RESUMO
BACKGROUND: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (Pâ¯=â¯.886). In the first 2â¯weeks ADIR was higher than ADBR (Pâ¯=â¯.013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (Pâ¯=â¯.003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (Pâ¯=â¯.012 and Pâ¯=â¯.022, respectively). CONCLUSIONS: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1â¯year after PCI. ADIR was greater than ADBR in the first 2â¯weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.
Assuntos
Síndrome Coronariana Aguda/terapia , Hemorragia/epidemiologia , Isquemia/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Idoso , Clopidogrel/uso terapêutico , Feminino , Hemorragia/etiologia , Humanos , Isquemia/etiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Complicações Pós-Operatórias/etiologia , Cloridrato de Prasugrel/uso terapêutico , Recidiva , Sistema de Registros , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico , Fatores de TempoRESUMO
Vascular smooth muscle cells (VSMCs) transdifferentiate into osteoblast-like cells during vascular calcification, inducing active remodeling and calcification of the extracellular matrix (ECM). Intracellular and extracellular enzymes, such as lysyl hydroxylase 1 (PLOD1) and lysyl oxidase (LOX), contribute to ECM maturation and stabilization. We assessed the contribution of these enzymes to hyperphosphatemia-induced calcification. Human and murine VSMCs were differentiated into functional osteoblast-like cells by high-phosphate medium (HPM) conditioning. HPM promoted ECM calcification and up-regulated osteoblast markers associated with induction of LOX and PLOD1 expression and with an increase in ECM-insoluble collagen deposition. Murine VSMCs from transgenic mice overexpressing LOX (TgLOX) exhibited an increase in HPM-dependent calcification and osteoblast commitment compared with wild-type cells. Similarly, enhanced HPM-induced calcification was detected in aorta from TgLOX. Conversely, ß-aminopropionitrile (a LOX inhibitor) and LOX knockdown abrogated VSMC calcification and transdifferentiation. We found a significant positive association between LOX expression and vascular calcification in human atherosclerotic lesions. Likewise, 2,2'-dipyridil (a PLOD inhibitor) and PLOD1 knockdown impaired HPM-induced ECM mineralization and osteoblast commitment. Our findings identify LOX and PLOD as critical players in vascular calcification and highlight the importance of ECM remodeling in this process.-Jover, E., Silvente, A., Marín, F., Martínez-González, J., Orriols, M., Martinez, C. M., Puche, C. M., Valdés, M., Rodriguez, C., Hernández-Romero, D. Inhibition of enzymes involved in collagen cross-linking reduces vascular smooth muscle cell calcification.
Assuntos
Colágeno/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Calcificação Vascular/metabolismo , Aminopropionitrilo/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/fisiologia , Transdiferenciação Celular/efeitos dos fármacos , Transdiferenciação Celular/fisiologia , Células Cultivadas , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/fisiologia , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Proteína-Lisina 6-Oxidase/metabolismo , Calcificação Vascular/tratamento farmacológicoRESUMO
The TIMI-AF score was described to predict net clinical outcomes (NCOs) in atrial fibrillation (AF) patients receiving warfarin. However, this score derived from the ENGAGE AF-TIMI 48 trial, and no external validation exists in real world clinical practice. We tested the long-term predictive performance of the TIMI-AF score in comparison with CHA2DS2-VASc and HAS-BLED in a 'real-world' cohort of anticoagulated AF patients. METHODS: We included 1156 consecutive AF patients stable on vitamin K antagonist (INR 2.0-3.0) during 6 months. The baseline risk of NCOs (composite of stroke, life-threatening bleeding, or all-cause mortality) was calculated using the novel TIMI-AF score. During follow-up, all NCOs were recorded and the predictive performance and clinical usefulness of TIMI-AF was compared with CHA2DS2-VASc and HAS-BLED. RESULTS: During 6.5 years (IQR 4.3-7.9), there were 563 NCOs (7.49%/year). 'Low-risk' (6.07%/year) and 'medium-risk' (9.49%/year) patients defined by the TIMI-AF suffered more endpoints that low- and medium-risk patients of CHA2DS2-VASc and HAS-BLED (2.37%/year and 4.40%/year for low risk; 3.48%/year and 6.39%/year for medium risk, respectively). The predictive performance of TIMI-AF was not different from CHA2DS2-VASc (0.678 vs 0.677, P = .963) or HAS-BLED (0.644 vs 0.671, P = .054). Discrimination and reclassification did not show improvement of prediction using the TIMI-AF score, and decision curves analysis did not demonstrate higher net benefit. CONCLUSIONS: In VKA-experienced AF patients, the TIMI-AF score has limited usefulness predicting NCOs over a long-term period of follow-up. This novel score was not superior to CHA2DS2-VASc and HAS-BLED identifying low-risk AF patients.
