High-density lipoprotein and the risk of recurrent venous thromboembolism

BACKGROUND - High-density lipoprotein (HDL) protects against arterial atherothrombosis, but it is unknown whether it protects against recurrent venous thromboembolism. METHODS AND RESULTS - We studied 772 patients after a first spontaneous venous thromboembolism (average follow-up 48 months) and recorded the end point of symptomatic recurrent venous thromboembolism, which developed in 100 of the 772 patients. The relationship between plasma lipoprotein parameters and recurrence was evaluated. Plasma apolipoproteins AI and B were measured by immunoassays for all subjects. Compared with those without recurrence, patients with recurrence had lower mean (±SD) levels of apolipoprotein AI (1.12±0.22 versus 1.23±0.27 mg/mL, P<0.001) but similar apolipoprotein B levels. The relative risk of recurrence was 0.87 (95% CI, 0.80 to 0.94) for each increase of 0.1 mg/mL in plasma apolipoprotein AI. Compared with patients with apolipoprotein AI levels in the lowest tertile (<1.07 mg/mL), the relative risk of recurrence was 0.46 (95% CI, 0.27 to 0.77) for the highest-tertile patients (apolipoprotein AI >1.30 mg/mL) and 0.78 (95% CI, 0.50 to 1.22) for midtertile patients (apolipoprotein AI of 1.07 to 1.30 mg/mL). Using nuclear magnetic resonance, we determined the levels of 10 major lipoprotein subclasses and HDL cholesterol for 71 patients with recurrence and 142 matched patients without recurrence. We found a strong trend for association between recurrence and low levels of HDL particles and HDL cholesterol. CONCLUSIONS - Patients with high levels of apolipoprotein AI and HDL have a decreased risk of recurrent venous thromboembolism. © 2007 American Heart Association, Inc.

High-density lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men

Background-Although dyslipoproteinemia is associated with arterial atherothrombosis, little is known about plasma lipoproteins in venous thrombosis patients. Methods and Results-We determined plasma lipoprotein subclass concentrations using nuclear magnetic resonance spectroscopy and antigenic levels of apolipoproteins AI and B in blood samples from 49 male venous thrombosis patients and matched controls aged <55 years. Venous thrombosis patients had significantly lower levels of HDL particles, large HDL particles, HDL cholesterol, and apolipoprotein AI and significantly higher levels of LDL particles and small LDL particles. The quartile-based odds ratios for decreased HDL particle and apolipoprotein AI levels in patients compared with controls were 6.5 and 6.0 (95% CI, 2.3 to 19 and 2.1 to 17), respectively. Odds ratios for apolipoprotein B/apolipoprotein AI ratio and LDL cholesterol/HDL cholesterol ratio were 6.3 and 2.7 (95% CI, 1.9 to 21 and 1.1 to 6.5), respectively. When polymorphisms in genes for hepatic lipase, endothelial lipase, and cholesteryl ester transfer protein were analyzed, patients differed significantly from controls in the allelic frequency for the TaqI B1/B2 polymorphism in cholesteryl ester transfer protein, consistent with the observed pattern of lower HDL and higher LDL. Conclusions-Venous thrombosis in men aged <55 years old is associated with dyslipoproteinemia involving lower levels of HDL particles, elevated levels of small LDL particles, and an elevated ratio of apolipoprotein B/apolipoprotein AI. This dyslipoproteinemia seems associated with a related cholesteryl ester transfer protein genotype difference. © 2005 American Heart Association, Inc.

Investigation of the low-density lipoprotein receptor gene and cholesterol as a risk factor for migraine

The Low-Density Lipoprotein Receptor (LDLR) gene is a cell surface receptor that plays an important role in cholesterol homeostasis. We investigated the (TA)n polymorphism in exon 18 of the LDLR gene on chromosome 19p13.2 performing an association analysis in 244 typical migraine-affected patients, 151 suffering from migraine with aura (MA), 96 with migraine without aura (MO) and 244 unaffected controls. The populations consisted of Caucasians only, and controls were age- and sex-matched. The results showed no significant difference between groups for allele frequency distributions of the (TA)n polymorphism even after separation of the migraine-affected individuals into subgroups of MA and MO affected patients. This is in contradiction to Mochi et al. who found a positive association of this variant with MO. Our study discusses possible differences between the two studies and extends this research by investigating circulating cholesterol levels in a migraine-affected population.

