New criteria of normal serum lipid levels in Japanese children: The nationwide study

AIM: To make new criteria of serum lipid levels in current Japanese children using the large nationwide data provided from Japan Association of Health Service for the analysis. METHODS: The subjects were schoolchildren who received screening and care programs for lifestyle related diseases since 1993-1999. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and triglyceride (TG) levels were measured, and low-density lipoprotein cholesterol (LDLC) levels were calculated. Serum lipid levels were analyzed by age and sex. For each serum lipid, we extracted age- and sex-specific group which the mean value was not statistically different from that in 1999 by Student's t-test analysis. RESULTS: The level below the 75th percentile was defined to be acceptable, from the 75th to 95th to be borderline and over the 95th to be high in TC/LDLC. The level below the fifth percentile in HDLC was defined to be low and the level over the 95th percentile in TG to be high. Therefore, TC level was categorized as follows: acceptable < 190 mg/dL; borderline 190-219 mg/dL; and high > 220 mg/dL. The LDLC level was also categorized into: acceptable < 110 mg/dL; borderline 110-139 mg/dL; and high > 140 mg/dL. The cut-off value in TG was determined to be 140 mg/dL and in HDLC was 40 mg/dL. CONCLUSIONS: This new criteria should prove valuable in health strategies for rational prevention and intervention in children. It should be emphasized to provide some intervention for Japanese children immediately.     

Impact of increasing adiposity in hyperlipidemic children

Despite lifestyle management, children with high-risk hyperlipidemias may become overweight, and this may further adversely impact their lipid profile. Regression analysis was used to determine changes over time in adiposity and their association with lipid profiles and other risk factors for hyperlipidemic children followed in a lipid disorder clinic. 184 patients were included. Median age at presentation was 7 years (2-17 years), and median duration of follow-up was 9 years (5-20 years). Mean initial total cholesterol was 6.9+/-1.6 mmol/L, low-density lipoproteins were 5.2+/-1.7 mmol/L, high-density lipoproteins were 1.2 +/- 0.4 mmol/L, triglycerides were 1.1+/-0.8 mmol/L, and body mass index z score was +0.4+/-1.0. A significant increase in body mass index z score (+0.032/year, P< .001) was observed. There was an associated significant increase in total cholesterol and triglyceride levels and decrease in high-density lipoprotein levels over time. Worsening adiposity is prevalent in hyperlipidemic children and adversely affects their lipid profiles and cardiovascular risk.     

Influence of food intake, age, gender, HbA1c, and BMI levels on plasma cholesterol in 29 979 children and adolescents with type 1 diabetes – reference data from the German diabetes documentation and quality management system (DPV)

Objective:  We investigated influences of a 12-h fast, age, gender, body mass index (BMI), hemoglobin A1c (HbA1c) on total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) to provide reference percentiles for TC, LDL-C, and HDL-C of patients with good diabetes control (HbA1c < 7.5%) and normal weight (BMI < 90th percentile).
Method:  A cross-sectional analysis of the diabetes documentation and quality management system using the diabetes data acquisition system for prospective surveillance (DPV) software included 29 979 patients with type 1 diabetes mellitus (T1DM) aged 1–20 yr (52.4% male) from 253 diabetes centers in Germany and Austria.
Results:  Fasting had no relevant influence on TC, LDL-C, and HDL-C. Multivariate regression analysis revealed strongest dependences of cholesterol on gender and HbA1c followed by BMI and age. Reference cholesterol percentiles of well-controlled and normal weight patients showed TC ≥4.40 mmol/L (170 mg/dL) corresponding to the 50th percentile in females and the 75th percentile in males. LDL-C ≥2.59 mmol/L (100 mg/dL) corresponded to the 50th–75th percentile in females and the 75th percentile in males.
Conclusions:  (i) Fasting is no precondition for the determination of TC, LDL-C, and HDL-C; (ii) TC, LDL-C, and HDL-C are strongest associated with gender and HbA1c followed by BMI and age; (iii) Gender- and age-adjusted cholesterol percentiles of well-controlled and normal weight patients with T1DM may serve as reference values and are similar to healthy German children; and (iv) Single target values for TC, LDL-C, and HDL-C based on healthy individuals' data do not sufficiently characterize abnormal cholesterol levels in young patients with T1DM.     

