RESUMO
BACKGROUND: Non-ST-elevation myocardial infarction (NSTEMI) carries a poor prognosis, and accurately prognostication has significant clinical importance. In this study, we analyzed the predictive value of the CHADS2, CHA2DS2-VASc, and R2-CHADS2scores for major adverse cardiac events (MACE) following percutaneous coronary intervention (PCI) in patients with NSTEMI using data from a prospective multicenter registry. METHODSâANDâRESULTS: The registry included 440 consecutive patients with NSTEMI and coronary artery disease who underwent successful PCI. Patients were clinically followed for up to 3 years or until the occurrence of MACE. MACE was defined as a composite of all-cause death and nonfatal MI. During the follow-up period, 55 patients (12.5%) experienced MACE. Risk analysis of MACE occurrence, adjusted for the multivariable model, demonstrated a significant increase in risk with higher CHADS2, CHA2DS2-VASc, and R2-CHADS2scores. Kaplan-Meier analysis showed a higher incidence of MACE in patients with higher CHADS2, CHA2DS2-VASc, and R2-CHADS2scores, both in the short- and long-term periods. CONCLUSIONS: Patients with NSTEMI and higher CHADS2, CHA2DS2-VASc, and R2-CHADS2scores displayed a greater incidence of MACE.
Assuntos
Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Sistema de Registros , Humanos , Idoso , Masculino , Feminino , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Medição de Risco , Estudos Prospectivos , Idoso de 80 Anos ou mais , Fatores de Risco , Prognóstico , Fatores de Tempo , Doença da Artéria Coronariana/mortalidade , SeguimentosRESUMO
ABSTRACT: The statin use in patients on hemodialysis remains controversial, and no beneficial effects of statin on the reduction of adverse cardiovascular events have been reported in these patients. This study used stratification analysis to examine the clinical factors in patients on hemodialysis who could benefit from statin for secondary prevention. This prospective multicenter study included 234 consecutive patients on hemodialysis with coronary artery disease who underwent successful reperfusion therapy with percutaneous coronary intervention. The patients were followed up for up to 3 years or until the occurrence of major adverse cardiac events (MACEs; defined as a composite of all-cause death and nonfatal myocardial infarction). Inverse probability of treatment weighting adjustment was used to remove the selection bias. During the median follow-up period of 30 months, MACEs occurred in 55 patients. Patients with MACEs had significantly lower statin therapy (P < 0.001). Multivariable Cox proportional hazards analysis showed that the patients on statins had a significantly reduced rate of MACE occurrence [adjusted hazard ratio 0.30 (0.11-0.81), P = 0.02]. The stratification analysis of outcomes according to the presence of clinical factors showed that beneficial effects of statin were associated with man, elderly, lower body mass index, lower abdominal circumference, hypertension, diabetes, higher C-reactive protein, symptomatic heart failure, lower left ventricular function, nonacute coronary syndrome, and shorter stent length. Statin was effective for the prevention of MACEs in patients on hemodialysis who underwent percutaneous coronary intervention. We identified specific clinical factors affecting statin effectiveness for secondary prevention.
Assuntos
Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Intervenção Coronária Percutânea , Idoso , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/terapia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Diálise Renal/efeitos adversos , Resultado do TratamentoRESUMO
Although coronary endothelial vasomotor dysfunction predicts future coronary events, few human studies have shown the relationship between persistent endothelial vasomotor dysfunction and major adverse cardiovascular events (MACE) using serial assessments in the same coronary artery. This study examined whether persistent endothelial vasomotor dysfunction is related to MACE occurrence in the infarct-related coronary artery (IRA) of ST-segment elevation myocardial infarction (STEMI) survivors using serial assessments of the coronary vasomotor response to acetylcholine (ACh). This study included 169 consecutive patients with a first acute STEMI due to left anterior descending coronary artery (LAD) occlusion and successful reperfusion therapy with percutaneous coronary intervention. Vasomotor response to ACh in the LAD was measured within 2 weeks of acute myocardial infarction (AMI) (first test) and repeated 6 months (second test) after AMI under optimal anti-atherosclerotic therapy. MACE was defined as the composite of all-cause death, non-fatal MI, angina recurrence requiring percutaneous intervention or surgical bypass, and hospitalization for heart failure. We followed up 126 patients for a period of ≤ 60 months until MACE occurrence after second test. Nineteen MACEs occurred during the follow-up. The log-rank test, Kaplan-Meier curves and univariate Cox proportional hazards regression analysis showed that MACE occurrence was significantly associated with the persistent impairment of epicardial coronary artery dilation and coronary blood flow increases in response to ACh (log-rank test, p < 0.001 and p < 0.001, respectively) (Hazard ratio, p = 0.001 and p = 0.002, respectively). Persistent impairment of endothelial vasomotor function in the infarct-related conduit arterial segment and resistance arteriole were the significant predictor of future MACE occurrence in STEMI survivors.
