RESUMEN
To evaluate relationships between lipid-lowering therapy, inflammation, and 3-year mortality in critical limb ischemia (CLI), 259 consecutive CLI patients underwent evaluation of medication, tumor necrosis factor-alpha, interleukin-6 (IL-6), neopterin, high-sensitivity C-reactive protein (hs-CRP), 8-epi-PGF(2 alpha), and endothelin-1. Mortality was assessed after 3 years. Sixty-one patients (24%) were on lipid-lowering therapy and 59 patients (97%) on statins. Patients on lipid-lowering therapy were younger and showed lower low-density lipoprotein cholesterol, hs-CRP, and IL-6 levels than patients without therapy. Three-year survival was higher among patients on lipid-lowering therapy. In logistic regression, the effect of lipid-lowering therapy on 3-year survival was significant with inflammatory markers entered into the model one by one but disappeared when all inflammatory markers were entered into the model together. In conclusion, hs-CRP and IL-6 levels were lower and 3-year survival was higher in CLI patients on lipid-lowering therapy.
Asunto(s)
Hipolipemiantes/uso terapéutico , Inflamación/sangre , Isquemia/mortalidad , Factores de Edad , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/tratamiento farmacológico , Interleucina-6/sangre , Isquemia/sangre , Modelos Logísticos , Masculino , Factores Sexuales , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Increased thrombin activation was documented in patients with abdominal aortic aneurysm (AAA). Activated protein C-protein C inhibitor (APC-PCI) complex, a new biological marker of thrombin generation, was measured in a population of 232 patients with AAA and a control group, and the association between aneurysm size, growth rate, and APC-PCI was studied. The patients were divided into cohorts according to AAA diameter and compared with a control group. APC-PCI was significantly higher in all AAA cohorts (n = 232; median, 0.36 microg/L; 10th to 90th percentile, 0.18-1.01) compared with the control group (n = 41; median, 0.19 microg/L; 10th to 90th percentile, 0.11-0.31; P < or = .001). APC-PCI correlated with AAA diameter (r = .22; P = .001), body mass index (r = -.19; P = .004), and age (r = .19; P = .004). APC-PCI did not correlate with AAA growth rate (r = .11; P = .14).
Asunto(s)
Aneurisma de la Aorta Abdominal/sangre , Coagulación Sanguínea , Inhibidor de Proteína C/sangre , Proteína C/metabolismo , Trombina/metabolismo , Factores de Edad , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/cirugía , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To examine prospectively whether inflammatory biomarkers and endothelin (ET)-1 are increased in patients with renal artery stenosis (RAS), and to investigate how treatment with percutaneous transluminal renal angioplasty (PTRA) affects these variables during the first month after intervention. METHODS: One hundred patients with suspected RAS undergoing renal angiography were included. PTRA was performed if the trans-stenotic mean arterial pressure gradient was>or=10 mmHg. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFalpha), neopterin, CD40 ligand (CD40L) and endothelin-1 (ET-1) were measured before, and 1 day and 1 month after PTRA (n=61) or diagnostic angiography only (n=39). RESULTS: At baseline there were no significant differences in inflammatory biomarkers or ET-1 levels between patients subsequently undergoing PTRA or angiography only. After angiography, IL-6 and hs-CRP had increased in both groups compared to baseline (P<0.001). At this time point hs-CRP (10.90+/-1.48 versus 6.37+/-1.61 mg/l; P<0.05) and IL-6 (13.70+/-0.94 versus 13.00+/-0.17 pg/ml; P<0.01) were higher in the PTRA group than in patients subjected to angiography only. One month after PTRA, systolic blood pressure and levels of IL-6 and ET-1 were lower than before intervention (P<0.05), whereas CD40L had increased compared to baseline (P<0.01). CONCLUSION: In patients with RAS, PTRA triggers rapid transient increases in hs-CRP and IL-6; however, 1 month after PTRA, both IL-6 and ET-1 had decreased compared to before intervention, indicating beneficial effects of PTRA on inflammation and the endothelin system.
