Background-Passive smoking is associated with early arterial damage in adults, but its effect on endothelial function in children is unknown. Methods and Results-Serum cotinine concentration was measured annually in children between 8 and 11 years of age who had participated since infancy in a randomized, prospective atherosclerosis prevention trial (Special Turku Coronary Risk Factor Intervention Project for children [STRIP]). At age 11, endothelium-dependent flow-mediated vasodilatory responses of the brachial artery were examined with high-resolution ultrasound in 402 children. These children were divided into 3 groups according to serum cotinine concentrations: the noncotinine group (nondetectable cotinine, nϭ229), the low cotinine group (cotinine between 0.2 and 1.6 ng/mL, nϭ134), and the top decile cotinine group (cotinine Ն1.7 ng/mL, nϭ39). Longitudinal cotinine data in children aged 8 to 11 years and ultrasound studies were available in 327 children. At age 11, the increase in cotinine concentration was associated with attenuated peak flow-mediated dilation response (meanϮSD: the noncotinine group 9.10Ϯ3.88%, the low-cotinine group 8.57Ϯ3.78%, and the top-decile cotinine group 7.73Ϯ3.85%; Pϭ0.03 for trend). Similarly, total dilation response (the area under the dilation response versus time curve between 40 and 180 seconds after hyperemia) was affected by the cotinine level (Pϭ0.02 for trend). These trends were not explained by traditional atherosclerosis risk factors. Arterial measures and passive smoking showed even stronger associations when longitudinal cotinine data were used (peak flow-mediated dilation, Pϭ0.01 for trend; total dilation response, Pϭ0.008 for trend). Conclusions-Exposure

A high serum LPS activity is strongly associated with cardiometabolic disorders, which supports the role of bacterial infections and immune response in their etiology.

To characterize brachial artery flow-mediated dilatation (FMD) in children, we monitored arterial diameter changes with ultrasound between 40 and 180 s after a 4.5-min forearm cuff occlusion-induced hyperemia in 105 healthy children (mean age, 11 yr; range, 9-16 yr). The peak FMD was 7.7 +/- 4.0% and occurred 79 +/- 33 s after cuff release. FMD at 60 s (5.3 +/- 4.0%) was significantly lower than the peak FMD (P < 0.0001). Twenty-three percent of the children (n = 24) reached peak FMD first after 110 s of postocclusion. Compared with others, these late responders weighed less, had smaller vessel size, and were more often girls, but had similar peak FMD. In multivariate analysis, FMD responses were inversely associated with brachial artery baseline diameter and serum cholesterol concentration. We conclude that the time to reach the peak FMD response in children varies considerably. When studying endothelial function in children with the use of the noninvasive ultrasound method, several brachial artery diameter measurements up to 120 s after cuff release are needed to determine the true FMD peak response.

Background-Early childhood introduction of nutritional habits aimed at atherosclerosis prevention reduces children's serum total cholesterol concentration, but its effect on vascular endothelial function is unknown. Methods and Results-Between 1990 and 1992, we randomized healthy 7-month-old infants (nϭ1062) to intervention (low-saturated-fat diet) and control (unrestricted diet) groups. At the age of 11 years, endothelium-dependent (flow-mediated) and endothelium-independent (nitrate-mediated) vasodilatory responses of the brachial artery were measured with high-resolution ultrasound in 179 intervention and 190 control children. The effect of intervention on endothelial function was significant in boys (Pϭ0.0034) but not in girls (Pϭ0.69). The maximum endotheliumdependent dilation response (meanϮSD) was 9.62Ϯ3.53% and 8.36Ϯ3.85% in intervention boys and control boys and 8.84Ϯ4.00% and 8.44Ϯ3.60% in intervention girls and control girls, respectively. Intervention had no effect on nitrate-mediated dilation. The difference in endothelial function in boys remained significant after adjustment for current serum total or LDL cholesterol but became nonsignificant after adjustment for mean cholesterol measured under 3 years of age (adjusted

Endotoxemia increases with severity of periodontitis. In periodontitis, LPS associates preferentially with the pro-atherogenic VLDL-IDL fraction. Periodontal treatment has only minor effects on plasma LPS activity or distribution, which reflects persistence of the disease.

