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Introduction: This study explored the ability of high-sensitivity C-reactive protein (hs-CRP) and glycosylated hemoglobin A1c (HbA1c) to predict adverse cardiac and cerebrovascular outcomes in patients with chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Methods: In total, 4083 consecutive patients with CCS undergoing PCI were investigated throughout 2013 at a single center. The primary endpoint was all-cause death at the 5-year follow-up. Hs-CRP and HbA1c data were collected on admission. Results: The highest quartile of hs-CRP had a significantly increased the risk of all-cause death, with an adjusted HR of 1.747 (95 % CI 1.066-2.863), while, there was no difference in all-cause death among the groups of HbA1c after adjustment, with an adjusted HR of 1.383 (95 % CI 0.716-2.674). The highest quartiles for hs-CRP and HbA1c in the study population had a significantly increased risk of major adverse cardiac and cerebrovascular events (MACCE), with an adjusted hazard ratios (HR) of 1.263 (95 % confidence intervals [CI] 1.032-1.545) for hs-CRP and an adjusted HR of 1.417 (95 % CI 1.091-1.840) for HbA1c. Remarkably, the incidence of all-cause death and that of MACCE were significantly increased when both hs-CRP and HbA1c were elevated (HR 1.971, 95 % CI 1.079-3.601, P = 0.027 and HR 1.560, 95 % CI 1.191-2.042), P = 0.001, respectively). Addition of hs-CRP and HbA1c to conventional risk factors significantly improved prediction of the risk of all cause death (net reclassification index 0.492, P < 0.001; integrated discrimination improvement 0.007, P = 0.011) and MACCE (net reclassification index 0.160, P < 0.001; integrated discrimination improvement 0.006, P < 0.001). Conclusions: Hs-CRP and HbA1c can serve as independent predictors of MACCE in patients with CCS undergoing PCI. Furthermore, a combination of hs-CRP and HbA1c could predict all cause death and MACCE better than each component individually.
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Reactive oxygen species (ROS), released as byproducts of mitochondrial metabolism or as products of NADPH oxidases and other processes, can directly oxidize the active-site cysteine (Cys) residue of protein tyrosine phosphatases (PTPs) in a mammalian cell. Robust degradation of irreversibly oxidized PTPs is essential for preventing accumulation of these permanently inactive enzymes. However, the mechanism underlying the degradation of these proteins was unknown. In this study, we found that the active-site Cys215 of endogenous PTP1B is sulfonated in H9c2 cardiomyocytes under physiological conditions. The sulfonation of Cys215 led PTP1B to exhibit a conformational change, and drive the subsequent ubiquitination and degradation of this protein. We then discovered that Cullin1, an E3 ligase, interacts with the Cys215-sulfonated PTP1B. The functional impairment of Cullin1 prevented PTP1B from oxidation-dependent ubiquitination and degradation in H9c2 cells. Moreover, delivery of the terminally oxidized PTP1B resulted in proteotoxicity-caused injury in the affected cells. In conclusion, we elucidate how sulfonation of the active-site Cys215 can direct turnover of endogenous PTP1B through the engagement of ubiquitin-proteasome system. These data highlight a novel mechanism that maintains PTP homeostasis in cardiomyocytes with constitutive ROS production.
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Cisteína , Ubiquitina-Proteína Ligases , Animais , Cisteína/metabolismo , Espécies Reativas de Oxigênio , Proteínas Tirosina Fosfatases , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Mamíferos/metabolismoRESUMO
BACKGROUND: The optimal apolipoprotein or lipid measures for identifying statin-treated patients with coronary artery disease (CAD) at residual cardiovascular risk remain controversial. This study aimed to compare the predictive powers of apolipoprotein B (apoB), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apoB/apolipoprotein A-1 (apoA-1) and non-HDL-C/HDL-C for myocardial infarction (MI) in CAD patients treated with statins in the setting of secondary prevention. METHODS: The study included 9191 statin-treated CAD patients with a five-year median follow-up. All measures were analyzed as continuous variables and concordance/discordance groups by medians. The hazard ratio (HR) with 95% CI was estimated by Cox proportional hazards regression. Patients were classified by the clinical presentation of CAD for further analysis. RESULTS: The high-apoB-low-LDL-C and the high-non-HDL-C-low-LDL-C categories yielded HR of 1.40 (95% CI: 1.04-1.88) and 1.51 (95% CI: 1.07-2.13) for MI, respectively, whereas discordant high LDL-C with low apoB or non-HDL-C was not associated with the risk of MI. No association of MI with discordant apoB versus non-HDL-C, apoB/apoA-1 versus apoB, non-HDL-C/HDL-C versus non-HDL-C, or apoB/apoA-1 versus non-HDL-C/HDL-C was observed. Similar patterns were found in patients with acute coronary syndrome. In contrast, no association was observed between any concordance/discordance category and the risk of MI in patients with chronic coronary syndrome. CONCLUSIONS: ApoB and non-HDL-C better predict MI in statin-treated CAD patients than LDL-C, especially in patients with acute coronary syndrome. ApoB/apoA-1 and non-HDL-C/HDL-C show no superiority to apoB and non-HDL-C for predicting MI.
