Do neonates with high serum cholesterol levels have a different high density lipoprotein composition?

In order to ascertain whether the high density lipoprotein (HDL) composition of neonates with high serum cholesterol levels (≥2.59 mmol/l or ≥100 mg/dl) differs from that of neonates with normal serum cholesterol levels (<2.59 mmol/l), 548 cord blood samples were examined from full-term newborns of the Toledo Study (Spain) of whom no perinatal factors were known which could alter cord blood lipid levels. Newborns were selected according to the following criteria: single and eutocic delivery with cephalic presentation, gestational age between the beginning of the 37th week and the end of the 41st week, body weight between 2.5 kg and 3.999 kg and an Apgar score of ≥7 and ≥9 at l min and 5 min, respectively. The prevalence of high serum total cholesterol (TC) level was greater (P < 0.02) in females than in males. Newborns with high TC levels had higher triglyceride (P < 0.01), HDL-cholesterol (P < 0.001) and apoprotein (Apo) A-I (P < 0.001) levels, and a higher TC/HDL-cholesterol ratio (P < 0.05), but a lower HDL-cholesterol/Apo A-I ratio (P < 0.05). ANOVA two-way analysis showed a significant effect of gender and serum cholesterol level and a statistical interaction of these two factors upon triglycerides, Apo A-I, and the HDL-cholesterol/Apo A-I ratio. However, HDL-cholesterol and the TC/HDL-cholesterol ratio were higher in neonates (males plus females) with high serum TC but they were not affected by sex. The larger HDL particles in males with high TC levels (HM) should be associated with the higher triglyceride level found in those individuals. Conclusion The composition of high density lipoproteins in newborns is influenced by the serum cholesterol level and by gender. Neonates with high total cholesterol have larger average high density lipoprotein (HDL) particles. If total cholesterol is elevated, HDL from males carries more cholesterol than HDL from females. Received: 26 November 1996 / Accepted: 7 January 1997     

Serum lipid and lipoprotein composition in infants of diabetic mothers

Diabetes mellitus (DM) alters carbohydrate and lipid metabolism to a great extent. This study was planned to determine whether infants of insulin dependent and gestational diabetic mothers have abnormal lipid metabolism. Three groups of newborns were included in the study; group I consisted of 7 infants of diabetic mothers (IDM) with insulin dependent DM (Type 1 DM), group Il of 18 infants of gestational diabetic mothers and group III of 20 control neonates whose mothers had no history of DM. Total cholesterol (TC), triglyceride (TG) and high density lipoprotein-cholesterol (HDL-C) values in groups I and II were no different compared to those in group III (p>0.05). However, low density lipoprotein-cholesterol (LDL-C) and LDL-C/HDL-C ratio were similar between groups I and II (p>0.05) but significantly higher in both infants of type I diabetic mothers and gestational diabetic mothers compared to control infants (p<0.05). Apolipoprotein A-I (Apo A-1) and apolipoprotein B (Apo B) levels, Apo A-I/Apo B and HDL-C/Apo A-I ratios were similar in between groups. However, Apo B/LDL-C ratio was significantly lower in groups I and II compared to control group (p<0.05). In conclusion, diabetes in pregnant women causes a tendency to LDL hypercholesterolemia in the offspring. These infants should be longitudinally followed up to assess whether this observation imposes an increased risk for atherosclerosis for advanced ages.     