Assuntos
Fibrilação Atrial , Hemorragia , Efeitos Adversos de Longa Duração , Acidente Vascular Cerebral/prevenção & controle , Varfarina , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Feminino , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Hemorragia/epidemiologia , Hemorragia/prevenção & controle , Humanos , Coeficiente Internacional Normatizado/métodos , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/etiologia , Efeitos Adversos de Longa Duração/mortalidade , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , Projetos de Pesquisa , Medição de Risco/métodos , Fatores de Risco , Espanha/epidemiologia , Acidente Vascular Cerebral/etiologia , Varfarina/administração & dosagem , Varfarina/efeitos adversosRESUMO
BACKGROUND: Polymorphisms in the vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes increase the bleeding risk in anticoagulated atrial fibrillation (AF) patients. Here, we aimed to investigate whether VKORC1 and CYP2C9 polymorphisms improved the predictive performance for major bleeding using the HAS-BLED score. MATERIAL AND METHODS: We recruited 652 consecutive AF patients stable on vitamin K antagonist (INR 2.0-3.0) during at least the previous 6 months. A baseline venous blood sample was obtained for DNA extraction. We gave an extra point to the HAS-BLED score if the patient was a simultaneous carrier of the VKORC1 and CYP2C9 polymorphisms related to bleeding, and we called this modified score "GEN|HAS-BLED." During a median follow-up of 7.6 years (IQR 5.6-8.0), all major bleeding events were recorded. RESULTS: During follow-up, 106 (16.2%) patients experienced a major bleeding (2.81%/y; 42 intracranial haemorrhages and 44 gastrointestinal bleeding) and 24 (3.7%) died from major bleeding (0.48%/y). Cox regression analyses demonstrated a significant association between HAS-BLED or GEN|HAS-BLED and major bleeds, both as continuous or categorical scores. Comparison of receiver operating characteristic (ROC) curves shows that original HAS-BLED clinical score had better predictive ability than GEN|HAS-BLED (0.660, 95% CI 0.622-0.696 vs 0.645, 95% CI 0.607-0.682; P = .030). Discrimination and reclassification analyses showed that GEN|HAS-BLED did not improve sensitivity compared with the original score and even showed significant negative reclassification. CONCLUSION: Adding pharmacogenetic factors (ie polymorphisms of the VKORC1 and CYP2C9 genes) to the HAS-BLED score does not improve the prediction or discrimination performance for major bleeding.
Assuntos
Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Citocromo P-450 CYP2C9/genética , Hemorragia/genética , Acidente Vascular Cerebral/prevenção & controle , Vitamina K Epóxido Redutases/genética , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/genética , Predisposição Genética para Doença , Hemorragia/induzido quimicamente , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/genética , Masculino , Farmacogenética , Polimorfismo Genético , Modelos de Riscos Proporcionais , Curva ROC , Medição de Risco , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Soluble fibrin monomer complex (SFMC) is a biomarker of fibrin formation abnormally elevated in clinical situations of hypercoagulability. OBJECTIVE: We investigated the association and predictive performance of SFMC for stroke, adverse cardiovascular events, cardiovascular mortality and all-cause mortality in a cohort of patients with atrial fibrillation (AF) receiving vitamin K antagonist (VKA) anticoagulant therapy. DESIGN: During the second semester of 2007, we included 1226 AF outpatients stable on VKAs (INR 2.0-3.0) over a period of 6 months. SFMC levels were assessed at baseline. During 6.5 (IQR 4.4-8.0) years of follow-up, we recorded all ischemic strokes, adverse cardiovascular events (composite of stroke, acute heart failure, acute coronary syndrome and cardiovascular death), cardiovascular deaths and all-cause deaths. PARTICIPANTS: All patients were recruited consecutively. We excluded patients with rheumatic mitral valves, prosthetic heart valves, acute coronary syndrome, stroke, hemodynamic instability, hospital admissions or surgical interventions within the preceding 6 months. MAIN MEASURES: SFMC levels were measured in plasma by immunoturbidimetry in an automated coagulometer (STALiatestFM, Diagnostica Stago, Asnieres, France). KEY RESULTS: We recorded 121 (1.52%/year) ischemic strokes, 257 (3.23%/year) cardiovascular events, 67 (0.84%/year) cardiovascular deaths and 486 (6.10%/year) all-cause deaths. SFMC >12 µg/mL was not associated with stroke but was associated with higher risk of cardiovascular events (HR 1.72, 95% CI 1.31-2.26), cardiovascular mortality (HR 2.16, 95% CI 1.30-3.57) and all-cause mortality (HR 1.26, 95% CI 1.03-1.55). When SFMC >12 µg/mL was added to the CHA2DS2-VASc, there were significant improvements in predictive performance, sensitivity and reclassification for adverse cardiovascular events (c-index: 0.645 vs. 0.660, p = 0.010; IDI = 0.013, p < 0.001; NRI = 0.121, p < 0.001) and cardiovascular mortality (c-index: 0.661 vs. 0.691, p = 0.006; IDI = 0.009, p = 0.049; NRI = 0.217, p < 0.001), but decision curves demonstrated a similar net benefit and clinical usefulness. CONCLUSIONS: In AF patients taking VKAs, high SFMC levels were associated with the risk of adverse cardiovascular events, cardiovascular mortality and all-cause mortality. The addition of SFMC to the CHA2DS2-VASc score improved its predictive performance for these outcomes, but failed to show an improvement in clinical usefulness.
