Hypercholesterolemic Children Research Articles

Elevated plasma lipoprotein(a) associated with abnormal stress thallium scans in children with familial hypercholesterolemia

Plasma lipoprotein(a) (Lp(a)) concentrations are associated with an increased risk of coronary artery disease in adults with familial hypercholesterolemia (FH). We hypothesized that Lp(a) concentrations in children with FH were higher among those with myocardial ischemia on stress thallium scans and among those with a family history of premature coronary artery disease. Twenty-nine asymptomatic heterozygotes with FH (range 9 to 23 years) and 7 homozygotes (range 4 to 13 years) were evaluated with clinical assessment, lipoprotein measurement and stress thallium scans. Compared with subjects with normal stress thallium scans, mean Lp(a) was significantly higher in homozygotes with stress thallium abnormalities (79 ± 18 vs 15 ± 5.5 mg/dl, p = 0.03), and tended to be higher in heterozygotes with stress thallium abnormalities (39 ± 12 vs 20 ± 4.2 mg/dl, p = 0.10). Lp(a) tended to be higher in heterozygotes with a family history of premature coronary artery disease (30 ± 6.4 vs 14 ± 4.1 mg/dl, p = 0.12). It is concluded that Lp(a) is higher in hypercholesterolemic children who have abnormal stress thallium scans. Lp(a) may be useful in assessing coronary artery disease risk in children with FH.

Cholesterol screening in children: should obesity be a risk factor?

To determine whether obesity should be added to the current American Academy of Pediatrics (AAP) criteria for cholesterol screening in childhood, the charts of 99 children referred for evaluation of either hypercholesterolemia (n = 53) or obesity (n = 45) were reviewed. Compared with obese children, nonobese hypercholesterolemic subjects were younger (8.4 vs 11.4 years) and had lower mean body mass index and % ideal body weight. Frequency of elevated (> 90th percentile for age) total and low-density lipoprotein cholesterols were similar in both groups. Fifty-three of 65 children who met the current AAP criteria were hypercholesterolemic, however, 23/76 hypercholesterolemic children failed to satisfy these screening criteria. Thirty-six of 45 obese children had cholesterol levels > 90th percentile, suggesting increased risk for hypercholesterolemia in this group. If obesity was added to the AAP criteria, 66/80 hypercholesterolemic subjects would have been identified. These modified criteria, vs AAP standards, significantly improved both their sensitivity (70 vs 87%, p < 0.02) and negative predictive value (45 vs 30%, p < 0.02). Pending further studies in larger pediatric populations, these data indicate that obesity should be considered a risk factor for hypercholesterolemia in childhood, and we recommend modifying the AAP screening criteria to include obese children.

FLUIDITY AND COMPOSITION OF PLASMA LIPOPROTEINS (PL) IN HYPERCHOLESTEROLEMIC CHILDREN

Aims: to evaluate possible changes in PL fluidity and composition in hypercholesterolemic children. Patients & Methods: 18 hypercholesterolemic children (mean total plasma cholesterol [TPC] 286 mg/dL, SD 86.0). mean age 10.3 years (SD 2.0). normal weight (mean BMI 17, SD 2.0); 14 controls (mean TPC 158.7 mg/dL. SD 22.0). mean age 10.3 (SD 1.0), normal weight (mean BMI 16. SD 1.0). TPC in hypercholesterolemic children significantly higher than in controls (p<0.001). Analysis of PL composition; study of LP fluidity by fluorescence polarization (FP) of 1.6-diphenyl-1, 3, 5-hexatriene (DPH). Results: significant increase of LDL-associated cholesterol (p<0.003) and VLDL-associated cholesterol (p<0.003) in hypercholesterolemic children compared to controls; FP values significantly higher in VLDL (p<0.01) and VLDL (p<0.001) of hypercholesterolemic children compared to controls, indicating lower LP fluidity in patients. Conclusions: our data suggest early changes in LP composition and fluidity in hypercholesterolemic children.

