RESUMEN
BACKGROUND: The utilisation of bioelectrical impedance analysis (BIA) in heart failure can be affected by many factors and its applicability remains controversial. The present study aimed to verify the adequacy of single-frequency BIA (SF-BIA) and multifrequency BIA (MF-BIA) compared to dual-energy x-ray absorptiometry (DEXA) for evaluating body composition in outpatients with heart failure. METHODS: In this cross-sectional study, 55 patients with stable heart failure and left ventricle ejection fraction ≤45% were evaluated for fat mass percentage, fat mass and fat-free mass by DEXA and compared with the results obtained by SF-BIA (single frequency of 50 kHz) and MF-BIA (frequencies of 20 and 100 kHz). RESULTS: MF-BIA and DEXA gave similar mean values for fat mass percentage, fat mass and fat-free mass, whereas values from SF-BIA were significantly different from DEXA. Both SF-BIA and MF-BIA measures of body composition correlated strongly with DEXA (r > 0.8; P < 0.001), except for fat mass assessed by SF-BIA, which showed a moderate correlation (r = 0.760; P < 0.001). MF-BIA also showed a better agreement with DEXA by Bland-Altman analysis in all measurements. However, both types of equipment showed wide limits of agreement and a significant relationship between variance and bias (Pitmans's test P > 0.05), except MF-BIA for fat-free mass. CONCLUSIONS: Compared with DEXA, MF-BIA showed better accuracy than SF-BIA, although both types of equipment showed wide limits of agreement. The BIA technique should be used with caution, and regression equations might be useful for correcting the observed variations, mainly in extreme values of body composition.
Asunto(s)
Absorciometría de Fotón , Tejido Adiposo , Composición Corporal , Impedancia Eléctrica , Insuficiencia Cardíaca , Tejido Adiposo/metabolismo , Anciano , Compartimentos de Líquidos Corporales , Índice de Masa Corporal , Estudios Transversales , Femenino , Insuficiencia Cardíaca/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).
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Disnea/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Natriuréticos/uso terapéutico , Péptido Natriurético Encefálico/uso terapéutico , Readmisión del Paciente/estadística & datos numéricos , Enfermedad Aguda , Anciano , Método Doble Ciego , Disnea/etiología , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Humanos , Hipotensión/inducido químicamente , Análisis de Intención de Tratar , Enfermedades Renales/etiología , Masculino , Persona de Mediana Edad , Natriuréticos/efectos adversos , Péptido Natriurético Encefálico/efectos adversos , RecurrenciaRESUMEN
Genetic polymorphisms of adrenergic receptors (ARs) have been associated with the development, progression, and prognosis of patients with heart failure (HF), with few data for the Brazilian population. We evaluated the role of the beta2-AR Thr164Ile polymorphism at codon 164 on prognosis in a prospective study on 315 adult Brazilian HF patients, predominantly middle-aged Caucasian men in functional class I-II, with severe left ventricular systolic dysfunction. Genomic DNA was extracted from peripheral blood and beta2-AR164 genotypes were detected by PCR followed by restriction fragment length analysis. During a median follow-up of 3 years, 95 deaths occurred and 57 (60%) were HF-related. Unexpectedly, Ile164 carriers (N = 12) had no HF-related events (log-rank P value = 0.13). Analysis using genotype combination with beta1-AR polymorphisms at codons 49 and 389 identified patients with favorable genotypes (Thr164Ile of beta2-AR, Gly49Gly of beta1-AR and/or Gly389Gly of beta1-AR), who had lower HF-related mortality (P = 0.01). In a Cox proportional hazard model adjusted for other clinical characteristics, having any of the favorable genotypes remained as independent predictor of all-cause (hazard ratio (HR): 0.41, 95%CI: 0.17-0.95) and HF-related mortality (HR: 0.12, 95%CI: 0.02-0.90). These data show that the beta2-AR Thr164Ile polymorphism had an impact on prognosis in a Brazilian cohort of HF patients. When combined with common beta1-AR polymorphisms, a group of patients with a combination of favorable genotypes could be identified.