Assuntos
Vasos Coronários/fisiopatologia , Endotélio Vascular/fisiopatologia , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Vasodilatação/fisiologia , Idoso , Angiografia Coronária , Vasos Coronários/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgiaRESUMO
BACKGROUND: Although animal studies showed that Follistatin-like 1 (FSTL1) exerts cardioprotective effects against ischemic injury, little is known in humans. We examined whether FSTL1 is secreted in an infarcted myocardium and whether its production is associated with left ventricular (LV) remodeling in survivors of acute myocardial infarction. METHODS AND RESULTS: FSTL1 levels were measured by enzyme-linked immunosorbent assay in plasma collected from the aortic root and the anterior interventricular vein in 93 patients with anterior acute myocardial infarction. Measurement of FSTL1 levels and left ventriculography were repeated during the early phase (2 weeks) and the chronic phase (6 months) after MI. A persistent increment in FSTL1 levels from the aortic root to the anterior interventricular vein, reflecting FSTL1 production in the infarcted myocardium at both the early and chronic phases, was seen in 22 patients (24%). A linear regression analysis revealed that a persistent transmyocardial increment in FSTL1 levels was significantly associated with percent changes in LV end-diastolic volume index, LV end-systolic volume index, and LV ejection fraction from the early to the chronic phase (râ¯=â¯0.44, 0.51, and -0.43, respectively, all P < .001). CONCLUSIONS: The persistent production of FSTL1 in the infarcted myocardium was associated with adverse LV remodeling in survivors of acute myocardial infarction.
Assuntos
Proteínas Relacionadas à Folistatina , Insuficiência Cardíaca , Infarto do Miocárdio , Animais , Folistatina , Proteínas Relacionadas à Folistatina/genética , Humanos , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio , Função Ventricular Esquerda , Remodelação VentricularRESUMO
BACKGROUND: The precise mechanisms underlying the high prevalence of pulmonary hypertension (PH) with increased pulmonary vascular resistance (PVR) in heart failure with preserved ejection fraction (HFpEF) remain largely unknown. Measurements of brachial-ankle pulse wave velocity (baPWV) have been shown to be useful for risk assessment in HF patients. Thus, this study sought to define the association of PVR with baPWV and clinical outcomes in HFpEF. METHODS AND RESULTS: Patients with HFpEF (nâ¯=â¯198) had measurements of baPWV and PVR by right heart catheterization, and were prospectively followed-up for <96 months or until the occurrence of a composite of all-cause death, hospitalization with worsening HF, and nonfatal acute coronary syndrome. RESULTS: Multivariate logistic analysis showed that baPWV was independently associated with PH with increased PVR (P < .001). During the follow-up period, 46 clinical events occurred. Multivariate Cox proportional hazards analysis showed that PH with increased PVR was a significant predictor of adverse outcomes after adjustment for conventional risk factors (HR 1.96, 95% CI 1.03-3.76, Pâ¯=â¯.04). CONCLUSIONS: PH with increased PVR was associated with increased baPWV and adverse clinical outcomes in HFpEF. Thus, increased arterial stiffness may contribute to increased risk predictability of PVR for patients with HFpEF.