Assuntos
Fibrilação Atrial/sangue , Fibrilação Atrial/mortalidade , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Mortalidade/tendências , Valor Preditivo dos Testes , Espanha/epidemiologiaRESUMO
BACKGROUND: Prasugrel has been shown to provide more potency and less variability than clopidogrel, but its potential temporal variability has not been described.MethodsâandâResults:We conducted a prospective open-label study, evaluating platelet reactivity overtime in acute coronary syndrome (ACS) patients on aspirin and clopidogrel (n=60) or prasugrel (n=61), after a percutaneous coronary intervention (PCI). Blood samples were taken at discharge and at 3 and 6 months. Platelet function tests included VerifyNow (VN-P2Y12), and Multiplate Aggregometry (MEA). By means of VN-P2Y12, prasugrel patients displayed significantly (P<0.001) higher platelet inhibition than clopidogrel patients over time, although there were not significant differences using MEA. Prasugrel patients showed higher platelet inhibition at baseline than at 3 months (59.3±8.1 vs. 105.0±49.2; P<0.001), without significant change at 6 months (107.9±72.0; P=0.919 vs. 3 months). Clopidogrel patients showed a similar trend (160.1±65.1, 184.8±62.7 and 185.0±53.3; baseline vs. 3 months P=0.060; 3 months vs. 6 months P=0.974). High platelet reactivity (HPR) was shown in 16.3% prasugrel patients, with no patient consistently remaining in HPR over time. HPR was detected in 36.6% of the clopidogrel patients, being consistently observed in 15.0% of them. Low platelet reactivity (LPR) was detected in 60.5% prasugrel and 9.8% clopidogrel patients. CONCLUSIONS: Prasugrel patients showed less temporal variation than patients on clopidogrel in terms of HPR. In contrast, higher variability in LPR was detected in prasugrel patients for up to 6 months' follow-up.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Clopidogrel/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Stents , Síndrome Coronariana Aguda/sangue , Idoso , Clopidogrel/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Cloridrato de Prasugrel/farmacologia , Estudos Prospectivos , Implantação de Prótese , Fatores de TempoRESUMO
BACKGROUND: Vascular disease is a frequent comorbidity in atrial fibrillation (AF) patients, resulting in concomitant use of antiplatelet therapy. In the present study, we investigated the incidence and risk of major bleeding, ischaemic stroke, and mortality in a cohort of AF patients taking acenocoumarol plus antiplatelet therapy, in comparison with AF patients taking only acenocoumarol monotherapy. METHODS: We consecutively included 1361 "real-world" AF patients stable for at least the previous 6 months on acenocoumarol (INR 2.0-3.0). The primary endpoint was major bleeding defined using the 2005 International Society on Thrombosis and Haemostasis (ISTH) criteria. As secondary endpoints, we analysed ischaemic strokes and all-cause mortality. During follow-up, all adverse events were recorded and compared within patients taking acenocoumarol plus antiplatelet therapy and patients taking only acenocoumarol. RESULTS: During 6.5 years (IQR 4.3-7.9) of follow-up, there were 250 (2.83%/year) bleeds, 130 (1.47%/year) ischaemic strokes and 511 (6.23%/year) deaths. After multivariate Cox regression analyses, combined antithrombotic therapy was associated with major bleeding (HR 1.40, 95% CI 1.01-1.94; P = .048), but not lower mortality (HR 0.95, 95% CI 0.75-1.21; P = .674) or ischaemic stroke (HR 1.45, 95% CI 0.97-2.17; P = .072). CONCLUSIONS: In AF patients, the risk of bleeding is higher when antiplatelet therapy is combined with acenocoumarol, but the risk of mortality and stroke was not significantly different from that of patients taking only acenocoumarol.