Effective Control of Hypercholesterolemia in Children with Dietary Interventions Based in Pediatric Practice

Background. Based on recent recommendations, the number of hypercholesterolemic children who would require dietary therapy could overwhelm current preventive pediatric cardiology resources. No previous studies have established the efficacy of such therapy in the pediatrician"s office. The purpose of this study was to evaluate two programs of office-based therapy. Methods. We randomly assigned 295 children with hypercholesterolemia (>185 mg/dl) two interventions: one single or four multiple 90-min sessions of family-oriented nutritional education, based in pediatric practices. We examined total cholesterol, 3-day food records, height and weight, and in the multisession group high-density lipoprotein cholesterol and triglycerides at the beginning and at intervals of 8.5–9 and 21 to 33 weeks (single-session and multisession groups, respectively). Results. Total cholesterol was lowered equally in both treatment groups over the course of the study. This was accompanied by dietary changes: a decrease in calories derived from total and saturated fats, and increased intake of fiber, protein, and carbohydrate. However, more single-session patients withdrew from the program during the study. Conclusions. The two interventions were equally effective in lowering total and low-density lipoprotein cholesterol and in reducing intake of total and saturated fat. However, the higher completion rate of the multisession group suggests that this approach may be the more effective.

Growth during treatment of familial hypercholesterolemia.

Treatment of hypercholesterolemic children with restriction of dietary saturated fat may result in an inadequate supply of energy for normal somatic growth. We examined the growth of 30 children with familial hypercholesterolemia, some of whom were also treated with colestipol, a bile acid-binding resin. The median duration of treatment was 8.5 years in 13 patients on diet only, and 5.5 years + 3.5 years in 17 patients treated with diet followed by diet and colestipol. Statistically significant reductions in serum total cholesterol were obtained in both groups. The SD scores for both height/age and weight/age decreased by approximately 0.4 during dietary treatment (p < 0.05), but were not affected by treatment with colestipol. These results document the risk of growth retardation during dietary treatment of children with familial hypercholesterolemia.

Time and cost analysis of a computer-assisted telephone interview system to collect dietary recalls.

This study, conducted in 1991, examined the time requirements and costs of obtaining 24-hour dietary recalls via telephone interviews using the University of Minnesota's microcomputer Nutrient Data System to conduct the interviews and compute the nutrient composition of the diets. The subjects were 156 hypercholesterolemic children (aged 4-10 years) and 102 hypercholesterolemic adults (aged 21-65 years), who were participating in ongoing cholesterol education programs. A total of 391 recalls were completed with the children and 278 with the adults. For each completed interview, 3.5 and 2.8 attempts were required, respectively. Evenings were the most productive time for completing interviews. All tasks associated with completing the interviews (attempts to call, interviews per se, and postinterview procedures) required an average of 39.7 and 35.5 minutes per completed interview with the children and adults, respectively. About half of these total times were actually devoted to conducting the interview. The costs per completed interview were $9.22 for the children versus $6.99 for the adults. This difference reflects the greater number of attempts required to reach the children, the longer duration of their interviews, and the higher intrastate toll rates for calls to them as compared with the interstate rates for calls to the adults.

Primary care physicians and children's blood cholesterol

Background. In a national survey sponsored by the National Heart, Lung, and Blood Institute, 62% of primary care physicians of children (under age 18 years) believed that high levels of low-density lipoprotein cholesterol in childhood had a great effect on subsequent heart disease risk. Results. About 75% believed high blood pressure, smoking, and diabetes had similar effects. Although routine cholesterol screening in children under age 10 was infrequent, 72% of physicians screened high risk children. The age at which screening was done varied markedly; more pediatricians screened children younger than 5 years. The majority of physicians who saw children with high blood cholesterol instituted nondrug therapy, with pediatricians being most apt to do so. Low saturated fat diets were prescribed by 26% of these physicians and 9% of physicians prescribed increased polyunsaturated diets. Twelve percent of physicians treating hypercholesterolemic children used lipid-lowering drugs. Among those using drugs, 9% based drug use on total blood cholesterol measurements only. Factors that affected physician treatment of childhood hypercholesterolemia included physician specialty type, organization of practice (group or solo), and the age distribution of the pediatric patient population.