Assuntos
Índice Tornozelo-Braço , Insuficiência Cardíaca , Análise de Onda de Pulso , Medição de Risco/métodos , Resistência Vascular , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/etiologia , Idoso , Cateterismo Cardíaco/métodos , Cateterismo Cardíaco/estatística & dados numéricos , Progressão da Doença , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão/epidemiologia , Masculino , Valor Preditivo dos Testes , Prognóstico , Volume SistólicoRESUMO
BACKGROUND: This study examined the predictive value of remnant lipoprotein levels for cardiovascular events (CVEs) in patients with stable coronary artery disease (CAD) and low-density lipoprotein cholesterol (LDL-C) levels <70 mg/dL on statin treatment.MethodsâandâResults:Serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol: RLP-C) were measured by an immunoseparation method in 247 consecutive patients with CAD who had on-statin LDL-C levels <70 mg/dL. All the patients were followed prospectively for a period of ≤60 months or until the occurrence of the primary composite endpoint of cardiac death, nonfatal myocardial infarction, unstable angina requiring coronary revascularization, worsening heart failure, peripheral artery disease, aortic event, and ischemic stroke. During a mean follow-up period of 38 months, 33 CVEs occurred. Kaplan-Meier analysis demonstrated that higher RLP-C levels (≥3.9 mg/dL, determined by ROC curve) resulted in a significantly higher probability for the primary endpoint than did lower RLP-C levels (<3.9 mg/dL) (P<0.01 by log-rank test). Stepwise multivariate Cox proportional hazard analysis showed that RLP-C was a significant predictor of the primary endpoint after adjustment for known risk factors and lipid variables including triglycerides, and total apolipoprotein B (hazard ratio 1.62, 95% confidence interval 1.26-2.07, P<0.01). CONCLUSIONS: RLP-C levels are a residual risk factor for future CVEs in patients with CAD and on-statin LDL-C <70 mg/dL.
Assuntos
LDL-Colesterol/sangue , Colesterol/sangue , Doença da Artéria Coronariana , Lipoproteínas/sangue , Triglicerídeos/sangue , Idoso , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Stromal cell-derived factor-1α (SDF-1α) is an inflammatory chemokine that plays a critical role in cardiovascular disease. Although persistent inflammation causes renal dysfunction, it remains unclear whether SDF-1α is related to progression of chronic kidney disease. This study examined whether high levels of SDF-1α are associated with future declines in renal function in patients with coronary artery disease (CAD). METHODS: Plasma levels of SDF-1α in the peripheral blood were measured by enzyme-linked immunosorbent assay in 344 patients with CAD. All patients were followed for 24 months or until the occurrence of renal dysfunction, defined as ≥ 25% decrease in estimated glomerular filtration rate (eGFR) from baseline. RESULTS: During the follow-up period, 36 patients developed renal dysfunction. Multivariate logistic regression analysis showed that high plasma levels of SDF-1α were significantly associated with progression of renal dysfunction (odds ratio 1.65; 95% confidence intervals 1.07-2.35, p = 0.03). In addition, high plasma levels of SDF-1α had a significant incremental effect on the predictive value of known risk factors for renal dysfunction in analyses using net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.58 [0.07-1.02], p < 0.01; and IDI 0.030 [0.001-0.085], p = 0.02). CONCLUSION: High plasma levels of SDF-1α were associated with the short-term decline of eGFR in patients with CAD. Thus, SDF-1α may be useful for predicting the progression of renal dysfunction in patients with CAD.
Assuntos
Quimiocina CXCL12/sangue , Doença da Artéria Coronariana/sangue , Taxa de Filtração Glomerular , Nefropatias/sangue , Rim/fisiopatologia , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Progressão da Doença , Feminino , Humanos , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Regulação para CimaRESUMO
Murine membrane-bound phospholipase A2 receptor 1 (PLA2R) is shed and released into plasma in a soluble form that retains all of the extracellular domains. Relatively little is known about human PLA2R. This study examined whether human soluble PLA2R has biological functions and whether soluble PLA2R exists in human plasma. Here, we showed that human recombinant soluble PLA2R (rsPLA2R) bound to collagen-I and inhibited interaction of collagen-I with the extracellular domain of integrin ß1 on the cell surface of human embryonic kidney 293 (HEK293) cells. As a result, rsPLA2R suppressed integrin ß1-mediated migratory responses of HEK293 cells to collagen-I in Boyden chamber experiments. Inhibition of phosphorylation of FAK Tyr397 was also observed. Similar results were obtained with experiments using soluble PLA2R released from HEK293 cells transfected with a construct encoding human soluble PLA2R. rsPLA2R lacking the fibronectin-like type II (FNII) domain had no inhibitory effects on cell responses to collagen-I, suggesting an important role of the FNII domain in the interaction of rsPLA2R with collagen-I. In addition, rsPLA2R suppressed the migratory response to collagen-IV and binding of collagen-IV to the cell surface of human podocytes that endogenously express membrane-bound, full-length PLA2R. Immunoprecipitation and Western blotting showed the existence of immunoreactive PLA2R in human plasma. In conclusion, human recombinant soluble PLA2R inhibits integrin ß1-mediated cell responses to collagens. Further studies are warranted to elucidate whether immunoreactive PLA2R in human plasma has the same properties as rsPLA2R.
