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Objective This study was aimed to determine how platelet reactivity (PR) on dual antiplatelet therapy predicts ischemic and bleeding events in patients underwent percutaneous coronary intervention (PCI). Design A total of 2768 patients who had received coronary stent implantation and had taken aspirin 100 mg in combination with clopidogrel 75 mg daily for > 5 days were consecutively screened and 1885 were enrolled. The recruited patients were followed-up for 12 months. The primary end-point was the net adverse clinical events (NACE) of cardiovascular death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and any bleeding. Result 1709 patients completed the clinical follow-up. By using the receiver operating characteristic (ROC) curve analysis, the optimal cut-off values were found to be 37.5 and 25.5% respectively in predicting ischemic and bleeding events. Patients were classified into 2 groups according to PR: inside the window group (IW) [adenosine diphosphate (ADP) induced platelet aggregation (PLADP) 25.5–37.4%)] and outside the window group (OW) (PLADP P = 0.004)] than that in the OW group during 12-month follow-up. Conclusion An optimal therapeutic window of 25.5–37.4% for PLADP predicts the lowest risk of NACE, which could be referred for tailored antiplatelet treatment while using LTA assay. Trial registration Trial registration number: ClinicalTrials.govNCT01968499. Registered 18 October 2013 - Retrospectively registered.

This study aimed to investigate the pharmacodynamic effects of indobufen and low-dose aspirin in patients with coronary atherosclerosis. In the first phase, 218 patients with coronary atherosclerosis were randomly assigned to receive aspirin 100 mg once daily (standard dose); 100 mg once every 2 days; 100 mg once every 3 days; 50 mg twice daily; 75 mg once daily; 50 mg once daily; or indobufen 100 mg twice daily for 1 month. In the second phase, 20 healthy subjects were treated with indobufen 100 mg twice daily for 1 week followed after a 2-week washout by aspirin 100 mg once daily for 1 week. The primary outcome was arachidonic acid-induced platelet aggregation (PLAA), and the secondary outcomes included plasma thromboxane B2 (TXB2) and urinary 11-dehydro-TXB2 (11-dh-TXB2) levels at the end of each treatment. In the first phase, compared with aspirin 100 mg once daily: all aspirin groups had similar suppression of PLAA whereas indobufen group had significantly less suppressed PLAA. Aspirin given every second or third day, and indobufen produced less suppression of plasma TXB2. All treatment regimens produced similar inhibition of 11-dh-TXB2. In the second phase, compared with aspirin, indobufen produced less suppression of plasma TXB2 at 8 h and 12 h after the last dose. Aspirin 50 mg twice daily, 75 mg once daily, and aspirin 50 mg once daily produce antiplatelet effects that are similar to aspirin 100 mg once daily. Aspirin given less often than once daily and indobufen 100 mg twice daily do not suppress platelets as effectively as aspirin 100 mg once daily.

Background and aims It has been reported that elevated serum uric acid (SUA) is related to inflammation and potentially to platelet hyper-reactivity. However, the relationship between elevated SUA and residual platelet reactivity is uncertain in patients on dual antiplatelet treatment (DAPT) with aspirin and clopidogrel. Methods and results A cross-sectional cohort study was conducted on 2569 patients undergoing DAPT with aspirin and clopidogrel. Patients' SUA levels, residual platelet aggregation, routine blood tests and clinical characteristics were recorded. The relationship between SUA level and residual platelet aggregation was assessed by correlation analysis, and the relationship between SUA level and the prevalence of clopidogrel low response (CLR) was assessed by multivariate logistic regression analysis. Adenosine diphosphate (ADP) induced platelet aggregation (PLADP) was higher in normal-SUA group than that in hyperuricemia group [30(21, 40) % vs. 27(19, 39) %, p = 0.032]. No significant difference was found for arachidonic acid (AA) induced platelet aggregation (PLAA) between the two groups [4(2, 5) % vs. 3(2, 5) %, p = 0.557]. The correlation between SUA and PLADP was statistically significant(r = −0.115, p Conclusion This is the largest study to date showing that in patients receiving DAPT with aspirin and clopidogrel, SUA is independently and negatively associated with the prevalence of clopidogrel low response. Clinical trial registration URL: http://www.clinicaltrials.gov Unique Identifier: NCT01955200.

BACKGROUND AND AIM Although the association between the eradication of Helicobacter pylori (H. pylori) and smoking has been confirmed through a meta-analysis, many new studies have reported inconsistent conclusions. An up-to-date meta-analysis based on published relevant studies was conducted in this study to address this issue. METHODS Eligible studies up to January 2021 were screened and retrieved using PubMed and Web of Science as well as by performing a manual review of references. We calculated the pooled odd ratios (OR) with the 95% confidence interval (CI). Subgroup and sensitivity analyses were also performed. Begg's test was used to determine the publication bias. RESULTS In total, 39 studies were included in the meta-analysis. The results showed that smoking increases the failure rate of H. pylori eradication treatment (OR = 1.70, 95%CI, 1.49-1.93). The risk of failure also increases with an increase in the smoking dose (>5 cigarettes per day) (OR = 2.59, 95%CI, 1.28-5.24) and the current smoking status (continued to smoke during treatment) (OR = 2.49, 95%CI, 1.52-4.06). Studies with a large proportion of patients with peptic ulcer (OR = 2.14, 95%CI, 1.51-3.02) revealed a higher failure rate among smokers than those with a low proportion of patients with peptic ulcer (OR = 1.57, 95%CI, 1.36-1.81). When vonoprazan (VPZ) was used to treat H. pylori infection, smoking did not affect the eradication rate (OR = 0.94, 95%CI, 0.51-1.75). CONCLUSION Smoking increases the failure rate of H. pylori eradication treatment. The risk of H. pylori eradication failure in smokers increases with a current smoking status and a high smoking dose. However, when VPZ is used to treat the H. pylori infection, smoking has no effect on the eradication rate.