小児期家族性高コレステロール血症ヘテロ接合体の検討およびコレスチラミン投与の臨床効果

小児期家族性高コレステロール血症ヘテロ接合体の検討およびコレスチラミン投与の臨床効果

Hypothyroidism in Otherwise Healthy Hypercholesterolemic Children

Atherosclerosis is the leading cause of death in the United States. Studies in adults have shown that intervention with combined diet and medication can reduce atherosclerotic plaque formation and, as a result, the incidence of symptomatic coronary artery disease.1-4 With a strong tradition of preventive medicine, the pediatric community has begun exploring the prevention of adult atherosclerosis through intervention in childhood. Although issues such as universal vs selective high-risk screening, ideal age for screening and intervention, and treatment regimens remain unresolved and controversial, many preventive cardiology clinics, as well as individual pediatricians, have been screening and treating children.5,6 As part of an initial evaluation of hypercholesterolemic children and prior to any intervention, it is important to determine whether other disease processes are contributing to the child's dyslipoproteinemia.

Pharmacologic and Surgical Treatment of Dyslipidemic Children and Adolescents

A wide variety of treatment modalities have been used in children with dyslipidemias to reduce the concentrations of atherogenic lipoprotein particles. Most of the published experience has focused upon children with familial hypercholesterolemia (FH). A variety of pharmacologic regimens have been utilized with variable degrees of success. The bile acid sequestrants colestipol and cholestyramine, lovastatin, pantethine, paraminosalicylic acid, and fenofibrate have all been successful in reducing total blood cholesterol concentrations by 18-24% in hypercholesterolemic children. Of these medications, only the bile acid sequestrants are not absorbed into the circulation. This theoretic advantage is paralled by long-term safety studies which indicate the absence of serious adverse effects with bile acid sequestrant therapy. Therefore, the bile acid sequestrants represent the drugs of choice in treating severely dyslipidemic children. In selected cases of profoundly dyslipidemic children, other therapeutic strategies have been utilized. Most of these efforts have been directed in the treatment of the child homozygous for FH. Despite the lipid lowering effects of partial ileal bypass surgery in hypercholesterolemic adults, homozygous familial hypercholesterolemic children are not adequately treated by this approach. Portacaval shunt has reduced the total cholesterol concentrations by 20-35% in homozygous FH children without having a negative impact on growth and development. These children have, however, gone on to develop atherosclerotic cardiovascular disease despite therapy. Liver transplantation has led to virtual normalization of the plasma lipoprotein concentrations in 3 children homozygous for familial hypercholesterolemia, and there is evidence for regression of vascular lesions in the coronary arteries in one of these children. However, considering the expense, the difficulty in posttransplantation management, and the irreversible nature of the therapy, liver transplantation should be reserved as the therapy of last resort for homozygous FH. The best therapy for FH homozygotes is the frequent removal of the atherogenic lipoproteins by one of the several apheresis procedures currently available. Total plasma exchange, immunoadsorption, membrane filtration, dextran sulfate adsorption, and heparin extracorporeal precipitation have all been used successfully in significantly reducing the concentrations of total and low-density lipoprotein cholesterol. Studies currently under way will more extensively evaluate the long-term safety as well as the efficacy of apheresis procedures.

Effect of Oat Bran/Soy Protein in Hypercholesterolemic Children

Effect of Oat Bran/Soy Protein in Hypercholesterolemic Children

A dietary education program for hypercholesterolemic children and their parents

A parent-child autotutorial dietary education program for 4- to 10-year-old, hypercholesterolemic children and their families was developed and pilot tested. The 10-lesson program, designed for weekly use at home, uses a "talking-book" approach (audiotapes with accompanying picture booklet) for the child. Parents are provided with information on ways to make recommended dietary changes, along with hands-on activities to do with the children. To help match the instructional approach to the wide developmental range within the children's age span, materials are divided into three program levels that use different story characters and concept presentations. During program development, evaluation by two children (and their parents) for each of the program levels guided the design and refinement of the lessons. A pilot test among 22 hypercholesterolemic children (whose treatment was limited to diet modification) revealed that children within the 4- to 10-year age range liked the "talking-book" approach and identified positively with the story characters. Parents indicated that their materials were clear and helpful. Between the baseline and 3-month follow-up visits, the children exhibited a significant increase in knowledge of heart healthy foods, a decrease in total fat consumption that approached significance, and a significant decrease in plasma low-density-lipoprotein cholesterol values.