Assuntos
Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Isquemia Encefálica/induzido quimicamente , Hemorragia/induzido quimicamente , Inibidores da Agregação Plaquetária/efeitos adversos , Idoso , Fibrilação Atrial/complicações , Isquemia Encefálica/mortalidade , Estudos de Coortes , Feminino , Hemorragia/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
Acute coronary syndromes (ACS) encompass unstable angina, non-ST segment elevation myocardial infarction, ST-segment elevation myocardial infarction and sudden cardiac death. They are commonly associated with the presence of vulnerable plaques in the coronary arteries and occur when a thrombus formed from a ruptured atheromatous plaque causes a prolonged occlusion of a coronary artery. The erosion of the vulnerable plaques results in the formation of luminal thrombi secondary to platelet activation and the release of thrombogenic elements within the atherosclerotic lesions. Proteomic approaches offer an unbiased platform for the comprehensive analysis of the whole proteome in a certain physiological time. Although mRNA expression is widely considered to be indicative of protein expression, protein levels are the result of protein synthesis and degradation, and RNA levels are not informative of protein degradation. In contrast, the proteomic technology investigates protein expression directly. This is particularly important in the context of atherosclerosis in which protein degradation is as decisive as protein synthesis. Moreover, proteomics reveals post-translational modifications known to be determinant for many human diseases. Clinically, there is increasing evidence for the role of proteomic technology in biomarker discovery that will provide novel information on the molecular events associated with ACS, and potentially lead to the identification of novel drug targets. In this review, we describe in detail the importance of proteomic approaches to identify new biomarkers associated with ACS from three perspectives: biomarkers associated with platelet metabolism; the study of proteomics of intravascular thrombi; and proteome analysis of membrane microparticles released from activated cells, mostly by platelets.
Assuntos
Síndrome Coronariana Aguda , Biomarcadores , Espectrometria de Massas/métodos , Proteômica/métodos , Plaquetas/metabolismo , Humanos , Trombose/metabolismoRESUMO
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by cardiomyocyte hypertrophy and fibrosis. Although is an autosomal dominant trait, a group of nonsarcomeric genes have been postulated as modifiers of the phenotypic heterogeneity. MATERIAL AND METHODS: We prospectively recruited 168 HCM patients and 136 healthy controls from three referral centres. Patients and controls were clinically stable at entry in the study. Nine polymorphisms previously associated with ventricular remodelling were determined: I/D ACE, AGTR1(A1666C), CYP11B2(C344T), PGC1-α(G482S), COLIA1(G2046T), ADRB1(R389G), NOS3(G894T), RETN(-420C>G) and CALM3(-34T>A). Their potential influence on prognosis, assessed by hospital admissions, and their cause were recorded. RESULTS: The median follow-up time was 49·5 months. Allele and genotype frequencies did not differ between patients and controls. Thirty-six patients (21·5%) required urgent hospitalization (18·5% for heart failure, 22·2% for atrial arrhythmias, 11·1% for ventricular arrhythmias, 29·6% for ischaemic heart disease, 14·8% for stroke and 3·7% for other reasons) with a hospitalization rate of 8·75% per year. Multivariate analysis showed an independent predictive value for noncarriers of polymorphic COL1A1 allele [HR: 2·76(1·26-6·05), P = 0·011] and a trend in homozygous carriers of ADRB1 Arg389 variant [HR: 1·98(0·99-4·02); P = 0·057]. CONCLUSION: Our study suggests that COL1A1 polymorphism (2046G>T) is an independent predictor of prognosis in HCM patients supporting the importance of nonsarcomeric genes on clinical prognosis in HCM.
Assuntos
Arritmias Cardíacas/genética , Cardiomiopatia Hipertrófica/genética , Isquemia Miocárdica/genética , Acidente Vascular Cerebral/genética , Remodelação Ventricular/genética , Adulto , Idoso , Alelos , Arritmias Cardíacas/complicações , Calmodulina/genética , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/fisiopatologia , Estudos de Casos e Controles , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Citocromo P-450 CYP11B2/genética , Feminino , Predisposição Genética para Doença , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Isquemia Miocárdica/complicações , Óxido Nítrico Sintase Tipo III/genética , Peptidil Dipeptidase A/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fenótipo , Polimorfismo Genético , Prognóstico , Estudos Prospectivos , Receptor Tipo 1 de Angiotensina/genética , Receptores Adrenérgicos beta 1/genética , Resistina/genética , Acidente Vascular Cerebral/complicações , Fatores de Transcrição/genéticaRESUMO
AIMS: Atrial fibrillation (AF) is associated with an increased morbidity and mortality after cardiac surgery. Von Willebrand factor (vWF) has been proposed as a biomarker of endothelial damage/dysfunction. We hypothesized that vWF levels could be used as valuable biomarker for AF occurrence after cardiac surgery. Moreover, we explored the potential association between vWF and tissue remodelling as possible implication in post-surgical AF. METHODS AND RESULTS: We prospectively recruited 100 consecutive patients who undergoing programmed cardiac surgery with cardiopulmonary bypass and with no previous history of AF. Plasma vWF levels were determined from citrated plasma samples. Right atrial appendage tissue was obtained during cardiac surgery, and vWF expression as well as interstitial fibrosis was analysed by immunostaining and Masson's trichrome, respectively. We found raised vWF plasma levels in ischaemic vs. valvular patients (200.2 ± 66.3 vs. 157.2 ± 84.3 IU/dL; P = 0.015). Fibrosis degree was associated with plasma vWF levels. Plasma vWF was an independent prognostic marker for AF development in ischaemic patients [odds ratio, OR 6.44 (95% confidence interval, CI 1.40-36.57), P = 0.035]. CONCLUSION: Plasma vWF levels are associated with tissue fibrosis in patients undergoing cardiac surgery and with post-surgical AF development in ischaemic patients. These findings suggest an association among vWF levels, atrial remodelling, and AF development. It is supported by higher vWF expression in right atrial tissue in ischaemic patients, who developed post-surgical AF.
