Association between multiple inflammatory biomarkers and remnant cholesterol levels in patients with percutaneous coronary intervention: A large-scale real-world study.

BACKGROUND AND AIM: Remnant cholesterol (RC) has garnered increasing attention recently due to its association with adverse cardiovascular events. However, the relationship between RC levels and inflammation remains unclear. The goal of this study was to investigate and compare the predictive value of multiple inflammatory biomarkers for high RC in patients with percutaneous coronary intervention (PCI). METHODS AND RESULTS: Initially, a total of 10,724 consecutive individuals hospitalized for PCI at Fu Wai Hospital in 2013 were enrolled. Finally, 9983 patients receiving dual antiplatelet therapy and drug-eluting stent were selected for analysis. The inflammatory biomarkers included high-sensitivity C-reactive protein (hs-CRP), hs-CRP-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lymphocyte-to-hs-CRP ratio (LCR), and systemic immune-inflammation index (SII). Patients were divided into higher RC and lower RC groups based on the median RC level. Multivariate logistic regression showed that hs-CRP (OR per SD: 1.254), CAR (OR per SD: 1.245), PLR (OR per SD: 1.139), and SII (OR per SD: 1.077) were associated with high RC (≥median), while LCR (OR per SD: 0.792) was associated with low RC (

Inflammation modifies the platelet reactivity among thrombocytopenia patients undergoing percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) patients combined with thrombocytopenia (TP) are usually considered to be at low ischemic risk, receiving less proper antiplatelet therapy. However, recent studies reported a paradoxical phenomenon that PCI patients with TP were prone to experience thrombotic events, while the mechanisms and future treatment remain unclear. We aim to investigate whether inflammation modifies platelet reactivity among these patients. Consecutive 10 724 patients undergoing PCI in Fuwai Hospital were enrolled throughout 2013. High-sensitivity C-reactive protein (hsCRP) ≥2 mg/L was considered inflammatory status. TP was defined as platelet count <150×109/L. High on-treatment platelet reactivity (HTPR) was defined as adenosine diphosphate-induced platelet maximum amplitude of thromboelastogram >47mm. Among 6617 patients finally included, 879 (13.3%) presented with TP. Multivariate logistic regression demonstrated that patients with TP were associated with a lower risk of HTPR (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.53-0.76) than those without TP in the overall cohort. In further analysis, among hsCRP <2 mg/L group, patients with TP exhibited a decreased risk of HTPR (OR 0.53, 95% CI 0.41-0.68); however, in hsCRP ≥2mg/L group, TP patients had a similar risk of HTPR as those without TP (OR 0.83, 95% CI 0.63-1.08). Additionally, these results remain consistent across subgroups, including patients presenting with acute coronary syndrome and chronic coronary syndrome. Inflammation modified the platelet reactivity of PCI patients with TP, providing new insights into the mechanisms of the increased thrombotic risk. Future management for this special population should pay more attention to inflammation status and timely adjustment of antiplatelet therapy in TP patients with inflammation.

What is the context? Recent studies reported a paradoxical phenomenon that percutaneous coronary intervention (PCI) patients with thrombocytopenia (TP) were prone to experience thrombotic events. The potential mechanisms underlying the increased thrombotic risk and how to manage antiplatelet therapy in PCI patients with TP remain unclear.Growing attention has been paid to immunothrombosis. Inflammation is closely associated with high-on treatment platelet reactivity (HTPR) and thrombotic risk.HTPR is an independent risk factor of thrombosis and can provide information for guiding antiplatelet therapy.What is new? This prospective cohort study enrolled 10 724 patients undergoing PCI in Fuwai Hospital (National Center for Cardiovascular Diseases, Beijing, China), with HTPR risk being the study endpoint of interest.We first reported that inflammation significantly modified the platelet reactivity of PCI patients with TP.When hsCRP level <2 mg/L, PCI patients with TP had a decreased risk of HTPR. However, when hsCRP ≥2 mg/L, TP patients had similar HTPR risk as those without TP.HsCRP levels could modify the relationship between TP and HTPR risks both in patients with acute coronary syndrome and chronic coronary syndrome.What is the impact? These results provide insights into potential mechanisms of the increased thrombotic risk in PCI patients with TP. Specifically, inflammation might be involved in the thrombotic risk of PCI patients with TP by modifying the platelet reactivity.As for future management, personalized antiplatelet therapy should be administrated to TP patients with inflammation status.

Chromatin remodeler Znhit1 controls bone morphogenetic protein signaling in embryonic lung tissue branching.

