Endothelial Dysfunction In Adolescents Research Articles

New indices in predicting cardiometabolic risk and its relation to endothelial dysfunction in adolescents: The HELENA study

Background and aimsBlood pressure (BP) changes and insulin resistance (IR) are important cardiometabolic risk (CMR) factors; their early identification can contribute to the reduction of cardiovascular events in adulthood. This necessitates the search for more accessible and easily applied indicators for their prediction. Therefore, this study aimed to evaluate the predictive power of the indices, TyG, TG/HDL-c, height-corrected lipid accumulation product (HLAP), and visceral adiposity index (VAI), in identifying the CMR obtained by high BP and IR and to verify their relationship with biomarkers of endothelial dysfunction (ED) in European adolescents. Methods and resultsThe anthropometric data and blood biomarkers of 744 adolescents (343 boys and 401 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study (HELENA-CSS), with a mean age of 14.67 (SD 1.15) years, were assessed. The adolescents were then classified according to the presence or absence of high BP and IR. The cut-off points of the indices evaluated for the identification of CMR were determined. The relationship between CMR diagnosed using these indices and ED biomarkers was tested. The HLAP and TG/HDL-c were fair predictors of CMR obtained by IR in male adolescents. These indices showed association with hsCRP in sVCAM-1 in boys, but it lost significance after adjusting for age and body mass index. ConclusionTG/HDL-c and HLAP indices showed a fair performance in predicting CMR, obtained by IR, in male adolescents. ED showed no association with the CMR identified by the indices.

Early Signs of Microvascular Endothelial Dysfunction in Adolescents with Newly Diagnosed Essential Hypertension.

Endothelial dysfunction represents one of the key pathomechanisms in many diseases, including hypertension. Peripheral arterial tonometry (PAT) evaluates the functional status of microvascular endothelium and offers a biomarker of early, potentially reversible, vascular damage. This study aimed to assess endothelial function using conventional and novel indices of PAT in pediatric hypertensives. As such, 100 adolescents with normal blood pressure, and essential and white-coat hypertension were examined using EndoPAT 2000. Conventional reactive hyperemia index (RHI) and novel indices of hyperemic response, including the area under the curve of hyperemic response (AUC), were evaluated. AUC was the only parameter sensitive to the effect of hypertension, with significantly lower values in essential hypertensives compared to normotensives and white-coat hypertensives (p = 0.024, p = 0.032, respectively). AUC was the only parameter significantly correlating with mean ambulatory monitored blood pressure (r = −0.231, p = 0.021). AUC showed a significant negative association with age (p = 0.039), but a significant positive association with pubertal status indexed by plasma levels of dehydroepiandrosterone (p = 0.027). This is the first study reporting early signs of microvascular endothelial dysfunction evaluated using PAT in adolescents with newly diagnosed essential hypertension. Detailed analysis of hyperemic response using overall magnitude indexed by AUC provided a more robust method compared to the conventional evaluation of RHI.

Characterization and assessment of endothelial dysfunction in adolescents with obesity and vitamin D deficiency