Serum total cholesterol screening for the detection of elevated low-density lipoprotein in children and adolescents: the Bogalusa Heart Study

The use of serum total cholesterol measurement was evaluated as a screening tool to predict elevated levels of low-density lipoprotein cholesterol in 2857 children and adolescents, aged 5 to 17 years, examined in 1981 and 1982. Subjects were from the biracial community of Bogalusa, Louisiana. For selected serum total cholesterol values (150 to 210 mg/dL, 3.88 to 5.43 mmol/L), sensitivities were higher for blacks than whites and higher for females than males, whereas the positive predictive values were higher for whites than blacks and higher for males than females. With the age-, race-, and sex-specific 95th percentiles of serum total cholesterol levels as cutoff points, only 44% to 50% of subjects with elevated low-density lipoprotein cholesterol levels (greater than or equal to 95th percentile) were detected, and approximately 50% of those identified had false-positive results. Lowering the serum total cholesterol cutoff point increased the sensitivity, but decreased the specificity and positive predictive value. At the 75th percentiles of serum total cholesterol levels, sensitivities were 92% to 95% for females and 100% for males and specificities were 78% to 79%, but the false-positive results increased to 81% to 84%. The low cost and ease of obtaining serum total cholesterol measurements contribute to its appeal as a screening tool for hyperlipidemia. However, its poor test characteristics make serum total cholesterol measurement inefficient as a screening tool for detecting elevated levels of low-density lipoprotein cholesterol in children and adolescents.     

Evaluation of Serum Lipid Levels in Children

This study aimed to establish reference values for serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in children. The study included samples from 4,102 healthy children (2,003 boys and 2,099 girls) ages 1–18 years. The serum levels of total cholesterol, triglycerides, and HDL-C were determined using the Advia 2400 autoanalyzer. The LDL-C levels were calculated using the Friedewald equation. The mean, standard deviation, and 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentile values of the biochemical parameters for boys and girls were detected. The total cholesterol and HDL-C levels were higher among the girls than among the boys in 15- to 18-year-old group. No significant difference was found for the other serum lipid levels among any of the age groups. This study provided pediatric reference intervals for the lipid parameters for children.     

Serum cholesterol and triglyceride distribution in 7767 school-aged Greek children

OBJECTIVE: To elucidate associations of age and sex with serum cholesterol and triglyceride levels and to provide for the first time percentile distribution data for pediatric lipids. PARTICIPANTS AND METHODS: A high sample of 7767 (3980 boys, 3787 girls) fasting schoolchildren, 6 to 14 years of age, were studied in Athens, Greece. RESULTS: The mean cholesterol ranged from 157 to 174 mg/dL for boys and from 158 to 172 mg/dL for girls peaking at 9 years of age for both sexes. Triglyceride levels also tended to increase gradually and to peak at 11 years of age for both sexes. The high-density lipoprotein cholesterol levels were highest at 9 years of age for both sexes and the low-density lipoprotein cholesterol levels also tended to peak at 9 years of age for boys and at 8 years of age for girls. Atherogenic indices ranged from 1.54 to 1.68 for boys and 1. 51 to 1.85 for girls. CONCLUSION: According to these findings, it could be suggested that diet changes in the Greek population, especially in children and adolescents, living in big cities is significantly influencing their total cholesterol profiles throughout the last 10 years.     

Treatment of type IIa hyperlipidemia in childhood by a simplified American Heart Association diet and fiber supplementation

