Objective-Elevated serum concentration of C-reactive protein (CRP) predicts cardiovascular events in adults. Because atherosclerosis begins in childhood, we undertook a study to determine whether changes in brachial artery endothelial function and the thickness of the carotid intima-media complex, 2 markers of early atherosclerosis, are related to CRP levels in healthy children. Methods and Results-Brachial artery flow-mediated dilatation (FMD) and carotid artery intima-media thickness (IMT) were measured with ultrasound in 79 children (aged 10.5Ϯ1.1 years). Compared with the children with CRP levels under the detection limit (Ͻ0.1 mg/L, nϭ40, group 1), the children with higher CRP (0. 4 -8 Experimental studies have shown that CRP can be found in arterial walls affected by atherosclerosis but not in healthy vessel walls. 9 In a concentrationdependent manner, CRP directly increases endothelial production and the expression of monocyte chemoattractant protein-1 10 and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1). 11 CRP also influences monocyte chemotaxis during atherogenesis, and the deposition of CRP precedes and mediates the appearance of monocytes in early atherosclerotic lesions. 12 Recently, it has been shown that CRP mediates the uptake of native LDL into macrophages, which is a novel mechanism for foam cell formation without biochemical modification of LDL. 13 Thus, together, these data suggest that CRP may have a direct proatherogenic role by disturbing endothelial function and promoting the formation of early atherosclerotic lesions. Because atherosclerosis begins in childhood, we undertook a study to assess whether changes in brachial artery reactivity and the thickness of the carotid intima-media complex (intima-media thickness [IMT]), 2 markers of early atherosclerosis, are related to serum CRP levels in healthy children. The study of arterial changes in children can provide unique data on early atherosclerosis and its determinants that are not obscured by other chronic diseases or lifestyle habits. Methods SubjectsWe studied 79 children; all were healthy nonsmokers without any regular medication and with no family history of premature vascular disease. None of the children had had symptoms of infection during the 2 weeks before the study. Subjects were children of the hospital staff members (nϭ36) and children participating in a risk factor study (nϭ44). 14 Children's parents were asked about their smoking (smoking/nonsmoking) on a questionnaire. The study protocol was approved by the local Ethics Committee. Legal guardians gave written informed consent. Ultrasound StudiesAll studies were performed in the morning to fasting subjects with the use of a Sequoia 512 mainframe (Acuson) and 13.0-MHz linear array transducer. All ultrasound scans were performed by an expe-

High serum C-reactive protein concentrations in acute myocardial infarction patients treated with thrombolytic drugs predict increased mortality up to 6 months following the infarction. Accordingly, reduction of inflammatory reaction by successful thrombolytic treatment may make an important contribution to the survival benefit of thrombolytic treatment of acute myocardial infarction.

Objective-Obesity is associated with endothelial dysfunction that may contribute to the development of atherosclerosis.We studied whether weight reduction improves endothelial function in overweight individuals. Methods and Results-Flow-mediated endothelium-dependent vasodilation of the brachial artery was measured in 67 adults (age: 46Ϯ7 years, body mass index: 35.2Ϯ5.4 kg/m 2 ) before and after a 6-week weight reduction program induced by very-low-calorie diet (daily energy: 580 kcal/2.3 MJ). Caloric restriction reduced body weight from 101Ϯ18 to 90Ϯ17 kg. Flow-mediated vasodilation increased from 5.5%Ϯ3.7 to 8.8%Ϯ3.7% (PϽ0.0001). Nitrate-mediated vasodilation was not significantly affected. The improvement in flow-mediated dilation was associated with the reduction in plasma glucose concentration (Pϭ0.0003). This relationship was independent of changes in weight, serum lipids, oxidized LDL, C-reactive protein, adiponectin, blood pressure, and insulin. Key Words: endothelium Ⅲ obesity Ⅲ risk factors Ⅲ glucose Ⅲ weight reduction T he vascular endothelium plays an important role in the regulation of arterial tone, thrombosis, and inflammation. Endothelial dysfunction may predispose arteries to the development of atherosclerotic lesions and is pathophysiologically linked to acute cardiovascular syndromes. 1 A common condition associated with endothelial dysfunction is obesity. Endothelial-dependent vascular responses to both agoniststimulated 2,3 and flow-mediated vasodilation 4 have been shown to be blunted in obese individuals. The mechanisms of obesity-induced endothelial dysfunction may be multifactorial, because excess adipose tissue induces several metabolic changes that may interfere with normal endothelial function. These may include dyslipidemia, elevated blood pressure, increased inflammation, oxidative stress, and changes in glucose metabolism. 5 Although weight reduction is known to reduce several of these risk factors for endothelial dysfunction, it is inadequately known whether endothelial function can be improved by reducing weight. We hypothesized that weight loss induced by very-low-calorie diet would enhance flow-mediated endothelium-dependent vasodilation in overweight adults. To gain insight for possible mechanisms of weight-loss-mediated changes in flow-mediated dilation, we also measured changes in several potential biochemical determinants of endothelial function. Conclusions-Weight Methods SubjectsWe recruited overweight (body mass index Ͼ27kg/m 2 ) men and women from an occupational health service clinic. The exclusion criteria included diabetes, pregnancy, gout, gall stone disease, alcohol/drug abuse, liver/kidney disorder, psychiatric disorder, and use of cholesterol lowering medication.Of the 74 subjects enrolled, 47 women and 20 men completed the 6-week program (9.5% dropout rate). Sixteen women were postmenopausal (2 using hormone replacement therapy), 19 subjects had treatment for hypertension, and there were 7 smokers and 13 ex-smokers. Most participants (65%) were sedentary, engag...

