RESUMEN
OBJECTIVE: To study the prognostic value of neutrophil gelatinase-associated lipocalin (NGAL) in chronic heart failure (HF) of ischaemic aetiology. BACKGROUND: Neutrophil gelatinase-associated lipocalin is a marker of kidney injury as well as matrix degradation and inflammation and has previously been shown to be increased in HF. We investigated whether serum NGAL levels could provide prognostic information in chronic HF. METHODS: We assessed NGAL as a predictor of primary outcomes (cardiovascular death, nonfatal stroke and nonfatal myocardial infarction, n = 307) and all-cause mortality (n = 321), cardiovascular mortality (n = 259) and hospitalization (n = 647) as well as the number of hospitalizations during follow-up for all (n = 1934) and CV causes (n = 1204) in 1415 patients with chronic HF (≥60 years, New York Heart Association class II-IV, ischaemic systolic HF) in the CORONA population, randomly assigned to 10 mg rosuvastatin or placebo. Results. Multivariate analysis revealed that NGAL added significant information when adjusting for clinical variables, but was no longer significant when further adjusting for apolipoprotein A-1 (ApoA-1), glomerular filtration rate (GFR), C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). However, belonging to the highest NGAL tertile was associated with more frequent hospitalization, even after adjusting for clinical variables, GFR and ApoA-1, but not after adjusting for CRP and NT-proBNP. There was no interaction between rosuvastatin treatment and NGAL. Conclusion. Neutrophil gelatinase-associated lipocalin added no significant information to NT-proBNP and GFR in a multivariate model for primary and secondary end-points.
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Fluorobencenos/uso terapéutico , Insuficiencia Cardíaca , Lipocalinas/sangre , Proteínas Proto-Oncogénicas/sangre , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Proteínas de Fase Aguda , Anciano , Apolipoproteína A-I/metabolismo , Biomarcadores , Proteína C-Reactiva/metabolismo , Enfermedad Crónica , Femenino , Tasa de Filtración Glomerular , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lipocalina 2 , Masculino , Persona de Mediana Edad , Análisis Multivariante , Péptido Natriurético Encefálico/metabolismo , Noruega , Readmisión del Paciente/estadística & datos numéricos , Fragmentos de Péptidos/metabolismo , Valor Predictivo de las Pruebas , Pronóstico , Rosuvastatina Cálcica , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: The principal aim of this study was to determine whether the amount of visceral adipose tissue (VAT) is more related than subcutaneous adipose tissue (SAT) to atherosclerosis assessed by whole-body MRA (WBMRA). A further objective was to investigate whether traditional risk factors, inflammation, or adipokines could explain the hypothesized relationship between VAT and atherosclerosis. METHODS: Men and women aged 70 were recruited from the general population into the Prospective Investigation of The Vasculature in Uppsala Seniors (PIVUS) and 306 of them underwent WBMRA in a clinical 1.5-T scanner. The arterial tree was assessed for degree of stenosis or occlusion and a total atherosclerotic score (TAS) was established. Information on risk factors and BMI and on SAT and VAT, segmented on an axial MR scan was collected. Adiponectin, leptin, and high sensitive C-reactive protein (hsCRP) were measured in serum. HOMA index was used as a marker of insulin resistance. RESULTS: VAT was related to TAS independently of gender, total obesity (BMI), amount of SAT, hsCRP and also to the traditional risk factors included in the Framingham risk score (FRS) in an elderly population. Adiponectin or the HOMA insulin resistance, but not leptin or VAT, together with FRS was significantly related to TAS in a multiple censored regression model. CONCLUSION: Adiponectin attenuated the relationship between VAT and TAS, suggesting that adiponectin and insulin resistance is an important link between visceral adiposity and atherosclerosis.