High on-treatment platelet reactivity (HOPR) is associated with increased risk of cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We randomised post-PCI patients with HOPR after 5 days of standard dual antiplatelet therapy (DAPT) to intensified therapy with aspirin 100 mg once daily in combination with either clopidogrel 150 mg once daily, clopidogrel 75 mg once daily plus cilostazol 100 mg twice daily, ticagrelor 90 mg twice daily, or standard therapy with clopidogrel 75 mg once daily (STD) for 1 month, after which all patients were switched to standard DAPT for a further 11 months. The primary outcome was residual HOPR rate at 1 month. We screened 1724 patients with light transmission aggregation studies and randomised 434 with HOPR. At 1 month the proportion of patients with persistent HOPR was significantly lower in the intensified therapy groups compared with STD group. Compared to the group receiving STD therapy, those receiving intensified therapy had significantly lower rate of major adverse cardiovascular events (MACE) at both 1 month and 12 months with no significant increase in bleeding. In patients with post-PCI HOPR, 1 month of intensified antiplatelet therapy provides greater platelet inhibition and improves outcomes without increasing bleeding. Clinical Trial Registration URL: http://www.clinicaltrials.gov; Unique Identifier: NCT01955200.

BACKGROUND This study was conducted to analyze the influences of stent surface area (SSA), platelet distribution width (PDW), and the joint effect of these 2 risk factors on major adverse cardiovascular events (MACEs) in patients treated with percutaneous coronary intervention (PCI) together with drug-eluting stent (DES) implantation. METHODS Based on a cross-sectional survey conducted between 2011 and 2012, a prospective cohort study was enrolled consiting of 442 patients who had undergone PCI with DES implantation. We categorized the participants into 4 subgroups according to PDW and SSA. Cox proportional hazards models were applied to explore the correlation of PDW and SSA with MACE incidence. RESULTS During the 12 months of follow-up time, 87 patients experienced MACEs, which included 4 deaths (4.6%), 5 nonfatal myocardial infarctions (MIs) (5.75%), 9 ischemic strokes (10.34%), and 73 clinically relevant bleeding episodes (83.91%). The risks of MACEs were decreased by SSA and increased by PDW. However, the association of PDW or SSA with MACE was not statistically significant. Compared with the patients with PDW ≥13.5% and SSA

Myocardial infarction (MI) is one of the leading causes of death worldwide, and knowing the early warning signs of MI is lifesaving. To expand our knowledge of MI, we analyzed plasma metabolites in MI and non-MI chest pain cases to identify markers for alerting about MI occurrence based on metabolomics. A total of 230 volunteers were recruited, consisting of 146 chest pain patients admitted with suspected MI (85 MIs and 61 non-MI chest pain cases) and 84 control individuals. Non-MI cardiac chest pain cases include unstable angina (UA), myocarditis, valvular heart diseases, etc. The blood samples of all suspected MI cases were collected not longer than 6 h since the onset of chest pain. Gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry were applied to identify and quantify the plasma metabolites. Multivariate statistical analysis was utilized to analyze the data, and principal component analysis showed MI could be clearly distinguished from non-MI chest pain cases (including UA and other cases) in the scores plot of metabolomic data, better than that based on the data constructed with medical history and clinical biochemical parameters. Pathway analysis highlighted an upregulated methionine metabolism and downregulated arginine biosynthesis in MI cases. Receiver operating characteristic curve (ROC) and adjusted odds ratio (OR) were calculated to evaluate potential markers for the diagnosis and prediction ability of MI (MI vs. non-MI cases). Finally, gene expression profiles from the Gene Expression Omnibus (GEO) database were briefly discussed to study differential metabolites' connection with plasma transcriptomics. Deoxyuridine (dU), homoserine, and methionine scored highly in ROC analysis (AUC > 0.91), sensitivity (>80%), and specificity (>94%), and they were correlated to LDH and AST (p < 0.05). OR values suggested, after adjusting for gender, age, lipid levels, smoking, type II diabetes, and hypertension history, that high levels of dU of positive logOR = 3.01, methionine of logOR = 3.48, and homoserine of logOR = 1.61 and low levels of isopentenyl diphosphate (IDP) of negative logOR = −5.15, uracil of logOR = −2.38, and arginine of logOR = −0.82 were independent risk factors of MI. Our study highlighted that metabolites belonging to pyrimidine, methionine, and arginine metabolism are deeply influenced in MI plasma samples. dU, homoserine, and methionine are potential markers to recognize MI cases from other cardiac chest pain cases after the onset of chest pains. Individuals with high plasma abundance of dU, homoserine, or methionine have increased risk of MI, too.

