RESUMEN
We examined whether resting levels and exercise-induced changes during exercise ECG stress test (EST) of cardiac Troponin T (cTnT), NT-proBNP and prothrombotic markers were affected by revascularization in patients with coronary artery disease (CAD).EST1 was performed before coronary angiography and revascularization, and patients (n = 20) with confirmed CAD, performed another EST (EST2) 9 weeks later. Blood samples were drawn at rest and within five min after termination of ESTs.cTnT and NT-proBNP increased during exercise at both ESTs (p < 0.001, all). Resting cTnT levels at EST2 versus EST1 were significantly higher (p = 0.02) whereas NT-proBNP did not differ. At both visits, increased D-dimer (p = 0.008 and <0.001), pro-thrombin fragment 1 + 2 (p = 0.009 and 0.001) and tissue factor pathway inhibitor (TFPI) (p < 0.001 and 0.001) during exercise were demonstrated. Resting levels of endogenous thrombin potential (ETP) and TFPI were reduced at EST2 versus EST1 (p < 0.01).Revascularization did not affect exercise-induced release of cardiac and prothrombotic biomarkers and did not reduce resting levels of cTnT or NT-proBNP, suggesting revascularization per se not to prevent secretion of biomarkers. The lower resting levels of ETP and TFPI after revascularization may however, be indicative of reduced thrombin generation and endothelial activation.Clinicaltrials.gov, CADENCE, NCT01495091 https://clinicaltrials.gov/ct2/show/NCT01495091?term = 01495091&draw = 2&rank = 1.
Asunto(s)
Enfermedad de la Arteria Coronaria , Biomarcadores , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/cirugía , Humanos , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Trombina , Troponina TRESUMEN
This most comprehensive analysis to date of γδ T cells in the murine uterus reveals them to compose a unique local T-cell compartment. Consistent with earlier reports, most cells expressed a canonical Vγ6Vδ1 TCR, and produced interleukin (IL)-17A upon stimulation. Nonetheless, contrasting with earlier reports, uterine γδ T cells were not obviously intraepithelial, being more akin to sub-epithelial Vγ6Vδ1+ T cells at several other anatomical sites. By contrast to other tissues however, the uterine compartment also included non-Vγ6+, IFN-γ-producing cells; was strikingly enriched in young mice; expressed genes hitherto associated with the uterus, including the progesterone receptor; and did not require microbes for development and/or maintenance. This notwithstanding, γδ T-cell deficiency severely impaired resistance to reproductive tract infection by Candida albicans, associated with decreased responses of IL-17-dependent neutrophils. These findings emphasise tissue-specific complexities of different mucosal γδ cell compartments, and their evident importance in lymphoid stress-surveillance against barrier infection.
Asunto(s)
Candida albicans/fisiología , Candidiasis/inmunología , Neutrófilos/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Linfocitos T/inmunología , Útero/inmunología , Vagina/inmunología , Animales , Resistencia a la Enfermedad , Femenino , Humanos , Interferón gamma/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Vagina/microbiologíaRESUMEN
OBJECTIVE: Marine polyunsaturated n-3 fatty acids (n-3 PUFA) may have cardioprotective effects and beneficial influence on the fibrotic process. We evaluated the associations between serum marine n-3 PUFA and selected biomarkers of fibrosis and cardiac remodeling in elderly patients with acute myocardial infarction. SETTING: From the ongoing OMega-3 fatty acids in Elderly patients with Myocardial Infarction (OMEMI) trial, 299 patients were investigated. Soluble ST2 (sST2), Galectin-3 (Gal-3) and the serum content of major marine n-3 and n-6 PUFA were analyzed 2-8 weeks after the index acute myocardial infarction. RESULTS: Gal-3 was inversely correlated to eicosapentaenoic acid (r = -.120, p = .039) and docosahexaenoic acid (r = -.125, p = .031) and positively correlated to the n-6/n-3 ratio (r = .131, p = .023). Gal-3 levels were significantly higher in diabetics vs non-diabetics (12.00 vs 9.61 ng/mL, p = .007) and in patients with NYHA class ≥III for dyspnea at inclusion (11.33 vs 9.75 ng/mL, p = .006). CONCLUSIONS: The associations between the marine n-3 PUFA and levels of Gal-3 indicate beneficial effects of n-3 PUFA on cardiac remodeling in an elderly population with acute myocardial infarction.