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Adiponectina/metabolismo , Angiografía/métodos , Aterosclerosis/patología , Resistencia a la Insulina , Grasa Intraabdominal/metabolismo , Grasa Intraabdominal/patología , Adipoquinas/metabolismo , Anciano , Aterosclerosis/metabolismo , Femenino , Humanos , Inflamación , Angiografía por Resonancia Magnética/métodos , Masculino , Obesidad , Factores de Riesgo , Imagen de Cuerpo EnteroRESUMEN
BACKGROUND AND AIMS: Impaired glucose tolerance (IGT) is regarded as a transient metabolic state leading to type-2 diabetes, and is known to predict future risk of cardiovascular disease. This study was designed to investigate if IGT is associated with subclinical atherosclerosis. METHODS AND RESULTS: In a population-based cohort of 64-year-old women, a group with IGT determined by repeated oral glucose tolerance tests (n=205) was compared with healthy women with normal glucose tolerance (NGT, n=188). Intima-media thickness (IMT) and plaques in the common carotid arteries (CCA) and bulbs were measured by ultrasound. The 95% confidence interval (CI) of the difference between the IGT and NGT groups was -0.03 to 0.03mm. There was no difference in carotid bulb IMT or in the occurrence, size, and characteristics of plaques between the IGT and NGT groups. A meta-analysis was used to calculate summary measures of 12 reviewed studies showing a difference of 0.030 (95% CI 0.012-0.048) mm in carotid IMT between IGT and NGT groups. Heterogeneity in IMT differences between studies was shown. CONCLUSIONS: In our population-based cohort of 64-year-old women, IGT was not associated with increased occurrence of subclinical atherosclerosis. However, a meta-analysis of 12 studies, including our current study, showed that IGT was associated with a small increase in the CCA IMT.
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Enfermedades de las Arterias Carótidas/epidemiología , Arteria Carótida Común/patología , Intolerancia a la Glucosa , Túnica Íntima/patología , Túnica Media/patología , Enfermedades de las Arterias Carótidas/etiología , Enfermedades de las Arterias Carótidas/patología , Arteria Carótida Común/diagnóstico por imagen , Estudios de Casos y Controles , Estudios de Cohortes , Estudios Transversales , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Persona de Mediana Edad , Factores de Riesgo , Suecia/epidemiología , UltrasonografíaRESUMEN
OBJECTIVE: The aim of this study was to elucidate the relationship between the echogenicity of carotid artery plaques and the following risk factors: circulating oxLDL, hsCRP, the metabolic syndrome (MetS), and several of the traditional cardiovascular (CV) risk factors. MATERIAL AND METHODS: A cross-sectional population-based study of 513 sixty-one-year-old men. The levels of circulating oxLDL were determined in plasma samples by sandwich ELISA utilizing a specific murine monoclonal antibody (mAb-4E6). High-sensitivity CRP was measured in plasma by ELISA. Plaque occurrence, size and echogenicity were evaluated from B-mode ultrasound registrations in the carotid arteries. Plaque echogenicity was assessed based on a four-graded classification scale. RESULTS: A higher frequency of echolucent carotid plaques was observed with increasing levels of oxLDL and systolic blood pressure (p = 0.008 and p = 0.041, respectively). Subjects with the MetS had a significantly higher frequency of echogenic plaques than subjects without the MetS (p = 0.009). In a multiple logistic regression analysis, oxLDL turned out to be independently associated with echolucent carotid plaques. CONCLUSIONS: The occurrence of echolucent carotid plaques was associated with oxLDL and systolic blood pressure, and oxLDL was associated with echolucent carotid plaques independently of systolic blood pressure.