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The study aimed to determine whether gut-brain communication could be modulated by epigallocatechin-3-gallate (EGCG) in a mouse aging model that was established by daily injection of D-galactose (D-gal) for 10 weeks. Our results showed that EGCG could improve aging-associated changes by increasing the immune organ indexes, brain index, and learning and memory ability in vivo. EGCG-triggered aging prevention was associated with the reduction of lipid peroxidation and elevation of enzymatic and non-enzymatic antioxidant activities in the brain. Concomitantly, treatment of D-gal-induced aging in mice with EGCG significantly reduced corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone, suggesting that EGCG-exerted protection of the aging brain was involved in the inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. Further data concerning intestinal function showed that EGCG could enhance fecal moisture in vitro and reduce the pH value of feces in aging mice when compared to the D-gal group, suggesting that EGCG played beneficial roles in the intestine of aging mice. Moreover, short-chain fatty acids (SCFAs), the mediators of gut-brain communication, were significantly increased in the intestinal contents of aging mice by treatment with EGCG. Therefore, the tea polyphenol EGCG showing anti-aging properties was demonstrated to be implicated in modulating gut-brain communication by attenuating the HPA axis and enhancing the content of SCFAs.
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Catequina , Galactose , Animais , Camundongos , Galactose/efeitos adversos , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Catequina/farmacologia , Envelhecimento , Encéfalo , Modelos Animais de Doenças , Chá/químicaRESUMO
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.
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Diabetes Gestacional , Hiperglicemia , Obesidade Infantil , Complicações na Gravidez , Criança , Recém-Nascido , Gravidez , Humanos , Feminino , Diabetes Gestacional/epidemiologia , Resultado da Gravidez , Glicemia/metabolismo , Estudos Retrospectivos , Controle GlicêmicoRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases are often comorbid conditions, their co-occurrence yields worse outcomes than either condition alone. This study aimed to investigate COPD impacts on the five-year prognosis of patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: Patients with CHD who underwent PCI in 2013 were recruited, and divided into COPD group and non-COPD group. Adverse events occurring among those groups were recorded during the five-year follow-up period after PCI, including all-cause death and cardiogenic death, myocardial infarction, repeated revascularization, as well as stroke and bleeding events. Major adverse cardiac and cerebral events were a composite of all-cause death, myocardial infarction, repeated revascularization and stroke. RESULTS: A total of 9843 patients were consecutively enrolled, of which 229 patients (2.3%) had COPD. Compared to non-COPD patients, COPD patients were older, along with poorer estimated glomerular filtration rate and lower left ventricular ejection fraction. Five-year follow-up results showed that incidences of all-cause death and cardiogenic death, as well as major adverse cardiac and cerebral events, for the COPD group were significantly higher than for non-COPD group (10.5% vs. 3.9%, 7.4% vs. 2.3%, and 30.1% vs. 22.6%, respectively). COPD was found under multivariate Cox regression analysis, adjusted for confounding factors, to be an independent predictor of all-cause death [odds ratio (OR) = 1.76, 95% CI: 1.15-2.70, P = 0.009] and cardiogenic death (OR = 2.02, 95% CI: 1.21-3.39, P = 0.007). CONCLUSIONS: COPD is an independent predictive factor for clinical mortality, in which CHD patients with COPD are associated with worse prognosis than CHD patients with non-COPD.