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目的通过最新一轮的北京地区儿童青少年血脂调查,建立新的正常参考值。方法于2004-09,随机选取7~18岁北京市中小学生共971人,均来自北京市区及郊区各县。根据年龄(每3岁为一年龄段)及性别分为8组(7~9岁男、女组;~12岁男、女组;~15岁男、女组;~18岁男、女组),应用日立7060型全自动生化分析仪检测其空腹血浆总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)浓度,分别取TC、LDL-C第75百分位及第90百分位点作为临界高限及高胆固醇血症浓度,取TG第90百分位点作为高甘油三酯血症浓度,取HDL-C第5百分位点作为低高密度脂蛋白浓度,建立北京地区儿童血脂参考值。结果971名儿童的血浆脂蛋白含量值呈正偏态分布,7~9岁男女性别组间血脂4项浓度;~12岁性别组间TG含量女高于男,余3项无统计学差异;~15岁性别组间TC及LDL-C含量女高于男,余2项无统计学差异;~18岁性别组间TC及HDL-C女高于男,余2项无统计学差异。结论通过对971名北京市中小学生的血脂调查,建立了北京地区不同年龄性别儿童青少年的血脂正常值,确立了临界高胆固醇和高胆固醇血症浓度、高甘油三酯血症浓度和低高密度脂蛋白浓度。     

An eight-week trial investigating the efficacy and tolerability of atorvastatin for children and adolescents with heterozygous familial hypercholesterolemia

This study aimed to assess the efficacy and tolerability of atorvastatin in Tanner stage (TS) 1 patients ages 6 to 10?years and TS ??2 patients ages 10 to <18?years with genetically confirmed heterozygous familial hypercholesterolemia (HeFH) and a low density lipoprotein cholesterol (LDL-C) level of 4?mmol/l (155?mg/dl) or higher. In this open-label, 8-week study, 15 TS 1 children were treated initially with atorvastatin 5?mg/day and 24 TS ??2 children with 10?mg/day. Doses were doubled at week 4 if the LDL-C target (<3.35?mmol/l [130?mg/dl]) was not achieved. The efficacy variables were the percentage change from baseline in LDL-C, total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), and apolipoprotein (Apo) A-I and Apo B. Safety evaluations included clinical monitoring, subject-reported adverse events (AEs), vital signs, and clinical laboratory tests. The mean values for LDL-C, TC, VLDL-C, and Apo B decreased by week 2 among all TS 1 and TS ??2 patients, whereas TG, HDL-C, and Apo A-I varied considerably from week to week. After 8?weeks, the mean reduction in LDL-C was ?40.7%?±?8.4 for the TS 1 children and ?39.7%?±?10.3 for the TS ??2 children. For the TS 1 patients, the mean reductions were ?34.1%?±?6.9 for TC and ?6.0%?±?32.1 for TG. The corresponding changes for the TS ??2 patients were ?35.6%?±?9.5 for TC and ?21.1%?±?29.7 for TG. Four patients experienced mild to moderate treatment-related AEs. No serious AEs or discontinuations were reported. Overall, no difference in safety or tolerability was observed between the younger and older cohorts. Across the range of exposures after atorvastatin 5 to 10?mg (TS 1) or atorvastatin 10 to 20?mg (TS ??2) doses for 8?weeks, clinically meaningful reductions in LDL-C, TC, VLDL-C, and Apo were observed with atorvastatin in pediatric patients who had HeFH. Atorvastatin also was well tolerated in this population.     

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目的探讨单纯性肥胖儿童载脂蛋白(apolipoprotein,Apo)E基因多态性的分布及其对血脂、脂蛋白、载脂蛋白的影响,及其与冠状动脉、心电图改变的关系。并对其早期预测和疾病预防提供理论依据。方法选择2002年12月至2004年12月潍坊医学院附属医院儿科的6～14岁单纯性肥胖儿童89例和健康儿童76例。抽取外周静脉血,测定血清中甘油三酯(TG),总胆固醇(TC),高密度脂蛋白胆固醇(HDLC),低密度脂蛋白胆固醇(LDLC),载脂蛋白A1(ApoA1),载脂蛋白B100(ApoB100)浓度。应用改良的聚合酶链式反应限制性片段长度多态性(PCRRFLP)分析及聚丙烯酰胺凝胶电泳测定儿童ApoE基因型。结果共检出4种ApoE基因型,E3/3、E4/3、E2/3、E4/2,以ε3为最常见。与健康儿童比较,肥胖儿童ε4等位基因频率增高,差异有显著性(P<0.05)。结论单纯性肥胖儿童有ApoE基因多态性的变化,且明显影响小儿血浆脂类代谢,肥胖儿童ApoE4与冠心病有密切相关性。     

