

AIMS: Glycogen synthase kinase-3ß (GSK-3ß) and mitochondrial permeability transition pore (mPTP) play an important role in myocardial ischemia-reperfusion injury. The aim of this study was to investigate whether postconditioning with rosuvastatin is able to reduce myocardial ischemia-reperfusion injury and clarify the potential mechanisms. METHODS: Isolated rat hearts underwent 30 minutes of ischemia and 60 minutes of reperfusion in the presence or absence of rosuvastatin (1-50 nmol/L). The activity of signaling pathway was determined by Western blot analysis, and Ca2+ -induced mPTP opening was assessed by the use of a potentiometric method. RESULTS: Rosuvastatin significantly reduced myocardial infarct size and improved cardiac function at 5 and 10 nmol/L. Protection disappeared at higher concentration and reverted to increased damage at 50 nmol/L. At 5 nmol/L, rosuvastatin increased the phosphorylation of protein kinase B (Akt) and GSK-3ß, concomitant with a higher Ca2+ load required to open the mPTP. Rosuvastatin postconditioning also significantly increased superoxide dismutase activity and reduced malondialdehyde and radical oxygen species level. LY294002, phosphatidylinositol-3-kinase (PI3K) inhibitors, abolished these protective effects of rosuvastatin postconditioning. CONCLUSION: Rosuvastatin prevents myocardial ischemia-reperfusion injury by inducing phosphorylation of PI3K-Akt and GSK-3ß, preventing oxidative stress and subsequent inhibition of mPTP opening.

Effect of cyclosporin A intervention on the immunological mechanisms of coronary heart disease and restenosis.

The present study aimed to investigate the effect of cyclosporin A (CSA) intervention on the immunological mechanisms underlying coronary heart disease (CHD) and restenosis (RS) in rabbits. A total of 48 rabbits were randomly divided into normal control (N), N + CSA, CHD model, CHD + CSA, RS model and RS + CSA groups. Rabbits in the respective groups received different treatments prior to sacrifice at the end of week 12. Iliac arteries were harvested from the rabbits for morphological analysis and to determine the mRNA and protein expression levels of cluster of differentiation (CD) 40/CD40 ligand (CD40L), CD134/CD134 ligand (CD134L) and inflammatory factors, including matrix metalloproteinase (MMP)-1, MMP-9, vascular cell adhesion protein (VCAM)-1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, by reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining. As compared with the N group, the mRNA expression levels of MMP-9, VCAM-1 and TNF-α were significantly increased in the CHD and RS groups (P<0.05), but were significantly decreased in the groups with CSA intervention, as compared with those without CSA intervention (P<0.05). Conversely, there were no significant differences in the expression levels of MMP-1 and IL-6 among the six groups, although a decreasing trend of IL-6 expression was observed following intervention with CSA. Furthermore, there were significant differences in the mRNA and protein expression levels of CD40/CD40L and CD134/CD134L among the N, CHD and RS groups (P<0.05), and between the groups with and without CSA intervention. The present study demonstrated that CSA intervention exerted beneficial effects on CHD and RS, and further studies are required to investigate the mechanisms underlying the effects of CSA on CHD.