Background: A unique human plasma metabolic pattern of myocardial infarction (MI) has been recognized for over a decade. The discriminant metabolites are potential diagnosis and warning markers, and have connections with traditional cardiovascular risk factors and circulating transcriptomics. Methods: A total of 146 chest pain (85 MIs and 61 non-MI chest pain cases) and 84 control individuals were recruited. GC/MS and LC/MS were applied to identify and quantify the plasma metabolites. The metabolites were analyzed by multivariate statistical analysis to describe different patterns of CADs with chest pain. Receiver operating characteristic （ROC） and odds ratio (OR) were calculated to identify potential markers of MI cases, and the markers were further evaluated based on human circulating transcriptomics from the GEO database. The correlation of metabolites to clinical indices was assessed. Results: MI can be clearly distinguished from non-MI chest pain cases by the metabolites we identified, better than by medical history combined with routine biochemical parameters. Pathway analysis highlighted an upregulated methionine metabolism and downregulated arginine biosynthesis that were deeply involved in MI cases. Among all the metabolites, deoxyuridine (dU) and methionine scored highly in ROC (>0.91) and are related to LDH and AST (p2) suggested, with or without adjusting by lipid levels, age, smoking, diabetes and hypertension, that dU and methionine are risk factors for alerting about MI occurrence. Transcriptomics data showed elevations of plasma CDA and UPP1, and a decrease of cardiac MARS, which are consistent with the increased levels of plasma dU and methionine, respectively. Conclusions: For the first time, dU and methionine were suggested as markers for MI diagnosis and as high-risk markers to alert about an onset of MI. Plasma metabolite changes are not only directly related to cardiac damage but also could be related to circulating cells.

Background Genetic polymorphisms of key proteins involved in clopidogrel absorption, metabolism, and action may contribute to variability in platelet inhibition in patients undergoing percutaneous coronary intervention (PCI), but their impacts on cardiovascular outcomes remain unclear. Purpose To examine the associations between genetic polymorphisms and cardiovascular outcomes in Chinese patients undergoing PCI and treated with clopidogrel and aspirin. Methods This prospective cohort study consecutively enrolled 2,453 post-PCI patients treated with clopidogrel and aspirin. Adenosine diphosphate-induced platelet aggregation was measured by light transmission aggregometry. A total of 40 single nucleotide polymorphisms (SNPs) of 18 genes selected according to published studies were investigated using an improved multiplex ligation detection reaction technique. The primary outcome was major adverse cardiovascular event (MACE), the composite of cardiovascular death, non-fatal myocardial infarction (MI), and ischemic stroke within one year after PCI. Results We restricted the analyses to the first 1,452 patients who had finished one-year follow-up and complete data on genotyping and platelet aggregation. 44 (3.03%) patients suffered MACE. Among the 40 SNPs, only the A-allele carriers of CYP2C19*2 had a significant higher risk of MACE (adjusted HR 2.05; 95% CI, 1.01–4.19; p=0.048) and platelet aggregation than non-A-carriers after adjusting age, sex, MI presentation, and left ventricular ejection fraction. CYP2C19*3, CYP2B6 rs3745274, and PEAR1 rs12041331 variants were also significantly associated with platelet aggregation (all p Conclusion About 54.2% of Chinese patients with PCI were A-allele carriers of CYP2C19*2, who face a two-fold higher risk of MACE than non-A-allele carriers in Chinese patients after PCI. It would help identify low clopidogrel responders and optimize antiplatelet therapy before drug administration. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Funding of China

Background Hepatitis B virus (HBV) infection has been reported to down-regulate the expression of CYP2C19 gene, which may decrease the bioactivation of clopidogrel into active metabolites. We aimed to evaluate the impact of HBV infection on platelet response to clopidogrel in patients undergoing coronary stent implantation. Methods A total of 1805 patients who had received coronary stent implantation and taken aspirin 100 mg in combination with clopidogrel 75 mg daily ≥5 days were consecutively recruited. The serologic identifications for HBV, platelet aggregations in response to arachidonic acid (PLAA) and adenosine diphosphate (PLADP), as well as ABCB1, CYP2C19, CYP3A5, PON1 and P2RY12 genotypes were determined. Clopidogrel low response (CLR) was defined as PLADP > 40%. Results Among the recruited subjects, 102 patients showed hepatitis B surface antigen (HBsAg) positive and 1703 patients negative. PLADP was significantly higher in HBsAg positive group than that in HBsAg negative group [38 (24–48) % vs. 29 (20–39) %, p Conclusions HBV infection is an independent risk factor of CLR, in addition to CYP2C19 gene mutations. (Pharmacogenetic and Pharmacokinetic Study of Clopidogrel; NCT01968499 ).

The aim of this study was to investigate the association among the PlA1/A2 gene polymorphism, laboratory aspirin resistance and adverse clinical outcomes in coronary artery disease (CAD) patients who were on aspirin maintainance therapy. A comprehensive literature search was performed and 35 eligible clinical trials including 19025 CAD patients were recruited. Adverse clinical outcomes involving all-cause death, non-fatal myocardial infarction (MI), ischemic stroke and target vessel revascularization (TVR) were analyzed. The definition of aspirin resistance in each study was accepted. Meta-analysis was performed using the Review Manager 5.3.5 System. In CAD patients, the PlA2 gene carriers had similar incidence of laboratory aspirin resistance compared to those with PlA1/A1 genotype [29.7% vs 28.3%, OR = 0.94 (95% CI 0.63 to 1.40, P = 0.74)], and there were no significant differences in the adverse clinical outcomes between the PlA2 carriers and the PlA1/A1 genotype patients. However, the laboratory aspirin non-responders had higher risks of death [7.9% vs. 2.5%, OR = 2.42 (95% CI 1.86 to 3.15, P