Serum apolipoproteins A-I and B in male and female full-term new borns of the Toledo study (Spain)

Cord serum apolipoproteins (Apo) A-I and B from 548 healthy, full-term singletons were studied. Females displayed slightly, but significantly, higher Apo A-I levels ( p < 0.001) than males. Particularly at weeks 38 and 39 ( p < 0.05), whereas Apo B was not gender affected but likewise increased ( p < 0.05) between weeks 37 and 41. Apo A-I values increased ( p < 0.05) with gestational age in males, but with birthweight in females. Results suggest that small gender and age-related metabolic differences exist at birth in terms infants     

Selected trace elements and minerals in cord blood: association with lipids and lipoproteins at birth

Recent studies have found that some minerals are associated with lipoprotein metabolism, peroxidation and coronary heart disease. The present study was designed to obtain information on the relationship between the concentrations of minerals and trace elements and those of lipids, lipoproteins and apolipoproteins (Apo) in cord blood. Seventy-nine healthy singleton normoweight full-term newborns without foetal distress according to Apgar scores were studied. The quartile distribution of neonates, according to serum concentrations of the different minerals studied, displayed significant differences in lipid values between infants in the lowest and highest quartiles of: magnesium, for HDL-cholesterol, Apo A-I, Apo B and the HDL-cholesterol/Apo A-I ratio; iron, for HDL-cholesterol and the HDL-cholesterol/Apo A-I ratio; copper, for triglycerides and the LDL-cholesterol/Apo B ratio. With the exception of calcium, several significant correlations were found between the minerals and trace elements and the lipids, Apo and lipoproteins tested.     

Is premature adrenarche a risk factor for atherogenesis?

BACKGROUND: The aim of this study was to evaluate serum lipids and atherosclerosis risk in children with premature adrenarche (PA) in comparison with age-matched controls. METHODS: Lipid profile, glucose, insulin, and insulin-like growth factor binding protein-1 (IGFBP-1) levels were studied in 24 girls with premature adrenarche and 13 healthy age-matched controls after overnight fasting. RESULTS: The bone age, weight and body mass index were higher in the premature adrenarche group than the control group. Systolic, diastolic and mean arterial blood pressure of patients were higher than controls. The mean total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), TC/high-density lipoprotein-cholesterol (HDL-C) and LDL-C/HDL-C ratio, and atherogenic index were significantly higher in the premature adrenarche group compared to the control group. There was no significant difference in the levels of apolipoprotein A1, apolipoprotein B and lipoprotein (a) in both groups. In the premature adrenarche group there were inverse correlations between the levels of IGFBP-1 and TC/HDL-C (rho, -0.54; P, 0.011), and LDL-C/HDL-C (rho, -0.50; P < 0.05) and atherogenic index (AI; rho, -0.54; P < 0.05). Dehydroepiandrosterone sulfate levels of the patients was negatively correlated with AI and TC/HDL-C (rho, -0.0503, P < 0.05). CONCLUSIONS: Girls with premature adrenarche should be investigated for serum lipids, and atherogenic risk criteria should be assessed periodically in the follow up of patients with PA, as PA seems to be a risk factor for future atherosclerosis.     

Serum lipid profile in children receiving anti-epileptic drug monotherapy: is it atherogenic?

The effect of anti-epileptic drugs (AEDs) on serum lipid profile is controversial in children as well as in adults. We longitudinally studied serum lipid profile in 34 newly diagnosed epileptic children receiving AED monotherapy with valproic acid (VPA), carbamazepine (CBZ) or phenobarbital (PB). Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), apolipoprotein Al (Apo A1) and apolipoprotein B (Apo B) were measured at baseline and after 2 years of AED monotherapy. Atherosclerotic indices of TC/ HDL-C and Apo A1/Apo B ratios were calculated. Although there were some alterations in serum lipid profile with AED without statistical significance, the atherosclerotic indices of TC/HDL-C and Apo A1/Apo B ratios did not change significantly after 2 years of monotherapy. Only serum TGs levels significantly decreased with VPA monotherapy. These data suggest that 2 years AED monotherapy with VPA, CBZ or PB did not cause a significant level of concern for an atherogenic effect in children with epilepsy.     