RESUMEN
RATIONALE: The heterodimer IL-12 is an inducer of Th1 responses and stimulates INFÆ´ production. Micro-RNA-21 (miR-21) is described as a key regulator of the pro-inflammatory response and has IL-12p35 mRNA as one of its main targets. The IL-12p40 1188A/C genetic variant located in 3'untranslated region (UTR), thus environmentally exposed, has further been reported to modify IL-12 levels. We have previously reported on the lowering effect of cigarette smoke on circulating IL-12 in patients with coronary artery disease (CAD). OBJECTIVES: To explore if cigarette smoking affects IL-12p35, IL-12p40, INFÆ´ and miR-21 gene-expression and further modulates any effect of the IL-12p40 polymorphism on circulating IL-12 levels. METHODS AND RESULTS: The IL-12p40 1188A/C polymorphism was analyzed in 1001 stable CAD patients, of which 330 subjects were included for IL-12p35, IL-12p40 and INFÆ´ gene-expression analyses in circulating leukocytes and 200 were further selected for plasma miR-21 analysis. Smoking associated with lower expression of miR-21 and its target IL-12p35 mRNA (adjusted p<0.05, both) whereas the influence on INFÆ´ expression tended to be high-dose reliant (p = 0.057). The IL-12p40 CC genotype associated with elevated circulating IL-12 levels, however, when stratified according to smoking, only in the non-smoking group (adjusted p < 0.05). Although the markers were mainly downregulated in current smokers, their inter-correlations were potentiated. CONCLUSION: Smoking associated with reduced miR-21 gene-repression and the results can therefore not explain the previously observed reduction in circulating IL-12. Smoking attenuated the IL-12 pro-inflammatory axis in which the investigated IL-12p40 genetic variant may have different clinical impact in smokers vs non-smokers.
Asunto(s)
Fumar Cigarrillos , Enfermedad de la Arteria Coronaria/etiología , Regulación de la Expresión Génica , Interleucina-12/genética , MicroARNs/genética , Adulto , Anciano , Biomarcadores , Fumar Cigarrillos/efectos adversos , Enfermedad de la Arteria Coronaria/metabolismo , Citocinas/genética , Citocinas/metabolismo , Femenino , Genotipo , Humanos , Interleucina-12/metabolismo , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
INTRODUCTION: Platelet activation, thrombin generation and fibrin formation play important roles in intracoronary thrombus formation, which may lead to acute myocardial infarction. We investigated whether the prothrombotic markers D-dimer, pro-thrombin fragment 1 + 2 (F1 + 2) and endogenous thrombin potential (ETP) are associated with myocardial necrosis assessed by Troponin T (TnT), and left ventricular impairment assessed by left ventricular ejection fraction (LVEF) and N-terminal pro b-type natriuretic peptide (NT-proBNP). MATERIALS/METHODS: Patients (n = 987) with ST-elevation mycardial infarction (STEMI) were included. Blood samples were drawn at a median time of 24 h after onset of symptoms. RESULTS: Statistically significant correlations were found between both peak TnT and D-dimer (p < 0.001) and F1 + 2 (p < 0.001), and between NT-proBNP and D-dimer (p = 0.001) and F1 + 2 (p < 0.001). When dividing TnT and NT-proBNP levels into quartiles there were significant trends for increased levels of both markers across quartiles (all p < 0.001) D-dimer remained significantly associated with NT-proBNP after adjustments for covariates (p = 0.001) whereas the association between NTproBNP and F1 + 2 was no longer statistically significant (p = 0.324). A significant inverse correlation was found between LVEF and D-dimer (p < 0.001) and F1 + 2 (p = 0.013). When dichotomizing LVEF levels at 40 %, we observed significantly higher levels of both D-dimer (p < 0.001) and F1 + 2 (p = 0.016) in the group with low EF (n = 147). SUMMARY/CONCLUSION: In our cohort of STEMI patients we demonstrated that levels of D-dimer and F1 + 2 were significantly associated with myocardial necrosis as assessed by peak TnT. High levels of these coagulation markers in patients with low LVEF and high NTproBNP may indicate a hypercoagulable state in patients with impaired myocardial function.