Assuntos
Fibrilação Atrial/etiologia , Ponte de Artéria Coronária/efeitos adversos , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Isquemia Miocárdica/cirurgia , Fator de von Willebrand/metabolismo , Idoso , Apêndice Atrial/patologia , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Remodelamento Atrial , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Feminino , Fibrose , Doenças das Valvas Cardíacas/sangue , Doenças das Valvas Cardíacas/diagnóstico , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND: Patients with nonvalvular atrial fibrillation (AF) who undergo electrical cardioversion (ECV) tend to be younger and have less comorbidity. Long-term anticoagulation after ECV should be based on thromboembolic risk. We sought to study the long-term incidence of thromboembolic events (TE), factors related to TE and compare the predictive value of the CHADS2and CHA2DS2-VASc scores in this particular population. METHODSâANDâRESULTS: From January 2008 to June 2012, 571 ECV were performed in 406 consecutive patients with nonvalvular AF. Risk factors for TE and factors related to anticoagulation therapy after ECV were registered. During a follow-up of approximately 2 years, the annual incidence of TE was 1.9%. Factors associated with TE were: poor quality anticoagulation control (hazard ratio [HR]: 2.91; 95% confidence interval [CI]: 1.10-7.80; P=0.03), cessation of anticoagulation after ECV (HR: 8.80; 95% CI: 3.11-25.10; P<0.001), age ≥65 years (HR: 13.65; 95% CI: 1.74-107.16; P=0.01), CHADS2score (HR: 1.59; 95% CI: 1.10-2.29; P=0.01) and CHA2DS2-VASc score (HR: 1.67; 95% CI: 1.30-2.22; P<0.001). Both risk scores predicted TE [c-statistic for CHADS2: 0.68 (95% CI: 0.62-0.74; P=0.005), for CHA2DS2-VASc: 0.75 (95% CI: 0.70-0.80; P<0.001)]. Based on c-statistics, the predictive accuracy of CHA2DS2-VASc was superior (difference between areas: 0.064±0.031; P=0.0403). CONCLUSIONS: Important determinants of long-term occurrence of TE after ECV were related to anticoagulant therapy (poor quality anticoagulation and cessation of this therapy over follow-up). The CHA2DS2-VASc score successfully predicts TE after ECV, having better predictive accuracy than the CHADS2score. (Circ J 2016; 80: 605-612).
Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial , Cardioversão Elétrica , Tromboembolia , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Fatores de TempoRESUMO
BACKGROUND: Several bleeding risk scores have been validated in patients with atrial fibrillation (AF). The ORBIT score has been recently proposed as a simple score with the best ability to predict major bleeding. The present study aimed to test the hypothesis that the ORBIT score was superior to the HAS-BLED score for predicting major bleeding and death in "real world" anticoagulated AF patients. METHODSâANDâRESULTS: We analyzed the predictive performance for bleeding and death of 406 AF patients who underwent 571 electrical cardioversion procedures and 1,276 patients with permanent/persistent AF from the FANTASIIA registry. In the cardioversion population, 21 patients had major bleeding events and 26 patients died. The predictive performance for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.77 (95% CI 0.66-0.88) and 0.82 (95% CI 0.77-0.93), respectively; P=0.080). For the FANTASIIA population, 46 patients had major bleeding events and 50 patients died. The predictive performances for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.63 (95% CI 0.56-0.71) and 0.70 (95% CI 0.62-0.77), respectively; P=0.116). For death, the predictive performances of HAS-BLED and ORBIT were not significantly different in both populations. The ORBIT score categorized most patients as "low risk". CONCLUSIONS: Despite the original claims in its derivation paper, the ORBIT score was not superior to HAS-BLED for predicting major bleeding and death in a "real world" oral anticoagulated AF population. (Circ J 2016; 80: 2102-2108).