Background. Obesity and vitamin D deficiency in children are widespread in economically developed countries. Among children with obesity and components of the metabolic syndrome, vitamin D deficiency is more common than in children with a normal body mass index (BMI). The growth of metabolic disorders, atherosclerosis, early onset of type 2 diabetes mellitus lead to fatal vascular accidents in young people, and therefore the search for new ways of early diagnosis of these processes is relevant.
 Aim. To study of the relationship of endothelial dysfunction with vitamin D deficiency, obesity and associated metabolic disorders among adolescents in Saint Petersburg.
 Materials and methods. 5 adolescents aged 1416 years (150.76 years) with primary obesity were examined. Anthropometric parameters were studied: waist circumference, weight, height, calculation of BMI, stage of puberty according to Tanner. Laboratory examination included the following parameters: serum glucose, cholesterol, triglycerides, high density lipoproteins, low density lipoproteins, insulin, 25(OH)D. Atherogenicity index (AI), insulin resistance index (HOMA-IR), vitamin D sufficiency were calculated. Endothelial function was assessed by the value of the reactive hyperemia index (RHI), automatically calculated by the EndoPAT 2000 device (Itamar Medical, Israel).
 Results. All examined patients had abdominal obesity (median BMI 33.5 kg/m2 [30.9; 34.2]) and reduced vitamin D supply (median 25(OH)D 17.2 ng/ml). Hypercholesterolemia and dyslipidemia due to an increase in low density lipoproteins were diagnosed in 1 (20%) case. Dyslipidemia due to a decrease in high density lipoproteins was detected in 3 (60%) patients. An increase in IA was found in 4 (80%) people. Insulin resistance was present in 60% of the examined, the median value of HOMA-IR was 5.6. The median RHI was 1.74 [1.72; 2.13]. Optimum RHI values were observed in 2 (40%) patients; in most (60%) adolescents, the RHI values corresponded to subnormal values and were close to the lower limit of this zone. A significant inverse correlation of RHI with AI was obtained (R=-0.63, p0.05).
 Conclusion. Taking into account the risk factors previously identified in the examined patients (dyslipidemia, insulin resistance, reduced vitamin D supply), endothelial dysfunction in these patients was regarded as a cardiovascular risk factor. A manageable risk factor is a reduced supply of vitamin D, which can be corrected by an additional donation of cholecalciferol.

Arsenic exposure from drinking water and endothelial dysfunction in Bangladeshi adolescents

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, with ∼80% of CVD-related deaths occurring in low- and middle-income countries. Growing evidence suggests that chronic arsenic exposure may contribute to CVD through its effect on endothelial function in adults. However, few studies have examined the influence of arsenic exposure on cardiovascular health in children and adolescents. To examine arsenic's relation to preclinical markers of endothelial dysfunction, we enrolled 200 adolescent children (ages 15–19 years; median 17) of adult participants in the Health Effects of Arsenic Longitudinal Study (HEALS), in Araihazar, Bangladesh. Participants' arsenic exposure was determined by recall of lifetime well usage for drinking water. As part of HEALS, wells were color-coded to indicate arsenic level (<10 μg/L, 10–50 μg/L, >50 μg/L). Endothelial function was measured by recording fingertip arterial pulsatile volume change and reactive hyperemia index (RHI) score, an independent CVD risk factor, was calculated from these measurements. In linear regression models adjusted for participant's sex, age, education, maternal education, land ownership and body weight, individuals who reported always drinking water from wells with >50 μg/L arsenic had a 11.75% lower level of RHI (95% CI: −21.26, −1.09, p = 0.03), as compared to participants who drank exclusively from wells with ≤50 μg/L arsenic. Sex-stratified analyses suggest that these associations were stronger in female participants. As compared to individuals who drank exclusively from wells with ≤50 μg/L arsenic, the use of wells with >50 μg/L arsenic was associated with 14.36% lower RHI (95% CI: −25.69, −1.29, p = 0.03) in females, as compared to 5.35% lower RHI (95% CI: −22.28, 15.37, p = 0.58) in males for the same comparison. Our results suggest that chronic arsenic exposure may be related to endothelial dysfunction in adolescents, especially among females. Further work is needed to confirm these findings and examine whether these changes may increase risk of later adverse cardiovascular health events.

Association between Urinary Phthalate Metabolites and Markers of Endothelial Dysfunction in Adolescents and Young Adults

Endothelial function is crucial in the pathogenesis of circulatory and cardiovascular toxicity; epidemiologic research investigating the association between phthalate exposure and endothelial dysfunction remains limited. We examined the associations between exposures to specific phthalates (di-2-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP) and circulating endothelial and platelet microparticles (EMPs and PMPs) in adolescents and young adults. Of the 697 participants recruited, anthropometric measurements and health-related behaviors relevant to cardiovascular risks were collected and assessed. Urine and serum were collected and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and flow cytometry. Multiple linear regression indicated that increases in urinary concentrations of ΣDEHP and MnBP (mono-n-butyl phthalate), across quartiles, were positively associated with serum EMPs level (p for trend <0.001 and <0.001; β = 0.798 and 0.007; standard error = 0.189 and 0.001, respectively). Moreover, female and overweight subjects had higher MnBP, and males were more vulnerable to DnBP exposure compared to females. In conclusion, our results demonstrate a dose-response relationship between exposures to phthalates (ΣDEHP and MnBP) and microparticle formation (EMPs and PMPs) in adolescents and young adults. The findings indicate that exposures to phthalates of both low and high-molecular weight are positively associated with microparticle production, and might contribute to endothelial dysfunction; such damage might manifest in the form of atherosclerotic-related vascular diseases. Future in vivo and in vitro studies are warranted to elucidate whether a causal relationship exists between phthalate exposure and EMPs and PMPs.