RESUMEN
Although aspirin is effective in secondary prevention in coronary heart disease, new thromboembolic events in patients on aspirin are frequently seen. In trials on aspirin-treated patients, platelet function tests have revealed large variability in platelet aggregation. This phenomenon has been named aspirin resistance, aspirin non-responsiveness or high-on-aspirin residual platelet reactivity. The mechanism of aspirin antiplatelet effect is due to the inhibition of cyclooxygenase-1 enzyme in platelets. In some trials, almost all patients on aspirin have a very low level of serum thromboxane B2, indicating that the measured platelet reactivity in aspirin-treated patients might be due to platelet activation via other pathways, such as ADP or thrombin. The prevalence of real aspirin resistance seems to be very low, and probably the term "high-on-aspirin residual platelet reactivity" should be preferred to describe this phenomenon.
Asunto(s)
Aspirina/farmacología , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Animales , Aspirina/efectos adversos , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/prevención & control , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Humanos , Activación Plaquetaria/fisiología , Agregación Plaquetaria/fisiología , Inhibidores de Agregación Plaquetaria/efectos adversos , Pruebas de Función Plaquetaria/métodosRESUMEN
INTRODUCTION: Reports on the content of aspirated coronary thrombi have until now mainly focused on cellular components. We investigated the genetic expression of selected mediators and proteases actively involved in the pathophysiological process of acute myocardial infarction in aspirated coronary thrombi. MATERIALS AND METHODS: In this cross-sectional study, RNA from coronary thrombi in 67 subjects with acute myocardial infarction was isolated. Gene expression arrays of selected markers were performed by RT-PCR with relative quantification. RESULTS: Twenty of 22 markers were expressed in >50% of the samples. The relative quantification of P-selectin correlated negatively to total ischemic time (p=0.01), while genes related to fibrinolysis (t-PA, u-PA, PAI-1), inflammation (PTX3, CXCL9, MCP-1, IL18, TNFα) and plaque instability (MMP-2 and TIMP-1) correlated positively to total ischemic time (all<0.05). Long ischemic time (>4.0 hours) associated with a relative reduction in the expression of P-selectin and a relative increase in the expression of t-PA, u-PA, PAI-1, PTX3, CXCL9, MCP-1, IL-18, TNFα, MMP-2 and TIMP-1. The presence of type 2 diabetes associated with 3.2-fold increased PAI-1 expression (adjusted p=0.033), while the presence of hypertension associated with about 50% reduction of IL-8 and TIMP-1. Smoking and overweight did not affect any markers. CONCLUSIONS: The gene expression profile from coronary thrombi differed according to ischemic time, shown by reduced content of platelet markers and increased content of fibrinolytic, inflammatory and plaque instability mediators over time. Patients with type 2 diabetes showed increased expression of PAI-1, indicative of reduced fibrinolysis.
Asunto(s)
Trombosis Coronaria/genética , Infarto del Miocardio/genética , Enfermedad Aguda , Estudios de Cohortes , Trombosis Coronaria/complicaciones , Estudios Transversales , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatologíaRESUMEN
Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.