Thirty-six children identified as having primary type IIa hypercholesterolemia were treated with a diet restricting the intake of saturated fat to 10% of total energy and supplemented with soluble fiber for 8.1 +/- 2.4 (mean +/- SEM) months. In 14 of 36 patients first treated with the American Heart Association "Step-One" diet for 8.0 +/- 1.1 months, total cholesterol level dropped from 257.9 +/- 15.8 mg/dL to 240.6 +/- 10.9 mg/dL; the low-density lipoprotein cholesterol level dropped from 191.8 +/- 17.4 mg/dL to 175.0 +/- 11.7 mg/dL; the high-density lipoprotein cholesterol level dropped from 42.8 +/- 1.94 mg/dL to 41.6 +/- 1.68 mg/dL; and triglyceride concentration rose from 115.9 +/- 13.7 mg/dL to 128.1 +/- 14.1 mg/dL. The 36 patients treated with saturated fat-restrictive diets and supplemental soluble fiber diets had a reduction of total cholesterol levels from 249.2 +/- 7.66 mg/dL to 207.1 +/- 6.31 mg/dL and a low-density lipoprotein cholesterol level reduction from 184.7 +/- 7.55 mg/dL to 142.6 +/- 6.7 mg/dL, a reduction of 18% and 23%, respectively. There was no significant change in high-density lipoprotein cholesterol levels (46.4 +/- 1.9 mg/dL vs 44.3 +/- 2.1 mg/dL) or in triglyceride concentrations (94.2 +/- 7.43 mg/dL vs 102.2 +/- 8.45 mg/dL). In addition, the reduction in serum lipoprotein concentrations resulting from this program was significantly greater than the concentrations resulting from the American Heart Association diet alone. The different responses to these regimens suggest that a simplified diet and soluble fiber supplementation is well tolerated and reduces total and low-density lipoprotein cholesterol levels more effectively than the standard American Heart Association diet in children.     

Serum homocysteine and lipoprotein (a) concentrations in hypercholesterolemic and normocholesterolemic children

The relationship between lipids, lipoproteins, total homocysteine, and lipoprotein (a) was studied in hypercholesterolemic and normocholesterolemic children. In hypercholesterolemic children, concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein B, and triglycerides were significantly higher compared to levels in controls, whereas concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I were lower compared to those in the control group. Total serum homocysteine concentrations in children with a positive family history for cardiovascular disease CHD(+) (7.28 micromol/L) were significantly higher than those in the control group (5.45 micromol/L), and in the group of CHD(-) children (5.25 micromol/L). The median value of lipoprotein (a) in patients was 31.5 mg/dL (range, 11-209 mg/dL) and in the control group, 19 mg/dL (range, 11-95 mg/dL). Concentrations of Lp (a), exceeding 30 mg/dL, were present in 45% of CHD(+) children, in 29% of CHD(-) children, and in only 11% of the control group.     

Serum lipids and glucose control: the SEARCH for Diabetes in Youth study

OBJECTIVE: To assess the relationship of serum lipid concentrations with glucose control in youth with diabetes mellitus. DESIGN: Cross-sectional analyses of data from the SEARCH for Diabetes in Youth study. SETTING: Multicenter study of youth with diabetes onset at younger than 20 years. PATIENTS/ PARTICIPANTS: Nineteen hundred seventy-three SEARCH participants aged 10 years or older with hemoglobin A(1c) and fasting total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride measured at the SEARCH study examination. MAIN EXPOSURE: Hemoglobin A(1c). OUTCOME MEASURE: Lipid concentrations. RESULTS: There were significant trends of higher levels of TC, LDL-C, triglyceride, and non-HDL-C (but not HDL-C) with higher hemoglobin A(1c) concentrations for both diabetes types. The slopes of TC increase were 7.8 mg/dL (0.20 mmol/L) per unit increase in hemoglobin A(1c) for type 1 and 8.1 mg/dL (0.21 mmol/L) for type 2. Levels of TC, LDL-C, triglyceride, and non-HDL-C were all significantly higher (all P values <.001) in type 2 than in type 1 diabetes (mean differences in milligrams per deciliter [millimoles per liter], +13.6 [+0.35] for TC; +8.3 [+0.22] for LDL-C; +66.3 [+0.75] for triglyceride; +25.5 [+0.66] for non-HDL-C). Levels of HDL-C were lower in youth with type 2 diabetes (mean difference, -11.9 mg/dL [-0.31 mmol/L]). Among those with type 1 diabetes in poor glycemic control, 35%, 27%, and 12% had high concentrations of TC (>or=200 mg/dL [5.17 mmol/L]), LDL-C (>or=130 mg/dL [3.36 mmol/L]), and triglyceride (>or=200 mg/dL [2.26 mmol/L]), respectively. In youth with type 2 diabetes in poor glycemic control, percentages with high levels of TC, LDL-C, and triglycerides were 65%, 43%, and 40%, respectively. CONCLUSIONS: Glycemic control and lipid levels are independently associated in youth with both type 1 and type 2 diabetes.     

