RESUMEN
OBJECTIVES: The consequences of non-adherence to prescribed cardiovascular drugs can be serious, with cardiovascular complications having been reported in both secondary and primary prevention. The objective of this study was to develop a new scale to assess medication adherence in patients with cardiovascular diseases during their hospitalization. METHODS: A cohort of 219 high risk cardiovascular patients was evaluated for this study. Data on reasons for non-adherence were collected using the newly developed Medication Adherence Scale in Cardiovascular disorders (Mascard) and compared with physician assessment during medical consultations and the control of their cardiovascular risk factors. RESULTS: The Mascard consists of 5 items has good psychometric properties and validity and correlated with physician assessment and control of cardiovascular risk factors. CONCLUSIONS: This rapid and easy to use scale may be useful for health care practitioners in their assessment of medication adherence in inpatients with cardiovascular disorders.
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Fármacos Cardiovasculares , Enfermedades Cardiovasculares , Fármacos Cardiovasculares/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Hospitales , Humanos , Cumplimiento de la Medicación , Prevención PrimariaRESUMEN
INTRODUCTION: Atherosclerosis is a major cause of ischemic stroke. Despite important therapeutic advances, the risk of recurrence of vascular events remains very high. The partial failure of these strategies is to some extent related to the lack of patient adherence to their treatments and to the fact that therapeutic targets are not reached. The aim of the present study was to evaluate the influence of a short atherosclerosis prevention program on vascular risk reduction in stroke patients. PATIENTS AND METHODS: Ninety-five patients with a first ischemic stroke related to atherosclerosis or with a high vascular risk profile were recruited. Three months later, a global evaluation of the atherosclerotic disease and of the vascular risk factors was performed combined with several education sessions on vascular risk factors and way of life. A follow-up evaluation was performed several months later to investigate the number of vascular events and the vascular risk profile. RESULTS: Median follow-up was 684 days after stroke. At follow-up, 91.3% of patients were taking a cholesterol-lowering drug, 95.6% an anti-thrombotic agent, and 78% an angiotensin converting enzyme inhibitor. A persistent decrease in tobacco use and an improvement in glycemic control were observed. During follow-up, 3.2% of patients died; none of the deaths were related to a vascular event. During the 22-month follow-up, 7.6% of patients experienced a major vascular event, acute coronary syndrome or stroke. CONCLUSION: Compared with results in the literature, this study illustrates the positive influence of a short atherosclerosis prevention program combining depiction of atherosclerotic lesions and education of vascular risk factors on the quality of long-term post-stroke prevention.
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Aterosclerosis/prevención & control , Accidente Cerebrovascular/terapia , Síndrome Coronario Agudo/prevención & control , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Anticolesterolemiantes/uso terapéutico , Glucemia/metabolismo , Isquemia Encefálica/complicaciones , Femenino , Fibrinolíticos/uso terapéutico , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Conducta de Reducción del Riesgo , Cese del Hábito de Fumar , Accidente Cerebrovascular/etiología , Sobrevida , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/fisiopatología , Enfermedades Vasculares/prevención & control , Función Ventricular Izquierda/fisiologíaRESUMEN
Balloon angioplasty disrupts the protective endothelial lining of the arterial wall, rendering arteries susceptible to thrombosis and intimal thickening. We show here that vascular endothelial growth factor (VEGF), an endothelial cell mitogen, is upregulated in medial smooth muscle cells of the arterial wall in response to balloon injury. Both protein kinase C (PKC) and tyrosine kinase pp60src mediate augmented VEGF expression. In contrast, nitric oxide (NO) donors inhibit PKC-induced VEGF upregulation by interfering with binding of the transcription factor activator protein-1 (AP-1) to the VEGF promoter. Inhibition of VEGF promoter activation suggests that NO secreted by a restored endothelium functions as the negative feedback mechanism that downregulates VEGF expression to basal levels. Administration of a neutralizing VEGF antibody impaired reendothelialization following balloon injury performed in vivo. These findings establish a reciprocal relation between VEGF and NO in the endogenous regulation of endothelial integrity following arterial injury.