Asunto(s)
Insuficiencia Cardíaca/genética , Polimorfismo Genético/genética , Receptores Adrenérgicos beta 2/genética , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
Genetic polymorphisms of adrenergic receptors (ARs) have been associated with the development, progression, and prognosis of patients with heart failure (HF), with few data for the Brazilian population. We evaluated the role of the β2-AR Thr164Ile polymorphism at codon 164 on prognosis in a prospective study on 315 adult Brazilian HF patients, predominantly middle-aged Caucasian men in functional class I-II, with severe left ventricular systolic dysfunction. Genomic DNA was extracted from peripheral blood and β2-AR164 genotypes were detected by PCR followed by restriction fragment length analysis. During a median follow-up of 3 years, 95 deaths occurred and 57 (60 percent) were HF-related. Unexpectedly, Ile164 carriers (N = 12) had no HF-related events (log-rank P value = 0.13). Analysis using genotype combination with β1-AR polymorphisms at codons 49 and 389 identified patients with favorable genotypes (Thr164Ile of β2-AR, Gly49Gly of β1-AR and/or Gly389Gly of β1-AR), who had lower HF-related mortality (P = 0.01). In a Cox proportional hazard model adjusted for other clinical characteristics, having any of the favorable genotypes remained as independent predictor of all-cause (hazard ratio (HR): 0.41, 95 percentCI: 0.17-0.95) and HF-related mortality (HR: 0.12, 95 percentCI: 0.02-0.90). These data show that the β2-AR Thr164Ile polymorphism had an impact on prognosis in a Brazilian cohort of HF patients. When combined with common β1-AR polymorphisms, a group of patients with a combination of favorable genotypes could be identified.
Asunto(s)
Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Cardíaca/genética , Polimorfismo Genético/genética , /genética , Estudios de Cohortes , Predisposición Genética a la Enfermedad , Genotipo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
The main function of the cardiac adrenergic system is to regulate cardiac work both in physiologic and pathologic states. A better understanding of this system has permitted the elucidation of its role in the development and progression of heart failure. Regardless of the initial insult, depressed cardiac output results in sympathetic activation. Adrenergic receptors provide a limiting step to this activation and their sustained recruitment in chronic heart failure has proven to be deleterious to the failing heart. This concept has been confirmed by examining the effect of beta-blockers on the progression of heart failure. Studies of adrenergic receptor polymorphisms have recently focused on their impact on the adrenergic system regarding its adaptive mechanisms, susceptibilities and pharmacological responses. In this article, we review the function of the adrenergic system and its maladaptive responses in heart failure. Next, we discuss major adrenergic receptor polymorphisms and their consequences for heart failure risk, progression and prognosis. Finally, we discuss possible therapeutic implications resulting from the understanding of polymorphisms and the identification of individual genetic characteristics.
Asunto(s)
Gasto Cardíaco Bajo/genética , Polimorfismo Genético/genética , Receptores Adrenérgicos alfa/genética , Receptores Adrenérgicos beta/genética , Gasto Cardíaco Bajo/fisiopatología , Progresión de la Enfermedad , Humanos , Pronóstico , Receptores Adrenérgicos alfa/fisiología , Receptores Adrenérgicos beta/fisiologíaRESUMEN
The main function of the cardiac adrenergic system is to regulate cardiac work both in physiologic and pathologic states. A better understanding of this system has permitted the elucidation of its role in the development and progression of heart failure. Regardless of the initial insult, depressed cardiac output results in sympathetic activation. Adrenergic receptors provide a limiting step to this activation and their sustained recruitment in chronic heart failure has proven to be deleterious to the failing heart. This concept has been confirmed by examining the effect of ß-blockers on the progression of heart failure. Studies of adrenergic receptor polymorphisms have recently focused on their impact on the adrenergic system regarding its adaptive mechanisms, susceptibilities and pharmacological responses. In this article, we review the function of the adrenergic system and its maladaptive responses in heart failure. Next, we discuss major adrenergic receptor polymorphisms and their consequences for heart failure risk, progression and prognosis. Finally, we discuss possible therapeutic implications resulting from the understanding of polymorphisms and the identification of individual genetic characteristics.