Association of HincII RFLP of low density lipoprotein receptor gene with obesity in essential hypertensives

Obese (BMI ≥ 26 kg/m 2; n = 51) and lean (BMI <26 kg/m 2; n = 61) Caucasian patients with severe, familial essential hypertension, were compared with respect to genotype and allele frequencies of a HincII RFLP of the low density lipoprotein receptor gene (LDLR). A similar analysis was performed in obese (n = 28) and lean (n = 68) normotensives. A significant association of the C allele of the T→C variant responsible for this RFLP was seen with obesity (χ 2 = 4.6, P = 0.029) in the hypertensive, but not in the normotensive, group (odds ratio = 3.0 for the CC genotype and 2.7 for CT). Furthermore, BMI tracked with genotypes of this allele in the hypertensives (P = 0.046). No significant genotypic relationship was apparent for plasma lipids. Significant linkage disequilibrium was, moreover, noted between the HincII RFLP and an ApaLI RFLP (χ 2 = 33, P<0.0005) that has previously shown even stronger association with obesity (odds ratio 19.6 for cases homozygous for the susceptibility allele and 15.2 for het-erozygotes). The present study therefore adds to our previous evidence implicating LDLR as a locus for obesity in patients with essential hypertension.

Cross-sectional study of a microsatellite marker in the low density lipoprotein receptor gene in obese normotensives

1. The low density lipoprotein receptor is an important regulator of serum cholesterol which may have implications for the development of both hypertension and obesity. In this study, genotypes for a low density lipoprotein receptor gene (LDLR) dinucleotide polymorphism were determined in both lean and obese normotensive populations. 2. In previous cross-sectional association studies an ApaLI and a HincII polymorphism for LDLR were shown to be associated with obesity in essential hypertensives. However, these polymorphisms did not show an association with obesity in normotensives. 3. In contrast, this study reports that preliminary results for an LDLR microsatellite marker, located more towards the 3' end of the gene, show a significant association with obesity in the normotensive population studied. These results indicate that LDLR could play an important role in the development of obesity, which might be independent of hypertension.

Porphyromonas gingivalis lipopolysaccharide alters atherosclerotic-related gene expression in oxidized low-density-lipoprotein-induced macrophages and foam cells

The molecular mechanism between atherosclerosis formation and periodontal pathogens is not clear although positive correlation between periodontal infections and cardiovascular diseases has been reported. Objective: To determine if atherosclerosis related genes were affected in foam cells during and after its formation by P. gingivalis lipopolysaccharide (LPS) stimulation. Methods: Macrophages from human THP-1 monocytes were treated with oxidized low density lipoprotein (oxLDL) to induce the formation of foam cells. P. gingivalis LPS was added to cultures of either oxLDL-induced macrophages or foam cells. The expression of atherosclerosis related genes was assayed by quantitative real time PCR and the protein production of granulocyte-macrophage colony-stimulating factor（GM-CSF）, monocyte chemotactic protein-1 (MCP-1), IL-1β, IL-10 and IL-12 was determined by ELISA. Nuclear translocation of NF-κB P65 was detected by immunocytochemistry and western blot was used to evaluate IKB-α degradation to confirm the NF-κB pathway activation. Results: P. gingivalis LPS stimulated atherosclerosis related gene expression in foam cells and increased oxLDL induced expression of chemokines, adhesion molecules, growth factors, apoptotic genes, and nuclear receptors in macrophages. Transcription of the pro-inflammatory cytokines IL-1β and IL-12 was elevated in response to LPS in both macrophages and foam cells, whereas the anti-inflammatory cytokine IL-10 was not affected. Increased NF-κB pathway activation was also observed in LPS and oxLDL co-stimulated macrophages. Conclusion: P. gingivalis LPS appears to be an important factor in the development of atherosclerosis by stimulation of atherosclerosis related gene expression in both macrophages and foam cells via activation of the NF-κB pathway.