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Arterias Carótidas/diagnóstico por imagen , Estenosis Carotídea/sangre , Estenosis Carotídea/diagnóstico por imagen , Lipoproteínas LDL/sangre , Proteína C-Reactiva/metabolismo , Arterias Carótidas/patología , Estenosis Carotídea/complicaciones , Humanos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Análisis de Regresión , Factores de Riesgo , UltrasonografíaRESUMEN
BACKGROUND: Inflammation has repeatedly been demonstrated to be associated with the metabolic syndrome (MetS) and insulin resistance, but the relative importance of different aspects of the inflammatory process is largely unexplored. DESIGN: We measured circulating interleukins (IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10); other cytokines (tumour necrosis factor-alpha, interferon gamma and monocyte chemotactic protein-1), cell adhesion molecules [vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, E-selectin, P-selectin, l-selectin], and systemic inflammation markers [C-reactive protein (CRP) and leukocyte count] in 943 70 year old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. We related these biomarkers to MetS and the homeostasis model assessment insulin resistance index (HOMA-IR). RESULTS: In a multivariable model including all inflammatory markers conjointly together with sex, log VCAM-1 [odds ratio (OR), 1.45; 95% confidence interval (CI), 1.22-1.72 per 1 SD increase; P < 0.0001], log E-selectin (OR, 1.33; 95% CI, 1.12-1.57 per 1SD increase; P = 0.001), and log CRP (OR, 1.41; 95% CI, 1.20-1.66 per 1-SD increase; P < 0.0001) were independently associated with MetS. These biomarkers were also independently associated with HOMA-IR. CONCLUSIONS: Among 17 inflammatory biomarkers, most of them previously not examined in relation to MetS and insulin resistance, VCAM-1, E-selectin and CRP demonstrated the strongest associations with MetS and insulin resistance in our community based sample of the elderly. The relative importance of these biomarkers in predicting the development of MetS, insulin resistance and cardiovascular disease needs to be further examined in a longitudinal setting.
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Biomarcadores/análisis , Inflamación/metabolismo , Síndrome Metabólico/metabolismo , Anciano , Biomarcadores/sangre , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/sangre , Citocinas/análisis , Citocinas/sangre , Femenino , Humanos , Inflamación/sangre , Masculino , Síndrome Metabólico/sangre , Modelos Biológicos , Estadística como AsuntoRESUMEN
OBJECTIVES: To examine whether circulating levels of matrix metalloproteinase 9 (MMP-9) were associated with ultrasound-assessed intima-media thickness (IMT) and echolucent plaques in the carotid and femoral arteries. To examine preanalytical sources of variability in MMP-9 concentrations related to sampling procedures. SUBJECTS AND DESIGN: Plasma and serum MMP-9 levels were compared with ultrasound assessed measures of femoral and carotid atherosclerosis, in a cross-sectional study of 61-year-old men (n = 473). Preanalytical sources of variability in MMP-9 levels were examined in 10 healthy subjects. Main outcome measures were circulating levels of MMP-9 in serum and plasma, IMT of the carotid and femoral arteries, and plaque status based on size and echolucency. SETTING: Research unit at university hospital. RESULTS: Plasma concentrations of total and active MMP-9 were associated with femoral artery IMT independently of traditional cardiovascular risk factors, and were higher in subjects with moderate to large femoral plaques. Plasma MMP-9 concentration was higher in men with echolucent femoral plaques (P = 0.006) compared with subjects without femoral plaques. No similar associations were found for carotid plaques. MMP-9 concentrations were higher in serum than in plasma, and higher when sampling was performed with Vacutainer than with syringe. MMP-9 levels in serum were more strongly associated with peripheral neutrophil count compared with MMP-9 levels in plasma. CONCLUSIONS: Plasma MMP-9 levels were associated with atherosclerosis in the femoral artery, and total MMP-9 concentration was higher in men with echolucent femoral plaques. The choice of sample material and sampling method affect the measurements of circulating MMP-9 levels.
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Aterosclerosis/enzimología , Metaloproteinasa 9 de la Matriz/sangre , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/patología , Biomarcadores/sangre , Recolección de Muestras de Sangre/métodos , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/enzimología , Enfermedades de las Arterias Carótidas/patología , Arteria Carótida Común/diagnóstico por imagen , Arteria Carótida Común/patología , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/patología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Túnica Íntima/diagnóstico por imagen , Túnica Íntima/patología , Túnica Media/diagnóstico por imagen , Túnica Media/patología , UltrasonografíaRESUMEN
OBJECTIVES: Few studies have investigated the composition of unstable coronary plaques in vivo in humans. The aims of this study were to investigate if substances released from plaques during percutaneous coronary intervention (PCI) under distal protection could give information about plaque composition and also indicate possible biomarkers in plasma that may be used to identify patients at risk. METHODS AND RESULTS: Twenty patients with acute coronary syndromes undergoing PCI with distal protection were included. Plasma samples were taken before, during, and after the PCI in the aortic root, locally in the culprit vessel and intravenously. Plasma was analysed for possible markers of plaque instability. During PCI, local increases were observed for matrix metalloproteinase 9 (MMP-9), protein (P < 0.001) as well as activity (P < 0.001), interleukin 6 (IL-6; P < 0.01) and oxidized low-density lipoprotein (oxLDL; P = 0.01) in the culprit coronary artery. A systemic inflammatory response was also seen with increased levels of IL-10, MMP-3, serum amyloid A and C-reactive protein, but with no increase in MMP-9. CONCLUSIONS: Our study shows that local sampling of blood under distal protection may be used to analyse coronary plaques and to identify biomarkers for unstable plaques. Our results suggest that MMP-9 is a potential biomarker, and that IL-6, MMP9 and possibly oxLDL are released from plaques.