Branching morphogenesis is a key process essential for lung and other organ development in which cellular and tissue architecture branch out to maximize surface area. While this process is known to be regulated by differential gene expression of ligands and receptors, how chromatin remodeling regulates this process remains unclear. Znhit1 (zinc finger HIT-type containing 1), acting as a chromatin remodeler, has previously been shown to control the deposition of the histone variant H2A.Z. Here, we demonstrate that Znhit1 also plays an important role in regulating lung branching. Using Znhit1 conditional KO mice, we show that Znhit1 deficiency in the embryonic lung epithelium leads to failure of branching morphogenesis and neonatal lethality, which is accompanied by reduced cell proliferation and increased cell apoptosis of the epithelium. The results from the transcriptome and the chromatin immunoprecipitation assay reveal that this is partially regulated by the derepression of Bmp4, encoding bone morphogenetic protein (BMP) 4, which is a direct target of H2A.Z. Furthermore, we show that inhibition of BMP signaling by the protein inhibitor Noggin rescues the lung branching defects of Znhit1 mutants ex vivo. Taken together, our study identifies the critical role of Znhit1/H2A.Z in embryonic lung morphogenesis via the regulation of BMP signaling.

HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins.

BACKGROUND: To investigate the association of HMGCR and NPC1L1 gene polymorphisms with residual cholesterol risk (RCR) in patients with premature triple-vessel disease (PTVD). METHODS: Three SNPs within HMGCR including rs12916, rs2303151, and rs4629571, and four SNPs within NPC1L1 including rs11763759, rs4720470, rs2072183, and rs2073547 were genotyped. RCR was defined as achieved low-density lipoprotein cholesterol (LDL-C) concentrations after statins higher than 1.8 mmol/L (70 mg/dL). RESULTS: Finally, a total of 609 PTVD patients treated with moderate-intensity statins were included who were divided into two groups: non-RCR group (n = 88) and RCR group (n = 521) according to LDL-C concentrations. Multivariate logistic regression showed the homozygotes for the minor allele of rs12916 within HMGCR gene (CC) were associated with a 2.08 times higher risk of RCR in recessive model [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.16-3.75]. In codominant model, the individuals homozygous for the minor allele of rs12916 (CC) were associated with a 2.26 times higher risk of RCR (OR: 2.26, 95% CI: 1.16-4.43) while the heterozygous individuals (CT) were not, compared with the individuals homozygous for the major allele of rs12916 (TT). There was no significant association between the SNPs within NPC1L1 gene and RCR in various models. CONCLUSIONS: We first reported that the variant homozygous CC of rs12916 within HMGCR gene may incur a significantly higher risk of RCR in PTVD patients treated with statins, providing new insights into early individualized guidance of precise lipid-lowering treatment.

Novel polymorphism of the HMGCR gene related to the risk of diabetes in premature triple-vessel disease patients.

BACKGROUND: Coronary heart disease and diabetes are highly interrelated and complex diseases. We proposed to investigate the association of genetic polymorphisms of the lipoprotein important regulatory genes Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with premature triple-vessel coronary disease (PTVD) with diabetes, blood glucose and body mass index. METHODS: Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183 and rs2073547) of NPC1L1 and three SNPs (rs12916, rs2303151 and rs4629571) of HMGCR were genotyped in 872 PTVD patients. RESULTS: After performing logistic regression analysis adjusted for age and sex, rs2303151 of HMGCR was related to the risk of diabetes in the dominance model (odds ratio = 1.35, 95% confidence interval = 1.01-1.80, p = 0.04). However, the four SNPs of NPC1L1 were not associated with the risk of diabetes. Further analyses showed that neither the above SNPs of NPC1L1, nor the SNPs of HMGCR were related to blood glucose and body mass index (all p > 0.05). CONCLUSIONS: We report that rs2303151 is a novel polymorphism of the HMGCR gene related to the risk of diabetes in PTVD patients, which suggests HMGCR may be a potential common targeted pathogenic pathways between coronary heart disease and diabetes.

High fibrinogen-to-albumin ratio with type 2 diabetes mellitus is associated with poor prognosis in patients undergoing percutaneous coronary intervention: 5-year findings from a large cohort.