Marked association of a RFLP for the low density lipoprotein receptor gene with obesity in essential hypertensives

RFLPs at the low density lipoprotein receptor locus (LDLR) display marked linkage disequilibrium between each other. Cross-sectional analysis of a bi-alleleic ApaLI RFLP of LDLR showed that the 9.4- and 6.6-kb alleles were present in similar frequency between a group of 84 Caucasian essential hypertensive (HT) and a group of 96 normotensive subjects whose parents each had a similar blood pressure status at age > or = 50. After subdividing HTs into lean and obese, however, the frequency of the 6.6-kb allele in the 27 HTs with BMI > or = 26 kg/m2 was 0.63, compared with 0.39 for HTs with BMI < 26 (chi 2 = 8.8; P = 0.004). The difference in genotype frequencies was even more striking (chi 2 = 23; P = 0.00008), with a virtual absence of 9.4-kb homozygotes in the obese HT group (1 vs 22). Genetic variation at LDLR (19p13.2) is thus associated with obesity in HT.

Association of a low density lipoprotein receptor microsatellite variant with obesity

OBJECTIVE To determine whether a microsatellite polymorphism located towards the 3' end of the low density lipoprotein receptor gene (LDLR) is associated with obesity. DESIGN A cross-sectional case-control study. SUBJECTS One hundred and seven obese individuals, defined as a body mass index (BMI) ≤ 26 kg/m2, and 163 lean individuals, defined as a BMI < 26 kg/m2. MEASUREMENTS BMI, blood pressure, serum lipids, alleles of LDLR microsatellite (106 bp, 108 bp and 112 bp). RESULTS There was a significant association between variants of the LDLR microsatellite and obesity, in the overall tested population, due to a contributing effect in females (χ2 = 12.3, P = 0.002), but not in males (χ2 = 0.3, P = 0.87). In females, individuals with the 106 bp allele were more likely to be lean, while individuals with the 112 bp and/or 108 bp alleles tended to be obese. CONCLUSIONS These results suggest that in females, LDLR may play a role in the development of obesity.

Effect of a single session of exercise on lipoprotein(a)

Lipoprotein(a) (Lp(a)) is bound to apolipoprotein B-100 by disulfide linkage and is associated in the upper density range of low density lipoprotein cholesterol. Persons with elevated concentrations of Lp(a) are regarded as having an increased risk for premature coronary artery disease. Although many studies exist evaluating the effects of a single session of exercise on lipids and lipoproteins, little information is available concerning the effects of exercise on Lp(a). Therefore, the purpose of this study was to determine the effects of a single exercise session on plasma Lp(a). Twelve physically active men completed two 30-min submaximal treadmill exercise sessions: low intensity (LI, 50% VO2max) and high intensity (HI, 80% VO2max). Blood samples were obtained immediately before and after exercise. Total cholesterol (LI: before 4.22 +/- 0.26, after 4.24 +/- 0.28; HI: before 4.24 +/- 0.31, after 4.11 +/- 0.28 mmol . l(-1), mean +/- SE) and triglyceride (LI: before 1.14 +/- 0.16, after 1.06 +/- 0.16; HI: before 1.12 +/- 0.19, after 1.21 +/- 0.19 mmol . l(-1)) concentrations did not differ immediately after either exercise session, nor did Lp(a) concentrations differ immediately after either exercise session (LI: before 4.1 +/- 2.2, after 4.0 +/- 2.1; HI: before 3.9 +/- 2.2, after 3.7 +/- 2.0 mg . dl(-1)). These results suggest that neither a low nor a high intensity exercise session lasting 30 min in duration has an immediate effect on plasma Lp(a).