Plasma Lipid and Apolipoprotein Levels in Children Hereditarily Predisposed to Coronary Heart Disease

ABSTRACT. Plasma lipids and apoproteins A-I, A-II and B levels were measured in 125 children whose fathers had coronary atherosclerosis (paternal coronary heart disease group), in 172 children with blood pressure lability and in 154 children selected at random from a representative subsample (reference). The paternal coronary heart disease group had, compared with the reference group, lower levels of high density lipoprotein cholesterol and apoprotein A-I, higher levels of low density lipoprotein cholesterol, triglycerides and apoprotein B, and also a higher ratio of apoprotein B to apoprotein A-I. The paternal coronary heart disease group subjects with blood pressure lability had the most pronounced changes in the lipoprotein spectrum, which were similar to atherogenic changes in the lipoprotein profile, characteristic of patients with coronary atherosclerosis.     

Plasma lipid and apolipoprotein levels in children hereditarily predisposed to coronary heart disease

Plasma lipids and apoproteins A-I, A-II and B levels were measured in 125 children whose fathers had coronary atherosclerosis (paternal coronary heart disease group), in 172 children with blood pressure lability and in 154 children selected at random from a representative subsample (reference). The paternal coronary heart disease group had, compared with the reference group, lower levels of high density lipoprotein cholesterol and apoprotein A-I, higher levels of low density lipoprotein cholesterol, triglycerides and apoprotein B, and also a higher ratio of apoprotein B to apoprotein A-I. The paternal coronary heart disease group subjects with blood pressure lability had the most pronounced changes in the lipoprotein spectrum, which were similar to atherogenic changes in the lipoprotein profile, characteristic of patients with coronary atherosclerosis.     

Serum lipid profile in obese children in China

BACKGROUND: The aim of the present study was to examine the serum lipid profile in obese Chinese children, their serum lipid and apolipoprotein A-I (apoA-I) and B (apoB) levels were examined. METHODS: The subjects were 153 patients (109 male and 44 female) aged 4-16 years with obesity, who attended the outpatient clinic of Beijing Children's Hospital. Percentage bodyweight (%BW) ([(bodyweight - standard weight)/standard weight]x 100) were obtained. Skinfold thickness and hip and waist circumference were measured. Percentage body fat (%BF) was estimated by bioelectrical impedance analyzer. Serum total cholesterol (TC), high density lipoprotein cholesterol (HDLC), triglyceride (TG), apoA-I and apoB levels were also measured. RESULTS: TC showed an acceptable level in 86.8% of obese children. The prevalence of high TC levels (3.3%) or high LDLC levels (6.0%) was rather low. The HDLC level was reduced in 31.3% of obese children. Anthropometric variables had no linear relationship to TC, HDLC, TG, LDLC, apoA-I or apoB, but in the older age group (over 10 years old) %BW and %BF showed a weak correlation with HDLC (r = -0.202, r = -0.211, respectively). CONCLUSION: In obese Chinese children, HDLC as well as TC levels should be examined in order to assess coronary risk.     

Changes in apolipoproteins during the acute phase of Kawasaki disease

To determine disturbances of lipid metabolism in patients with Kawasaki disease, we investigated changes in the serum levels of apolipoproteins and serum lipids. Results were as follows. Total serum cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) decreased during the early stage of Kawasaki disease. The apo A-I and A-II levels were low until the 2nd week of illness. Apo B decreased during the 1st week of illness, but rose slightly during the 2nd and 3rd weeks. The apo B/apo A-I ratio and the apo B/TC ratio were high in the early stages of illness. The group of patients with coronary artery lesions showed low levels of TC and HDL-C, and low levels of apo A-I, A-II and B during the early stages, compared with the group without coronary artery lesions. The apo B/TC ratio was significantly higher in the patients with coronary artery lesions during the 2nd week of illness. Our findings suggest an association between changes in serum lipids and apolipoproteins and coronary artery involvement in Kawasaki disease. These abnormalities may indicate the presence of early coronary arteriosclerosis.     