Assuntos
Fibrilação Atrial , Cardioversão Elétrica/efeitos adversos , Hemorragia , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/terapia , Cardioversão Elétrica/métodos , Feminino , Hemorragia/etiologia , Hemorragia/mortalidade , Hemorragia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Fatores de RiscoRESUMO
Immunological molecules are implicated in inflammatory disorders, including inflammatory bowel disease (IBD; Crohn disease [CD] and ulcerative colitis [UC]). Killer cell immunoglobulin-like receptors (KIRs) are also genetically variable proteins involved in immune function. They are expressed by NK cells and certain T lymphocytes, regulate specificity and function by interaction with HLA Class I molecules, may be either inhibitory or activating and are polymorphic both in terms of alleles and haplotype gene content. Genetic associations between activating KIRs and certain autoimmune and inflammatory diseases have been reported; however, a possible association between KIR and IBD remains unclear. The aim of this study was to determine the relationship between KIR repertoire and IBD pathologies in a Spanish cohort. KIR variability was analyzed using PCR-sequence specific oligonucleotide probes (SSOP). Inhibitory KIR2DL5 was found more frequently in UC and IBD patient groups than in healthy controls (P = 0.028 and P = 0.01, respectively), as was activating KIR2DS1 (P = 0.02, Pc > 0.05, UC vs. Controls; P = 0.001, Pc = 0.01, IBD vs Controls; P = 0.01, Pc > 0.05, Controls vs CR), KIR2DS5 (P = 0.0028, Pc = 0.04, Controls vs UC; P = 0.0001, Pc = 0.0017, Controls vs IBD; P = 0.01, Pc > 0.05, Controls vs CD) and KIR3DS1 (P = 0.012, Pc > 0.05, Controls vs IBD). Our data suggest that imbalance between activating and inhibitory KIR may partially explain the different pathogeneses of these IBDs and that there is a hypothetical role for the telomeric B region (which contains both KIR2DS5 and KIR2DS1) in these diseases.
Assuntos
Variação Genética , Doenças Inflamatórias Intestinais/genética , Receptores KIR/genética , População Branca/genética , Adolescente , Adulto , Alelos , Criança , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Masculino , Pessoa de Meia-Idade , Espanha , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Adulto JovemRESUMO
Everolimus-eluting bioabsorbable scaffolds (BVSs) have exhibited similar long-term clinical outcomes compared to its everolimus-eluting metallic counterparts. However, reports from earlier studies have shown a signal for an increased rate of stent thrombosis. The aim of the current investigation is to describe the platelet reactivity profiles over time in patients treated with everolimus-eluting BVS in comparison to everolimus-eluting metallic stents. This is a pilot study in which patients on aspirin and clopidogrel with at least 1 everolimus-eluting BVS were included (n = 24). Patients with at least 1 everolimus-eluting metallic stent implanted were included as control group (n = 25). Blood samples were taken at time of discharge and at 3- and 6-month follow-up. Platelet function tests included VerifyNow (VN-P2Y12), multiplate aggregometry (MEA), and light transmission aggregometry (LTA). There was no difference in platelet reactivity at discharge, 3- and 6-month visits (unadjusted p = 0.733 and p = 0.582; p = 0.432 and p = 0.899 after adjusting for discharge value platelet reactivity0, respectively) using VN-P2Y12. Similar findings were observed with LTA. However, patients with BVS showed significantly higher platelet reactivity than patients with metallic stents at 3 and 6 months in the crude analysis (p = 0.003) and after adjusting for discharge value (p = 0.013) measured with ADP-MEA. There were no differences in platelet reactivity mediated by the T × A2 pathway between both groups. Finally, there is no statistical difference in high on-clopidogrel platelet reactivity (HPR) rate between both groups. The results of this pilot study suggest that BVS might have different platelet reactivity profiles, and warrants further investigation in dedicated clinical studies.