Effects of four different single exercise sessions on lipids, lipoproteins, and lipoprotein lipase

The purpose of this study was to determine the threshold of exercise energy expenditure necessary to change blood lipid and lipoprotein concentrations and lipoprotein lipase activity (LPLA) in healthy, trained men. On different days, 11 men (age, 26.7 +/- 6.1 yr; body fat, 11.0 +/- 1.5%) completed four separate, randomly assigned, submaximal treadmill sessions at 70% maximal O-2 consumption. During each session 800, 1,100, 1,300, or 1,500 kcal were expended. Compared with immediately before exercise, high-density lipoprotein cholesterol (HDL-C) concentration was significantly elevated 24 h after exercise (P < 0.05) in the 1,100-, 1,300-, and 1,500-kcal sessions. HDL-C concentration was also elevated (P < 0.05) immediately after and 48 h after exercise in the 1,500-kcal session. Compared with values 24 h before exercise, LPLA. was significantly greater (P < 0.05) 24 h after exercise in the 1,100-, 1,300-, and 1,500-kcal sessions and remained elevated 48 h after exercise in the 1,500-kcal session. These data indicate that, in healthy, trained men, 1,100 kcal of energy expenditure are necessary to elicit increased HDL-C concentrations. These HDL-C changes coincided with increased LPLA.

Plasma lipid and lipoprotein responses during exercise

The purpose of this study was to examine the effect of prolonged exercise oil plasma lipid and lipoprotein concentrations and to identify caloric time-points where changes occurred. Eleven active male Subjects ran oil a treadmill at 70%,, of maximal fitness (VO2max) and expended 6 278.7 kilojoules (Kj) energy (1500 kcal). Blood samples were obtained at the 4185.8 Kj (1000 kcal) time-point during exercise and at each additional 418.6 Kj (100 kcal) expenditure until 6278.7 Kj was expended. After correcting for plasma volume changes, decreases in low-density lipoprotein cholesterol (LDL-C) were observed during exercise at time-points corresponding to 4604.4 and 5441.5 Kj (1100 and 1300 kcal) of energy expenditure, and immediately after exercise. Total cholesterol concentrations decreased significantly at exercise kilojoule expenditures of 4604.4, 5441.5 and 5860.1 (1100, 1300 and 1400 kcal). There were also exercise induced increases in high-density lipoprotein cholesterol (HDL-C) and HDL2-C concentrations immediately after exercise. Although acute lipid and lipoprotein changes are typically reported in the days following exercise, the Current data indicate that some lipoprotein concentrations change during acute exercise. Our data suggest that a threshold of exercise may be necessary to change lipoproteins during exercise. Future work Should identify potential mechanisms (lipoprotein lipase, cholesterol ester transport protein, LDL uptake) that alter lipoprotein concentrations during prolonged exercise.

Association of a low density lipoprotein receptor microsatellite variant with obesity

OBJECTIVE: To determine whether a microsatellite polymorphism located towards the 3' end of the low density lipoprotein receptor gene (LDLR) is associated with obesity. DESIGN: A cross-sectional case-control study. SUBJECTS: One hundred and seven obese individuals, defined as a body mass index (BMI) > or = 26 kg/m2, and 163 lean individuals, defined as a BMI < 26 kg/m2. MEASUREMENTS: BMI, blood pressure, serum lipids, alleles of LDLR microsatellite (106 bp, 108 bp and 112 bp). RESULTS: There was a significant association between variants of the LDLR microsatellite and obesity, in the overall tested population, due to a contributing effect in females (chi 2 = 12.3, P = 0.002), but not in males (chi 2 = 0.3, P = 0.87). In females, individuals with the 106 bp allele were more likely to be lean, while individuals with the 112 bp and/or 108 bp alleles tended to be obese. CONCLUSIONS: These results suggest that in females, LDLR may play a role in the development of obesity.

Increased cardio-metabolic risk is associated with increased TV viewing time

Purpose: Television viewing time, independent of leisure-time physical activity, has cross-sectional relationships with the metabolic syndrome and its individual components. We examined whether baseline and five-year changes in self-reported television viewing time are associated with changes in continuous biomarkers of cardio-metabolic risk (waist circumference, triglycerides, high density lipoprotein cholesterol, systolic and diastolic blood pressure, fasting plasma glucose; and a clustered cardio-metabolic risk score) in Australian adults. Methods: AusDiab is a prospective, population-based cohort study with biological, behavioral, and demographic measures collected in 1999–2000 and 2004–2005. Non-institutionalized adults aged ≥ 25 years were measured at baseline (11,247; 55% of those completing an initial household interview); 6,400 took part in the five-year follow-up biomedical examination, and 3,846 met the inclusion criteria for this analysis. Multiple linear regression analysis was used and unstandardized B coefficients (95% CI) are provided. Results: Baseline television viewing time (10 hours/week unit) was not significantly associated with change in any of the biomarkers of cardio-metabolic risk. Increases in television viewing time over five years (10 hours/week unit) were associated with increases in: waist circumference (cm) (men: 0.43 (0.08, 0.78), P = 0.02; women: 0.68 (0.30, 1.05), P <0.001), diastolic blood pressure (mmHg) (women: 0.47 (0.02, 0.92), P = 0.04), and the clustered cardio-metabolic risk score (women: 0.03 (0.01, 0.05), P = 0.007). These associations were independent of baseline television viewing time and baseline and change in physical activity and other potential confounders. Conclusion: These findings indicate that an increase in television viewing time is associated with adverse cardio-metabolic biomarker changes. Further prospective studies using objective measures of several sedentary behaviors are required to confirm causality of the associations found.