The association between metabolic components and markers of inflammatory and endothelial dysfunction in adolescents, based on the Ewha Birth and Growth Cohort Study.

We assessed the association between metabolic health and markers of inflammation and of endothelial dysfunction using data from the Ewha Birth and Growth Cohort Study. The data of 195 subjects aged 13–15 years were analyzed. To assess metabolic syndrome, continuous metabolic syndrome (cMets) scores were calculated. We measured the levels of high-sensitivity C-reactive protein (hs-CRP), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) as markers of inflammation and endothelial dysfunction. An increase of one SD in the cMets score resulted in a 1.25-fold (95% CI 1.10–1.42) increase in the risk of acute inflammatory status and a 1.26-fold (95% CI 1.11–1.43) increase in the risk of endothelial dysfunction as defined by ICAM-1, while VCAM-1 showed a meaningless trend. Of the metabolic components, body mass index (BMI) was positively associated with elevated hs-CRP levels and high-density lipoprotein cholesterol (HDL-c) levels were negatively associated with elevated ICAM-1 levels. Additionally, a mediation analysis showed that a high BMI was directly related to elevated hs-CRP levels and indirectly related to elevated ICAM-1 levels via HDL-c. Our findings show that poor metabolic health was related to an unfavorable inflammatory status and endothelial dysfunction in adolescents.

Higher Hepcidin Levels Associate with Visceral Fat and Cardiometabolic Risk in Obese Adolescents

Background: Hepcidin is a hormone that regulates iron flow in plasma, its production is induced by an iron overload and by inflammation. Some studies conducted in children and adolescents report an iron deficiency secondary to obesity-related to elevated levels of hepcidin. Although it is know hepcidin rises when IL6 increases, the relationship between hepcidin, dyslipidemia, IR, visceral adiposity index (VAI) and endothelial dysfunction in adolescents with obesity is unclear. Aims: We set out to explore the difference of hepcidin, iron metabolism markers and IL-6 between obese and no obese adolescents, and identify associations of with inflammation, dyslipidemia, insulin resistance, and endothelial dysfunction. Methods: Cross-sectional study of 29 obese adolescents and 30 controls subjects (normal BMI) from Guanajuato, Mexico. Anthropometric measurements and blood pressure were conducted using standard methods, VAI was calculated. Iron metabolism markers (hepcidin, transferrin, ferritin, soluble transferrin receptor -sTFR) were assayed by ELISA, as well as IL-6. Lipid profile and insulin were measured by standard auto-analyzer methods. We calculated HOMA index. sdLDL was analyzed by gradient electrophoresis using the Lipoprint LDL method from Quantimetrix. Flow-mediated vasodilation (FMD) and arterial stiffness were measured by ultrasound. The Ethical Committee of the University of Guanajuato approved this study and informed consent was obtained from the participant adolescents and their parents. Results: The obesity group showed significantly higher levels of hepcidin 14070.8 ± 7113.5 vs 8419.1 ± 4826.8c; IL-6 2.0 (1.0-4.9) vs 0.9 (0.5-1.3)c and ferritin 94.4 ± 82.4 vs 55.1 ± 39.6a. No significant difference was found for transferrin, sTFR and sTFR index. Obese adolescents showed significantly lower HDL-C (58.2 ± 9.6 vs 63.6 ± 5.0a mg/dl and higher levels of TG 139.3 ± 64.2 vs 83.2 ± 42.9c; mg/dl, sdLDL% 3.78 ± 4 vs 1.85 ±2.7a; HOMA (3.34 (2.4-5.5) vs 1.8 (1.2-2.2)d; VAI 1.6 ± 0.8 vs 0.9 ± 0.5c. FMD was significantly lower in obese adolescents 20.64 ± 7.1 vs 27.7 ± 9.3b. Hepcidin correlated positively with VAI r=0.29a; IL-6 r=0.35b; TG r=0.38b; sdLDL3% r=0.31a; HOMA r=0.29a; SBP r=0.36b; arterial stiffness r=0.29a; and negatively with FMD r=-0.29a. IL-6 correlated positively with VAI r=0.30 a and HOMA r=0.36 b ap<0.05; bp<0.01, cp<0.001; dp<0.0001 Conclusions: Adolescents with obesity show higher hepcidin levels that are associated with cardiometabolic risk markers such as IR, VAI, atherogenic dyslipidemia and endothelial dysfunction, while IL-6 was only associated with IR, and VAI. This suggests that hepcidin is a valuable marker of inflammation regardless of changes in iron metabolism and total body iron (TBI) as demonstrated by unchanged sTFR and TBI as sTFR/ferritin index. Long term effects of higher hepcidin levels on iron status should be explored.