Asunto(s)
Angioplastia , Biomarcadores/sangre , Endotelina-1/sangre , Inflamación/metabolismo , Interleucina-6/sangre , Riñón/irrigación sanguínea , Anciano , Angioplastia/métodos , Presión Sanguínea , Femenino , Humanos , Riñón/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: The aim of the present study was to evaluate weather early supervised exercise improves recanalization of acute deep vein thrombosis (DVT) and reduces symptoms. PATIENTS AND METHODS: From September 2001 to March 2004, of 381 patients, 72 eligible patients were included and with a mean age 54 +/- 14 years, 39 (52%) men with deep vein thrombosis (DVT) proven with phlebography were randomized to: an exercise group (n = 36) receiving routine anticoagulation, class II compression stockings and additionally supervised exercise and a control group (n = 36) receiving the same therapy but no exercise. Patients were followed-up during six months. Phlebography was scored initially and at six-months. RESULTS: There were at inclusion no differences between the two groups regarding age, body weight, body mass index (BMI), calf circumference of the affected leg, and overall quality of life estimated by visual analog scale (VAS)-scale. In both groups there were significant reductions regarding calf circumference in the affected leg compared to the inclusion time, both at one-month (P = 0.0012) and six month (P = 0.0002) follow-up. The degree of recanalization of the affected venous segments was high and did not differ between groups. There were no recurrent DVT or pulmonary emboli or other treatment complications in any individual during the six-month follow-up period. CONCLUSIONS: Early exercise did not acutely exacerbate the risk of complications in patients with DVT. No benefits of early exercise were seen regarding the degree of recanalization of the thrombi, or faster resolution of pain or swelling. Nevertheless, our study shows that early exercise/ambulation is safe in combination with anticoagulation and compression stockings for the majority of patients with DVT.
Asunto(s)
Ambulación Precoz , Terapia por Ejercicio , Trombosis de la Vena/terapia , Adulto , Anciano , Atención Ambulatoria , Anticoagulantes/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor , Flebografía , Calidad de Vida , Medias de Compresión , Resultado del TratamientoRESUMEN
Patients with critical limb ischemia (CLI) have a high frequency of concomitant coronary heart disease and congestive heart failure. The aim of the study was to evaluate cardiac function in relation to inflammatory markers and 1-year mortality rate among patients with CLI. The authors investigated 232 consecutive patients with CLI by means of electrocardiogram (ECG), and measurements of endothelin (ET)-1, tumor necrosis factor alpha (TNF)alpha, interleukin (IL)-6, neopterin, CD40 ligand, and 8-epi-prostaglandin (PG)F2alpha in plasma. Echocardiography (echo) was performed in 88 (38%) patients. One-year mortality rate was assessed after prospective follow-up. One hundred and eighty-six (80%) patients had sinus rhythm (SR), 36 (16%) had atrial fibrillation or flutter (AF), and 10 (4%) pacemaker rhythm. Ischemic ECG changes occurred in 143 (62%) patients. Patients with AF showed higher IL-6 (p = 0.0296) and neopterin (p = 0.0494) concentrations. Patients with ischemic ECG changes showed higher ET-1 (p = 0.0303), 8-epi-PGF2alpha (p = 0.0027), neopterin (p = 0.0004) concentrations and 1-year mortality rate (p = 0.0105). The difference in ET-1 remained in logistic regression (p = 0.0152). Internal diameter of the left ventricle on echo correlated with IL-6 (r = 0.345, p = 0.0017), TNFalpha (r = 0.240, p = 0.0273), and neopterin (r = 0.327, p = 0.0028). Internal diameter of the left atrium correlated with TNFalpha (r = 0.384, p = 0.0092) and neopterin (r = 0.526, p = 0.0004), and ejection fraction (EF) correlated inversely with IL-6 (r = -0.380, p = 0.0015) and neopterin (r = -0.346, p = 0.0038). Patients with EF <40% showed higher (p = 0.0462) 1-year mortality rate than patients with EF >40%. In conclusion, in critical limb ischemia, cardiac rhythm disturbances and ischemic ECG changes were related to inflammatory mediators and predicted 1-year mortality rate. The inflammatory mediators correlated with echocardiographic signs of congestive heart failure.
