the worldwide prevalence of childhood obesity has increased from 4.2% to 6.7% during the last two decades . data from 144 countries suggest that about 43 million children are overweight and obese and 92 millions are at risk of becoming obese later on their life . pediatric obesity is a major health problem and is dramatically increasing in greece [ 2 , 3 ] . consequences such as hypertension , type 2 diabetes ( t2d ) , non - alcoholic fatty liver disease ( nafld ) , hyperlipidemia , hyperglycemia and insulin resistance ( ir ) are serious health issues that have been found to be established at young ages in pediatric population in greece [ 4 - 6 ] . cardiovascular ( cv ) risk in children becomes significant from the 85th percentile for weight and above where other risk factors changes are observed , such as high - density lipoprotein ( hdl ) , low - density lipoprotein ( ldl ) , triglyceride ( tg ) and total cholesterol ( tc ) . atherosclerosis is a process that starts in early life as berenson et al have reported , body mass index ( bmi ) , high blood pressure ( bp ) and high concentrations of ldl , tc and low hdl were strongly associated with the extension of lesions in the coronary arteries . a variety of inflammatory variables have been also found to be associated with cv risk in obese children . kim et al   observed in 354 children , that the obese group had higher levels of high - sensitivity c - reactive protein ( hscrp ) , interleukin and tumor necrosis factor- compared to the non - obese ones . ir is another well - known cv risk factor in adults and has been proved to have a very strong association with pediatric obesity . in addition , metabolic syndrome , which is basically a cluster of cv risk factors such as hyperinsulinemia , obesity , hypertension and hyperlipidemia , has been observed in obese children . as biomarkers of lipid metabolism , apolipoprotein a ( apoa ) and apolipoprotein b ( apob ) in addition , lipoprotein(a ) ( lp(a ) ) which is mainly produced by monocytes / macrophages and primarily bound to ldl cholesterol in the peripheral circulation , was found to be predictive for cv events in adults . finally , family history ( fh ) is another important and independent cv risk factor , especially for early - onset disease . many studies have shown a two- to three - fold increase in cvd given a first - degree relative with cvd and the strength of this association increases as the number of affected first - degree relatives increases [ 13 , 14 ] . the purpose of this study was to identify and examine the effects of possible cv risk factors in obese and non - obese children with and without fh of cvd . sixty - eight ( 68 ) children and adolescents aged 7 - 13 years ( 35 obese and 33 controls ) participated in the study . all subjects were recruited from a pediatric obesity outpatient s clinic and a clinic for lipids and prevention of cvd in childhood . the power calculation to have the appropriate number to contact the study was 32 children . a detailed medical history was taken of each child by a pediatrician of our clinic . children with clinical evidence of diabetes , cv , liver disease and use of alcohol , drugs or other disease were excluded from the study . the latter was defined as positive if there was a first - degree male relative ( father or grandfather ) diagnosed with cvd under the age of 55 or a first - degree female relative ( mother or grandmother ) diagnosed with cvd under the age of 65 . the term cvd includes all the diseases of the heart and circulation including coronary heart disease ( angina and heart attack ) , heart failure , congenital heart disease and stroke . the ethical committee of the aristotle university of thessaloniki approved the study and a written informed consent form was also obtained from the children s guardians who participated in the study . anthropometrical indices such as height , weight , tanner stage and waist circumference were measured in all children . body weight was measured to the nearest ( 0.1 kg ) wearing light clothes and without shoes using seca 700 model - scale . obesity was defined by the new revised international child bmi cut - offs for sex , according to the world obesity federation ( previously iotf ) . the subjects were in seated position , with arm flexed at the level of the heart . the length of the cuff s bladder was at least equal to 80% of the circumference of the upper arm . the bp was measured three times and the mean average was considered to be the overall bp value . normal systolic bp was defined when percentile was < 90th percentile , pre - hypertensive when percentile  90th and < 95th and hypertensive was defined as either systolic and/or diastolic bp  95th percentile measured upon three or more occasions . children and adolescents whose bp exceeded 120/80 mm hg were considered pre - hypertensive even if the blood pressure was < 90th percentile . a blood sample of 5 ml was drawn by venipuncture after the subjects had fasted overnight for 10 h. fasting serum tc , hdl - cholesterol and tgs were ascertained with direct measurement assays using standard laboratory methods ( roche diagnostics ) while ldl - cholesterol was calculated using friedwald s equation . fasting blood glucose and serum insulin levels were assessed by enzymatic method with hexokinase and electrochemiluminescence