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Síndrome Coronario Agudo/terapia , Angioplastia Coronaria con Balón/métodos , Proteínas Sanguíneas/análisis , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/terapia , Metaloproteinasa 9 de la Matriz/sangre , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/inmunología , Adulto , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Enfermedad de la Arteria Coronaria/inmunología , Femenino , Humanos , Interleucina-10/sangre , Interleucina-6/sangre , Lipoproteínas LDL/sangre , Masculino , Metaloproteinasa 3 de la Matriz/sangre , Persona de Mediana Edad , Proteína Amiloide A Sérica/análisis , Manejo de Especímenes , Estadísticas no ParamétricasAsunto(s)
Diabetes Mellitus/sangre , Tasa de Filtración Glomerular , Resistina/sangre , Índice de Masa Corporal , Proteína C-Reactiva/análisis , Estudios de Cohortes , Creatinina/sangre , Diabetes Mellitus/fisiopatología , Ensayo de Inmunoadsorción Enzimática , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Recuento de Leucocitos , Persona de Mediana Edad , Análisis MultivarianteRESUMEN
OBJECTIVE: To examine whether serum adiponectin concentrations were associated with subclinical atherosclerosis assessed as intima media thickness (IMT) in the carotid arteries in Caucasian women with varying degrees of glucose tolerance. RESEARCH DESIGN AND METHODS: From a population-based cohort of 64-year-old Swedish women, 533 subjects with type 2 diabetes (DM2, n=177), impaired glucose tolerance (IGT; n=178) or normal glucose tolerance (NGT, n=178) were recruited. Anthropometrics, usual cardiovascular risk factors were examined and ultrasound examination of the carotid arteries was performed. RESULTS: Women with low adiponectin concentrations were characterized by thick IMT, higher prevalence of DM2, history of previous myocardial infarction, angina pectoris, anti-hypertensive treatment and high body mass index (BMI), waist circumference, plasma insulin, serum triglycerides, fasting glucose, HbA1c, and low serum HDL cholesterol levels. Carotid IMT correlated with HbA1c (r=0.24, P<0.001), waist circumference (r=0.22, P<0.001), plasma insulin (r=0.19, P<0.001), BMI (r=0.18, P<0.001), DM2 (r=0.16, P<0.001), systolic blood pressure (r=0.16, P<0.001), blood glucose (r=0.16, P<0.001), triglycerides (r=0.15, P<0.001), and reversely to adiponectin (r=-0.11, P=0.01), HDL cholesterol (r=-0.13, P=0.004), and alcohol intake (r=-0.087, P<0.05). A more detailed analysis of underlying associations was difficult due to a high co-linearity between these variable. CONCLUSIONS: Low serum adiponectin concentrations were associated with increased carotid artery IMT, and several risk factors for cardiovascular diseases, mainly those constituting the metabolic syndrome.