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Background: Hyperuricemia has recently been identified as a risk factor of cardiovascular diseases; however, prognostic value of hyperuricemia in patients with ST-segment elevation myocardial infarction (STEMI) remained unclear. Simultaneously, the mechanism of this possible relationship has not been clarified. At present, some views believe that hyperuricemia may be related to the inflammatory response. Our study aimed to investigate the association between hyperuricemia and long-term poor prognosis and inflammation in STEMI patients undergoing percutaneous coronary intervention (PCI). Methods: A total of 1,448 consecutive patients with STEMI were studied throughout 2013 at a single center. The primary endpoint was all-cause death at 2- and 5-year follow-up. Inflammatory biomarkers were collected on admission of those patients: high sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count. Results: Hyperuricemia was associated with higher 2- and 5-year all-cause death in STEME patients compared to normouricemia (5.5% vs. 1.4%, P <0.001; 8.0% vs 3.9%, P = 0.004; respectively). After multivariable adjustment, hyperuricemia was still an independent predictor of 2-year all-cause death (hazard ratio (HR) =4.332, 95% confidence interval (CI): 1.990-9.430, P <0.001) and 5-year all-cause death (HR =2.063, 95% CI: 1.186-3.590, P =0.010). However, there was no difference in hs-CRP, ESR, and WBC count on admission in STEMI patients with hyperuricemia compared to normouricemia (P >0.05). Conclusions: Hyperuricemia was associated with higher risks of 2- and 5-year all-cause deaths in patients with STEMI undergoing PCI. However, this study did not find a correlation between hyperuricemia and inflammatory responses in newly admitted STEMI patients.
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Hiperuricemia , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Proteína C-Reativa/análise , Humanos , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Resultado do TratamentoRESUMO
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.
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Lipoproteína(a)/metabolismo , Intervenção Coronária Percutânea/métodos , Agregação Plaquetária/fisiologia , Trombose/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: To evaluate the clinical impact of ß-blocker in patients with adequate left ventricular ejection function (LVEF) who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). METHODS: A total of 10,724 consecutive patients who underwent PCI throughout 2013 were prospectively enrolled in the study. Among these, we analyzed 5,631 ACS patients who were discharged with LVEF ≥ 40%. Patients were then compared according to the ß-blocker prescription at discharge. RESULTS: During a 2-year follow-up, no significant association was observed of ß-blocker use with all-cause mortality (with ß-blockers 47/5,043 (0.9%) vs. without ß-blocker use 8/588 (1.4%); hazard ratio (HR) 0.762, 95% confidence interval 0.36 to 1.64; P = 0.485), cardiac death, myocardial infarction (MI), or major adverse cardiovascular and cerebrovascular events. Subgroup analysis demonstrated that the ß-blocker use at discharge reduced the 2-year mortality in patients with unstable angina (UA) (HR 0.42, 95% CI 0.19 to 0.94, P = 0.034). Landmark analysis at 1 year showed that patients with UA who were discharged with ß-blockers had lower mortality (HR 0.17, 95% CI 0.04-0.65, P = 0.010) and cardiac death (HR 0.12, 95% CI 0.01-0.99, P = 0.049) than those discharged without ß-blockers. However, the benefit was lost beyond 1 year. No differences in outcomes were recorded in the AMI or overall population. CONCLUSIONS: We present that ß-blocker significantly lowers the rate of all-cause death up to 1 year, in UA patients who have undergone PCI and have adequate LVEF. Its role in patients with AMI also deserves further exploration.
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Síndrome Coronariana Aguda/terapia , Antagonistas Adrenérgicos beta/uso terapêutico , Alta do Paciente , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/fisiopatologia , Causas de Morte , China , Progressão da Doença , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Estudos Prospectivos , Fatores de Risco , Stents , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
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.