immunoassay  eclia  , respectively . ir was calculated by means of the homeostasis model assessment ( homa ) with the homa calculator ( university of oxford , diabetes trials unit , the oxford centre for diabetes , endocrinology and metabolism ) . the shapiro - wilk statistic was used to test the normality assumption of the numerical variables of the study . the main effect of the group ( normal , obese ) of fh of cvd ( positive , negative ) and their interaction effect were assessed with two - way anova for normally distributed variables and with kruskal - wallis test for non - normally distributed data . in case of anova , pairwise comparisons were conducted with bonferroni method , while mann - whitney u test with bonferroni adjusted p - values was used for pairwise comparisons after the kruskal - wallis test . comparisons between boys and girls were done with independent samples t - test ( normally distributed data ) or with mann - whitney u test ( non - normally distributed data ) . univariate and multivariate logistic regression models were used to associate systolic bp , tc , tg , hdl , apoa , hscrp , fasting insulin 0 ' and homa - ir with group ( normal , obese ) and fh of cvd ( positive , negative ) . results of those models included odds ratios ( or ) , 95% confidence intervals ( cis ) , sensitivity and specificity . the overall analysis was performed with ibm statistics spss 20.0 and the statistical significance was set at p < 0.05 . anthropometrical indices such as height , weight , tanner stage and waist circumference were measured in all children . body weight was measured to the nearest ( 0.1 kg ) wearing light clothes and without shoes using seca 700 model - scale . obesity was defined by the new revised international child bmi cut - offs for sex , according to the world obesity federation ( previously iotf ) . the subjects were in seated position , with arm flexed at the level of the heart . the length of the cuff s bladder was at least equal to 80% of the circumference of the upper arm . the bp was measured three times and the mean average was considered to be the overall bp value . normal systolic bp was defined when percentile was < 90th percentile , pre - hypertensive when percentile  90th and < 95th and hypertensive was defined as either systolic and/or diastolic bp  95th percentile measured upon three or more occasions . children and adolescents whose bp exceeded 120/80 mm hg were considered pre - hypertensive even if the blood pressure was < 90th percentile . a blood sample of 5 ml was drawn by venipuncture after the subjects had fasted overnight for 10 h. fasting serum tc , hdl - cholesterol and tgs were ascertained with direct measurement assays using standard laboratory methods ( roche diagnostics ) while ldl - cholesterol was calculated using friedwald s equation . fasting blood glucose and serum insulin levels were assessed by enzymatic method with hexokinase and electrochemiluminescence immunoassay  eclia  , respectively . ir was calculated by means of the homeostasis model assessment ( homa ) with the homa calculator ( university of oxford , diabetes trials unit , the oxford centre for diabetes , endocrinology and metabolism ) . the shapiro - wilk statistic was used to test the normality assumption of the numerical variables of the study . the main effect of the group ( normal , obese ) of fh of cvd ( positive , negative ) and their interaction effect were assessed with two - way anova for normally distributed variables and with kruskal - wallis test for non - normally distributed data . in case of anova , pairwise comparisons were conducted with bonferroni method , while mann - whitney u test with bonferroni adjusted p - values was used for pairwise comparisons after the kruskal - wallis test . comparisons between boys and girls were done with independent samples t - test ( normally distributed data ) or with mann - whitney u test ( non - normally distributed data ) . univariate and multivariate logistic regression models were used to associate systolic bp , tc , tg , hdl , apoa , hscrp , fasting insulin 0 ' and homa - ir with group ( normal , obese ) and fh of cvd ( positive , negative ) . results of those models included odds ratios ( or ) , 95% confidence intervals ( cis ) , sensitivity and specificity . the overall analysis was performed with ibm statistics spss 20.0 and the statistical significance was set at p < 0.05 . fifteen ( 15 ) out of the 35 obese ones had positive fh of cvd while eight children out of the 33 non - obese ones had positive fh of cvd . sbp , tc , tg , hscrp , fasting plasma insulin ( fpi ) and homa - ir levels were found statistically significantly higher in the obese group compared to the normal one . additionally , hdl and apoa levels were observed to be statistically significantly lower in the obese children compared to their normal peers . moreover , apoa , hscrp and fpi levels were significantly higher in the obese children with fh of cvd compared to those without fh of cvd ( table 2 ) . figure 1 depicts the strong positive relation of fpi with homa - ir ( r = 0.998 , p < 0.001 ) . relation of homa with ir ( r = 0.998 , p < 0.001 ) .   