Asunto(s)
Anticoagulantes/administración & dosificación , Coagulación Sanguínea/efectos de los fármacos , Cardiología/normas , Cardiopatías/tratamiento farmacológico , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/tratamiento farmacológico , Anticoagulantes/efectos adversos , Fibrilación Atrial/sangre , Fibrilación Atrial/tratamiento farmacológico , Vías de Administración de Medicamentos , Cardiopatías/sangre , Cardiopatías/diagnóstico , Implantación de Prótesis de Válvulas Cardíacas/normas , Humanos , Intervención Coronaria Percutánea/normas , Resultado del TratamientoRESUMEN
Lifestyle modifications to reduce risk factors for cardiovascular diseases such as blood pressure (BP) and smoking have been emphasized. Fruits and vegetables may modify such risk factors. The major aim of this randomized, controlled trial was to investigate the effects of (1) kiwifruits and (2) an antioxidant-rich diet compared with (3) a control group on BP and platelet aggregation (that is, whole-blood platelet aggregation) after 8 weeks in male smokers (age 44-74 years, n=102). The kiwifruit group received 3 kiwifruits per day, whereas the antioxidant-rich diet group received a comprehensive combination of antioxidant-rich foods. In the kiwifruit group, reductions of 10 mm Hg in systolic BP and 9 mm Hg in diastolic BP were observed (P=0.019 and P=0.016 (change from baseline in the kiwifruit group compared with change from baseline in the control group)). In the antioxidant-rich diet group, a reduction of 10 mm Hg in systolic BP was observed among hypertensives (P=0.045). Additionally, a 15% reduction in platelet aggregation and an 11% reduction in angiotensin-converting enzyme activity was observed in the kiwifruit group (P=0.009 and P=0.034). No effects on these parameters were observed in the antioxidant-rich diet group. This study suggest that intake of kiwifruit may have beneficial effects on BP and platelet aggregation in male smokers.
Asunto(s)
Actinidia , Antioxidantes/farmacología , Presión Sanguínea/efectos de los fármacos , Frutas , Agregación Plaquetaria/efectos de los fármacos , Fumar/tratamiento farmacológico , Adulto , Anciano , Determinación de la Presión Sanguínea , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: Obese patients are at high risk of developing cardiovascular disease. Several studies suggest obesity as an independent risk factor. Adipose tissue is now accepted as an endocrine organ that produces and secretes a variety of cytokines, hormones and other metabolic players involved in the pathogenesis of atherosclerosis. Among this versatile group of mediators and effectors of inflammation and atherothrombosis, we have studied the expression of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor-1 (PAI-1), interleukin-18 (IL-18) and interleukin-6 (IL-6). All these markers, in their circulatory form, have been associated with cardiovascular disease. However, there is no much data available on their expression in adipose tissue in human subjects with and without cardiovascular disease. MATERIAL AND METHODS: We successfully isolated RNA from subcutaneous fat biopsies of 61 patients with or without cardiovascular disease. We then measured the RNA expression of MMP-9, TIMP-1, PAI-1, IL-18 and IL-6 with Real-Time PCR, using relative quantification. RESULTS: Albeit not statistically significant, all inflammatory mediators - except IL-18 - were highly expressed in patients with cardiovascular disease (n = 16) compared with those without (n = 45). Pooling the gene expression data, trying to capture the overall inflammatory activity in adipose tissue in a score system, we observed a highly significant association with CVD. CONCLUSIONS: Trying to capture the overall inflammatory activity, in addition to the mass of adipose tissue, could provide useful hints towards a pathogenetic link between obesity and presence of cardiovascular disease.