Asunto(s)
Extremidades/irrigación sanguínea , Insuficiencia Cardíaca/fisiopatología , Mediadores de Inflamación/sangre , Isquemia/mortalidad , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas/sangre , Arritmias Cardíacas/mortalidad , Arritmias Cardíacas/fisiopatología , Ecocardiografía , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Humanos , Interleucina-6/sangre , Isquemia/sangre , Isquemia/fisiopatología , Masculino , Isquemia Miocárdica/sangre , Isquemia Miocárdica/mortalidad , Isquemia Miocárdica/fisiopatología , Neopterin/sangre , Estudios Prospectivos , Tasa de Supervivencia , Factor de Necrosis Tumoral alfa/metabolismo , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: The concentration of the complex between activated protein C (APC) and protein C inhibitor (PCI) is a measure of thrombin generation. We studied whether it can provide information useful for the diagnosis and treatment of arterial vascular disease. METHODS: Blood was obtained from 429 vascular patients admitted consecutively during September 2004 to March 2005. The APC-PCI complex was measured by using a sandwich immunofluorometric method. The patients were divided into cohorts according to the planned treatment and compared with a control group of healthy individuals. RESULTS: The APC-PCI complex concentration varied from 0.08 to 2.50 microg/L. In the cohort of patients with aortic aneurysms (n = 78), the median APC-PCI value was 0.45 (10th to 90th percentile, 0.24-1.47), and values were clearly increased compared with all other cohorts (P < .0001). Patients with carotid disease (n = 73) yielded a median of 0.22 (10th to 90th percentile, 0.15-0.48). The median for claudicants (n = 74) was 0.26 microg/L (10th to 90th percentile, 0.15-0.75), which was higher than in those (n = 97) with critical ischemia (0.20; 10th to 90th percentile, 0.13-0.36; P < .0023). The cohort with other forms of atherosclerotic disease (n = 40) had a median of 0.23 (10th to 90th percentile, 0.14-0.42), whereas the value for a cohort of 21 patients with venous disease was 0.19 (10th to 90th percentile, 0.10-0.34). The median was 0.15 (10th to 90th percentile, 0.10-0.23) for the control group (n = 121). CONCLUSIONS: Patients with atherosclerosis had an increased APC-PCI concentration that corresponded to increased generation of thrombin. Patients with aortic aneurysm had a threefold higher median concentration than the control group. We suggest that this remarkable increase is caused by the local activation of coagulation, and we surmise that APC-PCI measurements can be used as a screening tool to identify patients with aortic aneurysms.
Asunto(s)
Aneurisma de la Aorta Abdominal/diagnóstico , Inhibidor de Proteína C/sangre , Proteína C/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/sangre , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Biomarcadores/sangre , Estenosis Carotídea/sangre , Estenosis Carotídea/diagnóstico , Estudios de Cohortes , Activación Enzimática , Femenino , Humanos , Claudicación Intermitente/sangre , Claudicación Intermitente/diagnóstico , Isquemia/sangre , Isquemia/diagnóstico , Pierna/irrigación sanguínea , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Valores de Referencia , Estadística como Asunto , Trombina/metabolismoAsunto(s)
Enfermedades Cardiovasculares , Manejo de la Enfermedad , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/cirugía , Enfermedades Cardiovasculares/terapia , Humanos , Isquemia/diagnóstico , Isquemia/cirugía , Isquemia/terapia , Pierna/irrigación sanguínea , Admisión del Paciente , Pautas de la Práctica en Medicina , Atención Primaria de Salud , Derivación y Consulta , Procedimientos Quirúrgicos Vasculares/métodosRESUMEN
OBJECTIVE: The atherosclerotic process has inflammatory features. Patients with peripheral atherosclerosis and critical limb ischemia have a poor prognosis. This study evaluated the hypothesis that inflammatory markers are associated with mortality among patients admitted to the hospital because of critical limb ischemia. METHODS: This was a prospective, single-center, 1-year, follow-up study of 259 consecutive patients with critical limb ischemia who were admitted to a secondary referral center of vascular diseases. Interventions included evaluation of intercurrent disease, ankle and arm blood pressures, plasma glucose and lipid levels, plasma homocysteine, cardiolipin antibodies, resistance to activated protein C, plasma endothelin-1, and the inflammatory mediators tumor necrosis factor-alpha, interleukin-6, neopterin, high-sensitivity C-reactive protein, CD40 ligand, and 8-iso-prostaglandin F alpha in plasma. The main outcome measure was total mortality and causes of death assessed 1 year after admission. RESULTS: During the first year after admission, 61 patients (24%) died. These patients were older (P < .0001), showed a higher leukocyte count (P = .0011) and levels of serum creatinine (P < .0001), lower levels of high-density lipoprotein (HDL) cholesterol (P = .003) and frequency of active treatment (P = .014) than the 198 (76%) survivors. More nonsurvivors had gangrene (P < .0001), and fewer (P = .004) had lipid-lowering treatment. The plasma levels of interleukin-6 (P < .0001), tumor necrosis factor-alpha (P < .0001), neopterin (P < .0001), and high-sensitivity C-reactive protein (P = .002) at admission for critical limb ischemia were all significantly lower in the survivors, whereas there was no difference concerning CD40 ligand. In logistic regression adjusted for age, sex, lipid-lowering therapy, active treatment, gangrene, leukocyte count, creatinine, and serum HDL cholesterol, the inflammatory mediators tumor necrosis factor-alpha (P = .0084), neopterin (P = .0035), but not interleukin-6 (P = .585) or high-sensitivity C-reactive protein (P = .314) were independent risk variables of death within 1 year. CONCLUSIONS: Increased age, leukocyte count, creatinine, and inflammatory mediators, together with gangrene, were associated with 1-year mortality despite intervention in critical limb ischemia. For tumor necrosis factor-alpha and neopterin in plasma, this association was independent of the other parameters.