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Adiponectina/sangre , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Resistencia a la Insulina , Biomarcadores/sangre , Arterias Carótidas/diagnóstico por imagen , Estudios de Casos y Controles , Estudios de Cohortes , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico por imagen , Electrocardiografía , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Persona de Mediana Edad , Análisis de Regresión , Ultrasonografía , Población BlancaRESUMEN
OBJECTIVES: The aim of the present study was to investigate the association between serum concentrations of apoB, apoA-I and the apoB/apoA-I ratio and future cardiovascular events in a group of healthy 58-year-old men during 6.6 years of follow-up. A further aim was to investigate the concentrations of apoB, apoA-I and the apoB/apoA-I ratio to the association of plaque occurrence in the carotid and femoral arteries. BACKGROUND: Previous studies have shown that the apoB/apoA-I ratio is an important cardiovascular risk factor, whereas the association between apoB/apoA-I ratio and presence of atherosclerotic plaques in the carotid and femoral arteries has been less investigated. METHODS: The carotid and femoral arteries were examined by high-resolution B-mode ultrasound in 391, 58-year-old men identified by screening in the city of Göteborg, Sweden. Assessment of plaque occurrence and measurement of apolipoproteins (apoA-I and apoB) was performed. RESULTS: Subjects with an apoB/apoA-I ratio >/=0.9 had a significantly increased risk to suffer a cardiovascular event during 6.6 years of follow-up (OR 3.07, 95% CI 1.22-7.71), while no difference in risk for cardiovascular events was observed for subjects with LDL cholesterol >3.4 mmol/L compared to subjects <3.4 mmol/L (OR 1.04, 95% CI 0.37-2.46). A greater risk for plaques in the femoral artery was also observed in subjects with an apoB/apoA-I ratio >/=0.9 compared to subjects <0.9 (OR 3.06, 95% CI 1.22-7.70). In a multiple logistic regression model, both elevated apoB/apoA-I ratio and plaque occurrence in the femoral artery were of significant importance for cardiovascular events during follow-up. CONCLUSIONS: The results showed that the apoB/apoA-I ratio was associated with arteriosclerosis in the femoral artery, and predicted future cardiovascular events. These observations, and the fact that apoB and apoA-I can be measured in the non-fasting state with high precision, in combination with the finding that LDL cholesterol did not predict cardiovascular disease, support results from other studies that the apoB/apoA-I ratio may be a superior risk marker for cardiovascular disease.
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Apolipoproteína A-I/sangre , Apolipoproteínas B/sangre , Arteriopatías Oclusivas/sangre , Aterosclerosis/sangre , Arteria Femoral , Arteriopatías Oclusivas/etiología , Aterosclerosis/complicaciones , Biomarcadores/sangre , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Valores de Referencia , Factores de RiesgoRESUMEN
OBJECTIVES: Matrix metalloproteinase-3 (MMP-3) is implicated in the formation of atherosclerotic plaques, and the MMP-3 -1612 5A/6A polymorphism is associated with myocardial infarction (MI) and stable coronary artery disease (CAD). The present study examined whether the -1612 5A/6A polymorphism in the promoter region of the MMP-3 gene influences serum concentrations of MMP-3 and whether serum concentrations of MMP-3 are related to extent of coronary atherosclerosis and risk of MI. DESIGN AND SUBJECTS: This case-control study was conducted in three hospitals in the northern part of Stockholm. A total of 755 MI patients aged below 60 were screened, 433 entered and 387 completed the study. Three hundred and eighty-seven sex- and age-matched control subjects were recruited from the general population of the same county. METHODS: The MMP-3 genotype was determined by Pyrosequencing(TM) and the serum MMP-3 concentration was quantified with an immunoassay. Severity and extension of CAD was assessed by quantitative coronary angiography in a subgroup of patients (n=243). RESULTS: Patients had lower serum MMP-3 concentration than controls. There was a strong association between MMP-3 -1612 5A/6A genotype and serum concentrations of MMP-3. The presence of one or two copies of the 6A-allele was associated with a graded increase in serum MMP-3. In female patients there was an inverse correlation (r=-0.39, P<0.05) between serum MMP-3 concentration and plaque area. Conclusion. In conclusion, the serum concentration of MMP-3 is influenced by MMP-3 -1612 5A/6A genotype and associated with MI.