Asunto(s)
Tejido Adiposo/metabolismo , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Obesidad/complicaciones , Anciano , Enfermedades Cardiovasculares/patología , Estudios Transversales , Humanos , Interleucina-18/metabolismo , Interleucina-6/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Obesidad/metabolismo , Inhibidor 1 de Activador Plasminogénico/metabolismo , ARN Mensajero/metabolismo , Factores de Riesgo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Túnica Media/patologíaRESUMEN
BACKGROUND: Both Type 2 diabetes and cardiovascular disease have been associated with enhanced coagulation and suppressed fibrinolysis. OBJECTIVES: To investigate a possible relationship between selected hemostatic variables and abnormal glucose regulation (AGR) in patients with acute ST-elevation myocardial infarction (STEMI) without known diabetes and to study changes in selected hemostatic variables from baseline to follow-up in STEMI patients with or without AGR. METHODS: Plasminogen activator inhibitor-1 (PAI-1) activity, tissue plasminogen activator (t-PA) antigen, prothrombin fragment 1+2 (F(1+2)) and von Willebrand factor (vWF) were measured in fasting blood samples from 199 STEMI patients 16.5 h (median time) after admission and 3 months later. All patients were classified into normal glucose regulation (NGR) or AGR based on an oral glucose tolerance test at follow-up, according to the WHO criteria. RESULTS: High PAI-1 activity (≥ 75th percentile) measured in-hospital was associated with AGR (n = 49) with an adjusted odds ratio of 2.2 (95% confidence interval, 1.1, 4.4). In addition, high levels of t-PA antigen (≥ 75th percentile) were associated with AGR (adjusted odds ratio, 3.5; 95% confidence inteval, 1.5, 8.2), but only in men. Changes in the levels of F(1+2) were significantly more pronounced in patients with AGR compared with NGR (adjusted P = 0.04). CONCLUSION: Elevated levels of PAI-1 activity and t-PA antigen measured in-hospital in STEMI patients were associated with AGR classified at 3-month follow-up. Additionally, changes in the levels of F(1+2) were more pronounced in patients with AGR compared with NGR. The data suggest an enhanced prothrombotic state after an acute STEMI in patients with AGR without known diabetes.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Intolerancia a la Glucosa/sangre , Hemostasis , Infarto del Miocardio/sangre , Inhibidor 1 de Activador Plasminogénico/sangre , Activador de Tejido Plasminógeno/sangre , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Intolerancia a la Glucosa/diagnóstico , Prueba de Tolerancia a la Glucosa , Humanos , Pacientes Internos , Modelos Logísticos , Masculino , Infarto del Miocardio/diagnóstico , Noruega , Oportunidad Relativa , Fragmentos de Péptidos/sangre , Estudios Prospectivos , Protrombina , Factores de Tiempo , Regulación hacia Arriba , Factor de von Willebrand/metabolismoRESUMEN
Longevity and reduced mortality and cardiovascular disease (CVD) mortality and morbidity compared with the general population are described among former athletes in a few studies only. The aim of the study was to assess the outcomes of mortality and CVD morbidity after 30 years follow-up in long-term cross country skiers. The study was based on three different age groups of 122 long-term long-endurance cross country skiers participating in studies in 1976 and 1981. A total of 78/85 skiers completed the 28-30 year follow-up, while 37 were dead. Causes of deaths through 2006 were ascertained using the National Death Register. Morbidity or mortality data were available in 115 subjects. Total deaths were 31% compared with 40% in the general male population (P=0.04). Exercise electrocardiographic ST-depression in 1981 was associated with the later appearance of coronary heart disease (HR 2.90; P=0.033). Body mass index and average systolic blood pressure from 1976 to 1981 were predictors of later appearance of CVD (HR 1.23; P=0.034 and HR 1.03; P=0.048, respectively). Long-term aerobic exercise appears to be associated with reduced all-cause mortality.
Asunto(s)
Enfermedades Cardiovasculares/fisiopatología , Mortalidad/tendencias , Resistencia Física/fisiología , Esquí/fisiología , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Causas de Muerte , Electrocardiografía , Humanos , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Modelos de Riesgos Proporcionales , Sistema de Registros , Análisis de SupervivenciaRESUMEN
The aim of this echocardiographic study was to evaluate the effects of long-term endurance training on cardiac structure and function in three different age groups of 48 healthy middle-aged and old former or still active male cross country skiers (23 in age group I: age 58.6 ± 2.2 years; 21 in age group II: age 74.9 ± 2.2 years; four in age group III: age 89.5 ± 1.9 years). The two oldest age groups were combined and compared with age group I. No significant differences in left atrial or ventricular dimensions between these two age groups were found. A high proportion of enlarged left atrial dimensions were found among all subjects with 80% exceeding the upper reference limit of 40 mm in diameter (LADs) and 94% exceeding the upper reference limit of 20 cm(2) in area (LAAs). Mean values for LADs (mm) and LAAs (cm(2) ) were: group I: 41.9 ± 4.7 and 24.7 ± 3.3; group II: 43.5 ± 4.8 and 25.2 ± 3.7; group III: 44.5 ± 4.7 and 25.8 ± 3.7. Left ventricular diastolic diameter exceeded the upper reference limits of >54 mm in 20 subjects among all. The groups had preserved systolic and age-related diastolic function.