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Síndrome Coronariana Aguda/patologia , Síndrome Coronariana Aguda/cirurgia , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/complicações , Idoso , China , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Inflammation plays a pivotal role in coronary artery disease (CAD). Few data from large-size studies are available on the association of high-sensitivity C-reactive protein (hs-CRP) and severity of CAD. Our aim was to investigate their relationship as well as their impact on long-term outcomes in patients undergoing percutaneous coronary intervention. METHODS: In 2013, 10,020 patients were consecutively included. Patients were divided into three groups based on hs-CRP on admission: 0-3mg/L (n=6978, 69.6%), 3.01-10mg/L (n=1997, 19.9%), >10mg/L (n=1045, 10.4%). Disease severity was determined by SYNTAX score (SS). Their differences were assessed in SS and major adverse cardiovascular events (MACEs, including all-cause death, myocardial infarction, revascularization, and in-stent thrombosis) among groups. RESULTS: The mean follow-up period was 874 days. Patients with elevated hs-CRP were older, had more risk factors such as hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, and cigarette smoking. Multivariate regression analysis showed that hs-CRP >10mg/L (OR 1.49, 95% confidence interval 1.21-1.84, p<0.001), age, previous myocardial infarction, serum creatinine, and left ventricular ejection fraction were independent predictors of intermediate-high SS (>22). Subgroup analysis indicated that the relation between hs-CRP and SS was also consistent in acute coronary syndrome and its subtypes. Although elevated hs-CRP was positively associated with increased rates of MACEs (11.0% versus 12.1% versus 14.3%, p=0.006), death (1.0% versus 1.3% versus 3.0%, p<0.001), and revascularization (8.6% versus 10.4% versus 10.0%, p=0.032), it did not show any prognostic effect for adverse outcomes in multivariate regression analyses (all adjusted p> 0.05). While SS>22 remained independently predictive of MACEs and revascularization after adjusting confounders, the risks of which were increased by 56% and 68%, respectively. CONCLUSION: Serum hs-CRP could be a useful biomarker for indicating CAD severity and could aid in risk stratification.
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Proteína C-Reativa/análise , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Neovascularização Patológica/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Índice de Gravidade de Doença , Trombose/etiologia , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
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.
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Doença da Artéria Coronariana/terapia , Lipoproteína(a)/sangue , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Idoso , Pequim/epidemiologia , Biomarcadores/sangue , Causas de Morte , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Hemorragia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Prevalência , Recidiva , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Stents , Acidente Vascular Cerebral/mortalidade , Trombose/mortalidade , Fatores de Tempo , Resultado do TratamentoRESUMO
Geminin is a master regulator of cell-cycle progression that ensures the timely onset of DNA replication and prevents re-replication in vertebrates and invertebrates. Previously, we identified two Geminin genes, BmGeminin1 and BmGeminn2, in the silkworm Bombyx mori, and we found that RNA interference of BmGeminin1 led to re-replication. However, the function of BmGeminin2 remains poorly understood. In this study, we found that knockdown of BmGeminin2 can improve cell proliferation, and upregulated G2/M-associated gene-cyclinB/CDK1 expression. Then, we performed yeast two-hybrid screening to identify interacting proteins. Our results yielded 23 interacting proteins, which are involved in DNA replication, chromosome stabilization, embryonic development, energy, defense, protein processing, or structural protein. Here, we focused on BmRRS1, a chromosome congression-related protein that is closely related to cell cycle G2/M progression. The interaction between BmGeminin2 and BmRRS1 was confirmed by immunofluorescence and immunoprecipitation. Analysis of its expression profile showed that BmRRS1 was related to BmGeminin2. In addition, BmGeminin2 overexpression downregulated the BmRRS1 transcript. Knockdown of BmGeminin2 led to upregulation of the BmRRS1 transcript. Furthermore, overexpression of BmRRS1 can upregulate G2/M-associated gene-cyclinB/CDK1 expression, and improved cell proliferation, consistent with the effects of BmGeminin2 knockout. In addition, BmRRS1 RNA interference can eliminate the impact of BmGem2 knockout on cell proliferation, the ratio of cell cycle stage and the expression of cyclinB/CDK1. These data suggested that the cell proliferation advantage of BmGeminin2 knockout was closely related to BmRRS1. Our findings provide insight into the functions of Geminin and the mechanisms underlying the regulation of the cell cycle in the silkworm.