Assuntos
Movimento Celular/fisiologia , Colágeno Tipo I/metabolismo , Integrinas/metabolismo , Receptores da Fosfolipase A2/metabolismo , Animais , Células COS , Linhagem Celular , Membrana Celular/metabolismo , Chlorocebus aethiops , Colágeno Tipo IV/metabolismo , Fibronectinas/metabolismo , Células HEK293 , Humanos , Fosforilação/fisiologia , Podócitos/metabolismoRESUMO
A 77-year-old woman with arteriovenous shunt for hemodialysis in the left forearm suffered from subarachnoid hemorrhage due to the rupture of a saccular aneurysm located on the left lateral wall of vertebrobasilar junction. Her left subclavian artery was severely stenosed and subclavian steal phenomenon was demonstrated on the digital subtraction angiography. Embolization of the parent artery including the aneurysm using detachable coils resulted in the successful obliteration of the aneurysm through the revascularized left subclavian artery. This is the first case in which the vertebrobasilar junction aneurysm would be caused by the hemodynamic stress due to the subclavian steal phenomenon combined with the shunt for hemodialysis in the left forearm.
Assuntos
Aneurisma Roto/complicações , Aneurisma Intracraniano/complicações , Síndrome do Roubo Subclávio/etiologia , Artéria Vertebral , Idoso , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/fisiopatologia , Aneurisma Roto/terapia , Angiografia Digital , Angioplastia com Balão , Artéria Basilar/diagnóstico por imagem , Artéria Basilar/fisiopatologia , Angiografia Cerebral/métodos , Circulação Cerebrovascular , Angiografia por Tomografia Computadorizada , Embolização Terapêutica , Evolução Fatal , Feminino , Hemodinâmica , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/fisiopatologia , Aneurisma Intracraniano/terapia , Síndrome do Roubo Subclávio/diagnóstico por imagem , Síndrome do Roubo Subclávio/fisiopatologia , Síndrome do Roubo Subclávio/terapia , Resultado do Tratamento , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/fisiopatologiaRESUMO
RATIONALE: Recent evidence indicates that the biological effects of secretory phospholipase A2 (sPLA2) cannot be fully explained by its catalytic activity. A cell surface receptor for sPLA2 (PLA2 receptor 1 [PLA2R]) and its high-affinity ligands (including sPLA2-IB, sPLA2-IIE, and sPLA2-X) are expressed in the infarcted myocardium. OBJECTIVE: This study asked whether PLA2R might play a pathogenic role in myocardial infarction (MI) using mice lacking PLA2R (PLA2R(-/-)). METHODS AND RESULTS: MI was induced by permanent ligation of the left coronary artery. PLA2R(-/-) mice exhibited higher rates of cardiac rupture after MI compared with PLA2R wild-type (PLA2R(+/+)) mice (46% versus 21%, respectively; P=0.015). PLA2R(-/-) mice had a 31% decrease in collagen content and a 45% decrease in the number of α-smooth muscle actin-positive fibroblasts in the infarcted region compared with PLA2R(+/+) mice. PLA2R was primarily found in myofibroblasts in the infarcted region. PLA2R(-/-) myofibroblasts were impaired in collagen-dependent migration, proliferation, and activation of focal adhesion kinase in response to sPLA2-IB. Binding of sPLA2-IB to PLA2R promoted migration and proliferation of myofibroblasts through functional interaction with integrin ß1, independent of the catalytic activity of sPLA2-IB. In rescue experiments, the injection of PLA2R(+/+) myofibroblasts into the infarcted myocardium prevented post-MI cardiac rupture and reversed the decrease in collagen content in the infarcted region in PLA2R(-/-) mice. CONCLUSIONS: PLA2R deficiency increased the susceptibility to post-MI cardiac rupture through impaired healing of the infarcted region. This might be partly explained by a reduction in integrin ß1-mediated migratory and proliferative responses of PLA2R(-/-) myofibroblasts.