Assuntos
Implantes Absorvíveis , Plaquetas/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/terapia , Everolimo/administração & dosagem , Ativação Plaquetária , Alicerces Teciduais , Difosfato de Adenosina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Materiais Biomiméticos , Plaquetas/efeitos dos fármacos , Doença da Artéria Coronariana/diagnóstico , Stents Farmacológicos , Everolimo/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Projetos Piloto , Agregação Plaquetária , Inibidores da Agregação Plaquetária , Testes de Função Plaquetária , Estudos Prospectivos , Receptores Purinérgicos P2/metabolismo , Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo , Transdução de Sinais , Adulto JovemRESUMO
The pathophysiology of acute coronary syndrome (ACS) involves platelet activation and thrombus formation after the rupture of atherosclerotic plaques. Thrombin is generated at the blood-plaque interface in association with cellular membranes on cells and platelets. Thrombin also amplifies the response to the tissue injury, coagulation and platelet response, so the treatment of ACS is based on the combined use of both antiplatelet (such as aspirin, clopidogrel, prasugrel and ticagrelor) and antithrombotic drugs (unfractionated heparin, enoxaparin, fondaparinux and bivalirudin). Bivalirudin competitively inhibits thrombin with high affinity, a predictable response from its linear pharmacokinetics and short action. However, a present remarkable controversy exists between the latest main Guidelines in Clinical Practice and the key trials evaluating the use of bivalirudin in ACS. The aim of this review is to update the development of bivalirudin, including pharmacological properties, obtained information from clinical trials evaluating efficacy and safety of bivalirudin in ACS; as well as the recommendations of clinical Guidelines.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/metabolismo , Hirudinas/farmacologia , Fragmentos de Peptídeos/farmacologia , Trombina/metabolismo , Síndrome Coronariana Aguda/fisiopatologia , Anticoagulantes/uso terapêutico , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Feminino , Humanos , Masculino , Fragmentos de Peptídeos/uso terapêutico , Guias de Prática Clínica como Assunto , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Trombina/antagonistas & inibidoresRESUMO
Calumenin inhibits gamma-carboxylation of matrix-Gla-protein preventing BMP2-dependent calcification. Our aim was to explore the clinical relevance and functionality of the CALU polymorphism rs1043550, and the relationship of calumenin time-dependent expression profile with the active calcification of human vascular smooth muscle cells (hVSMC). Coronary artery calcium score and lesion severity were assessed by cardiac computed tomography in 139 consecutive low-risk patients genotyped for rs1043550. Polymorphic (G) allele carriage was associated with lower calcium (OR: 6.19, p=0.042). Calcified arteries from CALU 'A' allele carriers undergoing cardiovascular surgery exhibited higher residual calcification, higher calumenin immunostaining and lower matrix-Gla-protein, contrary to 'G' allele carriers. In a luciferase reporter system in vascular cells, polymorphic 'G' allele reduced the mRNA stability by 30% (p < 0.05). Osteogenic high-phosphate media induced active differentiation of hVSMC onto functional osteoblast-like cells as demonstrated by extracellular matrix mineralization and osteoblast markers expression. Calumenin was early over-expressed at day 3 (p < 0.05), but decreased thereafter (mRNA and protein) with implications on gamma-carboxylation system. Calumenin was found released and co-localizing with extracellular matrix calcifications. The CALU polymorphism rs1043550 affects mRNA stability and tissue availability of calumenin thus supporting the protective clinical significance. Calumenin shows a time-dependent profile during induced calcification. These data demonstrate a novel association of vascular calcification with the VSMC phenotypic transition into osteoblast-like cells. Moreover, hyperphosphatemic stimuli render calumenin accumulation in the mineralized extracellular matrix.
Assuntos
Alelos , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Polimorfismo de Nucleotídeo Único , Calcificação Vascular/genética , Calcificação Vascular/metabolismo , Cálcio/metabolismo , Técnicas de Cultura de Células , Diferenciação Celular , Células Cultivadas , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Estabilidade de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína de Matriz GlaRESUMO
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with decreased quality of life, and increased mortality and morbidity from stroke and thromboembolism. The underlying mechanisms involved in the development of AF have yet to be fully elucidated. However, once initiated, AF tends to self-perpetuate, due to structural and electrical remodeling in the atria. Currently, therapies for AF, such as, antiarrhythmic drugs and catheter ablation, have significant limitations. Antiarrhythmic drugs target one or a few cardiomyocyte ion channels and have considerable pro-arrhythmic and non-cardiac adverse effects. On the other hand, catheter ablation is an expensive treatment associated with measurable complications and its long-term success in management of AF is controversial. Current consensus guidelines recommend ß-blockers, amiodarone, digitalis glycosides and non-dihydropyridine calcium channel antagonists or a combination of them for AF treatment, but bradycardia and heart block may occur as an unwanted effect. On the other hand, antioxidant agents have recently attracted much interest in AF treatment because they have been associated with a reduction in lone AF and post-operative AF, and in some cases, with a decrease in long-term hospitalization time. Moreover, antioxidants can be considered a cheap treatment with reduced side effects. In this review, we will comprehensively review the effects and the mechanisms of action of several antioxidant agents, such as vitamin E, ascorbic acid, carotenoids, statins, omega-3 polyunsaturated fatty acids and N-acetylcysteine.
Assuntos
Antiarrítmicos/uso terapêutico , Antioxidantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Animais , Antiarrítmicos/efeitos adversos , Antioxidantes/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate more accurately than the Modification of Diet in Renal Disease (MDRD) Study equation. Our aim was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for major bleeding (MB) more accurately than the MDRD Study equation in patients with non-ST-segment elevation acute coronary syndromes (ACS). MATERIALS AND METHODS: Three hundred and fifty consecutive subjects with non-ST-segment elevation ACS (68 ± 12 years, 70% male) were studied. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations. The primary endpoint was the occurrence of MB during the follow-up, which was defined according to the Bleeding Academic Research Consortium Definition criteria as bleeding types 3-5. RESULTS: During the median follow-up of 589 days (interquartile range, 390-986), 27 patients had MB (0.04% events per person year). Patients with MB had worse kidney function parameters, regardless of the estimating equation used (P < 0.001). After multivariate Cox regression adjustment, both CysC-based CKD-EPI equations were independent predictors of MB (CKD-EPI(creatinine-cystatin) C per mL/min/1.73 m(2), HR = 0.973 (95%CI 0.955-0.991; P = 0.003) and CKD-EPI(cystatin) C per mL/min/1.73 m(2), HR = 0.976 (95%CI 0.976-0.992; P = 0.003), while the CKD-EPI(creatinine) and MDRD equations did not achieve statistical significance. Both CKD-EPI(creatine-cystatin) C and CKD-EPI(cystatin) C were associated with a significant improvement in MB risk reclassification. CONCLUSIONS: In this cohort of non-ST-segment elevation ACS patients with relatively preserved renal function, both CysC-based CKD-EPI equations improved ability to predict risk for MB and were superior to other equations for this application.