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Arterias/metabolismo , Factores de Crecimiento Endotelial/fisiología , Linfocinas/fisiología , Óxido Nítrico/fisiología , Animales , Arterias/enzimología , Proteína Tirosina Quinasa CSK , Técnicas de Cultivo , Factores de Crecimiento Endotelial/genética , Linfocinas/genética , Masculino , Regiones Promotoras Genéticas , Proteína Quinasa C/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular , Familia-src QuinasasRESUMEN
OBJECTIVES: The aim of this study was to compare the prevalence of abnormal glucose tolerance in patients stemming from two French ethnic groups and admitted for acute coronary syndrome (ACS) to intensive coronary care unit. MATERIALS AND METHODS: During a period of six months, 53 and 60 consecutive patients were enrolled at Fort-de-France (Martinique, French West Indies, Afrocaribbeans, group F) and at Bordeaux (France, Europeans, group B), respectively. Glucometabolic state was classified according to medical history and fasting glycemia measured from the fourth day after ACS. RESULTS: At baseline, 36% of the patients of group F and 20% of the patients of group B had previously known diabetes (p=0.06). Prevalence of hypertension was higher in Afrocaribbeans than in Europeans (60 versus 40%, p<0.05). According to fasting glycemia, newly detected diabetes were found in six Afrocaribbeans and only one was found in Europeans; two patients in group F and three patients in group B displayed impaired fasting glycemia. As a whole, 51% of Afrocaribbeans and 27% of Europeans showed abnormal glucose tolerance (p<0.05). Furthermore, Afrocaribbeans displayed lower levels of triglycerides and higher levels of HDL cholesterol than Europeans (p<0.05). CONCLUSION: Our study suggested a higher prevalence of impaired glucose metabolism in French Afrocaribbeans than in European counterparts after ACS. Furthermore, French Afrocaribbeans displayed a more favorable lipoprotein profile. These characteristics look like that of the American and British Afrocaribbeans, maybe because of a common genetic origin.
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Intolerancia a la Glucosa/epidemiología , Intolerancia a la Glucosa/metabolismo , Infarto del Miocardio/epidemiología , Infarto del Miocardio/metabolismo , Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/metabolismo , Factores de Edad , Anciano , Antropometría , Población Negra , Glucemia/metabolismo , Región del Caribe/etnología , HDL-Colesterol/sangre , Cuidados Críticos , Diabetes Mellitus/epidemiología , Etnicidad , Femenino , Francia/epidemiología , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Triglicéridos/sangre , Población BlancaRESUMEN
Ischemic disease represents the new epidemic worldwide. Animal models of ischemic disease are useful because they can help us to understand the underlying pathogenetic mechanisms and develop new therapies. The present review article summarizes the results of a consensus conference on the status and future development of experimentation in the field of cardiovascular medicine using murine models of peripheral and myocardial ischemia. The starting point was to recognize the limits of the approach, which mainly derive from species- and disease-related differences in cardiovascular physiology. For instance, the mouse heart beats at a rate 10 times faster than the human heart. Furthermore, healing processes are more rapid in animals, as they rely on mechanisms that may have lost relevance in man. The main objective of the authors was to propose general guidelines, diagnostic end points and relevance to clinical problems.
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Experimentación Animal , Modelos Animales de Enfermedad , Extremidades/irrigación sanguínea , Oclusión de Injerto Vascular/fisiopatología , Isquemia/fisiopatología , Isquemia Miocárdica/fisiopatología , Experimentación Animal/ética , Experimentación Animal/legislación & jurisprudencia , Animales , Aterosclerosis/cirugía , Comorbilidad , Consenso , Diabetes Mellitus Tipo 1/fisiopatología , Determinación de Punto Final , Oclusión de Injerto Vascular/terapia , Guías como Asunto , Humanos , Isquemia/terapia , Ratones , Isquemia Miocárdica/terapia , Medicina Regenerativa , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Especificidad de la Especie , Venas/trasplante , Cicatrización de HeridasRESUMEN
BACKGROUND: The impact of disordered lipid metabolism on collateral vessel development was studied in apolipoprotein (apo)E-/- mice with unilateral hindlimb ischemia. METHODS AND RESULTS: Hindlimb blood flow and capillary density were markedly reduced in apoE-/- mice versus C57 controls. This was associated with reduced expression of vascular endothelial growth factor (VEGF) in the ischemic limbs of apoE-/- mice. Cell-specific immunostaining localized VEGF protein expression to skeletal myocytes and infiltrating T cells in the ischemic limbs of C57 mice; in contrast, T-cell infiltrates in ischemic limbs of apoE-/- mice were severely reduced. The critical contribution of T cells to VEGF expression and collateral vessel growth was reinforced by the finding of accelerated limb necrosis in athymic nude mice with operatively induced hindlimb ischemia. Adenoviral VEGF gene transfer to apoE-/- mice resulted in marked augmentation of hindlimb blood flow and capillary density. CONCLUSIONS: These findings thus underscore the extent to which hyperlipidemia adversely affects native collateral development but does not preclude augmented collateral vessel growth in response to exogenous cytokines. Moreover, results obtained in the apoE-/- and athymic nude mice imply a critical role for infiltrating T cells as a source of VEGF in neovascularization of ischemic tissues.