Assuntos
Predisposição Genética para Doença/genética , Ruptura Cardíaca/genética , Ruptura Cardíaca/mortalidade , Infarto do Miocárdio/genética , Infarto do Miocárdio/mortalidade , Receptores da Fosfolipase A2/deficiência , Animais , Ruptura Cardíaca/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/patologia , Receptores da Fosfolipase A2/genética , Taxa de Sobrevida/tendências , Cicatrização/genéticaRESUMO
The role of stromal cell-derived factor-1α (SDF-1α) expressed in infarcted myocardium is unknown in humans. We examined whether SDF-1α produced in an infarcted myocardial lesion may play a role in left ventricle (LV) remodeling and dysfunction in patients with acute myocardial infarction (AMI). We measured SDF-1α levels in plasma obtained from aortic root (AO) and anterior interventricular vein (AIV) in the early phase (2 wk after MI) and the chronic phase (6 mo after MI) in 80 patients with anterior MI. An increment in SDF-1α level from AO to AIV, reflecting SDF-1α release from infarcted myocardium, was more frequent in patients with MI in the early phase of MI [n = 52 (65%), P = 0.03] but not in the chronic phase of MI [n = 46 (58%), P = 0.11] compared with that in control patients [n = 6/17 (35%)]. On linear regression analysis, the transmyocardial gradient in SDF-1α level in the chronic phase of MI was correlated with percentage changes in LV end-diastolic volume index (r = 0.39, P < 0.001), LV end-systolic volume index (r = 0.38, P < 0.001), and LV ejection fraction (r = -0.26, P = 0.01) 6 mo after AMI. By contrast, the transmyocardial gradient of SDF-1α in the early phase of MI had no significant correlations. In conclusion, the production of SDF-1α in infarcted myocardium in the chronic phase of MI was associated with LV adverse remodeling and progressive dysfunction in AMI survivors.
Assuntos
Quimiocina CXCL12/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Disfunção Ventricular Esquerda/metabolismo , Remodelação Ventricular , Idoso , Aorta , Estudos de Casos e Controles , Vasos Coronários , Progressão da Doença , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Volume Sistólico , Disfunção Ventricular Esquerda/fisiopatologiaAssuntos
Implantes Absorvíveis , Aneurisma Coronário/etiologia , Oclusão Coronária/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Sirolimo/administração & dosagem , Fármacos Cardiovasculares/administração & dosagem , Aneurisma Coronário/diagnóstico por imagem , Oclusão Coronária/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Fatores de Tempo , Resultado do TratamentoRESUMO
Secretory phospholipase A2 (sPLA2) plays a critical role in the genesis of lung inflammation through proinflammatory eicosanoids. A previous in vitro experiment showed a possible role of cell surface receptor for sPLA2 (PLA2R) in the clearance of extracellular sPLA2. PLA2R and groups IB and X sPLA2 are expressed in the lung. This study examined a pathogenic role of PLA2R in airway inflammation using PLA2R-deficient (PLA2R(-/-)) mice. Airway inflammation was induced by immunosensitization with OVA. Compared with wild-type (PLA2R(+/+)) mice, PLA2R(-/-) mice had a significantly greater infiltration of inflammatory cells around the airways, higher levels of groups IB and X sPLA2, eicosanoids, and Th2 cytokines, and higher numbers of eosinophils and neutrophils in bronchoalveolar lavage fluid after OVA treatment. In PLA2R(-/-) mice, intratracheally instilled [(125)I]-labeled sPLA2-IB was cleared much more slowly from bronchoalveolar lavage fluid compared with PLA2R(+/+) mice. The degradation of the instilled [(125)I]-labeled sPLA2-IB, as assessed by trichloroacetic acid-soluble radioactivity in bronchoalveolar lavage fluid after instillation, was lower in PLA2R(-/-) mice than in PLA2R(+/+) mice. In conclusion, PLA2R deficiency increased sPLA2-IB and -X levels in the lung through their impaired clearance from the lung, leading to exaggeration of lung inflammation induced by OVA treatment in a murine model.
Assuntos
Fosfolipases A2 do Grupo IB/metabolismo , Fosfolipases A2 do Grupo X/metabolismo , Pneumonia/imunologia , Receptores da Fosfolipase A2/genética , Receptores da Fosfolipase A2/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/citologia , Eicosanoides/metabolismo , Eosinófilos/imunologia , Feminino , Fosfolipases A2 do Grupo IB/imunologia , Fosfolipases A2 do Grupo X/imunologia , Pulmão/imunologia , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/imunologia , Ovalbumina/imunologia , Pneumonia/genética , Receptores da Fosfolipase A2/deficiênciaRESUMO
BACKGROUND: Ultrasound assessment of either intima-media thickness (IMT) or plaque echolucency of the carotid artery provides prognostic information on coronary events. This study examined the hypothesis that IMT and plaque echolucency of the carotid artery may remain useful for prediction of coronary events in patients with coronary artery disease (CAD) after achievement of LDL-C goals on statin therapy. METHODS AND RESULTS: Ultrasound assessment of carotid maximum IMT (maxIMT) and plaque echolucency with integrated backscatter (IBS) analysis was performed in 357 chronic CAD patients with LDL-C <100mg/dl on statin therapy. All patients were prospectively followed up until the occurrence of one of the following coronary events: cardiac death, non-fatal myocardial infarction, or unstable angina pectoris requiring unplanned revascularization. During a mean follow-up of 32±18 months, 33 coronary events occurred. On multivariate Cox proportional hazards analysis, plaque echolucency (lower IBS value) was a significant predictor of coronary events (HR, 0.44; 95% CI: 0.29-0.73; P=0.009), whereas maxIMT was not. The addition of plaque echolucency to traditional risk factors improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI; NRI, 0.59; P=0.0013; and IDI, 0.075; P=0.0009). CONCLUSIONS: Measurement of echolucency of the carotid artery was useful for assessment of residual coronary risk in CAD patients after LDL-C goal attainment on statin treatment.