Characterization of 33 488 children and adolescents with type 1 diabetes based on the gender‐specific increase of cardiovascular risk factors

Schwab KO, Doerfer J, Marg W, Schober E, Holl RW. Characterization of 33 488 children and adolescents with type 1 diabetes based on the gender‐specific increase of cardiovascular risk factors. Objectives: Characterization of children with type 1 diabetes (T1DM) regarding number and gender distribution of cardiovascular risk factors (cvRF) and of total cholesterol/high‐density lipoprotein cholesterol ratio (TC/HDL‐C ratio) for risk assessment. Methods: 33488 patients ≤18 years were included in this cross‐sectional analysis and placed into 5 categories by their number of cvRF. Dyslipidemia (TC >200 mg/dL, >5.17 mmol/L; and/or HDL‐C <35 mg/dL, <0.91 mmol/L; and/or LDL‐C >130 mg/dL, >3.36 mmol/L), elevated systolic and/or diastolic blood pressure (BP) ≥90th percentile, obesity >97th percentile, active smoking, and HbA1c ≥7.5% were considered as cvRF. Results: 65% had no or 1 cvRF. HbA1c ≥7.5% was the most frequently occurring cvRF followed by BP ≥90th percentile, dyslipidemia, smoking, and BMI >97th percentile. Age at diabetic onset ranged from 7.7 to 9.2 years and diabetes duration from 4.1 to 6.6 years. CvRF showed differences in disfavour of females except smoking and HDL‐C <35 mg/dL (0.91 mmol/L). Rate of females was 45% with 0 cvRF and 60% with 4 to 5 cvRF. TC/HDL‐C ratio showed no clear association to the number of cvRF. Conclusions: 35% of a pediatric T1DM population develops 2 or more cvRF thus increasing their cv risk in adulthood. With increasing numbers of cvRF, the percentage of girls is rising from 45% to 60% which might contribute to an assimilation of survival rates in female and male adults. TC/HDL ratio does not predict the extent of cardiovascular risk in pediatric T1DM.     

Total cholesterol and high-density lipoprotein levels in pediatric subjects with type 1 diabetes mellitus

This study reports serum lipid levels in 682 children with type 1 diabetes mellitus. We found that 3.5% of the subjects had a high-density lipoprotein (HDL) cholesterol level < 35 mg/dL, 15.4% had a total cholesterol (TC) level>200 mg/dL, and 18.6% were abnormal for either HDL or TC, compared with prevalences of 5.7%, 11.2%, and 16.3%, respectively, reported in the National Health and Nutrition Examination Survey 2001-02. Hemoglobin A1c value was significantly related to TC and non-HDL cholesterol levels.     

Measurement of apolipoprotein B as a screening test for identifying children with elevated levels of low-density lipoprotein cholesterol

We compared the efficacy of two screening tests, measurement of apolipoprotein B (apo B) levels and measurement of serum total cholesterol levels, in detecting elevated low-density lipoprotein cholesterol (LDL-C) values in children. We studied 2850 children, aged 5 to 17 years, who had fasting lipid, lipoprotein, and apolipoprotein levels measured as part of the Bogalusa Heart Study. The test characteristics of apo B were superior to those of serum total cholesterol in screening children to detect elevated levels of LDL-C (greater than or equal to 95th percentile) and moderately elevated LDL-C levels (greater than or equal to 80th percentile). Unusually high or low values of high-density lipoprotein cholesterol are responsible for most of the misclassification that occurs when measurement of total cholesterol is used as a screening test for identifying children with elevated levels of LDL-C. This confounding effect of high-density lipoprotein cholesterol was eliminated when measurement of apo B levels was used as a screening test. Because the apo B test is more specific at a given sensitivity than the total cholesterol test, the apo B test can cost more and still be less expensive as a screening strategy. As the methods for determining apolipoprotein levels become standardized and readily available, the measurement of apolipoproteins could be developed into superior screening tests for the identification of patients with dyslipidemias.     