BACKGROUND: Inflammation plays a crucial role in coronary atherosclerosis progression, and growing evidence has demonstrated that the fibrinogen-to-albumin ratio (FAR), as a novel inflammation biomarker, is associated with the severity of coronary artery disease (CAD). However, the long-term risk of cardiovascular events remains indistinct in patients with different level of FAR and different glycemic metabolism status. This study was to assess 5-year clinical outcomes of diabetic and non-diabetic patients who underwent percutaneous coronary intervention (PCI) with different level of FAR. METHODS: We consecutively enrolled 10,724 patients with CAD hospitalized for PCI and followed up for the major adverse cardiac and cerebrovascular events (MACCE) covering all-cause mortality, cardiac mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, and unplanned coronary revascularization. FAR was computed using the following formula: Fibrinogen (g/L)/Albumin (g/L). According to the optimal cut-off value of FAR for MACCE prediction, patients were divided into higher level of FAR (FAR-H) and lower level of FAR (FAR-L) subgroups, and were further categorized into four groups as FAR-H with DM and non-DM, and FAR-L with DM and non-DM. RESULTS: 5298 patients (58.36 ± 10.36 years, 77.7% male) were ultimately enrolled in the present study. A total of 1099 (20.7%) MACCEs were documented during the 5-year follow-up. The optimal cut-off value of FAR was 0.0783 by the surv_cutpoint function. Compared to ones with FAR-H and DM, patients with FAR-L and non-DM, FAR-H and non-DM, FAR-L and DM had decreased risk of MACCEs [adjusted hazard ratio (HR): 0.75, 95% confidence interval (CI) 0.64-0.89, P = 0.001; HR: 0.78, 95% CI 0.66-0.93, P = 0.006; HR: 0.81, 95% CI 0.68-0.97, P = 0.019; respectively]. Notably, non-diabetic patients with lower level of FAR also had lower all-cause mortality and cardiac mortality risk than those in the FAR-H/DM group (HR: 0.41, 95% CI 0.27-0.63, P < 0.001; HR: 0.30, 95% CI 0.17-0.53, P < 0.001; respectively). Multivariate Cox proportional hazards regression analysis also indicated the highest risk of MACCEs in patients with FAR-H and DM than others (P for trend = 0.005). In addition, post-hoc analysis revealed consistent effects on 5-year MACCE across various subgroups. CONCLUSION: In this real-world cohort study, higher level of FAR combined with DM was associated with worse 5-year outcomes among patients with CAD undergoing PCI. The level of FAR may help to identify high-risk individuals in this specific population, where more precise risk assessment should be performed.

Mycoplasma hominis bloodstream infection and persistent pneumonia in a neurosurgery patient: a case report.

BACKGROUND: Mycoplasma hominis is typically associated with a urogenital tract infection, while its association with bacteremia and pneumonia is rare and therefore easily overlooked. Here we report a M. hominis bloodstream infection and pneumonia in a surgical patient. CASE PRESENTATION: A 56-year-old male with symptoms of pneumonia underwent microsurgery and decompressive craniectomy after a left basal ganglia hemorrhage. The patient recovered well from surgery, but pulmonary symptoms progressively worsened, with antimicrobial therapies seemingly ineffective. Culturing of bilateral blood samples resulted in pin-point-sized colonies on blood agar plates, which were subsequently identified as M. hominis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Furthermore, sequencing of bronchoalveolar lavage samples also identified M. hominis as the main pathogen responsible for the pulmonary symptoms. The M. hominis strain was ciprofloxacin resistant, but susceptible to doxycycline and moxifloxacin. Doxycycline and moxifloxacin were subsequently used in a successful combination therapy that finally alleviated the patient's fever and resulted in absorption of pleural effusion. At 1-month follow-up, following complaints of dysuria, a prostate abscess containing M. hominis was detected as the likely primary source of infection. The abscess was successfully drained and treated with doxycycline. CONCLUSIONS: Mycoplasma hominis should be considered as a source of bloodstream infections and pneumonia, particularly when the response to standard antimicrobial therapy is limited. In this case, effective antimicrobial therapy was only commenced after identification of M. hominis and antimicrobial susceptibility testing.

Associations of lipid measures with total occlusion in patients with established coronary artery disease: a cross-sectional study.

BACKGROUND: Total occlusion is the most severe coronary lesion, indicating heavy ischemic burden and poor prognosis. The lipid profile is central to the development of atherosclerotic coronary lesions. Evidence on the optimal lipid measure to be monitored and managed in patients with established coronary artery disease (CAD) is inconclusive. METHODS: Total cholesterol (TC), total triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), nonhigh-density lipoprotein cholesterol (non-HDL-c), lipoprotein (a) [Lp(a)], apolipoprotein B (apoB), non-HDL-c/HDL-c, and apoB/apoA-1 were analyzed in quintiles and as continuous variables. The associations of lipid measures with total occlusion were tested using logistic regression models, visualized with restricted cubic splines, and compared by areas under the receiver operating characteristic curves (AUROC). Discordance analysis was performed when apoB/apoA-1 and non-HDL-c/HDL-c were not in concordance. RESULTS: The prospective cohort study included 10,003 patients (mean age: 58 years; women: 22.96%), with 1879 patients having total occlusion. The risks of total occlusion significantly increased with quintiles of Lp(a), non-HDL-c/HDL-c, and apoB/apoA-1 (all p for trend < 0.001). TG had no association with total occlusion. Restricted cubic splines indicate significant positive linear relations between the two ratios and total occlusion [odds ratio per 1-standard deviation increase (95% confidence interval): non-HDL-c/HDL-c: 1.135 (1.095-1.176), p < 0.001; apoB/apoA-1: 2.590 (2.049-3.274), p < 0.001]. The AUROCs of apoB/apoA-1 and non-HDL-c/HDL-c were significantly greater than those of single lipid measures. Elevation in the apoB/apoA-1 tertile significantly increased the risk of total occlusion at a given non-HDL-c/HDL-c tertile but not vice versa. CONCLUSION: ApoB/apoA-1 confers better predictive power for total occlusion than non-HDL-c/HDL-c and single lipid measures in established CAD patients.