Assuntos
Estenose das Carótidas , LDL-Colesterol/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Placa Aterosclerótica , Idoso , Angina Instável/sangue , Angina Instável/diagnóstico por imagem , Angina Instável/tratamento farmacológico , Angina Instável/etiologia , Estenose das Carótidas/sangue , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/tratamento farmacológico , Doença Crônica , Morte , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/tratamento farmacológico , Placa Aterosclerótica/sangue , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Estudos Retrospectivos , UltrassonografiaRESUMO
BACKGROUND: Patients who undergo percutaneous coronary intervention (PCI) with rotational atherectomy (RA) are at high risk of adverse clinical outcomes, and there are few clinical risk stratification tools for these patients. METHODS: We conducted a study with 196 patients who underwent PCI with RA out of 7391 patients who underwent PCI using a multicenter, prospective cohort registry. Patients were divided into three groups according to the tertiles of the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P): 65 patients in the T1 group (TRS 2°Pâ¯<â¯3), 66 patients in the T2 group (TRS 2°Pâ¯=â¯3), and 65 patients in the T3 group (TRS 2°Pâ¯>â¯3). The primary endpoint was the cumulative 2-year incidence of major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of cardiac death, acute coronary syndrome, and ischemic stroke. RESULTS: Cumulative 2-year MACCE occurred in 41 patients (24â¯%) during the follow-up period. The cumulative incidence of MACCE was significantly higher in the T3 group than in the T1 group (log-rank test, pâ¯=â¯0.02). Multivariate Cox analyses revealed that the T3 group was associated with an increased risk of MACCE compared to that of the T1 group (adjusted hazard ratio, 2.66; 95â¯% confidence interval, 1.04-6.77; pâ¯=â¯0.04). The addition of TRS 2°P to conventional risk factors, including male sex, number of diseased vessels, and low-density lipoprotein cholesterol levels, improved the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.39, pâ¯=â¯0.027; IDI 0.072, pâ¯<â¯0.001). CONCLUSIONS: Atherothrombotic risk stratification using TRS 2°P was useful in identifying high-risk patients with heavily calcified lesions following RA.
Assuntos
Aterectomia Coronária , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Masculino , Aterectomia Coronária/efeitos adversos , Doença da Artéria Coronariana/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Fatores de Risco , Medição de Risco , Estudos RetrospectivosRESUMO
BACKGROUND: Contrast-enhanced ultrasound (CEUS) in the carotid artery has potential as a technique for imaging plaque neovascularization. This study examined whether CEUS could provide information on the severity and instability of coronary artery disease (CAD). METHODS AND RESULTS: A total of 304 patients with CAD and carotid plaque underwent CEUS examination of the carotid artery. Intraplaque neovascularization was identified on the basis of microbubbles within the plaque and graded as: G0, not visible; G1, moderate; or G2, extensive microbubbles. The complexity and extent of the coronary lesions were assessed angiographically. A higher grade of CEUS-assessed plaque neovascularization of the carotid artery was associated significantly with greater complexity (ρ=0.48 by Spearman's rank correlation test) and extent (ρ=0.51) of coronary lesions. G2 plaque neovascularization was a risk for acute coronary syndrome, independent of traditional risk factors (odds ratio 1.91, 95% confidence interval 1.04-3.53, P<0.01). Subgroup analysis showed that carotid CEUS-assessed neovascularization regressed in 12 (46%) of 26 plaques in patients during 6 months of statin treatment, whereas regression occurred in 2 (14%) of 14 plaques in patients not taking a statin (P=0.04, Chi-square test). CONCLUSIONS: CEUS examination of the carotid artery may provide valuable information on the severity and instability of CAD and also the efficacy of antiatherosclerotic treatment.