Fish oil treatment of hyperlipidemia in children and adolescents receiving renal replacement therapy.

The effect of 8 weeks of daily oral fish oil supplementation in a dose of 3 to 8 g/d on serum lipid levels was studied in 16 patients, 7 to 8 years of age, who had end-stage renal disease and were receiving renal replacement therapy. Fasting serum cholesterol (CHOL), triglyceride (TG) levels, and lipoprotein profiles were measured before therapy, 8 weeks after fish oil supplementation, and 4 weeks after its cessation. During 8 weeks of treatment the mean serum CHOL level did not change. The mean serum TG level, however, decreased significantly (P less than .01) from 236 +/- 31 mg/dL to 171 +/- 21 mg/dL (27.5%). Four weeks after treatment was stopped, the mean serum TG level returned to a value not significantly different from the pretreatment level (208 +/- 30 mg/dL). In a subgroup of 11 excessively hyperlipidemic patients, with serum CHOL and TG levels greater than or equal to 50% of the 90th percentile for age and sex, the mean serum TG level decreased even more (30.8%), from 286 +/- 35 mg/dL to 198 +/- 24 mg/dL (P less than .01), and the mean CHOL/high-density lipoprotein CHOL ratio decreased from 8.4 +/- 1.2 to 7.4 +/- 1.3 (P less than .05). Blood pressure and platelet counts remained stable during the entire study period. Side effects of the treatment were minimal. These results show that dietary fish oil supplementation reduces serum TG levels in young patients receiving renal replacement therapy and improves their "atherogenic" serum lipoprotein profile.     

Vitamin D,Low-Grade Inflammation and Cardiovascular Risk in Young Children: A Pilot Study

Vitamin D has anti-inflammatory properties, and deficiency is prevalent in children. There is a paucity of data regarding vitamin D status and its correlation with low-grade inflammation and vasculature. We prospectively enrolled 25 children, 9–11 years old (13 male); 21 obese. Eight atherosclerosis-promoting risk factors were scored as categorical variables with the following thresholds defining abnormality: body mass index Z score ≥1.5; systolic blood pressure ≥95th percentile (for age, sex, and height); triglyceride ≥100 mg/dL; low-density lipoprotein cholesterol (LDL-C) ≥110 mg/dL; high-density lipoprotein cholesterol ≤45 mg/dL; hemoglobin A1C (HBA1C) ≥5.5; 25-hydroxyvitamin D [25(OH) D] ≤30 ng/mL, and tobacco smoke exposure. High-sensitivity C-reactive protein (hsCRP) was measured to assess low-grade inflammation and classified as low- (<1 mg/L), average- (1–3 mg/L), and high-risk (>3 to <10 mg/L) groups. The proportion of children within each hsCRP group who had above threshold risk factors was calculated. Carotid artery ultrasound was performed to measure carotid artery intima-media  thickness (CIMT). Median (range) for 25(OH) D was 24 (17–45) ng/mL. Eighteen were either 25 (OH) D deficient (<20 ng/mL) or insufficient (20–30 ng/mL), and seven were sufficient (>30 ng/mL). hsCRP was 1.7 (0.2–9.1) mg/L, with 11 being <1.0 mg/L, 8 between 1.0–3.0 and 6 > 3.0 to < 10.0 mg/L. Risk factor score was 3.9 ± 1.7 out of eight. 25(OH) D levels did not correlate with hsCRP or CIMT. While vitamin D deficiency, inflammation, and risk factors coexist at a very young age, causative mechanisms remain unclear.     