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Bombyx/genética , Proliferação de Células/genética , Proteínas de Insetos/genética , Animais , Linhagem Celular , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Expressão Gênica/genética , Interferência de RNA/fisiologia , Regulação para Cima/genéticaRESUMO
BACKGROUND: A novel risk model to predict long-term mortality in patients with acute coronary syndrome (ACS), derived from the EPICOR (long-term follow-up of antithrombotic management patterns in acute coronary syndrome patients) registry, has been released recently and its performance remains to be assessed. The objective is to evaluate the EPICOR score for 2-year mortality risk in ACS patients after percutaneous coronary intervention (PCI). METHODS: From January to December in 2013, a total of 6087 consecutive patients presenting with ACS who were scheduled for PCI were enrolled. Use online simplified EPICOR calculator to assess the expected risk of death. RESULTS: Sixty-eight patients (1.1%) died during 2-year follow-up. The areas under the receiver operating characteristics curve for mortality in the overall population, ST-segment elevation myocardial infarction (STEMI), and non-ST-segment elevation ACS were 0.712 (95% CI, 0.650-0.772; p < 0.001), 0.790 (95% CI, 0.676-0.903; p < 0.001), and 0.683 (95% CI, 0.615-0.751; p < 0.001), respectively. Moreover, it was noninferior to the updated Global Registry of Acute Coronary Events (GRACE) risk score. Patients were stratified into three categories: low-risk (n = 3382), medium-risk (n = 2547), and high-risk (n = 158). Kaplan-Meier curve demonstrated significant ongoing divergence in both mortality (0.6% vs 1.3% vs 9.5%; p < 0.001) and major adverse cardiovascular and cerebrovascular events (MACCEs) (11.8% vs 12.3% vs 19.6%; p = 0.014) among them. Multivariate Cox analysis revealed that medium- and high-risk groups predicted 2- and 12-fold hazards of death comparing to the lowest. Yet, it was not a significant predictor for MACCEs after adjusting confounding factors. CONCLUSION: The simplified EPICOR score showed fair discriminatory power of 2-year mortality in patients with ACS and an improved performance in the STEMI subgroup. It could aid in risk stratification of ACS patients as an independent predictor.
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Síndrome Coronariana Aguda/mortalidade , Fibrinolíticos/uso terapêutico , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: It is currently unclear if fibrinogen is a risk factor for adverse events in patients receiving percutaneous coronary intervention (PCI) or merely serves as a marker of pre-existing comorbidities and other causal factors. We therefore investigated the association between fibrinogen levels and 2-year all-cause mortality, and compared the additional predictive value of adding fibrinogen to a basic model including traditional risk factors in patients receiving contemporary PCI. METHODS: A total of 6293 patients undergoing PCI with measured baseline fibrinogen levels were enrolled from January to December 2013 in Fuwai Hospital. Patients were divided into three groups according to tertiles of baseline fibrinogen levels: low fibrinogen, <2.98 g/L; medium fibrinogen, 2.98 to 3.58 g/L; and high fibrinogen, ≥3.58 g/L. Independent predictors of 2-year clinical outcomes were determined by multivariate Cox proportional hazards regression modeling. The increased discriminative value of fibrinogen for predicting all-cause mortality was assessed using the C-statistic and integrated discrimination improvement (IDI). RESULTS: The 2-year all-cause mortality rate was 1.2%. It was significantly higher in the high fibrinogen compared with the low and medium fibrinogen groups according to Kaplan-Meier analyses (1.7% vs. 0.9% and 1.7% vs. 1.0%, respectively; log-rank, Pâ=â0.022). Fibrinogen was significantly associated with all-cause mortality according to multivariate Cox regression (hazard ratio 1.339, 95% confidence interval: 1.109-1.763, Pâ=â0.005), together with traditional risk factors including age, sex, diabetes mellitus, left ventricular ejection fraction, creatinine clearance, and low-density lipoprotein cholesterol. The area under the curve for all-cause mortality in the basic model including traditional risk factors was 0.776, and this value increased to 0.787 when fibrinogen was added to the model (IDIâ=â0.003, Zâ=â0.140, Pâ=â0.889). CONCLUSIONS: Fibrinogen is associated with 2-year all-cause mortality in patients receiving PCI, but provides no additional information over a model including traditional risk factors.