Screening of children with high familial risk of arteriosclerosis

Serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C) and total triglyceride levels were determined in children with high risk arteriosclerotic family history. Significantly higher TC and lower HDL-C levels were found in children whose parents' first arteriosclerotic sign had appeared before 40 years of age. There were no similar significant alterations observed in children whose parents' first arteriosclerotic symptom appeared after the forties. Screening therefore seems to be necessary in the offsprings of patients if the first sign of arteriosclerosis has been detected before 40 years of age.     

Serum apolipoproteins A-I and B in 2,854 children from a biracial community: Bogalusa Heart Study

Serum apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B) profiles were examined in 2,854 children, 5 to 17 years of age, from a total biracial community. Black boys had higher apo A-I levels than white boys (P less than .001), whereas girls showed no such race-related difference. Black-white difference in apo A-I persisted among boys with similar triglyceride levels provided that triglyceride levels were high. The ratio of high-density lipoprotein cholesterol (HDL-C)/apo A-I was higher in black than in white children, irrespective of sex (P less than .001). Only black children showed sex-related differences for apo A-I (boys greater than girls, P less than .05). Sex-related differences were seen in white children for HDL-C/apo A-I ratio (boys greater than girls, P less than .001) and in children of both races for apoB (girls greater than boys, P less than .01). Age-related changes were more apparent for apo A-I and HDL-C/apo A-I ratio than for apo B. A progressive decrease in apo A-I was noted during sexual maturation only in white boys. The magnitude of inverse association of apo B to HDL-C was less strong in black children (P less than .01). Although apo A-I was inversely correlated with very low-density lipoprotein cholesterol and triglycerides in white children, no association was noted in black children. These findings are indicative of intrinsic metabolic differences among the race-sex groups, resulting in variability in lipoprotein composition and levels and atherogenic potential.     

Lipid parameters in childhood cirrhosis and chronic liver disease

BACKGROUND: Alterations in lipid metabolism are well defined in liver disease. As there has not been an ample amount of work published regarding this topic in children, especially about apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B), theoretical knowledge depends on adult studies. In this study, we investigated serum lipid parameters of children with chronic liver disease and cirrhosis. METHODS: Serum triglyceride, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), plasma apo A-I and apo B levels of 82 children with chronic liver disease, 41 of whom had cirrhosis as well, were investigated. Twenty healthy children were selected as controls. RESULTS: While mean serum triglyceride and cholesterol levels were not different in chronic hepatitis, cirrhosis and healthy children, mean apo B level of cirrhotic group was higher than that of the control group (P < 0.05). Mean LDL and HDL values of children with chronic hepatitis were lower and mean apo B value was higher than those of the control group (P < 0.05, P < 0.05 and P < 0.001, respectively). Apolipoprotein A-I level was lower in cholestatic cirrhotic children than non-cholestatic children (P < 0.05). No statistical difference was detected in lipid parameters of children with or without malnutrition (P > 0.05). The mean HDL value of Child-Pugh B group was significantly lower when compared to Child-Pugh A group (P < 0.05). The mean apo A-I value of Child-Pugh A group was higher than those of Child-Pugh B and C groups (P < 0.05 and P < 0.001). CONCLUSION: Consequently, we found that among lipid parameters apo A-I was the most affected parameter in liver injury. Whether apo A-I level can be used as a prognostic criterion in childhood cirrhosis may require further study.     