Asunto(s)
Atrios Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Corazón/fisiología , Resistencia Física/fisiología , Esquí/fisiología , Anciano , Anciano de 80 o más Años , Presión Sanguínea , Ecocardiografía/métodos , Corazón/anatomía & histología , Frecuencia Cardíaca , Humanos , Masculino , Examen Físico , Encuestas y CuestionariosRESUMEN
Based on experience from randomised trials with n-3 PUFA we intend to answer some relevant questions in patients with coronary heart disease. In the SHOT study supplementation with 3.4 g/day of highly concentrated n-3 PUFA for 1 year significantly reduced the occlusion rate of venous aortocoronary bypass grafts, and this effect correlated significantly to the change in serum levels of n-3 fatty acids. In the CART study 5.1 g/day of highly concentrated n-3 PUFA did not reduce the incidence of restenosis after 6 months. If anything, a negative effect was observed. The background for this was probably a pro-oxidative and proinflammatory mechanism as elucidated in substudies. In the OVITES trial the addition of vitamin E did not counteract the proinflammatory effect of high amounts of n-3 PUFA supplementation as observed in CART, although circulating oxidative substances were unaffected. In the "Fiord-to-table" study replacement of fish oils by vegetable oils in the feed of farmed Atlantic salmon was mirrored in the fatty acid profile of the salmon fillets as well as in that of serum from patients after ingesting about 700 g/week for six weeks. A parallel reduction of the proinflammatory profile was observed only in patients who ingested salmon fed on fish oil.
Asunto(s)
Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Ácidos Grasos Omega-3/uso terapéutico , Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/uso terapéutico , Composición de Medicamentos , Ácido Eicosapentaenoico/administración & dosificación , Ácido Eicosapentaenoico/farmacología , Ácido Eicosapentaenoico/uso terapéutico , Ácidos Grasos Monoinsaturados , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/farmacología , Aceites de Pescado/farmacología , Humanos , Aceites de Plantas/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , Aceite de Brassica napus , Vitamina E/farmacologíaRESUMEN
The aim of the study was to assess longitudinal changes in cardiorespiratory function in different groups of current or former endurance trained male cross-country skiers. Three different age groups (n=122) took part in a similar study in 1976. Of 86 men still alive 78 responded (90.7%). Thirty-two from group I (age 58.7+/-2.3) and 36 from group II (age 74.5+/-2.5) participated in a maximum exercise test. We found significant difference in decline in VO2max between age groups (%/decade: 6.7+/-3.6 vs 13.9+/-3.2; P=0.0001 and in L/min/decade: 0.32+/-0.18 vs 0.53+/-0.14; P=0.0001). Men in group I (but only a tendency in group II) who were still competing and reported unchanged training patterns had a significant attenuated decline in VO2max (%/decade: 4.1+/-3.7 vs 8.1+/-2.8; P=0.003 and L/min: 0.19+/-0.0.17 vs 0.39+/-0.15; P=0.004). This study shows that lifelong endurance training does not stop the decline in VO2max with ageing, but vigorous training is important to attenuate the decline.
Asunto(s)
Esquí/fisiología , Adulto , Factores de Edad , Anciano , Prueba de Esfuerzo , Estudios de Seguimiento , Estado de Salud , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Capacidad VitalRESUMEN
OBJECTIVE: To investigate long-term safety and efficacy after intracoronary injection of autologous mononuclear bone marrow cells (mBMCs) in acute myocardial infarction (AMI). DESIGN: Randomised, controlled trial. SETTING: Two university hospitals in Oslo, Norway. PATIENTS: Patients from the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) study were re-assessed 3 years after inclusion. INTERVENTIONS: 100 patients with anterior wall ST-elevation myocardial infarction treated with acute percutaneous coronary intervention (PCI) were randomised to receive intracoronary injection of mBMCs (n = 50) or not (n = 50). MAIN OUTCOME MEASURES: Change in left ventricular (LV) ejection fraction (primary). Change in exercise capacity (peak VO(2)) and quality of life (secondary). Infarct size (additional aim), and safety. RESULTS: The rates of adverse clinical events in the groups were low and equal. There were no significant differences between groups in change of global LV systolic function by echocardiography or magnetic resonance imaging (MRI) during the follow-up. On exercise testing, the mBMC-treated patients had larger improvement in exercise time from 2-3 weeks to 3 years (1.5 minutes vs 0.6 minutes, p = 0.05), but the change in peak oxygen consumption did not differ (3.0 ml/kg/min vs 3.1 ml/kg/min, p = 0.75). CONCLUSION: The results indicate that intracoronary mBMC treatment in AMI is safe in the long term. A small improvement in exercise time in the mBMC group was found, but no other effects of treatment could be identified 3 years after cell therapy.