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Apolipoproteínas E/genética , Circulación Colateral/fisiología , Factores de Crecimiento Endotelial/genética , Linfocinas/genética , Adenoviridae/genética , Animales , Arteriosclerosis/diagnóstico por imagen , Arteriosclerosis/genética , Arteriosclerosis/fisiopatología , Velocidad del Flujo Sanguíneo , Factores de Crecimiento Endotelial/análisis , Citometría de Flujo , Expresión Génica/fisiología , Miembro Posterior/irrigación sanguínea , Miembro Posterior/patología , Hiperlipidemias/diagnóstico por imagen , Hiperlipidemias/genética , Hiperlipidemias/fisiopatología , Hibridación in Situ , Isquemia/diagnóstico por imagen , Isquemia/genética , Isquemia/fisiopatología , Operón Lac , Recuento de Linfocitos , Linfocinas/análisis , Macrófagos/química , Macrófagos/citología , Macrófagos/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Desnudos , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/química , Necrosis , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , ARN Mensajero/análisis , Proteínas Tirosina Quinasas Receptoras/genética , Receptores de Factores de Crecimiento/genética , Receptores de Factores de Crecimiento Endotelial Vascular , Linfocitos T/química , Linfocitos T/citología , Linfocitos T/fisiología , Transfección , Ultrasonografía Doppler , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
The Wnt genes encode a large family of secreted proteins that play a key role in embryonic development and tissue differentiation in many species (Rijsewijk et al., 1987; Nusse and Varmus, 1992). Genetic and biochemical studies have suggested that the frizzled proteins are cell surface receptors for Wnts (Vinson et al., 1989; Chan et al. , 1992; Bhanot et al., 1996; Wang et al., 1996). In parallel, a number of secreted frizzled-like proteins with a conserved N-terminal frizzled motif have been identified (Finch et al., 1997; Melkonyan et al., 1997; Rattner et al., 1997). One of these proteins, FrzA, the bovine counterpart of the murine sFRP-1 (93% identity) is involved in vascular cell growth control, binds Wg in vitro and antagonizes Xwnt-8 and hWnt-2 signaling in Xenopus embryos (Xu et al. , 1998; Duplàa et al., 1999). In this study, we report that sFRP-1 is expressed in the heart and in the visceral yolk sac during mouse development, and that sFRP-1 and mWnt-8 display overlapping expression patterns during heart morphogenesis. From 8.5 to 12.5 d.p. c., sFRP-1 is expressed in cardiomyocytes together with mWnt-8 but neither in the pericardium nor in the endocardium; at 17.5 d.p.c., they are no longer present in the heart. In mouse adult tissues, while sFRP-1 is highly detected in the aortic endothelium and media and in cardiomyocytes, mWnt-8 is not detected in these areas. Immunoprecipitation experiments demonstrates that FrzA binds to mWnt-8 in cell culture experiments.
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Antígenos CD/genética , Proteínas Portadoras/genética , Corazón/embriología , Proteínas/genética , Animales , Proteínas del Citoesqueleto , Femenino , Proteína-1 Reguladora de Fusión , Expresión Génica , Masculino , Ratones , Ratones Endogámicos C57BL , Morfogénesis , Proteínas Wnt , Proteínas de Pez CebraRESUMEN
Analysis of LacZ gene expression is conventionally inferred from blue staining that results from exposure of the transfected cells or tissue to the substrate 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal). Such histochemical staining reports not whether the gene product is present or absent, but where it is active. We investigated the hypothesis that identification of activity, as opposed to presence, of the enzyme underestimates gene expression following LacZ gene transfer. Under conditions optimized for in vitro histochemistry, up to 20% of cells stably transfected with nls-LacZ remained unstained by X-Gal. In contrast, immunostaining with a monoclonal or a polyclonal anti-beta-galactosidase (beta-Gal) antibody positively stained 99% of the cell nuclei. Following in vivo transfection of naked DNA encoding for nls-LacZ, X-Gal staining disclosed 2.7 +/- 1.7 positive nuclei per LacZ-transfected animal, or a transfection efficiency of 0.015%. In contrast, immunohistochemical staining disclosed 118 +/- 32.7 positive nuclei per transfected animal, yielding a transfection efficiency of 0.64% (p < 0.0001 versus X-Gal staining). Thus, 42.9 times more positive cells were detected by antibody than X-Gal staining. Finally, LacZ gene expression following intramuscular gene transfer with an adenoviral vector was observed in 7.6% of skeletal muscle cells assessed with X-Gal; anti-beta-Gal antibody identified 21.8% of cells as being successfully transfected (p < 0.0001). Thus, X-Gal histochemistry following gene transfer of constructs encoding LacZ may underestimate the anatomic extent of gene expression. The superior sensitivity of immunostaining suggests that anti-beta-Gal antibody represents the preferred analytical tool for light microscopic evaluation of LacZ gene transfer.