Background: The genetic determinants of response to clopidogrel and aspirin are incompletely characterized. Recently, PEAR1 (platelet endothelial aggregation receptor-1) rs12041331 polymorphism has been shown to influence the platelet reactivity, but its impact on cardiovascular outcomes remains unclear in patients treated with antiplatelet agents. Methods and Results: In this prospective cohort study, 2439 Chinese patients with acute coronary syndrome or stable coronary artery disease undergoing coronary stent implantation and receiving clopidogrel and aspirin were consecutively recruited. Their platelet reactivity was determined by light transmission aggregometry at 5 and 30 days after coronary intervention. Genotyping was performed using an improved multiplex ligation detection reaction technique. All patients completed a 30-day follow-up for clinical outcomes. Genotyping for PEAR1 showed 768 (38.3%) GG homozygotes, 941 (46.9%) GA heterozygotes, and 298 (14.8%) AA homozygotes. The 30-day incidence of major adverse cardiovascular events, the composite of cardiovascular death, nonfatal myocardial infarction, and ischemic stroke were significantly higher in AA homozygotes than in non-AA homozygotes (adjusted hazard ratio, 2.78; 95% CI, 1.13–6.82; P =0.026), irrespective of CYP2C19*2 loss-of-function polymorphism and known outcome predictors including age, sex, smoking, and diabetes mellitus. The ADP-induced platelet aggregation was significantly lower in AA homozygotes than that in GG homozygotes at both time points, although no significant difference was found for the arachidonic acid–induced platelet aggregation among the 3 groups. Conclusions: About 15% of Chinese patients undergoing coronary stent implantation were AA homozygotes for PEAR1 rs12041331. These patients had ≈3-fold increase in short-term major adverse cardiovascular events risk compared with non-AA homozygotes, and the adverse clinical outcome is unlikely to be mediated by suboptimal pharmacological response to aspirin or clopidogrel. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01968499.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel anti-hyperglycemic drugs for type 2 diabetes. It has been reported that DDP-4 inhibitor could exert pleiotropic effects on cardiovascular system. This study was to explore the effect and mechanism of vildagliptin on the stenosis of injured carotid artery in diabetic mouse. Twenty six-week-old male db/db mice (BKS) were randomized into vildagliptin treated and vehicle control groups. Ligation injury was first performed in left carotid arteries of all diabetic mice, then oral vildagliptin or equal amount of PBS was correspondingly administered to the mice from the next day to ligation injury for 4 weeks. Effects on proliferation were detected via histological and morphometric analysis. Endoplasmic reticulum (ER) stress and nuclear factor kappa B (NF-κB) markers were determined by immunoblot analysis. After 4 weeks of vildagliptin delivery, it was observed that the intimal area and neointimal thickness of the ligated carotid arteries were significantly reduced as compared to the control group. In vivo, vildagliptin suppressed the expressions of PCNA and α-SMA, phospho-p65, phospho-IKKα/β, GRP78 and CHOP, as well as IRE-1 in vascular smooth muscle cells (VSMCs). In vitro, the proliferation and hypertrophy of VSMCs were significantly inhibited by blocking the IRE-1 pathway, and the inhibition of phospho-IRE-1 expression down-regulated the expression of phospho-IKKα/β in VSMCs. Vildagliptin reduced the stenosis of injured carotid arteries in diabetic mice, and this effect was achieved via inhibiting the activation of ER stress/NF-κB pathway.

Background: Clopidogrel low response (CLR) is an independent risk factor of adverse outcomes in patients undergoing percutaneous coronary intervention (PCI), and intensified antiplatelet treatments (IAT) guided by platelet function assays might overcome laboratory CLR. However, whether IAT improves clinical outcomes is controversial. Methods: Relevant trials were identified in PubMed, the Cochrane Library, and the Chinese Medical Journal Network databases from their establishment to September 9, 2014. Trials were screened using predefined inclusion criteria. Conventional meta-analysis and cumulative meta-analysis were performed using the Review Manager 5.0 and STATA 12.0 software programs. Results: Thirteen randomized controlled trials involving 5111 patients with CLR were recruited. During a follow-up period of 1–12 months, the incidences of cardiovascular (CV) death, nonfatal myocardial infarction (MI), and stent thrombosis were significantly lower in the IAT arm than in the conventional antiplatelet treatment arm (relative risk [RR] = 0.45, 95% confidence interval [CI]: 0.36–0.57, P < 0.000,01), whereas bleeding was similar between the two arms (RR = 1.05, 95% CI: 0.86–1.27, P = 0.65). Conclusions: IAT guided by platelet function assays reduces the risk of CV death, nonfatal MI, and stent thrombosis (ST) without an increased risk of bleeding in patients undergoing PCI and with CLR.