miR-153-3p Attenuates the Development of Gastric Cancer by Suppressing SphK2.

Gastric cancer (GC) is the second leading cause of cancer-related mortality worldwide. MicroRNAs (miRNAs) have been extensively reported to play a role in GC development; however, it remains unknown whether miR-153-3p participates in the nosogenesis of GC. GC tissues along with the adjacent nontumor tissues were obtained from 50 patients with GC. Moreover, we incubated human GC cell lines (SGC7901, AGS, MGC803, and BGC823) and a gastric epithelial cell line (GES-1) and then transfected BGC823 cells with miR-153-3p and DNA/SphK2 vector to determine the action of miR-153-3p and SphK2 on GC. RT-qPCR was performed to determine the levels of miR-153-3p and sphingosine kinase 2 (SphK2). The viability of BGC823 cells was measured by the CCK-8 assay, while wound healing assays and transwell assays were used to measure the migration and invasion ability of BGC823 cells. Western blotting analysis and immunohistochemistry (IHC) were conducted to evaluate the level of SphK2. The binding ability of miR-153-3p and SphK2 was determined by dual-luciferase reporter assays. The expression level of miR-153-3p was reduced in GC tissues and cells, while the SphK2 was enhanced. An increase in miR-153-3p level led to a decline in the growth and metastasis of GC cells and increased their apoptosis. Moreover, a decrease in miR-153-3p level elevated GC cells growth and metastasis, and attenuated their apoptosis. SphK2 was also corroborated as a downstream gene of miR-153-3p. Here, SphK2 expression was elevated in GC tissues and cells, indicating SphK2 might be involved in the development of GC. Rescue assays showed that miR-153-3p could reverse the effect of SphK2 on the cell growth, metastasis, and the apoptosis of GC cells. In conclusion, this study showed that miR-153-3p suppressed the growth and metastasis in GC cells by regulating SphK2, which might facilitate the search for novel biomarkers to treat GC.

The relationship between poor glycaemic control at different time points of gestational diabetes mellitus and pregnancy outcomes.

We aimed to identify the complications of gestational diabetes mellitus (GDM) associated with poor control of fasting plasma glucose (FPG) and postload plasma glucose (PPG) on the 75-g oral glucose tolerance test (OGTT). This retrospective study included 997 singleton pregnancy GDM patients who were assigned to poor or good glycaemic control groups. Multivariate analysis indicated that poor FPG control and poor PPG control were both independent predictors of hypertensive disorder complicating pregnancy (HDCP) (odd ratio (OR) of 2.551 (95% CI [1.146-5.682], p = .022) and OR of 2.084 (95% [1.115-3.894], p = .021) compared with good glycaemic control groups, respectively). Poor PPG control promoted the rate of caesarean delivery (1.534 (95% CI [1.063-2.214]), p = .022), whereas good PPG control increased the risk of premature rupture of membranes (PROM) (0.373 (95% CI [0.228-0.611]), p < .001). Conclusively, poor control FPG and PPG dissimilarly affect pregnancy complications in GDM; these findings may help clinicians in the effective implementation of measures to prevent pregnancy complications in GDM.IMPACT STATEMENTWhat is already known on this subject? Previous studies displayed that GDM patients with 2-h PPG elevated at 24-28 week of gestation had a 2.254-fold increased risk of postpartum dysglycaemia. Abnormal plasma glucose in GDM mother increased the probability of childhood obesity in the offspring. With the implementation of China's second-child policy, the incidence of GDM is rising.What do the results of this study add? Our results indicated that the older patients with GDM, the greater the risk of abnormal plasma glucose control. In addition, maternal age and prenatal BMI were notably correlated with poor plasma glucose control of FPG and PPG, respectively. We also found that both poor FPG and PPG control notably increased the incidence of HDCP in pregnant women. The incidence of PROM was higher in the good PPG control group compared with the poor PPG control group.What are the implications of these findings for clinical practice and/or further research? This study displayed that the effects of poor FPG and PPG control on pregnancy complications and newborn outcomes were heterogeneous, which might be related to the specificity of plasma glucose metabolism at different time points. Good glycaemic control, especially PPG control, was of great significance for improving pregnancy complications and perinatal conditions.