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Técnicas de Transferencia de Gen , Operón Lac , Transfección , Adenoviridae/genética , Animales , Femenino , Vectores Genéticos , Histocitoquímica , Peroxidasa de Rábano Silvestre , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Conejos , Coloración y Etiquetado , beta-Galactosidasa/análisisRESUMEN
UNLABELLED: Reduction in transfection time and the ability to perform gene transfer in conjunction with endovascular stent implantation constitute two important challenges for percutaneous adenovirus-mediated gene transfer to vessel walls. Studies have suggested that the use of biocompatible polyol poloxamer 407 could be useful. We first evaluated the use of poloxamer 407 for percutaneous gene transfer in nonstented rabbit iliac arteries. A 200-microl mixture of Ad-RSVbetagal or Ad-CMVLuc in either phosphate-buffered saline (PBS) or 20% poloxamer was delivered. After 3 days, gene transfection was evaluated by X-Gal staining or measurement of luciferase activity. Poloxamer use resulted in a 3- to 15-fold increase in the percentage of transfected cells (X-Gal, p = 0.001) and a 16-fold increase in protein product (luciferase activity, p = 0.03), and allowed a decrease in transfection time from 30 to 5 min with minimal reduction in transfection efficiency. We then evaluated the feasibility of percutaneous gene transfer, using Ad-RSVbetagal diluted in pure PBS or 20% poloxamer, in conjunction with stent implantation. Gene delivery was performed either immediately before (pre-) or after (post-) stent implantation. When adenoviruses were diluted in PBS, gene transfer had a low efficiency (prestent, 0.3%; poststent, 0.2%; NS). With poloxamer, the efficacy was much higher (p = 0.0001) and similar "pre" (2.2%) or "post" (1.7%) stent delivery (NS). CONCLUSIONS: (1) The use of poloxamer, rather than PBS, as a vehicle increases the efficacy of percutaneous adenovirus-mediated gene transfer and reduces transfection time; (2) gene transfer performed during stent implantation with poloxamer is feasible and achieves a significant level of gene expression. Thus percutaneous gene delivery is applicable to conventional stents and could present an attractive method by which to achieve local biological effects in a stent environment.
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Adenovirus Humanos , Materiales Biocompatibles , Técnicas de Transferencia de Gen , Vectores Genéticos , Arteria Ilíaca/metabolismo , Poloxaleno , Stents , Transfección , Angioplastia Coronaria con Balón , Animales , Femenino , Genes Reporteros , Humanos , Operón Lac , Mediciones Luminiscentes , Conejos , Factores de TiempoRESUMEN
Adhesion of monocytes to the endothelium is an early event in the development of atherosclerosis. The possibility that low density lipoproteins enhance this process by activating monocytes was investigated using an in vitro adhesion test on endothelial cell monolayer cultures. Preincubation of monocytes with low density lipoprotein (LDL) (100 micrograms LDL protein/l x 10(6) cells/ml) for 15 min induced a 70% increase in adhesion to endothelial cells with a maximal effect at 100 micrograms LDL protein/ml and a short latency of effect (2 min). Anti-LDL receptor antibody, which inhibited LDL binding, blocked this activation. The LDL effect appeared to depend on receptor binding of LDL rather than on receptor-mediated endocytosis, since preincubation of monocytes with LDL at either 4 degrees C or 37 degrees C resulted in the same stimulation of adhesion. A cytofluorimetric study using integrin monoclonal antibodies (MAbs) against CD18 and CD11b did not reveal any increase in expression of the integrins on the surface of LDL-activated monocytes. However, a 30-min preincubation of monocytes with anti-CD18 abolished the LDL-activated adhesion. These results indicate that LDL induces a rapid activation of monocyte adhesiveness to endothelial cells. This effect appears to be mediated by interaction of LDL with its receptor rather than LDL-receptor complex internalization or integrin membrane mobilization from intracellular pools. The integrin system nevertheless appears to be involved.