Assuntos
Fibrinogênio/análise , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/terapia , Idoso , Jejum/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
This study aimed to evaluate the platelet reactivity in real-world patients with different chronic kidney disease (CKD) stages after percutaneous coronary intervention (PCI), and to examine whether high residual platelet reactivity (HRPR) is associated with higher incidence of adverse cardiovascular events in a 2-year follow up. A total of 10 724 consecutive patients receiving DAPT with aspirin and clopidogrel after PCI throughout 2013 were enrolled. We applied modified thromboelastography (mTEG) in 6745 patients. Kaplan-Meier analysis and Cox proportional regression analysis were applied to illustrate end points for patients. The prevalence of HRPR for adenosine diphosphate (ADP) was higher in patients with CKD3-5 than patients with CKD1-2 (47.0% vs. 37.3%, p = 0.002), but not for arachidonic acid (AA). No significant difference was observed for MACCE between patients with or without HRPR for ADP (HR 1.004, 95%CI: 0.864-1.167, p = 0.954). Patients with HRPR for ADP was associated with less bleeding events than patients without HRPR for ADP (HR 0.795, 95%CI: 0.643-0.982, p = 0.034). In this large cohort of real-world patients after PCI, the deterioration of renal function was linked to HRPR for ADP. HRPR was not associated with MACCE in patients with CKD in a 2-year follow up. Bleeding risks were significantly lower in PCI patients with versus without HRPR for ADP.
Assuntos
Plaquetas/metabolismo , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Feminino , Humanos , Masculino , Inibidores da Agregação Plaquetária/farmacologiaRESUMO
We aimed to determine the association of plasma lipoprotein(a) (Lp[a]) with long-term clinical outcomes in patients with chronic kidney disease (CKD) after percutaneous coronary intervention (PCI) in an observational cohort study. Four hundred and twenty-seven consecutive patients with CKD who underwent PCI from January 2013 to December 2013 were included in this study. Patients were divided into 2 groups according to median levels of Lp(a). Outcomes included 2-year risk of major adverse cardiovascular and cerebrovascular events (MACCEs) and bleeding according to Bleeding Academic Research Consortium definitions. Overall, median of Lp(a) in all the patients was 217.8 mg/L. The 2-year MACCE rate across the high Lp(a) and low Lp(a) group was 23.0% versus 15.4% (pâ¯=â¯0.047) and bleeding event rate of the two groups 8.9% versus 4.2% (pâ¯=â¯0.049). The Lp(a) was significantly and positively correlated with high-sensitivity C-reactive protein levels (r2â¯=â¯0.03, p < 0.001). Kaplan-Meier curves revealed that high Lp(a) had higher incidence of bleeding than low Lp(a) (pâ¯=â¯0.043) and had higher risk of MACCE (pâ¯=â¯0.049). Multivariable Cox regression analysis indicated that high Lp(a) was an independent predictor of Bleeding Academic Research Consortium bleeding compared with low Lp(a) (hazard ratios 2.29, 95% confidence intervals 1.01 to 5.15, pâ¯=â¯0.046). In conclusion, a high Lp(a) value may be associated with a poor prognosis after PCI for patients with CKD.
Assuntos
Doença da Artéria Coronariana/sangue , Lipoproteína(a)/sangue , Intervenção Coronária Percutânea/efeitos adversos , Hemorragia Pós-Operatória/epidemiologia , Insuficiência Renal Crônica/sangue , Idoso , Biomarcadores/sangue , China/epidemiologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Hemorragia Pós-Operatória/sangue , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: The patterns of nonadherence to antiplatelet regimen in stented patients (PARIS) thrombotic risk score are a novel score for predicting the risk of coronary thrombotic events (CTEs) after percutaneous coronary intervention (PCI) with drug-eluting stents. However, the prognostic value of this score has not been fully evaluated in non-Euro-American PCI populations. METHODS: We performed a prospective, observational study of 10,724 patients who underwent PCI in Fuwai hospital, China and evaluated the PARIS thrombotic risk score's predictive value of CTEs in the PCI population. The area under the receiver operating characteristic curve (AUROC) was used to assess the predictive value of the PARIS score for CTE. RESULTS: Among 9782 patients without in-hospital events, a total of 95 CTEs occurred during the 2-year follow-up. The PARIS score was significantly higher in patients with CTEs (3.38 ± 2.04) compared with patients without events (2.53 ± 1.70, P < 0.001). According to the risk stratification of the PARIS thrombotic score, the risk of CTEs in the high-risk group was 3.14 times higher than that in the low-risk group (hazard ratio [HR], 3.14; 95% confidence interval [CI], 1.92-5.13; P < 0.001). However, the risk of CTEs in the intermediate-risk and low-risk groups was not significant (HR, 1.39; 95% CI, [0.86-2.24]; P = 0.184). The PARIS score showed prognostic value in evaluating CTEs in the overall population (AUROC, 0.621; 95% CI, 0.561-0.681), the acute coronary syndrome (ACS) population (AUROC, 0.617; 95% CI, 0.534-0.700; P = 0.003), and the non-ACS population (AUROC, 0.647; 95% CI, 0.558-0.736; P = 0.001). CONCLUSIONS: In a real-world Chinese population, the PARIS thrombotic risk score shows a modest prognostic value for CTEs in patients after PCI. This score also has a predictive value for CTEs in the ACS and non-ACS subgroup populations.