Asunto(s)
Humanos , Gasto Cardíaco Bajo/genética , Gasto Cardíaco Bajo/fisiopatología , Polimorfismo Genético/genética , Receptores Adrenérgicos alfa/genética , Receptores Adrenérgicos beta/genética , Progresión de la Enfermedad , Pronóstico , Receptores Adrenérgicos alfa/fisiología , Receptores Adrenérgicos beta/fisiologíaRESUMEN
OBJECTIVES: To describe early sequential profiling of circulating levels of tumor necrosis factor alpha (TNF-alpha), TNF-1 and TNF-2 soluble receptors (sTNFR1 and sTNFR2), and of endothelin (ET-1) in patients with severe burn injury, and its association with mortality. DESIGN: Prospective study. SETTING: Intensive Care Burn Unit at a community hospital. PATIENTS: Twenty patients with total burn surface area (TBSA)> or = 30%. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients were enrolled within 6 h from the injury. Blood samples were drawn at zero, 6, 12, and 24 h for sequential ELISA measurement of plasma marker levels. Data are expressed as mean+/-SD. Age, TBSA, and inhalation injury were not significantly different between survivors ( n=9; 30+/-13 years, TBSA 40+/-12%) and nonsurvivors ( n=11, 38+/-15 years, TBSA 56+/-20%). sTNFR1 levels were increased in nonsurvivors (2937+/-1676 pg/ml; 4548+/-1436 pg/ml) as compared to survivors (1313+/-561 pg/ml; 2561+/-804 pg/ml) at 6 h and 24 h, respectively ( P=0.01 and 0.002). sTNFR2 levels were significantly increased in nonsurvivors (4617+/-1,876 pg/ml vs 2611+/-1,326 pg/ml) only at 6 h ( P=0.015). TNF-alpha and ET-1 levels were not different between nonsurvivors and survivors. After adjustment for TBSA, sTNFR1 and sTNFR2 remained significantly higher in nonsurvivors. CONCLUSION: Early and progressive increase in sTNFR1 and sTNFR2 levels is associated with higher risk for poor outcome in severely burned patients.
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Quemaduras/sangre , Quemaduras/mortalidad , Endotelina-1/sangre , Receptores del Factor de Necrosis Tumoral/sangre , Factor de Necrosis Tumoral alfa/análisis , APACHE , Adolescente , Adulto , Anciano , Análisis de Varianza , Biomarcadores/sangre , Femenino , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Adriamycin cardiotoxicity is associated with oxidative stress in the presence of globally depressed cardiac function. It is unknown if there is a similar profile with early diastolic changes and how it relates to baroreflex control of circulation. In this study, we evaluated baroreflex control of circulation in adriamycin-treated Wistar rats compared with controls, using invasive blood pressure recording processed by a data acquisition system (CODAS, 1 KHz). Baroreflex sensitivity was evaluated by modulating blood pressure with phenylephrine and sodium nitroprusside. Oxidative stress was quantified by chemiluminescence and by glutathione peroxidase enzyme activity. Diastolic dysfunction was characterized by increased left ventricle end-diastolic pressure in adriamycin-treated rats compared with controls with preserved ascending aortic flow. Baroreflex sensitivity in response to blood pressure elevation and reduction were similar in adriamycin (-2+/-0.27 and -3.19+/-0.56 bpm/mm Hg) and control rats (-1.35+/-0.15 and -2.52+/-0.39 bpm/mm Hg). Chemiluminescence was higher (20450+/-1286 versus 16517+/-1020 counts per second/mg protein) and glutathione peroxidase activity was lower (45.6+/-4.3 versus 76.4+/-6.9 micromol. min(-1). mg(-1) protein) in adriamycin rats compared with controls. Inverse correlations were observed between glutathione peroxidase activity and left ventricle end-diastolic pressure (r=-0.72, P=0.02), between baroreflex sensitivity to phenylephrine and left ventricle end-diastolic pressure (r=-0.77, P=0.004), and between chemiluminescence and baroreflex sensitivity to sodium nitroprusside (r=-0.75, P=0.02), whereas a positive correlation was observed between baroreflex sensitivity to sodium nitroprusside and glutathione peroxidase activity (r=0.7, P=0.04). Thus, adriamycin led to increased left ventricle end-diastolic pressure without changes in baroreflex sensitivity, and associated increased oxidative stress appeared to be related to reduction of reflex control of circulation.