Endothelial dysfunction in adolescents and young adults with nonalcoholic liver disease

Nonalcoholic liver disease is a global public health problem that increases cardiovascular morbidity and mortality in these patients. This paper discusses endothelial dysfunction among patients (adolescents and young adults) with nonalcoholic liver disease.

Effect of Low- Versus High-Intensity Exercise Training on Biomarkers of Inflammation and Endothelial Dysfunction in Adolescents With Obesity: A 6-Month Randomized Exercise Intervention Study.

To investigate the effects of a low- versus high-intensity aerobic training on biomarkers of inflammation and endothelial dysfunction in adolescents with obesity. Sixty-two adolescents with obesity [age = 15 (14) y, body mass index = 34.87(4.22) kg·m-2] were randomized to receive either a high-intensity training (HIT, n = 31) or a low-intensity training (LIT, n = 31) for 24weeks. All participants also received nutritional, psychological, and clinical counseling. Leptin, total and subtype leukocyte counts, tumor necrosis factor-alpha, interleukin-6, myeloperoxidase, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were obtained at baseline and after 24weeks. HIT reduced neutrophils [from 4.4(1.9) to 3.6(1.3) µL-1 × 103; P = .01] and monocytes [from 7.2(2.5) to 5.2 (1.8) µL-1 × 102; P < .01], but LIT increased neutrophils [from 4.5(1.7) to 5.2(3.3) µL-1 × 103; P = .01]. Although tumor necrosis factor-alpha increased in LIT [from 13.3 (7.5) to 17.7 (10.8) pg·mL-1; P = .01], it decreased in HIT [from 12.4 (7.5) to 11.3 (6.2) pg·mL-1; P = .01]. No changes in leukocyte counts, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and homeostasis assessment model for insulin resistance were observed. Both HIT and LIT improved the inflammatory profile. The study, however, indicated that the number of biomarkers and the magnitude of changes were higher in the HIT compared with LIT.

MV2-6 - Vascular compliance and endothelial dysfunction in adolescents born with intra uterine growth retardation

MV2-6 - Vascular compliance and endothelial dysfunction in adolescents born with intra uterine growth retardation

Urinary biomarkers as indicator of chronic inflammation and endothelial dysfunction in obese adolescents