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Endotelio Vascular/citología , Lipoproteínas LDL/farmacología , Monocitos/fisiología , Anticuerpos Monoclonales/farmacología , Antígenos CD/análisis , Arteriosclerosis/fisiopatología , Adhesión Celular , Humanos , Técnicas In Vitro , Lipoproteínas LDL/fisiología , Masculino , Monocitos/inmunologíaRESUMEN
Since mononuclear cells are recruited in atherosclerotic lesions, the expression of adhesion proteins by the arterial endothelium may play a major role in atherogenesis. The relationships between ICAM-1, E-selectin, and VCAM-1 expression on the arterial endothelium and the presence and degree of maturation of intimal macrophages in human atherosclerotic lesions was investigated. By quantitative double immunostaining with a pan-macrophage-specific monoclonal antibody, HAM-56, and a recently developed monoclonal antibody that is specific for mature macrophages, 3MA-B38, arterial sections were classified as (I) normal, (II) thickened without macrophage infiltration, (III) atherosclerotic with recent macrophage infiltration or (IV) atherosclerotic with infiltration of mature differentiated macrophages. A marked increase in the expression of ICAM-1, E-selectin, and VCAM-1 was observed on endothelial cells adjacent to recently recruited macrophages. Endothelial cells overlying differentiated macrophages exhibited a lower but significant increase in VCAM-1 expression, with no difference in ICAM-1 and E-selectin expression with respect to that observed in endothelium of normal arteries. These findings indicate that the endothelium covering the human arterial wall exhibits different states of activation as reflected by the expression of adhesion proteins, and that intimal monocyte/macrophage recruitment appears to depend on the level of expression of adhesion proteins.
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Anticuerpos Monoclonales , Arteriosclerosis/metabolismo , Moléculas de Adhesión Celular/metabolismo , Endotelio Vascular/metabolismo , Macrófagos/metabolismo , Monocitos/metabolismo , Adulto , Anticuerpos/inmunología , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Arteriosclerosis/inmunología , Arteriosclerosis/patología , Moléculas de Adhesión Celular/inmunología , División Celular , Células Cultivadas , Endotelio Vascular/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Arteria Femoral/metabolismo , Arteria Femoral/patología , Citometría de Flujo , Humanos , Immunoblotting , Inmunohistoquímica , Macrófagos/inmunología , Macrófagos/patología , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Monocitos/patología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Venas Umbilicales/metabolismo , Venas Umbilicales/patologíaRESUMEN
To assess the possible progression of coronary artery disease after percutaneous transluminal coronary angioplasty (PTCA) and its relation to risk factors and restenosis, 124 patients who underwent a first successful PTCA were studied. All had routine follow-up angiography 5 to 8 months after PTCA. Restenosis was defined as a 30% decrease in diameter stenosis or a return to greater than 50% stenosis, and progression (in any nondilated site) as a 20% decrease in diameter stenosis, assessed by a video-densitometric computer-assisted technique. Univariate and multivariate analysis with respect to progression was carried out for age, sex, initial unstable angina, previous myocardial infarction, diabetes mellitus, hypertension, hypercholesterolemia (greater than or equal to 6.2 mmol), smoking habits, Jenkins' score, dilated artery and restenosis. Forty-one patients (33%) had restenosis, and 23 (19%) had evidence of progression; 20 (87%) of these latter patients had restenosis and 3 (13%) did not. Univariate correlates of progression were: previous myocardial infarction (p less than 0.05), higher Jenkins' score (p less than 0.0003) and restenosis (p less than 0.0001). Restenosis was the only multivariate correlate (p less than 0.00003). Progression at routine angiography after PTCA is not rare, and appears to be related to both the initial extent of coronary artery disease and restenosis.
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Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria/terapia , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia , Factores de Riesgo , Factores de TiempoRESUMEN
To assess hemostatic risk factors for sudden death in patients with stable angina, 323 consecutive patients were recruited prospectively. Patients with clinical heart failure or recent myocardial infarction were excluded. The following clinical variables were recorded: age, gender, smoking habits, hypertension, previous myocardial infarction, left ventricular hypertrophy, and severe ventricular arrhythmia. Angiographic variables included coronary extent, assessed from Jenkins' and mean atherosclerotic scores, and left ventricular ejection fraction. Lipid variables included total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoproteins A-I and B. Hemostatic factors included fibrinogen, fibrinopeptide A, antithrombin III, factor VIII antigen, factor VIII coagulant, protein C, plasminogen, alpha 2 antiplasmin, euglobulin clot lysis time, tissue plasminogen activator before and after venous occlusion, and plasminogen activator inhibitor. There were 34 deaths, 19 of which were sudden during the follow-up period (60 +/- 17 months). The association between each variable and the risk of sudden death was assessed by calculating the relative risk with the Cox univariate model. All significant predictors from the univariate analysis were then incorporated in a Cox multivariate model to select the independent predictors of sudden death. The independent predictors of sudden death were left ventricular hypertrophy (p < 0.04), lower left ventricular ejection fraction (p < 0.04), and shorter euglobulin clot lysis time after venous occlusion (p < 0.02), whereas fibrinogen (p < 0.07) and Jenkins' score (p < 0.08) were borderline. Determination of hemostatic variables, especially those pertaining to dynamic fibrinolysis, may thus be of value in assessing risk of sudden death.