Genetic polymorphisms of key proteins involved in clopidogrel absorption, metabolism, and action may contribute to variability in platelet inhibition in patients undergoing percutaneous coronary intervention (PCI), but their impacts on cardiovascular outcomes remain unclear. In this study, we

Objectives: An increased rate of platelet production is a possible cause of reduced antithrombotic response to once-daily aspirin. Markers of immature platelets (IPs),such as immature platelet count (IPC), immature platelet fraction (IPF), and mean platelet volume (MPV) might be useful for identifying patients who have an increase in their rate of platelet production. However, their potential as markers of platelet production has not been rigorously evaluated. We aimed to investigate the utility of the IPC, IPF, and MPV as surrogates for increased platelet production using coronary artery bypass grafting (CABG) as a model of enhanced thrombopoiesis. Methods: Daily changes in platelet count, IPC, IPF, and MPV were followed in 45 patients undergoing CABG. Results: The rise in IP markers preceded that in the platelet count. IPC (16% per day increase from nadir) but not IPF or MPV showed a significant and sustained rise,which paralleled the pattern observed with platelet count (18% per day increase from nadir).Conclusions: Of the 3 markers, IPC was the most promising as surrogates for platelet production. Future studies should evaluate the utility of the IPC to identify patientswith cardiovascular disease with reduced response to aspirin who might benefit fromtwice-dailyaspirin. Refereed/Peer-reviewed

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.

INTRODUCTION Aspirin resistance (AR) has been reported to present after coronary artery bypass graft causing saphenous vein graft failure. We aimed to investigate the factors that affect the anti-platelet effect of aspirin after off-pump coronary artery bypass surgery (OPCAB). MATERIALS AND METHODS Thirty OPCAB candidates were successively recruited. Platelet count, platelet aggregation, reticulated platelet (RP), platelets' cyclooxygenase (COX)-1 and COX-2 expressions were determined during the peri-operative period. Besides, 10 healthy volunteers were enrolled to determine the onset of the anti-platelet effect of aspirin as comparison. RESULTS AND CONCLUSIONS The arachidonic acid-induced platelet aggregation (PLAA) decreased to

// Jie-Yin Liu 1, * , Qiao-Wei Jia 1, * , Xiao-Ling Zang 1 , Rong-Hu Wang 1 , Chun-Jian Li 1 , Lian-Sheng Wang 1 , Wen-Zhu Ma 1 , Zhi-Jian Yang 1 and En-Zhi Jia 1 1 First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China * These authors contributed equally to this work Correspondence to: En-Zhi Jia, email: enzhijia@njmu.edu.cn Keywords: high-sensitivity troponin T, the 99th percentile, myoglobin, creatine kinase-MB Received: May 03, 2017 Accepted: August 06, 2017 Published: August 18, 2017 ABSTRACT Background: Recently, very low concentrations of high-sensitivity cardiac troponin T (hs-cTnT), below the 99th percentile, have been used to immediately exclude acute myocardial infarction in certain patients without taking their age and sex into consideration. Results: The hs-cTnT values below the 99th percentile (≤ 14 ng/L) were higher in men ( p = 0.000) and significantly increased with age ( p = 0.000) among both men and women. In addition, hs-cTnT was positively associated with age ( r = 0.459, p = 0.000), myoglobin ( r = 0.392, p = 0.000), and creatine kinase-MB ( r = 0.133, p = 0.000). Moreover, males were younger ( p = 0.001) and had higher myoglobin ( p = 0.000) and creatine kinase-MB ( p = 0.000) concentrations than females. Materials and Methods: A total of 5585 consecutive subjects who presented with non-traumatic chest pain/discomfort to the inpatient, outpatient, or emergency department and who underwent high-sensitivity troponin T, myoglobin and creatine kinase-MB testing at presentation, with hs-cTnT below the 99thpercentile (≤ 14 ng/L), were eligible for enrollment. Conclusions: We suggest that patients’ age, sex and levels of myocardial injury biomarkers should be taken into consideration when ruling out acute myocardial infarction and/or adverse prognostic implications in patients who have very low hs-cTnT concentrations.

Early and intensive atorvastatin treatment can decrease nonsustained ventricular tachycardia (nsVT) in patients with ST-segment elevation myocardial infarction (STEMI). The objective of this study was to compare the effects of hydrophilic rosuvastatin and lipophilic atorvastatin on nsVT in STEMI patients treated with primary percutaneous coronary intervention (PCI). The data from a cohort of patients undergoing primary PCI at Jinhua Municipal Central Hospital from January 1, 2013 through June 30, 2016 were analyzed. The patients were divided into the rosuvastatin group and the atorvastatin group based on which kind of statins that they had received. The endpoint of the study was the occurrence of nsVT on either electrocardiogram monitoring or Holter monitoring. A total of 301 patients were enrolled in the study (rosuvastatin group: n = 103; atorvastatin group: n = 198). The baseline and procedural characteristics were similar between the two groups, except that total ischemic time in the rosuvastatin group was markedly longer than that in the atorvastatin group (8 (5–16) h vs. 6 (4–12) h; P = 0.001). The administration of rosuvastatin was significantly associated with lower occurrence of nsVT than that of atorvastatin (9.71 vs. 19.70%; P = 0.026). Multivariable logistic regression analysis suggested that the independent predictors of nsVT included rosuvastatin (odds ratio (OR) 0.397, 95% confidence interval (CI) 0.176–0.894), current smoking (OR 2.307, 95% CI 1.011–5.262), and left ventricular ejection fraction (LVEF) (OR 1.060, 95% CI 1.023–1.098). The effects of rosuvastatin on nsVT might be better than that of atorvastatin in STEMI patients undergoing primary PCI.