BackgroundObesity is a pro-inflammatory state that may predispose patients to acute coronary syndrome characterized by chronic low grade inflammation resulting in endothelial dysfunction (ED). The aim of the study was to evaluate urinary biomarkers of inflammation and ED in adolescents with obesity.MethodsSixty three subjects were recruited for the study. Twenty healthy adolescents with normal body mass (NW), 14 overweight (OW), 29 obese (OA) subjects were selected. An EndoPat 2000 device was used to measure the reactive hyperemia index (RHI). First morning fasting urine samples were tested for interleukin 6 (IL-6), endothelin 1 (ET-1), alpha-1-acid glycoprotein (AGP), tumor necrosis factor- α (TNF-α) and corrected to urinary creatinine.ResultsUrinary TNF-α was significantly higher in OA group (52.4 ± 15.3 pg/mg) compared to adolescents with NW (14.1 ± 1.2 pg/mg, P = 0.04). ET-1 levels were found to be higher in OW (5.18 ± 1.6 pg/mg) compared with NW (3 · 47 ± 0.3 pg/mg, P = 0.24); and higher in OA (8.48 ± 3.1 pg/mg) compared to both NW (P = 0.19) and OW (P = 0.40). Similarly a higher AGP level was observed in OW (864.8 ± 156 ng/mg) and OA (808.3 ± 186 ng/mg) compared to NW (653 ± 69 ng/mg) (P = 0.16 & 0.49 respectively). Inflammatory markers namely, TNF-α, IL-6 and AGP significantly and positively correlated with each other and with ET-1, a marker for endothelial dysfunction. This significant correlation was also observed when tested separately in the subgroups (NW, OW and OA). There were no differences in RHI levels among the study groups.ConclusionUrinary TNF-alpha is significantly elevated in obese adolescents and correlates with urinary ET-1, which is recognized as a biomarker for endothelial dysfunction. Since obesity is a chronic inflammatory state, elevated urinary TNF-alpha might be used as a non invasive tool to monitor the level of that inflammation.

Assessing endothelial dysfunction in adolescents and young adults with type 1 diabetes mellitus using a non-invasive heat stimulus.

Microvascular dysfunction is a key event in the development of atherosclerosis, which predates the clinical manifestations of vascular disease including stroke and myocardial infarction. Dysfunction of the microvasculature can be measured as a decreased microperfusion in response to heat. We sought to evaluate the microvasculature using heat among adolescents and young adults with type 1 diabetes (T1D) compared to healthy non-diabetic controls. We hypothesized that youth with T1D would have impaired microvascular function measured as decreased perfusion. We studied 181 adolescents and young adults with T1D and 96 age-, race-, and sex-matched healthy controls (mean age 19 yr). Patients were seen at an in-person study visit where demographics, anthropometrics, and laboratory data was obtained. Skin microvascular perfusion was measured on the volvar surface of the right forearm using a standard laser flow Doppler. Measurements were taken at baseline and after heating to 44° C. Youth with T1D had decreased microvascular perfusion as measured by lower percent change of perfusion units (1870 ± 945 vs. 2539 ± 1255, p < 0.01) and percent change in area under the curve (1870 ± 945 vs. 2539 ± 1255, p < 0.01) compared to controls. Glycosylated hemoglobin A1c (HbA1c) was found to be an independent determinant of microvascular function (p < 0.05). Adolescents and young adults with T1D have evidence of microvascular dysfunction that can be detected using heat, a non-invasive physiologic stimulus. HbA1c appears to play an independent role in determining microvascular perfusion suggesting tight glycemic control is probably important for the development of vascular disease.

Endothelial and metabolic disorders in adolescence: low birth weight is not an isolated risk factor.

Low birth weight (LBW) seems to be a determining factor for many cardiovascular diseases in adult life. The objectives of this study were to investigate the occurrence of metabolic syndrome (MetS) and endothelial dysfunction in adolescents with LBW and compare them with subjects with normal birth weights (NBW). This retrospective cohort study evaluated 172 adolescents (86 in each group) aged 10-20 years, who were born in a reference maternity hospital. The following criteria were adopted: International Diabetes Federation parameters for the diagnosis of MetS and flow-mediated brachial artery dilatation for endothelial dysfunction. Student's t-test or Mann-Whitney tests were used for continuous variables (depending on the normality of distribution evaluated by the Shapiro-Wilk test), and the Fisher exact test was used for categorical variables. The significance level was determined at 0.05. MetS was present in three cases of LBW and in four cases of NBW (p=0.70). The number of components of the syndrome was, on average, 0.6 and 0.5 in LBW and NBW, respectively (p=0.77). Endothelial dysfunction occurred in 25 (29.1%) cases of LBW and in 31 (36.1%) cases of NBW (p=0.33). LBW did not represent a risk factor in the occurrence of MetS or endothelial dysfunction in adolescence.