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Metaloproteinasa 3 de la Matriz/sangre , Infarto del Miocardio/genética , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Estudios de Casos y Controles , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/genética , Femenino , Genotipo , Humanos , Masculino , Metaloproteinasa 3 de la Matriz/genética , Persona de Mediana Edad , Fenotipo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: To examine the occurrence over time of the metabolic syndrome (MetS) according to different definitions and the relation to change during follow-up in carotid artery intima-media thickness (IMT), measured by ultrasound. DESIGN: A cohort of 316, originally 58-year-old men, initially free of diabetes and cardiovascular disease, was followed for 3.2 +/- 0.2 years. IMT was measured bilaterally by high-resolution B-mode ultrasound at baseline and follow-up. The MetS was classified according to slightly modified World Health Organization (WHO) and National Cholesterol Education Program (NCEP) criteria. RESULTS: In 88% WHO and NCEP definitions resulted in identical classifications. IMT was larger both at baseline and after 3 years in men fulfilling the criteria for the MetS, according to either of the definitions, compared to those without factors in the syndrome. Men who fulfilled the WHO criteria for the MetS, at the initial and final examination showed a statistically significant increase in carotid artery IMT during the study [76 (95% CI: 14-130) microm, n = 37]. Men fulfilling the WHO criteria for the MetS at baseline tended to have a larger annual increase in IMT than those not fulfilling the criteria or having no risk factors in the syndrome. CONCLUSIONS: More than 10% of the men had the MetS both at baseline and after 3 years, and this was associated with an increase in IMT using the WHO definition. Several of the components included in the MetS deteriorated during follow-up, i.e. body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, blood glucose and blood pressure.
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Arterias Carótidas/diagnóstico por imagen , Síndrome Metabólico/diagnóstico por imagen , Glucemia/análisis , Presión Sanguínea/fisiología , Índice de Masa Corporal , Estenosis Carotídea/diagnóstico por imagen , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Humanos , Insulina/sangre , Estudios Longitudinales , Masculino , Síndrome Metabólico/sangre , Persona de Mediana Edad , Factores de Riesgo , Fumar/efectos adversos , Triglicéridos/sangre , Túnica Íntima/diagnóstico por imagen , Ultrasonografía , Relación Cintura-CaderaRESUMEN
AIMS/HYPOTHESIS: Type 2 diabetes is a major risk factor for cardiovascular disease. Monocyte recruitment and inflammatory activation are crucial steps in the development of atherosclerosis and several receptors are involved in these processes. The aim of this study was to investigate levels of CD14 and the beta(2)-integrin subunits CD11b and CD18 on monocytes from women with diabetes or impaired glucose tolerance. METHODS: A population-based sample of 112 Swedish women, who were aged 64 years and had diabetes mellitus or impaired or normal glucose tolerance, was investigated. Cell surface receptors were analysed with flow cytometry and serum inflammation markers and soluble adhesion molecules with enzyme-linked methods. RESULTS: The monocytic CD14 expression and serum levels of C-reactive protein, IL-6 and soluble adhesion molecules were higher in the diabetes group than in the group with normal glucose tolerance. Monocytic CD18 was elevated both in the diabetes and in the impaired glucose tolerance groups. The levels of monocytic surface markers correlated with BMI and to a lesser extent with glycaemic control. CONCLUSIONS/INTERPRETATION: The increased monocytic expression of important surface receptors together with elevated serum inflammation markers supports the concept of increased inflammation in type 2 diabetes and may be an important factor for the risk of atherosclerosis.