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Angina de Pecho/complicaciones , Anticoagulantes/análisis , Factores de Coagulación Sanguínea/análisis , Muerte Súbita/etiología , Lípidos/sangre , Análisis de Varianza , Angina de Pecho/sangre , Angina de Pecho/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Discrepancies between success in experimental animals with a variety of pharmacologic strategies and failure with such agents in clinical trials have raised questions concerning the mechanism of restenosis. Recent observations suggest a potential implication for the adventitial (Adv) layer in neointimal formation. METHODS: The purpose of this study was to examine the Adv changes in the rat carotid artery subjected to balloon injury. These changes were characterized by morphometric, immunohistochemical, and electron microscopy analyses, with special attention devoted to early time-points post-injury. RESULTS: We report that the most important adventitial changes occurred in the first 48 h post-injury. Within 2 h there was extensive cell-loss by apoptosis and oncosis in the Adv and in the media; this was followed by the rapid onset of proliferation and a parallel slow increase in Adv thickening, reaching a maximum at 7 days. We further demonstrate an early migration of these Adv cells to the media and neointima. Moreover, we characterize the Adv cell phenotype with a panel of antibodies. Within 48 h after injury, a population of Adv cells expressed alpha-actin and vinculin with a maximum expression 7 days post-injury. At that time, these Adv cells started to express smooth muscle myosin heavy chain, a specific marker of smooth muscle cells. In parallel, we report an impaired production of elastic fibres in the Adv and medial layer. CONCLUSIONS: We reported a detailed time-course of adventitial changes after rat carotid injury (cell death, proliferation, migration and differentiation) that supports an important role of adventitia in neointima formation.
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Angioplastia/efectos adversos , Arteriosclerosis/cirugía , Traumatismos de las Arterias Carótidas/patología , Endotelio Vascular/patología , Análisis de Varianza , Animales , Arteriosclerosis/complicaciones , Traumatismos de las Arterias Carótidas/fisiopatología , Caspasa 3 , Caspasas/análisis , Muerte Celular , División Celular , Movimiento Celular , Fenómenos Fisiológicos Celulares , Endotelio Vascular/fisiopatología , Endotelio Vascular/ultraestructura , Modelos Animales , Fenotipo , Ratas , Recurrencia , Factores de TiempoRESUMEN
In an attempt to discern biological (such as thrombotic or fibrinolytic) risk factors in patients developing restenosis after percutaneous transluminal coronary angioplasty, the following factors were measured prior to angiography in a population of 23 patients (20 men, 3 women, mean age 57 +/- 5 yr) treated by a successful angioplasty (gain > 20% and residual stenosis < 50%) for stable angina pectoris and who had a routine angiographic restudy. The following factors were thus assessed: lipid factors: cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein AI, apolipoprotein B; coagulation factors: fibrinogen, antithrombin III, fibrinopeptide A, factor VIII coagulant, factor VIII antigen, protein C; factors of physiological fibrinolysis: plasminogen, alpha 2-antiplasmin, tissue plasminogen activator and euglobulin clot lysis time before and after venous occlusion, plasminogen activator inhibitor before venous occlusion; and factors of platelet release: beta-thromboglobulin, platelet factor 4. Also studied were clinical characteristics: age, gender, diabetes, hypertension, smoking habits, previous myocardial infarction; angiographic data: global extent of coronary artery disease, location of the stenosis in a bend or branch point, complexity of the lesion, initial and residual stenosis and treatment during follow-up. The coronary angiograms were analyzed by a computer-assisted method with automatic edge detection. On angiographic criteria, 6 patients (restenosis group) were judged to have developed a restenosis (30% decrease in diameter and/or return to a 50% stenosis). The other 17 patients (those without restenosis) were considered to have a persistent success. Apart from age (group without restenosis: 55 +/- 6; restenosis group 61 +/- 5, p < 0.04), there were no differences in clinical, angiographic or treatment variables. There were no differences in lipid factors, but significant differences were observed in hemostatic variables: fibrinogen (without restenosis: 3.18 +/- 0.83; restenosis: 3.83 +/- 0.51 milligrams, p = 0.05), tissue plasminogen activator before venous occlusion (without restenosis: 10.9 +/- 26.8; restenosis: 232.5 +/- 371.2 IU, p < 0.04), euglobulin clot lysis time after venous occlusion (without restenosis: 176.5 +/- 100.5; restenosis: 78.6 +/- 40.2 min, p < 0.05) and for marker of the platelet release: platelet factor 4 (without restenosis: 10.8 +/- 7.9; restenosis: 20.5 +/- 7.5 ng/l, p < 0.04). These findings indicate that patients developing restenosis after coronary angioplasty tend to have an imbalance in the prothrombotic-antithrombotic equilibrium prior to the procedure.