Assuntos
Artérias Carótidas/ultraestrutura , Doença da Artéria Coronariana/diagnóstico por imagem , Ecocardiografia , Neovascularização Patológica/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/etiologia , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/complicações , Neovascularização Patológica/tratamento farmacológico , Placa Aterosclerótica/complicações , Placa Aterosclerótica/tratamento farmacológico , Fatores de RiscoRESUMO
BACKGROUND: It is still unclear whether optimal medical therapy (OMT) after percutaneous coronary intervention (PCI) has beneficial effects on long-term clinical outcomes in patients aged ≥80 years with coronary artery disease (CAD). METHODS: This study analyzed the time to the first major adverse clinical event including death or nonfatal myocardial infarction (MI), for up to 3 years after PCI using multicenter registry data. Data for 1056 patients aged > 80 years successfully treated with PCI were included in the analysis. OMT was defined as a combination of antiplatelet drug, statin, beta-blocker, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker. RESULTS: In total, 204 (19%) patients in this study received OMT and 852 (81%)ãreceived sub-OMT. During a median follow-up of 725 days, adverse clinical events occurred in 183 patients (death, n=177; nonfatal MI, n=6). Kaplan-Meier analysis showed that patients who received OMT had a lower probability of adverse clinical events than those who received sub-OMT (p<0.01, log-rank test). Propensity score matching yielded 202 patient-pairs treated with OMT or sub-OMT, in whom 64 adverse clinical events (death, n=56, nonfatal MI, n=4) occurred during follow-up. OMT remained significant in the reduction of the risk of adverse clinical events in a multivariate Cox proportional hazards model (hazard ratio 0.44; 95% confidence interval 0.26-0.75; p=0.003). CONCLUSIONS: OMT after PCI was associated with significantly fewer adverse clinical events, including all-cause death and nonfatal MI, in patients aged ≥ 80 years with CAD. OMT might be safe and effective for these very elderly patients.
RESUMO
AIMS: The relationship between low body mass index (BMI) and prognostic factors for patients with coronary artery disease, commonly observed in elderly individuals in Japan, is important. Few studies have evaluated the prognosis for patients with low BMI after percutaneous coronary intervention (PCI). Using a multivariable-adjusted model and data from a prospective cohort registry, we analyzed the risk associated with low BMI for patients after PCI. METHODS: This prospective, multicenter registry included 5965 consecutive patients with coronary artery disease who underwent successful PCI. The patients were followed-up clinically for up to 3 years or until the occurrence of major adverse cardiac events. The primary endpoint was all-cause death and nonfatal myocardial infarction composite. RESULTS: Primary events occurred in 639 (10.7%) patients during the follow-up period. A risk analysis of the primary endpoint adjusted for the multivariable model showed a significant increase in risk for elderly individuals, underweight individuals [HR 1.43 (95% confidence interval (CI), 1.10-1.85), Pï¼0.001], those with diabetes mellitus (DM), peripheral artery disease, low left ventricular ejection fraction or acute coronary syndrome (ACS), and smokers. A stratified adjusted risk analysis based on BMI levels showed that the risk associated with underweight status was significantly pronounced for male patients, those aged 60-74 years, and those with DM or ACS. CONCLUSION: Underweight patients with several risk factors significantly increased risk after PCI. Furthermore, the risk associated with low BMI was significantly more pronounced for men, individuals aged 60-74 years, and patients with DM or ACS.
Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Diabetes Mellitus , Intervenção Coronária Percutânea , Idoso , Humanos , Masculino , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/cirurgia , Índice de Massa Corporal , Volume Sistólico , Intervenção Coronária Percutânea/efeitos adversos , Magreza/etiologia , Estudos Prospectivos , Resultado do Tratamento , Função Ventricular Esquerda , Fatores de Risco , Diabetes Mellitus/epidemiologia , Síndrome Coronariana Aguda/etiologiaRESUMO
Group X secretory PLA(2) (sPLA(2)-X) is expressed in neutrophils and plays a role in the pathogenesis of neutrophil-mediated tissue inflammation and injury. This study tested the hypothesis that sPLA(2)-X in neutrophils may contribute to the pathogenesis of abdominal aortic aneurysms (AAA) using sPLA(2)-X(-/-) mice. AAA was created by application of CaCl(2) to external surface of aorta. As a result, the aortas of sPLA(2)-X(-/-) mice had smaller diameters (percent increase from baseline; 24.8 ± 3.5% vs. 49.9 ± 9.1%, respectively; P < 0.01), a reduced grade of elastin degradation, and lower activities of elastase and gelatinase (26% and 19% lower, respectively) after CaCl(2) treatment compared with sPLA(2)-X(+/+) mice. In sPLA(2)-X(+/+) mice, immunofluorescence microscopic images showed that the immunoreactivity of sPLA(2)-X was detected only in neutrophils within aortic walls 3 days, 1, 2, and 6 wk after CaCl(2) treatment, whereas the immunoreactivity was not detected in macrophages or mast cells in aortic walls. sPLA(2)-X immunoreactivity also was colocalized in cells expressing matrix metalloproteinase (MMP)-9. Neutrophils isolated from sPLA(2)-X(-/-) mice had lower activities of elastase, gelatinase, and MMP-9 in response to stimuli compared with sPLA(2)-X(+/+) mice. The attenuated release of elastase and gelatinase from sPLA(2)-X(-/-) neutrophils was reversed by exogenous addition of mouse sPLA(2)-X protein. The adoptive transfer of sPLA(2)-X(+/+) neutrophils days 0 and 3 after CaCl(2) treatment reversed aortic diameters and elastin degradation grades in the lethally irradiated sPLA(2)-X(+/+) mice reconstituted with sPLA(2)-X(-/-) bone marrow to an extent similar to that seen in sPLA(2)-X(+/+) mice. In conclusion, sPLA(2)-X in neutrophils plays a pathogenic role in AAA in a mice model.
Assuntos
Aorta/enzimologia , Aneurisma da Aorta Abdominal/enzimologia , Fosfolipases A2 do Grupo X/metabolismo , Neutrófilos/enzimologia , Transferência Adotiva , Animais , Aorta/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/patologia , Transplante de Medula Óssea , Cloreto de Cálcio , Modelos Animais de Doenças , Elastina/metabolismo , Gelatinases/metabolismo , Fosfolipases A2 do Grupo X/deficiência , Fosfolipases A2 do Grupo X/genética , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia de Fluorescência , Neutrófilos/transplante , Elastase Pancreática/metabolismo , Fatores de TempoRESUMO
Group IVA cytosolic phospholipase A(2) (cPLA(2)α), which preferentially cleaves arachidonic acid from phospholipids, plays a role in apoptosis and tissue injury. Downstream signals in response to tumor necrosis factor (TNF)-α, a mediator of myocardial ischemia-reperfusion (I/R) injury, involve cPLA(2)α activation. This study examined the potential role of cPLA(2)α and its mechanistic link with TNF-α in myocardial I/R injury using cPLA(2)α knockout (cPLA(2)α(-/-)) mice. Myocardial I/R was created with 10-wk-old male mice by 1 h ligation of the left anterior descending coronary artery, followed by 24 h of reperfusion. As a result, compared with wild-type (cPLA(2)α(+/+)) mice, cPLA(2)α(-/-) mice had a 47% decrease in myocardial infarct size, preservation of echocardiographic left ventricle (LV) function (%fractional shortening: 14 vs. 21%, respectively), and lower content of leukotriene B(4) and thromboxane B(2) (62 and 50% lower, respectively) in the ischemic myocardium after I/R. Treatment with the TNF-α inhibitor (soluble TNF receptor II/IgG1 Fc fusion protein, sTNFR:Fc) decreased myocardial I/R injury and LV dysfunction in cPLA(2)α(+/+) mice but not cPLA(2)α(-/-) mice. sTNFR:Fc also suppressed cPLA(2)α phosphorylation in the ischemic myocardium after I/R of cPLA(2)α(+/+) mice. Similarly, sTNFR:Fc exerted protective effects against hypoxia-reoxygenation (H/R)-induced injury in the cultured cardiomyocytes from cPLA(2)α(+/+) mice but not cPLA(2)α(-/-) cardiomyocytes. H/R and TNF-α induced cPLA(2)α phosphorylation in cPLA(2)α(+/+) cardiomyocytes, which was reversible by sTNFR:Fc. In cPLA(2)α(-/-) cardiomyocytes, TNF-α induced apoptosis and release of arachidonic acid to a lesser extent than in cPLA(2)α(+/+) cardiomyocytes. In conclusion, disruption of cPLA(2)α attenuates myocardial I/R injury partly through inhibition of TNF-α-mediated pathways.