Asunto(s)
Barorreflejo/fisiología , Insuficiencia Cardíaca/fisiopatología , Estrés Oxidativo , Análisis de Varianza , Animales , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Doxorrubicina , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Nitroprusiato/farmacología , Fenilefrina/farmacología , Ratas , Ratas Wistar , Vasoconstrictores/farmacología , Vasodilatadores/farmacologíaAsunto(s)
Insuficiencia Cardíaca/sangre , Factor de Necrosis Tumoral alfa/biosíntesis , Adulto , Biomarcadores/sangre , Femenino , Insuficiencia Cardíaca/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Probabilidad , Pronóstico , Valores de Referencia , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Volumen Sistólico , Factor de Necrosis Tumoral alfa/análisisRESUMEN
OBJECTIVE: The association between cytokines and troponin-I with cardiac function after cardiac surgery with cardiopulmonary bypass remains a topic of continued investigation. METHODS: Serial measurements, within 24h following surgery, of tumor necrosis factor-alpha, its soluble receptors, and troponin-I were performed in patients with normal ejection fraction undergoing coronary artery bypass grafting. Ejection fraction was measured by radioisotopic ventriculography preoperatively, at 24h and at day 7 postoperatively. RESULTS: Of 19 patients studied (59+/-8.5 years), 10 (group 1) showed no changes in ejection fraction, 53+/-8% to 55+/-7%, and 9 (group 2) had a decrease in ejection fraction, 60+/-11% to 47+/-11% (p=0.015) before and 24h after coronary artery bypass grafting, respectively. All immunological variables, except tumor necrosis factor-alpha soluble receptor I at 3h postoperation (5.5+/- 0.5 in group 1 versus 5.9+/-0.2 pg/ml in group 2; p=0.048), were similar between groups. Postoperative troponin-I had an inverse correlation with ejection fraction at 24h (r= -0.44). CONCLUSIONS: Inflammatory activity, assessed based on tumor necrosis factor-alpha and its receptors, appears to play a minor role in cardiac dysfunction after cardiac surgery. Troponin I levels are inversely associated with early postoperative ejection fraction.
Asunto(s)
Citocinas/sangre , Circulación Extracorporea , Revascularización Miocárdica , Complicaciones Posoperatorias/sangre , Troponina I/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Biomarcadores/sangre , Circulación Extracorporea/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Receptores del Factor de Necrosis Tumoral/sangre , Volumen Sistólico , Disfunción Ventricular/sangre , Disfunción Ventricular/diagnósticoRESUMEN
OBJECTIVE: To compare circulating plasma levels of immunoinflammatory markers in patients with known de novo coronary artery disease and patients with postangioplasty restenosis. METHODS: Using enzymatic immunoabsorbent assay, we measured plasma levels of soluble interleukin-2 receptosr, tumor necrosis factor alpha, and soluble tumor necrosis alpha receptors I and II in 11 patients with restenosis postcoronary angioplasty (restenosis group), in 10 patients with primary atherosclerosis (de novo group) who were referred for coronary angiography because of stable or unstable angina, and in 9 healthy volunteers (control group). Levels of soluble interleukin-2 receptors were significantly higher in the de novo group compared with that in the restenosis and control groups. Levels were also higher in the restenosis group compared with that in the control group. Plasma levels of tumor necrosis alpha and receptor levels were significantly higher in the de novo group compared to with that in the restenosis and control groups, but levels in the restenosis group were not different from that in the controls. CONCLUSION: Coronary artery disease, either primary or secondary to restenosis, is associated with significant immunoinflammatory activity, which can be assessed by examining the extent of circulating plasma levels of inflammatory markers. Moreover, patients with de novo lesions appear to have increased inflammatory activity compared with patients with restenosis.
Asunto(s)
Angioplastia de Balón , Enfermedad de la Arteria Coronaria/sangre , Receptores de Interleucina-2/sangre , Factor de Necrosis Tumoral alfa/análisis , Análisis de Varianza , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad Coronaria/sangre , Femenino , Humanos , Masculino , Recurrencia , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: Endothelial markers endothelin 1 (ET-1) and von Willebrand factor (vWF) were assessed in patients with type 2 diabetes and dyslipidemia and in patients with hypercholesterolemia. RESEARCH DESIGN AND METHODS: In this case-control study, plasma ET-and vWF levels were measured by enzyme-linked immunosorbent assay in 35 normoalbuminuric type 2 diabetic patients with dyslipidemia (56+/-5 years), in 21 nondiabetic patients with hypercholesterolemia (52+/-7 years), and in 19 healthy control subjects (45+/-4 years). All of the individuals were normotensive and nonsmokers. Urinary albumin was measured by immunoturbidimetry. RESULTS: ET-1 levels were higher (P<0.0001) in type 2 diabetic dyslipidemic patients (1.62+/-0.73 pg/ml) than in both nondiabetic hypercholesterolemic patients (0.91+/-0.73 pg/ml) and control subjects (0.69+/-0.25 pg/ml). vWF levels were significantly increased (P = 0.02) in type 2 diabetic (185.49+/-72.1%) and hypercholesterolemic (163.29+/-50.7%) patients compared with control subjects (129.70+/-35.2%). In the multiple linear regression analysis. ET-1 was significantly associated (adjusted r2 = 0.42) with serum triglyceride levels (P<0.001), age (P<0.01), insulin sensitivity index (P<0.02), and albuminuria levels (P<0.04). vWF levels were associated (adjusted r2 = 0.22) with albuminuria (P<0.001), fibrinogen levels (P<0.02), and BMI (P<0.03). CONCLUSIONS: Compared with hypercholesterolemic patients, type 2 diabetic patients with dyslipidemia have increased levels of ET-1 and vWF which may indicate more pronounced endothelial injury. These findings appear to be related to components of the insulin resistance syndrome.