An invasive management strategy with percutaneous coronary intervention (PCI) is recommended in patients with acute coronary syndrome (ACS), with or without ST-segment elevation, who are eligible for revascularization. However, there is still wide variation observed in the real-life use of coronary

A number of treatment strategies for complex coronary lesions have been utilized in varying clinical settings over the last decade. However, cardiologists still encounter some difficult scenarios such as variant coronary artery origins, severely calcified and highly tortuous lesions. We report four cases in which the stents failed to cross lesions using the conventional percutaneous coronary intervention techniques, but all the target lesions were successfully stented finally using a new combined technique of anchor balloon assisted deep intubation of 5F “child‑in‑mother” catheter.Keywords: Anchor balloon, child‑in‑mother catheter, percutaneous coronary intervention

HOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA (lncRNA) that functions as an oncogenic molecule in different cancer cells. Genetic variants of HOTAIR may affect the activity of certain regulatory factors and further regulate the aberrant expression of HOTAIR, which might be underlying mechanisms that affect tumour susceptibility and prognosis. Recently, several studies have been performed to examine the possible link between polymorphisms in HOTAIR and cancer risk; however, the results have been inconclusive. Therefore, we performed a meta-analysis to estimate the associations between HOTAIR polymorphisms (rs920778, rs4759314 and rs1899663) and cancer risk. Eight studies comprising 7,151 cases and 8,740 controls were included in our study. Overall, no significant associations between the HOTAIR polymorphisms (rs920778, rs4759314 and rs1899663) and cancer risk were observed. However, in further stratified analyses, the variant T allele of rs920778 exhibited a significant increased risk of developing digestive cancers (dominant model: OR = 1.44; 95% CI = 1.31–1.59). These findings provided evidence that HOTAIR rs920778 may modify the susceptibility to certain cancer types. Further studies incorporating subjects with different ethnic backgrounds combined with re-sequencing of the marked region and functional evaluations are warranted.

article i nfo Introduction: Variability in platelet response to aspirin has been reported in patients undergoing cardiac sur- gery but has rarely been described in other operative settings and its mechanism remains uncertain. We per- formed a prospective cohort study to investigate the variability in platelet response to aspirin and to explore its mechanism in patients undergoing major orthopedic surgery. Materials and Methods: Twelve aspirin-treated patients undergoing elective hip or knee replacement were recruited. Once-daily aspirin was continued throughout the perioperative period. We measured platelet function using light transmission aggregation (LTA) in response to arachidonic acid (PLAA) and serum throm- boxane B2 (TXB2) at baseline (before surgery) as well as on days 1, 2, 3, 4, 5, 6, and 8 after surgery. We defined aspirin low response as a PLAA>20%. Results: Six patients exhibited aspirin low response, which typically started on post-operative days 3 or 4; the remaining 6 patients had normal response to aspirin. Compared to aspirin responders, patients with aspirin low response showed significantly higher serum TXB2 levels, a more pronounced early decrease in platelet count, and a significantly more rapid recovery of the platelet count after surgery. Conclusion: Aspirin response variability occurred in patients after major orthopedic surgery, with one-half of the patients in our study exhibiting post-operative aspirin low response. Increased platelet turnover might be a contributor to aspirin response variability after orthopedic surgery.

The aim of this study was to identify the synergistic effect of microRNA expression with classical risk factors of coronary heart disease (CHD) and to explore their diagnostic value for coronary stenotic lesions in subjects with CHD. Plasma samples were obtained from 66 subjects with CHD and from 58 control individuals. A quantitative reverse-transcription PCR (RT-qPCR) assay was conducted to confirm the relative expressions of the known CHD-related miRNAs. The severity of coronary atherosclerosis was based on the Gensini scoring system. The expression of miR-125b in plasma of the CHD group was lower than that of the non-CHD group (0.14 ± 0.09 vs. 0.18 ± 0.10, p = 0.055) and the miR-125b levels significantly decreased following an increasing Gensini score (P = 0.037). Spearman correlation analyses indicated the Gensini score was negatively associated with miR-125b (r = −0.215, p = 0.017). Of all the miRNAs, miR-125b showed the lowest AUC (0.405; 95% CI: 0.305 ~ 0.506, p = 0.070). We found several synergistic effects between miR-125b and classical risk factors, such as age, sex, CR, FBG and HDL-C; the proportion of CHD attributable to the interaction of miR-125b and age was as high as 80%. Therefore, miR-125b was shown to play an important role in individual’s susceptibility to developing CHD.

We performed a large, long-term cohort study to evaluate the association of renin-angiotensin-aldosterone system gene polymorphisms and baseline phenotypes to all-cause mortality among patients with angiographically confirmed coronary atherosclerosis. The study included 1075 subjects who underwent coronary angiography. Patients were genotyped for eight polymorphisms (rs4343, rs5186, rs5182, rs5049, rs5051, rs699, rs4762, and rs1799998), and their baseline plasma angiotensin II and aldosterone levels were measured. The interval between baseline and follow-up time-points ranged from 6.39 to 9.59 years. The results of multivariate regression analysis further indicated that high baseline angiotensin II levels (1.226 (1.024–1.468), p = 0.027) were independently associated with all-cause death. Therefore, we found that an increased baseline plasma angiotensin II level was associated with higher long-term all-cause mortality, even after correcting for established cardiovascular risk factors.