Asunto(s)
Angina de Pecho/epidemiología , Angioplastia Coronaria con Balón/normas , Anciano , Angina de Pecho/diagnóstico , Angina de Pecho/terapia , Apolipoproteínas/sangre , Factores de Coagulación Sanguínea/análisis , Colesterol/sangre , Comorbilidad , Angiografía Coronaria , Complicaciones de la Diabetes , Diagnóstico por Computador , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Recurrencia , Factores de Riesgo , Fumar/efectos adversos , Triglicéridos/sangreRESUMEN
The present study was designed to assess the prognostic value of clinical and angiographic factors, and especially restenosis or rapid progression in non-dilated sites, on major spontaneous coronary events at long-term follow-up after a first successful coronary angioplasty performed for angina pectoris. A second aim was to assess the prognostic factors and especially restenosis in asymptomatic patients after angioplasty. The first 352 consecutive patients undergoing a successful coronary angioplasty were selected and followed-up. The following variables: age, sex, unstable angina, previous myocardial infarction, diabetes, hypercholesterolemia, tobacco consumption, hypertension, fibrinogen, coronary extent, single or multiple dilatation, restenosis, new progression, clinical deterioration of anginal status just before angiographic restudy or asymptomatic status were subjected to a stepwise regression analysis. Restenosis (a loss of 30% in diameter and/or a return to a >50% stenosis) and progression in non-dilated segments (a 20% reduction in diameter) were assessed by a computer-assisted method. Cardiac death, new myocardial infarction or new unstable angina, at long-term follow-up after angiographic restudy, were regarded as spontaneous coronary events and pooled in a single dependent variable. Thus 41 patients had a coronary event. In the overall population, clinical deterioration of anginal status (p<0.001, relative risk: 3.65) and fibrinogen (p<0.05, relative risk: 1.03) were independent predictors of spontaneous coronary events. Restenosis or new progression were not predictors. In asymptomatic patients (n=187), fibrinogen (p<0.01, relative risk=1.06) was the only predictor and restenosis was not an independent predictor of spontaneous coronary events. The best predictor of spontaneous coronary events at long-term follow-up after a first successful coronary angioplasty is clinical deterioration in anginal status in the months following the procedure. Restenosis does not appear as an independent predictor. Rapid progression observed in non-dilated sites is not an important prognostic factor.
Asunto(s)
Angina de Pecho/cirugía , Angioplastia Coronaria con Balón , Enfermedad Coronaria/cirugía , Adulto , Anciano , Angina de Pecho/diagnóstico por imagen , Enfermedad Coronaria/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Radiografía , Recurrencia , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Estadísticas no ParamétricasRESUMEN
Sudden death is most common and often the first manifestation of coronary heart disease although its risk is difficult to predict. It has been studied mainly in patients with severe ventricular arrhythmia or recent myocardial infarction, but little is known about the different risk factors for short- and long-term risk of sudden death in patients with stable angina. To assess risk factors for sudden death in patients with stable angina and angiographically proven coronary artery disease, 319 consecutive patients were recruited prospectively and followed-up. Patients with clinical heart failure or recent myocardial infarction were excluded. Clinical, angiographic and biological variables were recorded. The association between each variable and the risk of sudden death was assessed in univariate and logistic multivariate analysis. There were 25 sudden deaths during the follow-up period (97+/-29 months). The univariate predictors in the short-term (2 years) were: peripheral arterial disease, left ventricular hypertrophy, low density lipoprotein cholesterol and ejection fraction. The independent predictors were: peripheral arterial disease (relative risk: 6.3), ejection fraction (relative risk 1.05) and low density lipoprotein (relative risk: 1.8). In the long-term (8-10 years), body mass index, coronary score, ejection fraction and fibrinogen were univariate predictors. Only body mass index (relative risk: 1. 2), ejection fraction (relative risk: 1.06) and fibrinogen (relative risk: 2) remained independent predictors. The risk factors for sudden death in stable angina were time-dependent, peripheral arterial disease appeared as the best predictor with LDL for short time, and body mass index (obesity: index >27) and fibrinogen for long time. Ejection fraction was the only time-independent predictor.