Suppression of Endothelial AGO1 Promotes Adipose Tissue Browning and Improves Metabolic Dysfunction.

BACKGROUND: Metabolic disorders such as obesity and diabetes mellitus can cause dysfunction of endothelial cells (ECs) and vascular rarefaction in adipose tissues. However, the modulatory role of ECs in adipose tissue function is not fully understood. Other than vascular endothelial growth factor-vascular endothelial growth factor receptor-mediated angiogenic signaling, little is known about the EC-derived signals in adipose tissue regulation. We previously identified Argonaute 1 (AGO1; a key component of microRNA-induced silencing complex) as a crucial regulator in hypoxia-induced angiogenesis. In this study, we intend to determine the AGO1-mediated EC transcriptome, the functional importance of AGO1-regulated endothelial function in vivo, and the relevance to adipose tissue function and obesity. METHODS: We generated and subjected mice with EC-AGO1 deletion (EC-AGO1-knockout [KO]) and their wild-type littermates to a fast food-mimicking, high-fat high-sucrose diet and profiled the metabolic phenotypes. We used crosslinking immunoprecipitation- and RNA-sequencing to identify the AGO1-mediated mechanisms underlying the observed metabolic phenotype of EC-AGO1-KO. We further leveraged cell cultures and mouse models to validate the functional importance of the identified molecular pathway, for which the translational relevance was explored using human endothelium isolated from healthy donors and donors with obesity/type 2 diabetes mellitus. RESULTS: We identified an antiobesity phenotype of EC-AGO1-KO, evident by lower body weight and body fat, improved insulin sensitivity, and enhanced energy expenditure. At the organ level, we observed the most significant phenotype in the subcutaneous and brown adipose tissues of KO mice, with greater vascularity and enhanced browning and thermogenesis. Mechanistically, EC-AGO1 suppression results in inhibition of thrombospondin-1 (THBS1/TSP1), an antiangiogenic and proinflammatory cytokine that promotes insulin resistance. In EC-AGO1-KO mice, overexpression of TSP1 substantially attenuated the beneficial phenotype. In human endothelium isolated from donors with obesity or type 2 diabetes mellitus, AGO1 and THBS1 are expressed at higher levels than the healthy controls, supporting a pathological role of this pathway. CONCLUSIONS: Our study suggests a novel mechanism by which ECs, through the AGO1-TSP1 pathway, control vascularization and function of adipose tissues, insulin sensitivity, and whole-body metabolic state.

Prognostic value of fibrinogen in patients with coronary artery disease and prediabetes or diabetes following percutaneous coronary intervention: 5-year findings from a large cohort study.

BACKGROUND: Fibrinogen (FIB) is an independent risk factor for mortality and cardiovascular events in the general population. However, the relationship between FIB and long-term mortality among CAD patients undergoing PCI remains unclear, especially in individuals complicated with diabetes mellitus (DM) or prediabetes (Pre-DM). METHODS: 6,140 patients with CAD undergoing PCI were included in the study and subsequently divided into three groups according to FIB levels (FIB-L, FIB-M, FIB-H). These patients were further grouped by glycemic status [normoglycemia (NG), Pre-DM, DM]. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. RESULTS: FIB was positively associated with hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) in CAD patients with and without DM (P < 0.001). During a median follow-up of 5.1 years (interquartile range 5.0-5.2 years), elevated FIB was significantly associated with long-term all-cause mortality (adjusted HR: 1.86; 95% CI 1.28-2.69; P = 0.001) and cardiac mortality (adjusted HR: 1.82; 95% CI 1.15-2.89; P = 0.011). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause and cardiac mortality compared with NG group (all P < 0.05). When grouped by both FIB levels and glycemic status, diabetic patients with medium and high FIB levels had higher risk of mortality [(adjusted HR: 2.57; 95% CI 1.12-5.89), (adjusted HR: 3.04; 95% CI 1.35-6.82), all P < 0.05]. Notably, prediabetic patients with high FIB also had higher mortality risk (adjusted HR: 2.27; 95% CI 1.01-5.12). CONCLUSIONS: FIB was independently associated with long-term all-cause and cardiac mortality among CAD patients undergoing PCI, especially in those with DM and Pre-DM. FIB test may help to identify high-risk individuals in this specific population.