载脂蛋白E基因多态性与原发性肾病综合征脂质代谢紊乱的关系

目的研究原发性肾病综合征(PNS)患儿载脂蛋白E(apoE)主要等位基因和基因型的分布规律,探讨apoE基因多态性与PNS脂质代谢紊乱的关系。方法检测PNS患儿46例和正常小儿39例血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、apoA1、apoB和apoA1/B,同时用聚合酶链反应-单链构象多态性(PCR-SSCP)结合测序的方法确定apoE基因型,并根据平衡法计算出各等位基因频率。结果1.肾病组TC、TG、HDL-C、LDL-C、apoB、apoA1/B均明显高于对照组(P均<0.01);2.肾病组apoE2/2频率显著高于对照组(χ2=4.50 P<0.05);3.肾病组不同基因型和等位基因各项血脂指标均未见明显差异。结论PNS患儿存在明显脂质代谢紊乱,apoE2/2频率显著增高,apoE基因多态性对PNS患儿血脂水平未见明显影响。     

Low density lipoprotein in neonates with high cord serum cholesterol levels

Differences in cord serum low density lipoprotein (LDL) composition between male and female neonates with normal or high (≥ 100 mg/dl or ≥ 2.59 mmol/1) serum cholesterol levels were studied in 548 full-term newborn infants of the Toledo Study (Spain), where the absence of known perinatal factors that would alter lipid levels in cord blood was confirmed. The percentage of females with a high serum total cholesterol (TC) level was higher ( p < 0.02) than that of males. ANOVA two-way analysis shows significant interaction of gender and cholesterol level upon LDL-cholesterol, triglycerides and LDL cholesterol/Apoprotein (Apo) B ratio. However, Apo B was higher in those neonates, both male and female, with high cholesterol levels. The LDL fraction carried about 55% of TC in females with high TC levels (HF), whereas it transported just 40% in males with high TC levels (HM). LDL appeared more enriched in cholesterol than in Apo B in HF than in HM ( p < 0.01). An increased level of small LDL particles should be associated with the higher triglyceride level found amongst HM. Results in LDL composition suggest that metabolic gender-related differences in infants with normal or high TC are presented at birth.     

Study of lipid profile in children of patients with premature coronary artery disease

The present study was conducted to assess the incidence and type of lipid disorders in children whose parents had premature coronary artery disease. Lipid profile of 250 children (Group A), or children whose parents had premature coronary artery disease (age < or 55 years) was compared with age-matched healthy controls ((Group B), whose parents had no evidence of coronary artery disease. Mean total cholesterol levels (TC), low density lipoprotein cholesterol (LDL) and triglycerides (TG) were significantly higher in Group A as compared to Group B. The absolute values of lipids, TC and LDL in Group A children were within the normal range for age. Abnormal high density lipoprotein (HDL) level and elevated triglyceride levels were present in 25% and 22.5%, respectively, in the children of this group.     

Apolipoproteins A-I and B in obese children

Body mass index (BMI), the distribution of fat, birth weight, physical fitness, apolipoproteins (apo) A-I and B, total cholesterol (TC), and high-density lipoprotein cholesterol (HDLC) were studied in 38 obese 10- to 11-year-olds in comparison to 52 age-matched controls. Obese children had higher concentration of apo B and a lower apo A-I:B ratio. Significant correlations were found between (a) apo A-I and physical fitness (r = 0.35, p less than 0.015), triceps skinfold thickness (r = 0.44, p less than 0.01), and birth weight (r = -0.33, p less than 0.05); (b) physical fitness and triceps skinfold thickness (r = 0.38, p less than 0.05), and (c) the apo A-I:B ratio and triceps skinfold thickness (r = 0.31, p less than 0.05). When both obese and control children were grouped together, a correlation was found between BMI and TC (r = 0.24, p less than 0.05), apo B (r = 0.37, p less than 0.001), and the apo A-I:B ratio (r = -0.31, p less than 0.01). Multiple regression analyses indicated a significant positive contribution to the apo A-I level by HDLC and physical fitness and a negative one by birth weight.