Asunto(s)
Angina de Pecho/complicaciones , Muerte Súbita Cardíaca/etiología , Adulto , Anciano , Angina de Pecho/sangre , Factores de Coagulación Sanguínea/análisis , Angiografía Coronaria , Femenino , Estudios de Seguimiento , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: The number of patients with pacemakers has been increasing and a large number of them will present with chest pain or symptoms suggesting angina pectoris. Myocardial ischemia and presence of coronary artery disease are difficult to detect and assess by noninvasive methods in patients with a pacemaker; the electrocardiogram (ECG) at rest and during exercise is usually very difficult to analyze in terms of ischemia or even presence of an acute myocardial infarction. HYPOTHESIS: To detect significant coronary stenosis in patients with previously implanted pacemakers, we tested a new stress echocardiography method using incremental ventricular pacing by already implanted pacemakers. METHODS: We studied prospectively 25 consecutive patients who underwent stress echocardiography with increasing ventricular pacing up to either 85% of the age-predicted maximal heart rate or chest pain. Positive tests were defined by new hypokinesia or worsening of a preexisting alteration in wall motion in at least two adjacent territories. All patients underwent coronary angiograms to define the presence and severity of coronary stenoses. RESULTS: Among the 25 tests, 11 (44%) were stopped for chest pain. 1 (4%) for moderate discomfort, 1 (4%) for a drop in blood pressure, and the target pacing rate was achieved in the tests of the remaining 12 patients (48%). There were no complications. Thirteen patients had significant stenoses. In 10 cases, stress echocardiography was a true positive test with respect to coronary angiography. There were 11 true negative, 1 false positive, and 3 false negative tests. The sensitivity was 77%, specificity was 90%, the positive predictive value was 91%, and the negative predictive value 79%. The accuracy was 84%. CONCLUSIONS: This new stress echocardiography method appears feasible, easy, safe, and effective for detection of significant coronary stenoses in patients with pacemakers.
Asunto(s)
Estimulación Cardíaca Artificial , Enfermedad Coronaria/diagnóstico por imagen , Ecocardiografía/métodos , Marcapaso Artificial , Anciano , Angiografía Coronaria , Interpretación Estadística de Datos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
Several epidemiological studies have shown decreased cardiovascular mortality and a lower incidence of coronary artery disease in subjects with high dietary intakes of Omega-3 polyunsaturated fatty acids. It has since been shown that Omega-3 fatty acids have a number of beneficial effects in the prevention of atherosclerosis in man: reduction of blood pressure, modifications of lipoprotein metabolism, modifications of haemostasis (increased bleeding time and reduced platelet aggregation), decreased plasma fibrinogen, modifications of the metabolism of arachidonic acid and its derivatives (decreased thromboxane and leukotriene synthesis, increased prostacyclin synthesis). Therefore, Omega-3 polyunsaturated fatty acids have several beneficial effects on the presumed mechanisms of atherogenesis and/or its complications: they could represent an original and seductive solution to the problem of prevention of cardiovascular disease.
Asunto(s)
Arteriosclerosis/prevención & control , Enfermedades Cardiovasculares/prevención & control , Ácidos Grasos Omega-3/uso terapéutico , Presión Sanguínea , Eicosanoides/metabolismo , Hemostasis , Humanos , Triglicéridos/sangreRESUMEN
Analysis of left ventricular volumes is a prognostic factor in cardiovascular disease. Echocardiography is a means of obtaining these parameters but is limited by poor reproducibility. Recently, a new echocardiographic technique, second harmonic imaging (SHI), developed through contrast agent methods, significantly improved the quality of imaging. The aim of this study was to demonstrate the value of SHI for assessing left ventricular volumes. Thirty patients admitted for cardiovascular evaluation and requiring angiocardiography underwent echocardiography with calculation of end diastolic (EDV) and end systolic volumes (ESV) of the left ventricle in fundamental (FI) and second harmonic (SHI) imaging. These measurements were compared with those of angiocardiography. The reproducibility of SHI was calculated after repetition of the measurements by two independent observers for both echocardiographic modes. There was a significant improvement of the parameters of linear regression in SHI compared with FI both for EDV (r = 0.93 versus 0.76) and for ESV (r = 0.94 versus 0.83), the reproducibility was also significantly improved in SHI (relative error of 5% versus 12% for intra-observer error and 6% versus 13% for inter-observer error). The authors conclude that SHI significantly improves two-dimensional imaging and provides a reliable and reproducible measurement of left ventricular volumes.