Waist circumference cut-off values for the prediction of cardiovascular risk factors clustering in Chinese school-aged children : a cross-sectional study

Background: Waist circumference has been identified as a valuable predictor of cardiovascular risk in children. The development of waist circumference percentiles and cut-offs for various ethnic groups are necessary because of differences in body composition. The purpose of this study was to develop waist circumference percentiles for Chinese children and to explore optimal waist circumference cut-off values for predicting cardiovascular risk factors clustering in this population.----- ----- Methods: Height, weight, and waist circumference were measured in 5529 children (2830 boys and 2699 girls) aged 6-12 years randomly selected from southern and northern China. Blood pressure, fasting triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and glucose were obtained in a subsample (n = 1845). Smoothed percentile curves were produced using the LMS method. Receiver-operating characteristic analysis was used to derive the optimal age- and gender-specific waist circumference thresholds for predicting the clustering of cardiovascular risk factors.----- ----- Results: Gender-specific waist circumference percentiles were constructed. The waist circumference thresholds were at the 90th and 84th percentiles for Chinese boys and girls respectively, with sensitivity and specificity ranging from 67% to 83%. The odds ratio of a clustering of cardiovascular risk factors among boys and girls with a higher value than cut-off points was 10.349 (95% confidence interval 4.466 to 23.979) and 8.084 (95% confidence interval 3.147 to 20.767) compared with their counterparts.----- ----- Conclusions: Percentile curves for waist circumference of Chinese children are provided. The cut-off point for waist circumference to predict cardiovascular risk factors clustering is at the 90th and 84th percentiles for Chinese boys and girls, respectively.

Body composition and its relationship to metabolic risk factors in Asian children