The association between metabolic syndrome and vascular endothelial dysfunction in adolescents

The aim of this study was to investigate the association between metabolic syndrome (MS) and vascular endothelial cell dysfunction (ECD) in adolescents. Sixty obese pediatric inpatients at the General Hospital of Tianjin Medical University from February 2011 to February 2012 were included. Among these, 30 patients were obese and 30 patients were diagnosed with MS. Thirty healthy subjects were randomly selected as the control group. A series of indices, including height, body weight, waist circumference, hip circumference, waist/hip circumference and body mass index (BMI), as well as total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels were evaluated. von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1) levels were determined using an enzyme linked immunosorbent assay (ELISA). Correlation analysis between height, body weight, waist circumference, hip circumference, waist/hip circumference, BMI, TC, TG, LDL, HDL and PAI-1, as well as vWF was performed. Significant increases of vWF and PAI-1 levels were observed in the MS group compared with the control group (P<0.05). For the adolescents in the obese group, a significant increase of PAI-1 level was observed compared with the control group (P<0.05). No significant difference was observed between the vWF levels in the obese and control groups. PAI-1 was positively associated with BMI, waist circumference, waist/hip circumference, TC, TG, LDL, fasting plasma glucose (FPG), fasting insulin (FINS), systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively (P<0.05). In addition, PAI-1 was negatively associated with HDL levels (P<0.05). PAI-1 and vWF may be used as biomarkers for the diagnosis of ECD. ECD in individuals with MS may be associated with obesity, blood fat, blood sugar and blood pressure. FPG, TC and TG may be risk factors for ECD.

Effects of a physical activity program on markers of endothelial dysfunction, oxidative stress, and metabolic status in adolescents with metabolic syndrome.

The metabolic syndrome (MetS) is a precursor of diabetes. Physical activity (PA) improves endothelial dysfunction and may benefit patients with MetS. Aims. To evaluate the effect of a physical activity (PA) program on markers of endothelial dysfunction and oxidative stress in adolescents with (MetS). Methods. We carried out a cohort study of 38 adolescents with and without MetS (18 females and 20 males). All participants completed a 3-month PA program. All variables of the MetS as well as markers of endothelial dysfunction and oxidative stress tests were evaluated. Results. Females with and without MetS showed significant differences for almost all components of the MetS, whereas males were significantly different in half of the components. After the PA program, components of the MetS were not different from baseline values except for HDL-C levels. Some baseline endothelial dysfunction markers were significantly different among adolescents with and without MetS; however, after the PA program, most of these markers significantly improved in subjects with and without MetS. Conclusion. PA improves the markers of endothelial dysfunction in adolescents with MetS although other changes in the components of the MetS were not observed. Perhaps the benefits of PA on all components of MetS would appear after a PA program with a longer duration.

Metabolic Syndrome Racial Differences in Adolescents

The metabolic syndrome consists of obesity, insulin resistance, dyslipidemia, atherosclerosis, and hypertension. Its clinical outcomes are stroke, myocardial infarction, and type 2 diabetes. Each of these is more frequent in African-Americans than in Caucasians. This is surprising since most studies indicate that the incidence of the metabolic syndrome is lower in African-American than Caucasian adults. There is growing evidence that adult cardiovascular disease has its origin in childhood and adolescents. Thus, it is important that we understand differences in the pathophysiological precursors to metabolic and cardiovascular disease in this age group. Many studies, but not all, have demonstrated that African-American children and adolescents are insulin resistant compared to similar age Caucasians. The increased insulin resistance occurs in spite of lower triglyceride levels. Low triglyceride levels are usually associated with increased insulin sensitivity. There is evidence that the relationship between triglycerides and insulin sensitivity differs between the two races. African-Americans compensate for the increased insulin resistance by increasing insulin secretion and insulin clearance. Interestingly, those studies that have not found increased insulin resistance in African-Americans have found increased insulin secretion suggesting the increased secretion may precede the insulin resistance. Hyperinsulinism and insulin resistance are linked to endothelial dysfunction in adults and African-American adolescents have poorer endothelial function than do Caucasians. In African-American adolescents, endothelial function decreases as insulin secretion increases. It is likely that the hyperinsulinism, insulin resistance and endothelial dysfunction in adolescent African-American adolescents play an important role in the increased rates of cardiovascular disease and type 2 diabetes. Future research should focus on the mechanisms of these abnormalities and ways to prevent their development in this age group.