in a univariate logistic regression model , none of the cv risk factors were related to children with and without fh of cvd ( table 3 ) . obese children have almost double risk of having high tc levels ( or : 1.965 95% ci : 1.935 - 2.970 , p < 0.031 ) , while for the sbp the risk was or : 1.045 , 95% ci : 1.016 - 1.074 , p < 0.002 . in this study , we attempt to identify any possible relation of cv risk factors in 68 obese and non - obese children with and without fh of cvd . in our study , obese children were found to have higher risk of abnormal total fasting serum cholesterol and systolic bp levels compared to normal children . a european pediatric cohort showed that high bp was seen in about 35% of overweight children . in another recent study   that covered 26,000 school children , the systolic hypertension observed was 5.3% , 12.3% and 14.6% for normal , overweight and obese children , respectively . high levels of hypertension reported in other studies from greece should be under serious concern . angelopoulos et al   examined 312 children aged 11 years and found prevalence rates of 29.4% and 11.8% for boys and 39% and 7.5% for girls . additionally , others examined 606 children from northern greece and reported a prevalence of systolic and diastolic hypertension of 12.3% and 15.1% for boys and 13.3% and 15.1% for girls , respectively . the probable mechanism of obesity - related hypertension might include ir , sodium retention , increased sympathetic nervous system activity and other factors . obesity is commonly associated with a combined dyslipidemia pattern with mild elevation in tc and ldl - cholesterol levels , moderate - to - severe elevation in tg level , and low hdl - cholesterol levels . in our study , the obese group presented significantly higher levels of tc , ldl and tg and lower levels of hdl compared to the non - obese group . in the multiple regression model weight loss should be the first priority in order to reduce tc and systolic bp in obese children . a few studies on children based on short - term weight loss over a few weeks showed an improvement of cv risk factor profile associated with obesity ( reduction of hypertension , tg , and tc ) [ 23 , 24 ] . additionally , a diet with total fat at 25 - 30% of calories , saturated fat at < 10% of calories , and cholesterol intake at < 300 mg / day , as recommended by the original ncep pediatric panel   has been shown to safely and effectively reduce the levels of tc and ldl - cholesterol in healthy children . the paradox in our study is that we did not find any relation in the logistic regression model , between homa and obesity or fh of cvd . this is possibly due to the effect of the small number of subjects included in the study . however , these results should not underestimate the significance of homa - ir , since ir is the main cause of hypertriglyceridemia , hyperlipidemia , decrease of hdl - cholesterol , and increased bp in obesity , and correlates to the degree of overweight . our study has its limitations , since information on genetics , physical activity , socioeconomic status and diet was not assessed . additionally , the small sample size also might affect some of the cardiometabolic risk factors related to obese children especially those with fh of cvd . apoa , hscrp and fpi levels were significantly higher in the obese children with fh of cvd compared to the ones without fh of cvd . apoa , hscrp and fpi levels were significantly higher in the obese children with fh of cvd compared to the ones without fh of cvd . tc and systolic bp were found to be independently associated with obesity . systolic blood pressure diastolic blood pressure high - density lipoprotein low - density lipoprotein positive family history of cvd negative family history of cvd fasting blood glucose fasting plasma insulin cardiovascular disease homeostasis model assessment non - alcoholic fatty liver disease
backgroundthe worldwide prevalence of childhood obesity has increased from 4.2% to 6.7% during the last two decades . 
 pediatric obesity is a major health problem , which is dramatically increasing in greece . 
 a variety of inflammatory variables have been also found to associate with cardiometabolic ( cv ) risk in obese children . 
 the purpose of this study was to identify and examine the effects of possible cv risk factors in obese and non - obese children with and without family history ( fh ) of cardiovascular disease ( cvd).methodssixty - eight ( 68 ) healthy children and adolescents aged 7 - 13 years participated in the study . 
 anthropometrical and biochemical indexes were obtained from all children as well as fh of cvd.resultssystolic blood pressure ( sbp ) , total cholesterol ( tc ) , triglyceride ( tg ) , high - sensitivity c - reactive protein ( hscrp ) , fasting plasma insulin ( fpi ) and homeostasis model assessment of insulin resistance ( homa - ir ) levels were found statistically significantly higher in the obese group compared to the non - obese one . high - density lipoprotein ( hdl ) 
 levels were observed to be statistically significantly lower in the obese children compared to their normal peers.conclusionsapolipoprotein a , hscrp and fpi levels were significantly higher in the obese children with fh of cvd compared to the ones without fh of cvd . 
 tc and sbp were found to be independently associated with obesity ( odds ratio ( or ) : 1.965 , 95% confidence interval ( ci ) : 1.935 - 2.97 , p < 0.031 and or : 1.045 , 95% ci : 1.016 - 1.074 , p < 0.002 , respectively ) .