Asunto(s)
Mediadores de Inflamación/sangre , Isquemia/mortalidad , Isquemia/fisiopatología , Pierna/irrigación sanguínea , Anciano , HDL-Colesterol/sangre , Creatinina/sangre , Femenino , Humanos , Recuento de Leucocitos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neopterin/sangre , Pronóstico , Estudios Prospectivos , Factor de Necrosis Tumoral alfa/análisisRESUMEN
INTRODUCTION: Aspirin is a common antiplatelet drug used in the prevention of ischemic stroke due to its inhibitory effect on platelet cyclooxygenase-1 (Cox-1). Patients can be categorized as either aspirin 'responders' or 'non-responders' depending on whether they are protected against a secondary stroke event or not. In this study, we have searched for variants of the Cox-1 gene that could possibly result in an unblocked and thus, aspirin-resistant Cox-1 enzyme and phenotype. MATERIALS AND METHODS: The Cox-1 gene was sequenced in 68 patients with recurrent ischemic stroke despite taking aspirin. The genotype distribution of identified variants was determined and compared with healthy control subjects. Mutations that involved amino acid substitutions of the mature Cox-1 molecule were analysed by molecular modelling and functional analysis using whole blood aggregometry. RESULTS: Fourteen variants of the Cox-1 gene were identified. Seven of the variants involved amino acid substitutions of the Cox-1 molecule. None of the mutations were located near the catalytic site as judged from a three-dimensional model of the human Cox-1. Carriers and non-carriers of one of the mutations behaved similarly when aggregation and granule content release function were studied using collagen, ADP and arachidonic acid as agonists. CONCLUSION: The results do not support the hypothesis that common variants of the Cox-1 gene results in unblocked Cox-1 molecules in aspirin non-responders.
Asunto(s)
Aspirina/farmacología , Resistencia a Medicamentos/genética , Isoenzimas/genética , Mutación Missense , Prostaglandina-Endoperóxido Sintasas/genética , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/genética , Anciano , Anciano de 80 o más Años , Ácido Araquidónico/farmacología , Estudios de Casos y Controles , Ciclooxigenasa 1 , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Humanos , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Modelos Moleculares , Farmacogenética , Agregación Plaquetaria/efectos de los fármacos , Recurrencia , Accidente Cerebrovascular/etiologíaRESUMEN
All 74 patients treated with vena cava filter insertion during 1991-2000 at Malmö University Hospital were reviewed. Thirty-nine patients (53%) died during follow-up. Indications for permanent filter insertion (n = 63, age 25-89 years, 35 men) were contraindication for or side effects of anticoagulant treatment, or pulmonary embolism during anticoagulant treatment. Temporary vena cava filters (n = 11, age 19-85 years, three men) were inserted during surgery or thrombolysis. No complications occurred during temporary filter insertion. During 33 (1-120) months of follow-up of patients with permanent vena cava filters 37 patients (59%) died, thrombosis of the inferior vena cava occurred in 14 patients (22%), and recurrent pulmonary embolism in five patients (8%). Vena cava filter insertion should be considered as an alternative treatment in a selected group of patients with contraindications to or insufficient effect of anticoagulant treatment.