The cardiovascular risk factor profile of Estonian school children

This cross-sectional study was undertaken to assess the occurrence of conventional cardiovascular risk factors in Estonian school children after the socioeconomic changes of the early 1990s. A total of 1018 9-, 12- and 15-y-old randomly selected children were studied for lipid and lipoprotein profiles, blood pressure, weight, height, regular smoking, physical activity and family history of premature cardiovascular disease. In 11-24 % of the children, total cholesterol levels were at or above the risk cut-off of 5.2 mmol l^-1, 3-5% of the children were considered to be obese and 6-12% had blood pressure higher than the age- and gender-specific 95th percentile of height. Of the 15-y-old girls and boys, 1% and 10%, respectively, admitted being daily smokers. Five percent of girls and 20% of boys smoked at least once a week. Ten to 18% of children reported little physical activity. According to age groups, 17-25% of the children had a family history of premature cardiovascular disease. The occurrence of three or more risk factors simultaneously characterized only the older age group, in which 2.3% of girls and 3.5% of boys exhibited clustering of potential cardiovascular risk factors. Our findings showed a relatively low frequency of obesity and low mean blood lipid levels with a high proportion of smokers among children in late puberty, implying that preventive efforts should focus on pubertal children to prevent adverse health behaviour.     

Parental history of cardiovascular disease as an indication for screening for lipoprotein abnormalities in children

We studied the relationship between parental history of cardiovascular disease and risk for adverse lipid and lipoprotein levels in a total community study of 3313 children (ages 4 to 17 years, 63% white, 37% black). Older white children (11 to 17 years) with a parental history of heart attack or diabetes were 4.3 and 5.6 times, respectively, more likely to have high levels (greater than or equal to 95th percentile) of serum total cholesterol than those without such a history (all p less than 0.05). White children with a parental history of heart attack or diabetes were twice as likely to have an elevated (greater than or equal to 95th percentile) low-density lipoprotein cholesterol (LDL-C) level than those without such a history (both p less than 0.05). In contrast, parental history of cardiovascular disease did not predict elevated levels of total cholesterol or LDL-C in black children. However, older black children with a parental history of heart attack, hypertension, or diabetes were 4 1/2 to 5 times more likely to have low levels (less than or equal to 5th percentile) of high-density lipoprotein cholesterol than those without such a history (all p less than 0.05). Only 40% of white children and 21% of black children with elevated LDL-C levels had a parental history of vascular disease. These findings raise questions about the current practice of screening only children with a family history of cardiovascular disease to identify those with elevated total cholesterol and LDL-C levels.     

Hyperlipidemia in school children with family histories of premature coronary heart disease

Children starting their schooling were given a questionnaire asking about the occurrence of premature (before 50 years of age in men, 55 years in women) coronary heart disease (CHD) in first degree relatives. 1,920 of 2,069 questionnaires were answered, 140 of the 7-year-old children were reported to have a first degree relative with premature CHD, 84 of these 140 families agreed to participate in our study. In 79 of the 84 families both the child and the parent at 'high risk' were tested. In the initial test 19 of 84 children had total cholesterol (TC) levels above the 95th percentile (greater than 5.35 mmol/l). In the repeat test 12 of the 19 TC tests remained abnormal and all 12 also had LDL-cholesterol (LDL-C) levels above the 95th percentile (greater than 3.40 mmol/l). None had abnormal HDL-cholesterol or triglyceride levels. Among the high risk parents, 12 of 79 had abnormal initial blood lipid tests. In the repeat test 10 parents had both TC and LDL-C levels above the 95th percentile. In five families both the child and the parent had abnormal TC and LDL-C levels. In conclusion, a considerable proportion of children and parents with family histories of premature CHD have TC and LDL-C concentrations above the 95th percentile (in the present study, about 40 individuals in 140 high-risk families, if the parent and child considered at high risk all had agreed to participate). Prevention of heart disease should begin in childhood when patterns of life-style are developed. Identification by obtained family histories as in the current study may be a method of choice.     