Assuntos
Síndrome Coronariana Aguda/metabolismo , Algoritmos , Creatinina/metabolismo , Cistatina C/metabolismo , Taxa de Filtração Glomerular , Hemorragia/metabolismo , Síndrome Coronariana Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Técnicas de Apoio para a Decisão , Feminino , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , EspanhaRESUMO
BACKGROUND: Atrial fibrillation (AF) is associated with high morbidity and mortality, even despite the use of oral anticoagulation (OAC). Soluble suppression of tumorigenicity-2 (sST2) is a member of the interleukin-1 receptor family [interleukin-1 receptor-like 1 (IL1RL1)], which has been associated with an increased risk of mortality and morbidity in heart failure or acute coronary syndrome. We assessed the predictive value of sST2 levels in an unselected 'real-world' cohort of anticoagulated AF patients. METHODS: We included 562 patients (49% male; median age 77 [IQR: 71-82]) with permanent AF who were stable (for at least 6 months) on OAC (INRs 2.0-3.0). sST2 levels were quantified by ELISA. Patients were followed-up for up to 4 years, and cardiovascular events and all-cause mortality were recorded. RESULTS: Median (IQR) of sST2 levels was 51.23 (39.09-67.40) µg/L. Median follow-up was 1587 days [IQR 1482-1617], and during this period, 91 patients died (16.2%, 3.72%/year). The c-statistic for predicting mortality with sST2 was 0.58 + 0.03; P = 0.017). On multivariate analysis, age [hazard ratio (HR) 1.09 (1.05-1.13); P < 0.001], diabetes mellitus [1.76 (1.08-2.88); P = 0.023], previous stroke [2.16 (1.29-3.60); P = 0.003] and sST2 levels [1.008 (1.002-1.14); P = 0.008] were independently associated with mortality. Concentrations of sST2 were also significantly associated with the risk of mortality, even after adjusting for the CHA2 DS2 -VASc score [HR: 1.007 (1.001-1.013); P = 0.014]. CONCLUSIONS: In an anticoagulated AF patient's cohort, sST2 levels are an independent predictive factor of all-cause mortality. sST2 levels could be a biomarker used to improve clinical risk assessment in anticoagulated AF patients.
Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Receptores de Superfície Celular/sangue , Acidente Vascular Cerebral/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/sangue , Fibrilação Atrial/complicações , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Coeficiente Internacional Normatizado , Estudos Longitudinais , Masculino , Mortalidade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Paravalvular aortic regurgitation after transcatheter aortic valve implantation is associated with a hemodynamic deterioration and a poor outcome. We aim to determine the early hemodynamic effect of paravalvular aortic regurgitation in relation with the change in the left ventricle filling pattern and to assess their clinical outcome. MATERIAL AND METHODS: Eighty-two consecutive patients referred for transcatheter aortic valve implantation were included. Patients were classified according to the change in the left ventricular filling pattern, and significant paravalvular aortic regurgitation (grade ≥ 2) was reported. Follow-up and incidence of death and hospitalization for heart failure were reported. RESULTS: Sixteen patients (19·5%) presented a worsening of left ventricular filling pattern. The incidence of significant paravalvular aortic regurgitation was higher in the group with a worsening of left ventricular filling pattern (56·3% vs. 19·7%; P = 0·009). In the multivariate analysis, the only variable significantly associated with the worsening of left ventricular filling pattern was the significant paravalvular aortic regurgitation (OR 4·84; 95% CI 1·23 - 19·1; P = 0·024). During the follow-up (642·5 days), there was a higher incidence of the endpoint of death or hospitalization for heart failure in the group with a worsening of left ventricular filling pattern (62·5% vs. 31·8%; P = 0·042) and a lower event-free survival rate (long rank test = 0·013). CONCLUSIONS: The presence of a significant paravalvular aortic regurgitation is associated with a worsening in parameters of diastolic function. This finding should alert the cardiologist as patients with a worsening of left ventricular filling pattern present a higher incidence of paravalvular aortic regurgitation and a less favourable outcome.