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Endotelina-1/sangre , Hipercolesterolemia/sangre , Hiperlipidemias/sangre , Factor de von Willebrand/análisis , Albuminuria , Presión Sanguínea , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/orina , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Hiperlipidemias/complicaciones , Lipoproteínas/sangre , Masculino , Persona de Mediana Edad , Valores de Referencia , Triglicéridos/sangreRESUMEN
OBJECTIVES: To determine the predictive value of early determination of tumor necrosis factor (TNF)-alpha, TNF-alpha 1 and 2 soluble receptors (sTNFR1 and sTNFR2) and endothelin-1 (ET-1) for mortality in patients with septic shock. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: Twenty-one patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients with septic shock had a pulmonary artery catheter inserted and blood samples drawn at time zero, 6, 12 and 24 h, simultaneously with hemodynamic assessments. Plasma levels of all markers were measured by ELISA. All patients were followed up to hospital discharge or death. Age and APACHE II scores were significantly higher in nonsurvivors (n = 11) than in survivors (n = 10). Hemodynamic assessments did not aid in the discrimination between the two groups of patients (P > 0.05). Levels of TNF-alpha were higher in nonsurvivors than in survivors at all time-points. sTNFR1 and sTNFR2 were also significantly elevated in nonsurvivors, but not in all measurements. Endothelin-1, however, was significantly higher in nonsurvivors than in survivors only at 6 h (P = 0.02). When both TNF-alpha and ET-1 were increased at early time-points, the best predictive values for mortality were obtained [positive and negative predictive values of 72 and 100% at 6 h, odds ratio 3.0, 95% CI (1.2-7.6)]. CONCLUSIONS: Increased levels of TNF-alpha were consistently higher at all time-points in nonsurvivors with septic shock. ET-1 levels, however, appeared also to be an early and sensitive predictor of mortality. Very early determination of TNF-alpha and ET-1 in septic shock may help to identify patients at higher risk for adverse outcome.
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Endotelina-1/sangre , Choque Séptico/sangre , Choque Séptico/mortalidad , Factor de Necrosis Tumoral alfa/metabolismo , APACHE , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/sangre , Enfermedad Crítica , Ensayo de Inmunoadsorción Enzimática , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Receptores del Factor de Necrosis Tumoral/sangre , Receptores Tipo I de Factores de Necrosis Tumoral , Receptores Tipo II del Factor de Necrosis TumoralAsunto(s)
Enfermedad Coronaria/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/epidemiología , Neuropatías Diabéticas/epidemiología , Enfermedades del Sistema Nervioso Autónomo/complicaciones , Brasil/epidemiología , Estudios de Casos y Controles , Enfermedad Coronaria/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Caracteres SexualesRESUMEN
AIMS: To assess plasma levels of vascular cellular adhesion molecule-1, a marker of endothelial dysfunction, in patients presenting with coronary syndromes submitted to coronary angiography. METHODS AND RESULTS: Plasma levels of soluble vascular cellular adhesion molecule-1 were measured by enzymatic immunoabsorbent assay in eight patients with angina-like chest pain and angiographically normal coronary arteries; in 14 patients with stable angina and in 18 patients with unstable angina, both with coronary lesions by angiography, and in 10 healthy volunteers. Levels of soluble vascular cellular adhesion molecule-1 were higher in unstable angina patients (1777+/-161 SE pg ml(-1)) compared to patients with stable angina (1178+/-206 SE pg ml(-1), P<0.05). Moreover, patients with angina-like chest pain and normal coronary arteries had significantly higher soluble vascular cellular adhesion molecule-1 levels (2307+/-295 SE pg ml(-1)) compared to stable angina patients (P<0.05), but similar levels compared to unstable angina patients. Patient groups had higher values of soluble vascular cellular adhesion molecule-1 compared to the control group (734+/-97 SE pg ml(-1)). CONCLUSIONS: Increased levels of soluble vascular cellular adhesion molecule-1 are associated with coronary artery disease in patients with anatomically established lesions. In patients free of flow-limiting lesions and angina-like chest pain, high levels of this marker may indicate endothelial dysfunction.