Long-Term Outcomes of Single-Vessel Percutaneous Coronary Intervention on Culprit Vessel vs. Multivessel Percutaneous Coronary Intervention in Non-ST-Segment Elevation Acute Coronary Syndrome Patients With Multivessel Coronary Artery Disease.

BACKGROUND: The optimal percutaneous coronary intervention (PCI) strategy for multivessel lesions in the setting of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains controversial. This study sought to compare long-term prognosis between single-vessel PCI (SV-PCI) and multivessel PCI (MV-PCI) in patients with multivessel coronary artery disease (MV-CAD) presenting with NSTE-ACS in a real-world population.Methods and Results:NSTE-ACS patients with MV-CAD undergoing PCI in Fuwai Hospital in 2013 were consecutively enrolled. SV-PCI was defined as targeting only the culprit vessel, whereas MV-PCI was defined as treating ≥1 coronary artery(s) in addition to the culprit vessel at the index procedure. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) at 2 years, consisting of all-cause death, cardiac death, myocardial infarction, unplanned revascularization, or stroke. A total of 3,338 patients were included. Both SV-PCI and MV-PCI were performed in 2,259 patients and 1,079 patients, respectively. During a median follow up of 2.1 years, the MACCE rates and adjusted risk were not significantly different between the SV-PCI and MV-PCI groups (13.1% vs. 14.0%, P=0.735; adjusted HR=0.967, 95% CI: 0.792-1.180). Similar results were observed in propensity-score matching and inverse probability of treatment weighting analyses. Subgroup analysis revealed a consistent effect on 2-year MACCE across different subgroups. CONCLUSIONS: In NSTE-ACS patients with MV-CAD, MV-PCI is not superior to SV-PCI in terms of long-term MACCE.

Evidence-based oral antiplatelet therapy among hospitalized Chinese patients with acute myocardial infarction: results from the Chinese acute myocardial infarction registry.

BACKGROUND: Oral antiplatelet therapy is the cornerstone of treatment for acute myocardial infaction (AMI). However, detailed usage data on oral antiplatelet therapy are lacking. METHODS: Using data from a nationally representative sample of patients with AMI, the detailed usage of oral antiplatelet therapy was analyzed in 40,202 consecutive eligible patients. RESULTS: The proportions of patients with AMI taking loading doses of aspirin and P2Y12 inhibitors were relatively low (62.2% and 63.6%, respectively), whereas approximately 90% of patients received maintenance doses of aspirin, P2Y12 inhibitors, and dual antiplatelet therapy. The proportions of patients taking loading doses of aspirin and P2Y12 inhibitors gradually decreased with age. Male sex, an educational level of at least college, an interval from onset to treatment of < 24 h, and primary PCI use were associated with a higher proportion of patients taking a loading dose of antiplatelet therapy, whereas those receiving conservative treatment had a lower rate of antiplatelet use (all P < 0.05). The proportion of patients taking loading doses of aspirin was highest in the western region, and that of patients taking loading doses of P2Y12 inhibitors was highest in the eastern region (P < 0.05). In addition, 76.7% of patients with ST-elevation MI and 91% of patients with non-ST-elevation MI received 300-mg loading dose of clopidogrel. CONCLUSIONS: The proportion of patients with AMI receiving loading doses of aspirin and P2Y12 inhibitors during hospitalization was relatively low, and this rate was affected by many factors, such as age, sex, educational level, region of residence, and the interval from onset to treatment. The underutilization of guideline-based P2Y12 inhibitors was also problematic. Hence, quality improvement initiatives are needed to enhance adherence to guidelines to improve consistent use of oral antiplatelet therapy. Trial registration The Chinese Acute Myocardial Infarction Registry; Trial registration number: ChiCTR-ONC-12002636; Registered 31 October 2012; http://www.chictr.org.cn/showproj.aspx?proj=6916.

Association of lipoprotein(a) with platelet aggregation and thrombogenicity in patients undergoing percutaneous coronary intervention.