Assuntos
Trombose Coronária/prevenção & controle , Intervenção Coronária Percutânea/efeitos adversos , Síndrome Coronariana Aguda/patologia , Síndrome Coronariana Aguda/prevenção & controle , Idoso , Povo Asiático , Trombose Coronária/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Prognóstico , Estudos Prospectivos , Medição de Risco , Trombose/prevenção & controleRESUMO
BACKGROUND: To improve outcomes in patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention remain an unmet clinical need. The study aimed to evaluate the efficacy and safety of G2-DESs and BP-DESs in patients with and without DM in a single center in China. METHODS: A total of 7666 consecutive patients who exclusively had G2-DES or BP-DES implantation throughout 2013 in our center were studied. The primary efficacy endpoint was any target lesion revascularization (TLR), whereas the primary safety endpoint was a composite of death or myocardial infarction (MI) at 2-year follow-up. RESULTS: G2-DESs had a similar occurrence of death, non-fatal MI, TLR, stroke, and stent thrombosis compared with BP-DESs in patients with DM (all P > 0.05). The incidence of TVR and TLR was lower for G2-DESs than for BP-DESs in patients without DM (3.2% vs. 5.1%, P = 0.002; 2.2% vs. 4.5%, P < 0.001, respectively). Kaplan-Meier analysis also showed better TVR- and TLR-free survival rates for G2-DESs than for BP-DESs in patients without DM. Multivariate analysis showed that a BP-DES was an independent risk factor for TLR (hazard ratio 1.963, 95% confidence interval 1.390-2.772, P < 0.001) in patients without DM, which was not predictive of other components of major adverse cardiac events (P > 0.05). CONCLUSIONS: G2-DESs have better efficacy, represented by a reduced risk of TLR, and similar safety compared with BP-DESs in patients without DM. G2-DESs have similar efficacy and safety compared with BP-DESs in patients with DM at 2-year follow-up.
Assuntos
Implantes Absorvíveis , Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/cirurgia , Diabetes Mellitus/epidemiologia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Polímeros/química , China/epidemiologia , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidade , Humanos , Incidência , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estudos Prospectivos , Desenho de Prótese , Recidiva , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Residual SYNTAX score (rSS) and its derived indexes including SYNTAX revascularization index (SRI) and clinical rSS had been developed to quantify and describe the extent of incomplete revascularization. This study was conducted to explore the utility of the three scores among real-world patients after percutaneous coronary intervention (PCI). METHODS: From January 2013 to December 2013, patients underwent PCI treatment at Fuwai Hospital were included. The primary endpoints were all-cause death and major adverse cardiovascular and cerebrovascular events. The secondary endpoints were myocardial infarction, revascularization, stroke, and stent thrombosis. Kaplan-Meier methodology was used to determine the outcomes. Cox multivariable regression was to test the associations between scores and all-cause mortality. RESULTS: A total of 10,344 patients were finally analyzed in this study. Kaplan-Meier survival analysis indicated that greater residual coronary lesions quantified by rSS and its derived indexes were associated with increased risk of adverse cardiovascular events. However, after multivariate analysis, only clinical rSS was an independent predictor of 2-year all-cause death (hazard ratio: 1.02, 95% confidence interval: 1.01-1.03, P < 0.01). By receiver operating characteristic (ROC) curve analysis, clinical rSS had superior predictability of 2-year all-cause death than rSS and SRI (area under ROC curve [AUC]: 0.59 vs. 0.56 vs. 0.56, all P < 0.01), whereas rSS was superior in predicting repeat revascularization than clinical rSS and SRI (AUC: 0.62 vs. 0.61 vs. 0.61; all P < 0.01). When comparing the predictive capability of rSS ≥8 with SRI <70%, their predictabilities were not significantly different. CONCLUSIONS: This study indicates that all three indexes (rSS, clinical rSS, and SRI) are able to risk-stratify patients and predict 2-year outcomes after PCI. However, their prognostic capabilities are different.