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Dolor en el Pecho/sangre , Angiografía Coronaria , Molécula 1 de Adhesión Celular Vascular/sangre , Angina de Pecho/sangre , Angina Inestable/sangre , Biomarcadores/sangre , Dolor en el Pecho/diagnóstico por imagen , Endotelio Vascular/fisiología , Femenino , Humanos , Técnicas de Inmunoadsorción , Masculino , Persona de Mediana EdadAsunto(s)
Trasplante de Corazón , Complicaciones Posoperatorias , Infecciones Bacterianas/etiología , Infecciones Bacterianas/prevención & control , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/terapia , Trasplante de Corazón/inmunología , Humanos , Cuidados Posoperatorios , Complicaciones Posoperatorias/microbiología , Complicaciones Posoperatorias/prevención & control , Infección de la Herida QuirúrgicaRESUMEN
Large vessel disease, a common feature of diabetes mellitus, appears to run an aggressive course, but its cellular and molecular aspects remain partially elucidated. Although in common atherosclerosis and especially in other forms of accelerated vasculopathy, immunoinflammatory mechanisms participate in the disease process, it is unclear whether this is present in diabetic vasculopathy. We hypothesized that diabetic macrovasculopathy, compared with classical atherosclerosis, is associated with increased immunoinflammatory features and matrix accumulation. In this study, vessel segments obtained after lower-limb amputation for advanced atherosclerotic disease, from type 2 diabetic patients (n = 20; 68.9+/-10.9 years) and nondiabetic patients (n = 16; 67.1+/-14.6 years) were analyzed. Histological characteristics (extent of intimal proliferation, cellularity, and fibrosis) were semiquantitatively graded in the two lesion types. Using immunohistochemistry, the presence of T cells and macrophages, accumulation of fibronectin, and expression of tumor necrosis factor-alpha was also assessed. Histological features of these advanced atherosclerotic lesions were similar in the two lesions examined. By immunohistochemistry, a similar pattern of T-cell and macrophage infiltration and fibronectin accumulation was observed. Nevertheless, increased expression of tumor necrosis factor-alpha was observed in diabetic lesions (13/19 patients had positive staining), whereas only 2 of 16 lesions from nondiabetic patients had positive staining (p < 0.003), with an odds ratio of 15.17 (confidence interval 2.12-139.5). These data suggest that increased expression of tumor necrosis factor-alpha observed in the diabetic lesions may reflect an enhanced inflammatory activity associated with the development of vascular lesions in type 2 diabetic patients.
Asunto(s)
Angiopatías Diabéticas/metabolismo , Arteria Femoral/metabolismo , Arterias Tibiales/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Anciano , Amputación Quirúrgica , Arteriosclerosis/metabolismo , Arteriosclerosis/patología , Biomarcadores , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/patología , Femenino , Arteria Femoral/patología , Fibronectinas/metabolismo , Humanos , Técnicas para Inmunoenzimas , Macrófagos/patología , Masculino , Estudios Prospectivos , Linfocitos T/patología , Arterias Tibiales/patologíaRESUMEN
The lesions of cardiac allograft vasculopathy are thought to be strongly related to an immune inflammatory process. Little is known about the biology of these eccentric lesions. However, transplant patients may present with focal disease. Coronary atherectomy provides a unique opportunity to study these clinically relevant lesions in surviving transplant patients. In this series we characterized the features of four lesions (two restenotic and two primary) from three cardiac transplant recipients who underwent coronary atherectomy. The histologic characteristics of the lesions were analyzed and immunohistochemistry was used to assess qualitatively the presence of specific markers of inflammation and the extracellular matrix component fibronectin. Histology showed cholesterol clefts, calcium deposits, and foam cells with low to moderate cellularity and moderate to high fibrosis. Interleukin (IL)-1ß was present in two lesions, but tumor necrosis factor (TNF)-α was absent. The adhesion molecules intercellular adhesion molecule (ICAM)-1 and vascular cellular adhesion molecule (VCAM)-1 and the integrins α5ß1 and α4 were present in all lesions. There was mild to moderate accumulation of fibronectin. Thus, atheroscleroticlike features were present with only low to moderate degrees of immune inflammation. Our findings suggest that eccentric focal plaques in cardiac allograft vasculopathy are less likely to be primarily related to a prominent immune inflammatory process and are similar to atherosclerosis. We speculate that these eccentric lesions that resemble atherosclerosis may be more related to the conventional risk factors for coronary artery disease frequently seen in this population.