This study aimed to evaluate the association of lipoprotein(a) levels with platelet aggregation and thrombogenicity in patients undergoing percutaneous coronary intervention (PCI), and to investigate the ischemic outcome on this population. Lipoprotein(a) and modified thrombelastography were measured in 6601 consecutive patients underwent PCI on dual antiplatelet therapy. Cox proportional regression analysis was applied to illustrate the ischemic events in a 2-year follow up. The mean levels of lipoprotein(a) were 29.0 mg/dl. Patients with higher lipoprotein(a) levels had significantly accelerated fibrin generation (lower K time and bigger α angle) and greater clot strength (higher maximum amplitude (MA)) than patients with lower lipoprotein(a) levels (P < .001). Moreover, the higher lipoprotein(a) group also exhibited significantly higher adenosine diphosphate (ADP) induced platelet aggregation (MAADP) by thrombelastography platelet mapping assay than lower lipoprotein(a) group. Cox regression analyzes revealed that patients with higher lipoprotein(a) levels had a 16% higher risk of major adverse cardiovascular and cerebrovascular events (HR 1.159, 95%CI: 1.005-1.337, P = .042) compared with patients with lower lipoprotein(a) levels. This association persisted after adjustment for a broad spectrum of risk factors (HR 1.174, 95%CI: 1.017-1.355, P = .028). High plasma lipoprotein(a) levels were associated with increased platelet aggregation and ischemic events in patients underwent PCI. Lipoprotein(a) might indicate the need for prolonged antiplatelet therapy.

Chemiluminescence Resonance Energy Transfer Efficiency and Donor-Acceptor Distance: from Qualitative to Quantitative.

Since its birth in 1967, the utilization of chemiluminescence resonance energy transfer (CRET) has made substantial progress in a variety of fields for its unique features. However, the quantitative relationship between CRET efficiency and donor-acceptor distance has not yet been determined owing to the difficulty in designing the variable lengths between chemiluminescent donors and acceptors. Herein, we synthesized three kinds of tetraphenylethene (TPE)-anchored cationic surfactants with aggregation-induced emission (AIE) characteristics. For the first time, it is quantitatively demonstrated that the CRET efficiency is inversely proportional to the sixth power of distance between luminol donors and TPE acceptors. The details disclosed in this contribute have provided the solid evidence that CRET follows Förster resonance theory. Our strategy would build a promising platform to control donor-acceptor distance, allowing to the interdisciplinary applications of CRET.

Two-Year Outcomes after Left Main Coronary Artery Percutaneous Coronary Intervention in Patients Presenting with Acute Coronary Syndrome.

OBJECTIVES: We aim to evaluate long-term outcomes after left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS). BACKGROUND: PCI of the LMCA has been an acceptable revascularization strategy in stable coronary artery disease. However, limited studies on long-term clinical outcomes of LMCA PCI in ACS patients are available. METHODS: A total of 6429 consecutive patients with ACS undergoing PCI in Fuwai Hospital in 2013 were enrolled. Patients are divided into LMCA group and Non-LMCA group according to whether the target lesion was located in LMCA. Prognosis impact on 2-year major adverse cardiovascular and cerebrovascular events (MACCE) is analyzed. RESULTS: 155 (2.4%) patients had target lesion in LMCA, while 6274 (97.6%) patients belong to the non-LMCA group. Compared with non-LMCA patients, LMCA patients have generally more comorbidities and worse baseline conditions. Two-year follow-up reveals that LMCA patients have significantly higher rate of cardiac death (2.6% vs. 0.7%, p = 0.034), myocardial infarction (7.1% vs. 1.8%, p < 0.001), in-stent thrombosis (4.5% vs. 0.8%, p < 0.001), and stroke (7.1% vs. 6.4%, p = 0.025). After adjusting for confounding factors, LMCA remains independently associated with higher 2-year myocardial infarction rate (HR = 2.585, 95% CI = 1.243-5.347, p = 0.011). CONCLUSION: LMCA-targeted PCI is an independent risk factor for 2-year myocardial infarction in ACS patients.

Susceptible gene polymorphism in patients with three-vessel coronary artery disease.

BACKGROUND: Data of susceptible gene polymorphisms related to progression of coronary atherosclerosis in patients with three-vessel disease (TVD) is limited in China. This case-control study aimed to analyze the differences of variant carrier frequencies between cases and controls, and to explain the possible genetic effects on the progression of TVD. METHODS: A total of 8943 TVD patients were consecutively enrolled. Major adverse cardiac and cerebrovascular events (MACCE) included all-cause death, acute myocardial infarction, repeat revascularization, readmission and stroke. Patients with 1-year MACCE in this cohort were selected as MACCE group. Blood samples from MACCE group and non-CAD control groups were collected, and a deoxyribonucleic acid library was created. A total of 34 tag or hot single nucleotide polymorphisms (SNPs) in six genes including CDKN2B-AS1, ADAMTS7, ABO, ADAMTS13, IL-18, and PECAM1 were analyzed by a SNPscan™ multi-genotyping kit. Carrier frequencies of each SNP were compared between the two groups using dominant, recessive and codominant allele model, respectively. Multivariate logistic regression model was established. RESULTS: Variant allele frequencies of rs10757274, rs1333042, rs1333049, rs4977574, rs9632884, rs1063192 and rs3217986 on CDKN2B-AS1 gene showed significant differences between the two groups in at least one allele model. Variant allele frequency of rs3217986 was not statistically significant after adjusting for the false discovery rate using Benjamini-Hochberg procedure (Q > 0.05). Variant allele frequencies of rs1333049, rs10757274, rs4977574 on CDKN2B-AS1 gene were significantly higher in MACCE group in all dominant, recessive and codominant models. Rs1055432 on ADAMTS13 and rs8176694 on ABO gene showed threshold significance between the two groups. After multivariable adjustment, G mutant homozygous rs9632884 (GG vs. GC + CC) (OR: 0.24; 95% CI: 0.09-0.65; P = 0.005) on CDKN2B-AS1 gene were independent protective factor of MACCE in recessive model. CONCLUSIONS: In patients with TVD in China, variant alleles on CDKN2B-AS1 gene may form part of the genetic basis of coronary atherosclerosis progression, promoting or suppressing ischemic events.