Subclinical Inflammation, Endothelial Progenitor Cell Depletion, and Endothelial Dysfunction in Adolescents with Obesity

Obesity related inflammation plays a key role in endothelial injury, which is an antecedent of adult cardiovascular disease. Few studies have attempted to define these relationships in children. We hypothesized that obesity is related to inflammation, endothelial progenitor cell (EPC) depletion, and endothelial dysfunction in adolescents. A total of 100 normal weight (n=45, BMI &lt;85th percentile for their age and sex) and obese (n=55, BMI &gt;95th) adolescents (9‐18 years of age) were recruited. Obese adolescents had higher glucose, total‐ and LDL‐cholesterol, and lower HDL‐cholesterol levels (p&lt;0.05). They had higher plasma hsCRP (6.40 +/‐ 8.93 vs. 0.45 +/‐ 0.90 mg/L, p&lt;0.001) and lower adiponectin (2410.72 +/‐ 727.69 vs. 3111.68 +/‐ 1063.18 mg/L, p&lt;0.01) levels. Meanwhile, the obese group had fewer EPCs, measured by flow cytometry (1.76 +/‐ 0.69 vs. 2.16 +/‐ 0.81 %, p&lt;0.01). Increased forearm vascular resistance (FVR) (mmHg/ml/100 ml/min) was also observed, both at basal condition (44.22 +/‐ 28.29 vs. 30.54 +/‐ 15.73, p&lt;0.01) and after ischemic test (9.34 +/‐ 5.90 vs. 6.31 +/‐ 5.04, p&lt;0.01), in obese children. Significant correlations were found between BMI and adiponectin (r= ‐0.46), EPC (r= ‐0.26), hsCRP (r=0.64), and FVR (basal: r=0.35; ischemia: r= 0.30). EPC was negatively correlated with hsCRP (r= ‐0.28), suggesting obesity‐related inflammation is involved in endothelial injury in adolescents.

Methylenetetrahydrofolate reductase and methionine synthase reductase gene polymorphisms and protection from microvascular complications in adolescents with type 1 diabetes

Folate status has been associated with endothelial dysfunction in adolescents with type 1 diabetes, and elevated total plasma homoocyst(e)ine (tHcy) is a risk for vascular disease in the non-diabetic population. Polymorphisms in genes involved in folate and homocysteine metabolism are implicated in vascular disease. We aimed to determine whether polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes are risk factors for early microvascular disease in a large group of adolescents with type 1 diabetes. Four hundred and eighty adolescents were screened annually for retinopathy and microalbuminuria for a median of 4 yr. Molecular analysis for the polymorphisms 677C-->T, 1298A-->C in MTHFR, and 66A-->G in MTRR was performed. The MTRR 66GG genotype reduced the risk for elevated albumin excretion rate (AER) (OR 0.47, CI 0.25, 0.88, p = 0.018) and showed a trend to reduced risk for microalbuminuria (OR 0.27, CI 0.06-1.21, p = 0.09). Survival without elevated AER was increased with the MTRR 66GG genotype (12.4 vs. 9.7 yr, p = 0.04) and with the MTHFR 1298CC genotype (15.2 vs. 10.2 yr, p = 0.007). Conversely, survival without retinopathy was reduced with the MTHFR 677TT and MTRR 66GG combined genotype (6.2 vs. 10.2 yr, p = 0.015). The MTRR 66GG and MTHFR 1298 CC genotypes may confer protection against early nephropathy, possibly because they are associated with lower tHcy. The MTHFR 677 TT was only related to earlier onset retinopathy in combination with MTRR 66GG.

Impairment of the Fibrinolytic System is Present and is a Marker for Endothelial Dysfunction in Adolescents after Kawasaki Disease

Impairment of the Fibrinolytic System is Present and is a Marker for Endothelial Dysfunction in Adolescents after Kawasaki Disease