Hyperlipidemia in School Children with Family Histories of Premature Coronary Heart Disease

ABSTRACT. Children starting their schooling were given a questionnaire asking about the occurrence of premature (before 50 years of age in men, 55 years in women) coronary heart disease (CHD) in first degree relatives. 1920 of 2069 questionnaires were answered, 140 of the 7-year-old children were reported to have a first degree relative with premature CHD. 84 of these 140 families agreed to participate in our study. In 79 of the 84 families both the child and the parent at 'high risk' were tested. In the initial test 19 of 84 children had total cholesterol (TC) levels above the 95th percentile (>5.35 mmol/l). In the repeat test 12 of the 19 TC tests remained abnormal and all 12 also had LDL-cholesterol (LDL-C) levels above the 95th percentile (>3.40 mmol/l). None had abnormal HDL-cbolesterol or triglyceride levels. Among the high risk parents, 12 of 79 had abnormal initial blood lipid tests. In the repeat test 10 parents had both TC and LDL-C levels above the 95th percentile. In five families both the child and the parent had abnormal TC and LDL-C levels. In conclusion, a considerable proportion of children and parents with family histories of premature CHD have TC and LDL-C concentrations above the 95th percentile (in the present study, about 40 individuals in 140 high-risk families, if the parent and child considered at high risk all had agreed to participate). Prevention of heart disease should begin in childhood when patterns of life-style are developed. Identification by obtained family histories as in the current study may be a method of choice.     

Family history fails to identify many children with severe hypercholesterolemia

Optimal strategies for identifying children with hypercholesterolemia have not been established. Several groups have advocated that testing of serum cholesterol levels be limited to those children who have family histories of hyperlipidemia or premature coronary heart disease. We studied the ability of comprehensive family histories to identify children with hyperlipidemia in a group of 114 children (mean age, 8 +/- 4 years) who were referred for treatment of hypercholesterolemia. A positive family history was defined according to guidelines of the American Academy of Pediatrics. The mean fasting total cholesterol in the children was 5.74 +/- 1.42 mmol/L (222 mg/dL). Family history was negative for hypercholesterolemia or premature coronary heart disease in 22 (22%) of 100 children with total cholesterol levels greater than the 75th percentile for their ages, in 13 (18.3%) of 71 children with total cholesterol levels greater than the 95th percentile for their ages, and in four (11.8%) of 34 children with presumed heterozygous familial hypercholesterolemia. Of the 78 children who had both hypercholesterolemia and positive family histories, hyperlipidemia was reported in 72 families, whereas premature heart disease was reported in only 27. We conclude that in a population of children referred because of known hypercholesterolemia, a detailed family history not only fails to identify many children with mild hypercholesterolemia, but also fails to identify a significant proportion of children with markedly elevated cholesterol levels. Additionally, in families of children with hypercholesterolemia, a history of hyperlipidemia is more common than a history of premature heart disease.     

Randomized placebo-controlled trial of metformin for adolescents with polycystic ovary syndrome

OBJECTIVE: To determine whether metformin or placebo could, in conjunction with healthy lifestyle counseling, decrease serum testosterone levels and related aberrations in adolescents with hyperandrogenism, hyperinsulinemia, and polycystic ovarian syndrome. DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: Pediatric university teaching hospital. PARTICIPANTS: Twenty-two adolescents aged 13 to 18 years with hyperinsulinemia and polycystic ovarian syndrome. INTERVENTION: Participants were randomly assigned to take a 12-week course of either metformin or placebo. MAIN OUTCOME MEASURES: Pretreatment and posttreatment oral glucose tolerance tests, fasting lipid profiles, and clinical measurements. RESULTS: There was a significant decline in mean serum testosterone concentration with metformin (-38.3 ng/dL) compared with placebo (-0.86 ng/dL) (95% confidence interval, -infinity to -0.29 for the mean difference between groups). At completion, the relative risk of menses was 2.50 times higher in the metformin group compared with the placebo (95% confidence interval, 1.12 to 5.58). Measures of insulin sensitivity, including insulin area under the curve and HOMA (homeostasis model assessment), demonstrated improvement only with metformin, but these did not reach statistical significance. High-density lipoprotein cholesterol levels increased by 6.98 mg/dL with metformin vs a decrease of -2.33 mg/dL with placebo (95% confidence interval, 0.78 to 18.23 for the mean difference between groups). There were no significant changes in body mass index, hirsutism, triglyceride levels, or total and low-density lipoprotein cholesterol levels. CONCLUSION: Metformin significantly lowered total testosterone concentrations, increased the likelihood of menses, and improved high-density lipoprotein cholesterol levels without affecting measures of insulin sensitivity or body weight.