Lipoprotein(a) levels are associated with coronary severity but not with outcomes in Chinese patients underwent percutaneous coronary intervention.

BACKGROUND AND AIMS: The association between lipoprotein(a) [Lp(a)] levels and the risk of cardiovascular disease is of great interest but still controversial. This study sought to investigate the impact of Lp(a) on coronary severity and long-term outcomes of patients who undergo percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 6714 consecutive patients who received PCI were enrolled to analyze the association between Lp(a) and coronary severity and major adverse cardiovascular and cerebrovascular events (MACCE). Patients were divided into tertiles according to Lp(a) levels on admission. Coronary severity was evaluated by SYNTAX scoring system. The MACCE included recurrent myocardial infarction, unplanned target vessel revascularization, stent thrombosis, ischemic stroke and all-cause mortality. Significantly, Lp(a) levels were positively associated with coronary severity (p < 0.001). Multivariate logistic regression analyses showed Lp(a) was an independent predictor of intermediate to high SYNTAX score. During an average of 874 days follow-up, 755 patients presented with MACCE (11.25%) were reported. The incidence rates of MACCE, all-cause mortality, cardiac death, target vessel revascularization, recurrent myocardial infarction, stent thrombosis, stroke and bleeding were not statistically different among the Lp(a) tertile groups. Furthermore, both Kaplan-Meier and Cox regression analyses found no relationship between Lp(a) and cardiovascular outcomes (p > 0.05). CONCLUSION: Lp(a) is an independent predictor of the prevalence of more complex coronary artery lesions (SYNTAX score ≥ 23) in patients with PCI. In addition, our study has shown that Lp(a) has no relationship with long-term cardiovascular outcomes in Chinese patients with PCI.

Impact of unknown diabetes and prediabetes on clinical outcomes in "nondiabetic" Chinese patients after a primary coronary intervention.

BACKGROUND AND AIM: To explore the prevalence of unknown diabetes (DM) or prediabetes (pre-DM) in "nondiabetic" patients and its association with 2-year clinical outcomes after primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: 5202 consecutive "nondiabetic" patients who underwent primary PCI at Fuwai Hospital from January to December 2013 were prospectively enrolled. The patients were grouped according to their glycemia status: unknown DM (HbA1c ≥ 47 mmol/L; FPG≥ 7.0 mmol/L), pre-DM (HbA1c 39-47 mmol/L; FPG: 5.6-6.9 mmol/L) and normoglycemia (NG, HbA1c < 39 mmol/L; FPG < 5.6 mmol/L). The main endpoint was 2-year major adverse cardiovascular events (MACE), including cardiac death, myocardial infarction, and target vessel revascularization. A total of 905 patients had unknown DM, and 3407 patients had pre-DM. Unknown DM and pre-DM were associated with aging (p < 0.001); a greater proportion of hypertension (p < 0.001), previous myocardial infarction (p < 0.001), and chronic kidney disease (p = 0.004). During the 2-year follow-up, the rate of MACE was significantly higher in the unknown DM and pre-DM groups than in the NG group (8.1% vs. 5.8% vs. 4.1%, respectively, p = 0.001). Multivariate analyses demonstrated that unknown DM was associated with a 1.9-fold higher event risk compared to NG (95% CI: 1.2-2.8). CONCLUSIONS: The prevalence of abnormal glucose metabolism was high in "nondiabetic" Chinese PCI patients. Patients with unknown DM and pre-DM had higher event risks than those with NG. In "nondiabetes" patients requiring PCI, routine assessment of HbA1c and FPG appears to be of value to identify patients with an increased event risk.