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Cystatin C is a non-glycated, 13-kDa basic protein produced by all nucleated cells. Recent studies have indicated that the plasma concentration of cystatin C is a better marker for glomerular filtration rate (GFR) than plasma creatinine, which is most commonly used for this purpose. We established reference values for plasma cystatin C in pre- or full-term infants and children. For comparison we also measured the creatinine concentration in the same samples. Cystatin C was measured by a commercially available immunoturbidimetric method with a Hitachi 704 analyzer in sera obtained from 58 pre-term infants, 50 full-term infants and 299 older children (132 girls, 167 boys, median age 4.17 years, range 8 days to 16 years). No sex differences were found. The pre-term infants had higher cystatin C concentrations (mean 1.88 mg/l, SD 0.36 mg/l) than the full-term (mean 1.70 mg/l, SD 0.26 mg/l, P=0.0145). The reference interval for pre-term infants calculated non-parametrically was 1.34-2.57 mg/l and for full-term infants 1.36-2.23 mg/l. The cystatin C concentration decreased rapidly after birth, and above 3 years of age did not depend on age. The reference interval for children 3-16 years of age calculated non-parametrically was 0.51-1.31 mg/l. Younger children (<1 year: 0.75-1.87 mg/l; 1-3 years: 0.68-1.60 mg/l) had slightly, but significantly, higher plasma cystatin C levels.

Serum C-reactive protein rises in acute myocardial infarction, correlating positively with infarct size if thrombolytic treatment is not given. This correlation disappears if thrombolytic treatment is given, although the serum C-reactive protein concentration is still associated with the clinical outcome of the patient. We studied the effect of early coronary recanalization induced by thrombolytic treatment alone or combined with coronary angioplasty on the infarct related rise in serum C-reactive protein concentration. The C-reactive protein response caused by the myocardial infarct was lower in patients with an open infarct-related coronary artery than in patients with a closed infarct-related coronary artery, or in control patients who did not receive thrombolytic therapy. In control patients we found the expected strong positive correlation between infarct size and serum C-reactive protein (r = 0.58; P < 0.001, n = 48), which was similar to that in patients with a closed infarct-related coronary artery (r = 0.62; P < 0.001, n = 17). In patients with an open infarct-related coronary artery the correlation between infarct size and serum C-reactive protein was much weaker (r = 30; P < 0.01, n = 91). Consequently infarct size explained approximately 35% of the variation in serum C-reactive protein values in the control patients and 36% in the patients with a closed infarct-related coronary artery, but only 9% of the variation in the patients with an open infarct-related artery. Ejection fraction correlated negatively with serum C-reactive protein in both control and recanalized patients. The association was again much stronger in the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystatin C is a non-glycated 13-kilodalton basic protein produced by all nucleated cells. The low molecular mass and the basic nature of cystatin C, in combination with its stable production rate, suggest that the glomerular filtration rate (GFR) is the major determinant of cystatin C concentration in the peripheral circulation. Recently published studies have shown that cystatin C correlates more strongly than creatinine with GFR measured using the 51Cr-EDTA clearance. The aim of this study was to evaluate serum cystatin C as a marker for GFR in children. GFR was determined on medical indications using the 51Cr-EDTA technique in pediatric patients (2-16 years) in our renal unit. Simultaneously their cystatin C and creatinine concentrations were also measured. Of our 52 patients, 19 had a reduced renal function (

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