OBJECTIVE -Insulin resistance is promoted already in childhood by obesity and possibly by high-saturated fat intake. We examined the effect of infancy onset biannually given dietary counseling on markers of insulin resistance in healthy 9-year-old children.RESEARCH DESIGN AND METHODS -Healthy 7-month-old infants (n ϭ 1,062) were randomized to the intervention (n ϭ 540) and control (n ϭ 522) groups. Each year, two individualized counseling sessions were organized to each intervention family. The purpose of counseling was to minimize children's exposure to known environmental atherosclerosis risk factors. Homeostasis model assessment of insulin resistance (HOMA-IR) index, serum lipids, blood pressure, and weight for height were determined in a random subgroup of 78 intervention children and 89 control children at the age of 9 years.RESULTS -Intervention children consumed less total and saturated fat than the control children (P ϭ 0.002 and Ͻ 0.0001, respectively). The HOMA-IR index was lower in intervention children than in control children (P ϭ 0.020). There was a significant association between saturated fat intake and HOMA-IR. In multivariate analyses including saturated fat intake, study group, and other determinants of HOMA-IR (serum triglyceride concentration, weight for height, and systolic blood pressure), study group was, whereas saturated fat intake was not, significantly associated with HOMA-IR. This suggests that the beneficial effect of intervention on insulin sensitivity was largely, but not fully, explained by the decrease in saturated fat intake.CONCLUSIONS -The long-term biannual dietary intervention decreases the intake of total and saturated fat and has a positive effect on insulin resistance index in 9-year-old children. Diabetes Care 29:781-785, 2006I nsulin resistance, defined as an inadequate metabolic response to plasma insulin at normal concentrations (1,2), is promoted by obesity and high intake of saturated fat (3-5), and up to 30% of overweight or obese individuals develop insulin resistance (6). Although the prevalence of the insulin resistance syndrome, i.e., a cluster of metabolic abnormalities associated with reduced insulin sensitivity, increases with age, it exists already in childhood (7,8). In adults, the insulin resistance syndrome is associated with type 2 diabetes and cardiovascular disease (1). Preventing obesity and sedentary lifestyle and supporting a healthy lifestyle are important preventive measures, particularly if started in childhood.The aim of the present study was to evaluate the effect of individualized repeatedly given dietary counseling aimed at a low-saturated fat low-cholesterol diet from the age of 7 years on serum insulin values and some other markers of the insulin resistance syndrome in 9-year-old healthy children. RESEARCH DESIGN AND METHODS -The study design of the ongoing prospective randomized Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) study, which began in 1990, has been published in detail (9,10). Briefly, 1,054 volu...

Background-Exposure to tobacco smoke is associated with markers of preclinical atherosclerosis in adults, but its effect on arterial structure in adolescents is unknown. Methods and Results-Healthy 13-year-old adolescents from the atherosclerosis prevention trial STRIP were studied.Maximum carotid and aortic intima-media thickness and brachial artery flow-mediated dilation were measured in 494 adolescents using high-resolution ultrasound. Serum lipid, lipoprotein, and apolipoprotein (Apo) A-I and B concentrations were determined using standard methods. Exposure to tobacco smoke was measured annually between ages 8 and 13 years using serum cotinine concentrations, analyzed with gas chromatography. To define longitudinal exposure, cotinine values of children having serum cotinine measured 2 to 6 times during follow-up were averaged and divided into tertiles (exposure groups): low (nϭ160), intermediate (nϭ171), and high (nϭ163 1 Passive smoking has been associated with attenuated endothelium-dependent dilation in young healthy adults. 2,3 We have previously shown in 11-year-old healthy children that tobacco smoke exposure is associated with endothelial dysfunction measured by flowmediated dilation (FMD) of the brachial artery. 4 In addition, both past and current passive smoking has been related with increased carotid intima-media thickness (cIMT) in adults. [5][6][7] Moreover, tobacco smoke exposure in pregnancy has recently been associated with increased aortic intima-media thickness (aIMT) in neonates 8 and increased cIMT in young adulthood. 9 Conventional cardiovascular risk factors have been related to early structural vascular wall changes in childhood, 10 -12 and exposure to cardiovascular risk factors in adolescence predicts increased adult cIMT. 13 However, none of the previous studies has examined the impact of exposure to tobacco smoke on IMT in healthy children or adolescents.Exposure to tobacco smoke may lead to alterations in serum lipid profile, especially to decrease in HDL cholesterol, in children 14,15 and adolescents. 16,17 In adults, heavy workplace exposure to tobacco smoke has been demonstrated to have an adverse influence on serum lipids. 18,19 Recently, it was indicated that maternal smoking in pregnancy is associ- 21 Exposure to tobacco smoke as indicated by objective measurement, serum cotinine concentration, has been frequently determined in school-aged children. The aim of the present study was to examine the effects of frequent exposure to tobacco smoke on vascular wall structure, endothelial function, and serum lipid profile in healthy 13-year-old adolescents. WHAT IS KNOWN• Exposure to environmental tobacco smoke is related to increased carotid intima-media thickness in adults, but this association has not been studied in children.• Exposure to environmental tobacco smoke may lead to alterations in serum lipid profile, but there are no data on the relations of tobacco smoke exposure and apolipoprotein levels in children. WHAT THE STUDY ADDS• This study shows that frequent exposure ...

Background-We previously showed that low-saturated-fat dietary intervention from infancy until 5 years of age safely and effectively reduced serum cholesterol concentration. We now report how such intervention influenced serum lipids, LDL particle size, and HDL subfractions in children when they reached the age of 7 years. Methods and Results-Healthy 7-month-old infants (nϭ1062) were randomized to the intervention (nϭ540) and control (nϭ522) groups. Each year, two individualized counseling sessions were organized to the intervention families. Serum lipid values were measured annually. The intervention boys had 0.20 to 0.39 mmol/L lower serum cholesterol values than the control boys throughout the follow-up (always PϽ0.05), but the values of the intervention and control girls did not differ. The LDL particle sizes and HDL subfractions were determined in a random subgroup of 96 intervention and 101 control children at the age of 7 years. The mean particle diameter of major LDL peak was 262.6 Å in the intervention boys and 258.5 Å in the control boys (Pϭ0.05), and 259.2 Å in the intervention girls and 261.3 Å in the control girls (Pϭ0.30). HDL 2 and HDL 3 cholesterol concentrations did not differ between the intervention and control children or between the two genders. Conclusions-The 7-year intervention favorably influenced not only the serum total and LDL cholesterol concentrations but also the LDL particle size in boys. LDL particle size remained unchanged in girls, as did HDL 2 and HDL 3 concentrations in both genders. (Circulation. 2003;108:672-677.)