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Antígenos CD18/sangre , Diabetes Mellitus/sangre , Intolerancia a la Glucosa/sangre , Inflamación/sangre , Receptores de Lipopolisacáridos/sangre , Antígenos CD/sangre , Arteriosclerosis/epidemiología , Biomarcadores/sangre , Índice de Masa Corporal , Antígeno CD11b/sangre , Diabetes Mellitus/fisiopatología , Femenino , Intolerancia a la Glucosa/fisiopatología , Prueba de Tolerancia a la Glucosa , Humanos , Persona de Mediana Edad , Monocitos/inmunología , Monocitos/fisiologíaRESUMEN
OBJECTIVE: To investigate the association between plasma oxidized low-density lipoprotein (OxLDL) and the progress of clinically silent atherosclerosis, as measured by ultrasound in the carotid arteries. DESIGN: Prospective, observational study with more than 3 years of follow-up. SETTING: One-centre study at university hospital. MATERIAL AND METHODS: The subjects (n = 326) were obtained by stratified sampling from a population sample of men who were 58 years old at baseline. Carotid artery intima-media thickness (IMT) was measured bilaterally by high-resolution B-mode ultrasound at baseline and after follow-up. Plasma OxLDL cholesterol concentrations and conventional cardiovascular risk factors were measured at study entry. Automated measurements of IMT were performed. Plaque occurrence and size were assessed (plaque status). Plasma OxLDL at entry was measured by a specific monoclonal antibody, mAb-4E6. RESULTS: OxLDL at entry, but not LDL cholesterol, was associated with the number and size of plaques at follow-up (P = 0.008), also after adjustment for plaque status at entry (P = 0.033). The plasma OxLDL concentration at entry was associated with change in carotid artery IMT (r = 0.17; P = 0.002) and in a stepwise multiple regression analysis this association remained after adjustment for other cardiovascular risk factors (P = 0.005). CONCLUSIONS: These results provide new information, supporting the concept that circulating OxLDL was associated with the silent phase of atherosclerosis progression in clinically healthy men independently of conventional risk factors.
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Arteriosclerosis/diagnóstico , Lipoproteínas LDL/sangre , Arteriosclerosis/sangre , Biomarcadores/sangre , LDL-Colesterol/sangre , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios ProspectivosRESUMEN
OBJECTIVE: Increased cardiovascular morbidity and mortality has been observed in patients with pituitary deficiency and untreated growth hormone deficiency (GHD). We investigated peripheral inflammatory and fibrinolytic markers and their associations with arterial intima-media thickness (IMT) in GHD. DESIGN: Cross-sectional study. PATIENTS: Thirty-four patients with GHD, but without cardiovascular disease, were compared to healthy controls matched for age, sex, body mass index (BMI) and smoking habits. MEASUREMENTS: IMT of the common carotid artery, C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) activity and tissue plasminogen activator antigen (tPA-ag) were measured. RESULTS: Median IL-6 concentrations were increased by 208% and 248% in GHD patients compared to BMI-matched and nonobese controls, respectively. Median CRP and tPA-ag levels were increased by 237% and 167% in patients compared to nonobese controls, but not significantly different compared to BMI-matched controls. Plasma levels of fibrinogen and PAI-1 activity did not differ between groups. Age, low-density lipoprotein (LDL) cholesterol, tPA-ag and IL-6 were positively correlated, and IGF-I was negatively correlated to IMT in the patient group, but only age and IL-6 were independently related to IMT. CONCLUSIONS: IL-6 concentrations were increased in GHD patients compared to controls and independently related to IMT in patients. This finding may help to explain the variance in IMT and the increased vascular morbidity and mortality in hypopituitary patients with GHD.
Asunto(s)
Proteína C-Reactiva/análisis , Arterias Carótidas/diagnóstico por imagen , Hormona del Crecimiento/deficiencia , Hipopituitarismo/sangre , Interleucina-6/sangre , Túnica Íntima/diagnóstico por imagen , Autoantígenos/sangre , Estudios de Casos y Controles , Enfermedad Coronaria/sangre , Estudios Transversales , Femenino , Fibrinógeno/análisis , Humanos , Hipopituitarismo/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis Multivariante , Inhibidor 1 de Activador Plasminogénico/análisis , Factores de Riesgo , Activador de Tejido Plasminógeno/inmunología , UltrasonografíaRESUMEN
OBJECTIVE: In a previously published randomized 6-year study we observed that multiple risk factor intervention reduced cardiovascular risk in high-risk hypertensive men, and that this effect was confined to patients with carotid artery plaques. Hypothetically, the underlying mechanism might have been a stabilization of echolucent, instable, rupture-prone plaques. The aim of the present study was to examine plaque characteristics by B-mode ultrasound in the previous intervention study, and also to investigate the relationship between plaque characteristics at baseline and cardiovascular events during the 6-year follow-up in the two randomization groups. METHODS: High resolution B-mode ultrasound was used to characterize plaque echogenicity in four subgroups - dominantly echolucent, substantially echolucent, dominantly echogenic, and uniformly echogenic. RESULTS: In the usual care group 17 of 32 (53%) patients with echolucent plaques at baseline suffered from a combined end-point (any death or nonfatal myocardial infarction or nonfatal stroke) during follow-up compared with seven of 28 (25%) patients in the intervention group (P = 0.036). The corresponding numbers in patients with echogenic plaques were n = 4/13 (31%) and n = 4/17 (24%), respectively (NS). In the usual care group 11 of 33 (33%) patients with no plaques suffered from a combined end-point during follow-up compared with 11 of 30 (37%) in the intervention group. CONCLUSION: Our data indicate that the beneficial effect of the multiple risk intervention programme was confined to those patients with echolucent plaques. The data have to be confirmed with a large-scale trial.