Obesity is a major public health problem in both developed and developing countries. The body mass index (BMI) is the most common index used to define obesity. The universal application of the same BMI classification across different ethnic groups is being challenged due to the inability of the index to differentiate fat mass (FM) and fat�]free mass (FFM) and the recognized ethnic differences in body composition. A better understanding of the body composition of Asian children from different backgrounds would help to better understand the obesity�]related health risks of people in this region. Moreover, the limitations of the BMI underscore the necessity to use where possible, more accurate measures of body fat assessment in research and clinical settings in addition to BMI, particularly in relation to the monitoring of prevention and treatment efforts. The aim of the first study was to determine the ethnic difference in the relationship between BMI and percent body fat (%BF) in pre�]pubertal Asian children from China, Lebanon, Malaysia, the Philippines, and Thailand. A total of 1039 children aged 8�]10 y were recruited using a non�]random purposive sampling approach aiming to encompass a wide BMI range from the five countries. Percent body fat (%BF) was determined using the deuterium dilution technique to quantify total body water (TBW) and subsequently derive proportions of FM and FFM. The study highlighted the sex and ethnic differences between BMI and %BF in Asian children from different countries. Girls had approximately 4.0% higher %BF compared with boys at a given BMI. Filipino boys tended to have a lower %BF than their Chinese, Lebanese, Malay and Thai counterparts at the same age and BMI level (corrected mean %BF was 25.7�}0.8%, 27.4�}0.4%, 27.1�}0.6%, 27.7�}0.5%, 28.1�}0.5% for Filipino, Chinese, Lebanese, Malay and Thai boys, respectively), although they differed significantly from Thai and Malay boys. Thai girls had approximately 2.0% higher %BF values than Chinese, Lebanese, Filipino and Malay counterparts (however no significant difference was seen among the four ethnic groups) at a given BMI (corrected mean %BF was 31.1�}0.5%, 28.6�}0.4%, 29.2�}0.6%, 29.5�}0.6%, 29.5�}0.5% for Thai, Chinese, Lebanese, Malay and Filipino girls, respectively). However, the ethnic difference in BMI�]%BF relationship varied by BMI. Compared with Caucasians, Asian children had a BMI 3�]6 units lower for a given %BF. More than one third of obese Asian children in the study were not identified using the WHO classification and more than half were not identified using the International Obesity Task Force (IOTF) classification. However, use of the Chinese classification increased the sensitivity by 19.7%, 18.1%, 2.3%, 2.3%, and 11.3% for Chinese, Lebanese, Malay, Filipino and Thai girls, respectively. A further aim of the first study was to determine the ethnic difference in body fat distribution in pre�]pubertal Asian children from China, Lebanon, Malaysia, and Thailand. The skin fold thicknesses, height, weight, waist circumference (WC) and total adiposity (as determined by deuterium dilution technique) of 922 children from the four countries was assessed. Chinese boys and girls had a similar trunk�]to�]extremity skin fold thickness ratio to Thai counterparts and both groups had higher ratios than the Malays and Lebanese at a given total FM. At a given BMI, both Chinese and Thai boys and girls had a higher WC than Malays and Lebanese (corrected mean WC was 68.1�}0.2 cm, 67.8�}0.3 cm, 65.8�}0.4 cm, 64.1�}0.3 cm for Chinese, Thai, Lebanese and Malay boys, respectively; 64.2�}0.2 cm, 65.0�}0.3 cm, 62.9�}0.4 cm, 60.6�}0.3 cm for Chinese, Thai, Lebanese and Malay girls, respectively). Chinese boys and girls had lower trunk fat adjusted subscapular/suprailiac skinfold ratio compared with Lebanese and Malay counterparts. The second study aimed to develop and cross�]validate bioelectrical impedance analysis (BIA) prediction equations of TBW and FFM for Asian pre�]pubertal children from China, Lebanon, Malaysia, the Philippines, and Thailand. Data on height, weight, age, gender, resistance and reactance measured by BIA were collected from 948 Asian children (492 boys and 456 girls) aged 8�]10 y from the five countries. The deuterium dilution technique was used as the criterion method for the estimation of TBW and FFM. The BIA equations were developed from the validation group (630 children randomly selected from the total sample) using stepwise multiple regression analysis and cross�]validated in a separate group (318 children) using the Bland�]Altman approach. Age, gender and ethnicity influenced the relationship between the resistance index (RI = height2/resistance), TBW and FFM. The BIA prediction equation for the estimation of TBW was: TBW (kg) = 0.231�~Height2 (cm)/resistance (ƒ¶) + 0.066�~Height (cm) + 0.188�~Weight (kg) + 0.128�~Age (yr) + 0.500�~Sex (male=1, female=0) . 