We sought to assess the incidence of aspirin resistance after off-pump coronary artery bypass (OPCAB) surgery, and investigate whether clopidogrel can improve aspirin response and be safely applied early after OPCAB surgery. Sixty patients who underwent standard OPCAB surgery were randomized into two groups. One group (30 patients) received mono-antiplatelet treatment (MAPT) with aspirin 100 mg daily and the other group received dual antiplatelet treatment (DAPT) with aspirin 100 mg daily plus clopidogrel 75 mg daily. Platelet aggregations in response to arachidonic acid (PLAA) and adenosine diphosphate (ADP) (PLADP) were measured preoperatively and on days 1 to 6, 8 and 10 after the antiplatelet agents were administered. A PLAA level above 20% was defined as aspirin resistance. Postoperative bleeding and other perioperative variables were also recorded. There were no significant differences between the two groups in baseline characteristics, average number of distal anastomosis, operation time, postoperative bleeding, ventilation time and postoperative hospital stay. However, the incidence of aspirin resistance was significantly lower in the DAPT group than that in the MAPT group on the first and second day after antiplatelet agents were given (62.1% vs. 32.1%, 34.5% vs. 10.7%, respectively, both P < 0.05). There was no significant difference in postoperative complication between the two groups. DAPT with aspirin and clopidogrel can be safely applied to OPCAB patients early after the procedure. Moreover, clopidogrel reduces the incidence of OPCAB-related aspirin resistance.

Objective This study was designed to examine the prevalence of unilateral and bilateral diagonal earlobe creases (DELCs) with respect to the diagnosis of coronary heart disease (CHD). Methods A total of 558 consecutive participants (402 males and 156 females) aged 36–91 years who underwent coronary angiography were enrolled in this study. The participants were classified as being without a DELC, having a unilateral DELC and having bilateral DELCs; participants with either a unilateral DELC or bilateral DELCs were defined as participants with DELCs. Significant CHD was defined as at least one major vessel with >50% stenosis, and coronary atherosclerosis severity was defined using the Gensini scoring system. Results In the present study, bilateral DELCs were more frequently among male (p=0.001), CHD (p=0.000), older people (p=0.000) and those with more severe coronary artery atherosclerosis (p=0.000). The results of the multiple regression analyses indicated that DELCs (OR, 4.861; 95% CI 3.093 to 7.642, p=0.000) remained independently associated with a risk of CHD. It was assumed that participants without a DELC have a certain background risk for CHD (OR is assumed to be 1); the results of the multivariate logistic regression indicated that the relative risk of CHD among participants with bilateral DELCs was 5.690 among all participants (OR, 5.690; 95% CI 3.450 to 9.384, p=0.000), 5.436 among male participants (OR, 5.436; 95% CI 2.808 to 10.523, p=0.000) and 7.148 among female participants (OR, 7.148; 95% CI 3.184 to 16.049, p=0.000). Moreover, a positive association between DELC and age (SI=1.21, SIM=1.65, AP =0.132), gender (SI=2.09, SIM=0.81, AP=0.49) and smoking status (SI=1.49, SIM=0.73, AP=0.29) was found, respectively. Conclusions The results of the present study indicated that DELCs are a simple and a feasible means of identifying CHD. However, the exact mechanism underlying the relationship between DELCs and CHD warrants further study.

Right-anterior-oblique (RAO) monoplane cineventriculography is usually applied in cardiac catheter labs to assess the left ventricular (LV) function. However, it is uncertain whether this technique is reliable in clinical routine. Unenhanced two-dimensional echocardiography was reported to underestimate left ventricular volumes. The aim of this study was to compare these two conventional techniques with cardiac magnetic resonance imaging (MRI), the present gold standard for the determination of LV function, to evaluate whether the results from the conventional techniques are reliable and in accordance with each other. Seventy-two patients were retrospectively recruited and analysis of the three techniques was performed. Compared with MRI, RAO cineventriculography underestimated LV end-systolic volumes (ESV), and overestimated LV ejection fraction (EF); two-dimensional echocardiography underestimated LV end-diastolic volume (EDV) and EF. Correlation coefficients on EDV, ESV, and EF were 0.8806, 0.9201, and 0.8864 between echocardiography and MRI (P < 0.01, for all), followed by 0.7718, 0.8835, and 0.7785, between cineventriculography and MRI (P < 0.01, for all), and 0.7006, 0.7680, and 0.7644 between cineventriculography and echocardiography (P < 0.01, for all). Echocardiography and MRI showed the highest inter-technique correlation coefficients, and the narrowest Bland-Altman limits of agreement for EDV, ESV and EF. EDV, ESV and EF determined by RAO monoplane cineventriculography, unenhanced two-dimensional echocardiography and MRI were in high accordance with each other, with wide variances between the techniques. Although not interchangeable, RAO monoplane cineventriculography, unenhanced two-dimensional echocardiography, and cardiac MRI are reliable tools in clinical routine for the assessment of LV volumes and function.