Asunto(s)
Enfermedades de las Arterias Carótidas/patología , Hipertensión/complicaciones , Infarto del Miocardio/prevención & control , Accidente Cerebrovascular/prevención & control , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/patología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/patología , Factores de Riesgo , Accidente Cerebrovascular/patología , UltrasonografíaRESUMEN
OBJECTIVE: To investigate the associations between markers of systemic and vascular inflammation, and indicators of vascular morphology and function. METHODS: In 59 apparently healthy individuals, we measured serum levels of highly sensitive C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Endothelium-dependent (EDV) and -independent (EIDV) vasodilatation was evaluated in the forearm by venous occlusion plethysmography and local infusions of methacholine and sodium nitroprussid. Endothelial function index (EFI) was expressed as the EDV/EIDV ratio. The intima-media thickness (IMT) of the common carotid artery was investigated with ultrasound (far wall). RESULTS: EFI was inversely related only to ICAM-1 (r=-0.31, P<0.02) by univariate analysis. This association remained significant after adjustment for age, sex, blood pressure, smoking and serum cholesterol. EFI did not relate to hsCRP, VCAM-1 or E-selectin. Neither hsCRP, nor the adhesion molecules were significantly related to carotid artery IMT. CONCLUSION: ICAM-1 was related to endothelial vasodilatory function, but not to IMT, suggesting that endothelial inflammatory activation is related to an impaired vascular relaxation in apparently healthy individuals.
Asunto(s)
Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Selectina E/sangre , Endotelio Vascular/inmunología , Molécula 1 de Adhesión Intercelular/sangre , Molécula 1 de Adhesión Celular Vascular/sangre , Vasodilatación/inmunología , Adulto , Anciano , Arteria Carótida Común/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Túnica Íntima/anatomía & histología , Túnica Íntima/inmunologíaRESUMEN
OBJECTIVES: To evaluate the endothelium-dependent flow-mediated vasodilatation (FMD) in the brachial artery and to study the relationship to insulin sensitivity and to the metabolic syndrome in 60-year-old clinically healthy men. SUBJECTS: The men were randomly selected from the general population (n = 55). The subjects with the metabolic syndrome were defined according to a definition proposed by a working group associated with the World Health Organization (WHO). METHODS: Ultrasound images for measurement of lumen diameter of the brachial artery were recorded before and after reactive hyperaemia induced by occlusion of the artery, both with and without ischaemic hand exercise during the occlusion. Insulin-mediated glucose uptake was determined by euglycaemic hyperinsulinaemic clamp as a measure of insulin sensitivity. RESULTS: The FMD was in the total group 3.2% when hyperaemia was induced by occlusion only and 8.7% after occlusion plus ischaemic hand exercise (P < 0.001, n = 51). However, no relationship was observed between any measure of FMD and insulin-mediated glucose uptake (r = -0.05 and r = 0.06, n = 47, P > 0.30). Furthermore, subjects with the metabolic syndrome (n = 13) did not differ in any measure of FMD compared with those with no risk factors (n = 11). CONCLUSION: In this study the ultrasound method to evaluate endothelial function did not show that low insulin sensitivity or the metabolic syndrome were associated with impaired FMD in otherwise clinically healthy 60-year-old men.