0.316�~Ethnicity (Thai ethnicity=1, others=0) �] 4.574, and for the estimation of FFM: FFM (kg) = 0.299�~Height2 (cm)/resistance (ƒ¶) + 0.086�~Height (cm) + 0.245�~Weight (kg) + 0.260�~Age (yr) + 0.901�~Sex (male=1, female=0) �] 0.415�~Ethnicity (Thai ethnicity=1, others=0) �] 6.952. The R2 was 88.0% (root mean square error, RSME = 1.3 kg), 88.3% (RSME = 1.7 kg) for TBW and FFM equation, respectively. No significant difference between measured and predicted TBW and between measured and predicted FFM for the whole cross�]validation sample was found (bias = �]0.1�}1.4 kg, pure error = 1.4�}2.0 kg for TBW and bias = �]0.2�}1.9 kg, pure error = 1.8�}2.6 kg for FFM). However, the prediction equation for estimation of TBW/FFM tended to overestimate TBW/FFM at lower levels while underestimate at higher levels of TBW/FFM. Accuracy of the general equation for TBW and FFM compared favorably with both BMI�]specific and ethnic�]specific equations. There were significant differences between predicted TBW and FFM from external BIA equations derived from Caucasian populations and measured values in Asian children. There were three specific aims of the third study. The first was to explore the relationship between obesity and metabolic syndrome and abnormalities in Chinese children. A total of 608 boys and 800 girls aged 6�]12 y were recruited from four cities in China. Three definitions of pediatric metabolic syndrome and abnormalities were used, including the International Diabetes Federation (IDF) and National Cholesterol Education Program (NCEP) definition for adults modified by Cook et al. and de Ferranti et al. The prevalence of metabolic syndrome varied with different definitions, was highest using the de Ferranti definition (5.4%, 24.6% and 42.0%, respectively for normal�]weight, overweight and obese children), followed by the Cook definition (1.5%, 8.1%, and 25.1%, respectively), and the IDF definition (0.5%, 1.8% and 8.3%, respectively). Overweight and obese children had a higher risk of developing the metabolic syndrome compared to normal�]weight children (odds ratio varied with different definitions from 3.958 to 6.866 for overweight children, and 12.640�]26.007 for obese children). Overweight and obesity also increased the risk of developing metabolic abnormalities. Central obesity and high triglycerides (TG) were the most common while hyperglycemia was the least frequent in Chinese children regardless of different definitions. The second purpose was to determine the best obesity index for the prediction of cardiovascular (CV) risk factor clustering across a 2�]y follow�]up among BMI, %BF, WC and waist�]to�]height ratio (WHtR) in Chinese children. Height, weight, WC, %BF as determined by BIA, blood pressure, TG, high�]density lipoprotein cholesterol (HDL�]C), and fasting glucose were collected at baseline and 2 years later in 292 boys and 277 girls aged 8�]10 y. The results showed the percentage of children who remained overweight/obese defined on the basis of BMI, WC, WHtR and %BF was 89.7%, 93.5%, 84.5%, and 80.4%, respectively after 2 years. Obesity indices at baseline significantly correlated with TG, HDL�]C, and blood pressure at both baseline and 2 years later with a similar strength of correlations. BMI at baseline explained the greatest variance of later blood pressure. WC at baseline explained the greatest variance of later HDL�]C and glucose, while WHtR at baseline was the main predictor of later TG. Receiver�]operating characteristic (ROC) analysis explored the ability of the four indices to identify the later presence of CV risk. The overweight/obese children defined on the basis of BMI, WC, WHtR or %BF were more likely to develop CV risk 2 years later with relative risk (RR) scores of 3.670, 3.762, 2.767, and 2.804, respectively. The final purpose of the third study was to develop age�] and gender�]specific percentiles of WC and WHtR and cut�]off points of WC and WHtR for the prediction of CV risk in Chinese children. Smoothed percentile curves of WC and WHtR were produced in 2830 boys and 2699 girls aged 6�]12 y randomly selected from southern and northern China using the LMS method. The optimal age�] and gender�]specific thresholds of WC and WHtR for the prediction of cardiovascular risk factors clustering were derived in a sub�]sample (n=1845) by ROC analysis. Age�] and gender�]specific WC and WHtR percentiles were constructed. The WC thresholds were at the 90th and 84th percentiles for Chinese boys and girls, respectively, with sensitivity and specificity ranging from 67.2% to 83.3%. The WHtR thresholds were at the 91st and 94th percentiles for Chinese boys and girls, respectively, with sensitivity and specificity ranging from 78.6% to 88.9%. The cut�]offs of both WC and WHtR were age�] and gender�]dependent. In conclusion, the current thesis quantifies the ethnic differences in the BMI�]%BF relationship and body fat distribution between Asian children from different origins and confirms the necessity to consider ethnic differences in body composition when developing BMI and other obesity index criteria for obesity in Asian children. Moreover, ethnicity is also important in BIA prediction equations. In addition, WC and WHtR percentiles and thresholds for the prediction of CV risk in Chinese children differ from other populations. Although there was no advantage of WC or WHtR over BMI or %BF in the prediction of CV risk, obese children had a higher risk of developing the metabolic syndrome and abnormalities than normal�]weight children regardless of the obesity index used.