Objectives. To observe the short- and long-term outcomes after percutaneous coronary intervention (PCI) in octogenarians (>80y.o.) at our institution.Method. All octogenarians who underwent PCI during the study period were retrospectively retrieved from our database and clinically followed. Major adverse cardiac (and cerebral) events (MAC(C)E) was considered as primary outcome.Results. From January 2003 to December 2007, 140 octogenarians (mean age: 85±3y.o., 79% of male) underwent PCI and were clinically followed 14±11months. Procedural success was obtained in 100 percent of patients with single vessel disease, in 96 percent of patients with double vessel disease, and in 75 percent of patients with triple vessel disease. In-hospital, 30 days, and one year MACE rates were 5%, 5%, and 10.7%, respectively. Impaired left ventricular (LV) ejection fraction (hazard ratio(HR)=0.909, 95% confidence interval(CI)=0.856to 0.964,P=.002), diabetes mellitus (HR=5.792, 95% CI=1.785to 18.796,P=.003), and low GFR (HR=2.943, 95% CI=1.161, to 7.464,P=.023) were independently associated with an increase risk of MACE at long-term followup.Conclusion. Coronary angiography can be successfully performed in elderly patients with single and double vessel disease. The results in triple vessel disease are encouraging. Low LV function, diabetes, and impaired renal function increase the risk of long-term major adverse cardiac events.

To investigate whether the tailored anti-platelet treatments (TAT) guided by the platelet function assays improve clinical outcome in patients undergoing percutaneous coronary intervention (PCI). We searched the bibliographic databases and the references of relevant articles, and recruited all

Objectives Computer tomography (CT) coronary angiography has been successfully integrated with the magnetic navigation system (MNS) to facilitate a roadmap assisted percutaneous coronary intervention (PCI) for coronary artery disease. But the priority of this new approach of PCI has not yet been investigated. The aim of this study was to compare the MNS and CT roadmap assisted PCI versus conventional PCI regarding the difference of contrast usage, x-ray exposure, and procedure success. Methods Thirty-eight patients with stable coronary artery disease were enrolled in the MNS group. Target vessels from pre-procedure CT coronary angiography were extracted, reconstructed, and finally transferred to the live fluoroscopic screen as roadmaps. Another 38 patients within the same study period were recruited in the conventional group, matched with the MNS group by the vessel and lesion type base on ACC/AHA criteria. Results The contrast usage for guidewire crossing was significantly lower in the MNS group than that in the conventional group (0.0 (0.0, 3.0) vs 5.0 (3.1, 6.8) ml; p 2 ; p=0.033). All the enrolled vessels were successfully intervened in both groups. Conclusions Compared to conventional PCI, the MNS and CT roadmap assisted PCI can reduce contrast usage and radiation dosage for guidewire crossing during the process of coronary intervention.

Objectives Guidelines recommend stopping aspirin and clopidogrel 7–10 days before surgery to allow time for replacement of permanently inhibited platelets by newly released uninhibited platelets. The purpose of this study was to determine the rate of offset of the anti-platelet effects of aspirin and clopidogrel after stopping treatment and the proportion of untreated donor platelets that are required to reverse their anti-platelet effects. Methods Cohort 1 consisted of 15 healthy subjects who received aspirin 81 mg/d or clopidogrel 75 mg/d for 7 days and underwent serial blood sampling until platelet function testing results normalised. Cohort 2 consisted of 36 healthy subjects who received aspirin 325 mg/d, clopidogrel 75 mg/d, aspirin 81 mg/d plus clopidogrel 75 mg/d or no treatment for 7 days and underwent a single blood sampling. Results In cohort 1, Arachidonic acid (AA)-induced light transmission aggregation (LTA) returned to baseline levels in all subjects within 4 days of stopping aspirin, coinciding with partial recovery of plasma thromboxane B 2 concentrations. ADP-induced LTA did not return to baseline levels until 10 days after stopping clopidogrel. In cohort 2, AA-induced LTA in patient treated with aspirin reached control levels after mixing with 30% untreated donor platelets whereas ADP-induced LTA in patients treated with clopidogrel reached control levels only after the addition of 90% or more donor platelets. Conclusions Platelet aggregation recovers within 4 days of stopping aspirin but clopidogrel must be stopped for 10 days to achieve a normal aggregatory response.

Background In order to identify miRNAs expression profiling from genome-wide screen for diagnosis of acute myocardial infarction (AMI) and angina pectoris (AP), we investigated the altered profile of serum microRNAs in AMI and AP patients at a relative early stage. Methods Serum samples were taken from 117 AMI patients, 182 AP patients and 100 age-and gender-matched controls. An initial screening of miRNAs expression was performed by Solexa sequencing. Differential expression was validated using RT-qPCR in individuals samples, the samples were arranged in a two-phase selection and validation. Results The Solexa sequencing results demonstrated marked upregulation of serum miRNAs in AMI patients compared with controls. RT-qPCR analysis identified a profile of six serum miRNAs (miR-1, miR-134, miR-186, miR-208, miR-223 and miR-499) as AMI biomarkers. MiR-208 and miR-499 were elevated higher in AP cases than in AMI cases. The ROC curves indicated a panel of six miRNAs has a great potential to offer sensitive and specific diagnostic tests for AMI. More especially, the panel of six miRNAs presents significantly differences between the AMI and AP cases. Conclusions The six-miRNAs signature identified from genome-wide serum miRNA expression profiling may serves as a fingerprint for AMI and AP diagnosis.

The aim of this study was to obtain best estimates of the efficacy and safety of cilostazol-based triple antiplatelet therapy (TAPT: aspirin, clopidogrel and cilostazol) compared with dual antiplatelet therapy (DAPT: aspirin and clopidogrel) in patients undergoing coronary stent implantation. We