Asunto(s)
Monocitos/trasplante , Infarto del Miocardio/terapia , Trasplante de Células Madre/métodos , Ecocardiografía , Prueba de Esfuerzo , Tolerancia al Ejercicio/fisiología , Femenino , Humanos , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Calidad de Vida , Volumen Sistólico , Trasplante Autólogo , Resultado del TratamientoRESUMEN
BACKGROUND: The beneficial impact of warfarin in preventing new events after AMI is well established. Decrease in thrombin generation seems to be the key element in anticoagulant treatment. OBJECTIVES: The aims were to investigate the effect of warfarin and platelet inhibition on thrombin generation, assessed by the endogenous thrombin potential (ETP), and study the relation between coagulation parameters and ETP in patients with AMI. PATIENTS/METHODS: In the present sub-study of the WARIS II trial, patients with AMI were randomly assigned to treatment with aspirin 160 mg/d (n=57), aspirin 75 mg/d and warfarin (INR 2.0-2.5) (n=68) or warfarin (INR 2.8-4.2) (n=61). Fasting blood samples were collected from patients at discharge from hospital and after 6 weeks treatment. RESULTS: Correlation analyses showed that both ETP and peak thrombin levels were significantly correlated with Factor VII Ag (r=0.38 and 0.36 respectively, p<0.01 for both) and with F1+2 (r=0.26 and 0.23 respectively, p=0.01 for both) at baseline. Antithrombotic treatment for 6 weeks caused a highly significant inhibition of ETP in patients treated with warfarin (-28%+/-5%, p<0.001), and patients treated with aspirin/warfarin (-24%+/-8%, p=0.04). Similarly, peak thrombin levels were reduced in patients treated with warfarin (-18%+/-7%, p=0.049) and aspirin/warfarin (-19%+/-5%, p=0.029), whereas an increase (12%+/-4%, p=0.029) occurred during aspirin treatment alone. F1+2 levels decreased by 64% and 58% in the warfarin and aspirin/warfarin groups, respectively (p=0.001 for both). CONCLUSIONS: In patients with AMI, warfarin significantly reduced the endogenous thrombin generation and the potential to generate thrombin in plasma ex vivo, whereas aspirin alone had no effect on thrombin generation in vivo or ex vivo, assessed by ETP.
Asunto(s)
Anticoagulantes/uso terapéutico , Aspirina/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombina/metabolismo , Warfarina/uso terapéutico , Pruebas de Coagulación Sanguínea , Quimioterapia Combinada , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangreRESUMEN
BACKGROUND: Matrix metalloproteinases (MMPs) are important in the atherosclerotic process. The relationship between MMPs and traditional risk factors for cardiovascular disease (CVD) and any influence of lifestyle changes are largely unknown. OBJECTIVES: In a factorial design, we studied the effects of 3 years of dietary counselling and/or n-3 PUFA supplementation (2.4 g/d) on the levels of MMP-9, tissue inhibitor of metalloproteinase (TIMP-1) and pregnancy-associated plasma protein (PAPP-A) in a population of elderly men at high risk of CVD (n = 563, age 70+/-6 years). We further explored the association between these markers and different disease entities, carotid intima media thickness (IMT) and traditional risk factors for CVD. RESULTS: Smokers had significantly higher levels of MMP-9 (p<0.0001), and TIMP-1 levels were lower in subjects with previous AMI (p = 0.021). MMP-9 was significantly correlated with LDL-C and inversely with HDL-C (both p<0.0001). There were no significant correlations between the measured variables and IMT. Significant reductions in MMP-9 and PAPP-A levels after 36 months were found in all study groups, however, with no between-group differences. CONCLUSIONS: The elevated levels of MMP-9 in smokers and the reduced levels of TIMP-1 in patients with previous AMI reflect an importance of MMPs in the development of CVD. Intervention with diet and/or n-3 PUFA supplementation did not influence the levels of MMP-9, TIMP-1 or PAPP-A in the present population.
Asunto(s)
Enfermedad Coronaria/prevención & control , Suplementos Dietéticos , Ácidos Grasos Omega-3/farmacología , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Proteína Plasmática A Asociada al Embarazo/efectos de los fármacos , Anciano , Estudios de Seguimiento , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Persona de Mediana Edad , Proteína Plasmática A Asociada al Embarazo/análisis , Factores de Riesgo , Factores de Tiempo , Inhibidor Tisular de Metaloproteinasa-1/sangreRESUMEN
Epidemiological data suggest that fruit and vegetable consumption is associated with a lowered risk of CVD. We assessed the association between the intima-media thickness (IMT) of the carotid artery and dietary intake of vegetables, fruit and berries in elderly men with a high risk of CVD. Subjects (age 70 +/- 5 years) were survivors from a cohort of 1232 men that participated in the Oslo Diet and Antismoking Study in 1972-3. Measurements of the carotid IMT by high resolution B-mode ultrasound, risk factor assessment and dietary data based on an FFQ were collected in 1997-9. Complete dietary and ultrasound data were available for 547 subjects. The carotid IMT in the highest quartile of dietary intake of fruit and berries was 0.89 (SE 0.18) mm compared with 0.96 (SE 0.25) mm in the lowest quartile, giving a mean difference of 0.075 (SE 0.027) mm (P = 0.033). In multivariate regression analysis increased intake of fruit and berries remained inversely associated with IMT after adjustment for age, cigarette smoking, dietary cholesterol and saturated fat, consumption of milk, cream and ice cream and energy intake (multivariate regression coefficient 0.257; R(2) 0.066; SE 0.209; P < 0.001). The difference of 348 g of fruit and berries per d between the lowest and highest quartile of intake was associated with a 5.5 % adjusted difference in mean IMT. These findings suggest that consumption of fruit and berries may be protective against carotid atherosclerosis in elderly men at high risk of CVD.
Asunto(s)
Enfermedades de las Arterias Carótidas/prevención & control , Dieta/estadística & datos numéricos , Frutas , Anciano , Presión Sanguínea , Arteria Carótida Común/anatomía & histología , Arteria Carótida Común/diagnóstico por imagen , Métodos Epidemiológicos , Conducta Alimentaria , Humanos , Lípidos/sangre , Masculino , Fumar/patología , Túnica Íntima/anatomía & histología , Túnica Íntima/diagnóstico por imagen , Túnica Media/anatomía & histología , Túnica Media/diagnóstico por imagen , UltrasonografíaRESUMEN
OBJECTIVE: To investigate the profile of circulating inflammatory markers after percutaneous coronary intervention (PCI) in patients with AMI or stable angina pectoris (AP). MATERIAL AND METHODS: Twenty patients with AMI and 10 with stable AP were treated with PCI of a central coronary artery. Blood samples were drawn immediately before PCI, in the AP group and after 3 and 12 h, days 1, 3, 5, 7 and 14 in both groups. RESULTS: Interleukin 6 increased in both groups to time-point 12 h and day 1 (peak), being significantly higher in the AMI group compared to the AP group at 3 and 12 h, and also at days 1 and 3. A similar profile was demonstrated for CRP with significantly higher levels in the AMI group at days 1, 3 and 5 compared to the AP group. A slightly different pattern was shown for Interleukin 10 (IL-10) with significantly higher levels in the AMI group at 3 and 12 h, days 1 and 14 compared to the AP group. CONCLUSION: AMI patients treated with PCI experienced a marked short-term increase in pro-inflammatory mediators as well as IL-10 compared to patients with stable angina pectoris treated with PCI.