Lipoprotein Profiles in Hypercholesterolemic Children

Atherosclerosis is a process that begins in early life. Coronary heart disease is the result of complex interactions among a variety of risk factors of which hypercholesterolemia is but one. During routine screening, 500 children were identified with total cholesterol levels above the 95th percentile of 5.2 mmol/L (200 mg/dL). Lipoprotein profiles were then performed to confirm and delineate their lipid abnormalities. A definable lipid disorder was present in 85% of such children. Abnormal lipoprotein patterns included 292 children with type IIa, 99 with type IIb, and 25 with type IV phenotypes. An abnormally low high-density lipoprotein cholesterol level of less than 0.9 mmol/L (35 mg/dL) was observed in 20 children. Only 5% of patients were identified as being hypercholesterolemic because they had high-density lipoprotein cholesterol levels above the 95th percentile of 1.8 mmol/L (70 mg/dL). Thirty-two percent of children with total cholesterol levels above 5.2 mmol/L had a family member (sibling, parent, uncle, aunt, or grandparent) with a myocardial infarction prior to 55 years of age. Data from this study support universal cholesterol testing after 3 years of age and lipoprotein profiles for those with levels above 5.2 mmol/L.

Cardiovascular findings in familial hypercholesterolemic children.

Four child patients (1 male and 3 females) with homozygous familial hypercholesterolemia (FH) were examined. They were 4y4m to 9y8m of age on admission. A female patient at age 5y7m on admission had already experienced anginal attacks. Ischemic change was found on exercise ECG in 2 patients. Grade 1/6 to 3/6 (Levine) systolic ejection type murmur was audible in all patients. Cardiac catheterization was carried out in all patients. Supravalvular aortic stenosis was found and so-called atherosclerotic wall thickening was also noticed in 3 of them. Narrowing of the coronary arteries was found in only 1 patient who complained of anginal pain. Supravalvular aortic stenosis was more prevalent than coronary artery disorders in FH children and this lesion was also detected by echocardiography. Therefore, follow-up by echocardiography seems to be very useful in assessing the progression of atherosclerosis in patients with severe hypercholesterolemia.

Response to Diet and Cholestyramine in a Patient with Sitosterolemia

In this report, an 11-year-old boy with diffuse tendinous and tuberous xanthomatosis and a plasma sterol concentration of 555 mg/dL, consisting primarily of cholesterol, is described. Three months after changing from an unrestricted diet to a cholesterol-lowering diet, his plasma sterol concentration decreased to 221 mg/dL. Because of the degree and rapidity of his response to diet, sitosterolemia was suspected. According to results of capillary gas-liquid chromatography of his plasma sterols, there was a sitosterol concentration of 31.3 mg/dL (normal less than 1.0 mg/dL), establishing the diagnosis of sitosterolemia. Addition of cholestyramine therapy (8 g/d) to a low sterol diet further lowered his plasma sterol concentration to 173 mg/dL and led to complete regression of all tuberous xanthomata. Tendinous xanthomata regressed at a slower rate. These findings show that the diagnosis of sitosterolemia should be suspected in severely hypercholesterolemic children (total cholesterol greater than 400 mg/dL) whose plasma cholesterol level is highly responsive to dietary manipulation. The rapid and sustained lowering of plasma cholesterol and regression of xanthomata after treatment with diet and cholestyramine suggest that sitosterolemia is a treatable cause of premature atherosclerosis.

Association of hypercholesterolemia and apolipoprotein E4 in school children

To investigate the association of apolipoprotein (APO) E4 and hypercholesterolemia in children, we studied the APOE phenotypes of 51 school-age children with hypercholesterolemia and of 51 age, sex and obesity index-matched controls with normocholesterolemia by two-dimensional gel electrophoresis APOE4 was present in 21 of 51 hypercholesterolemic children (41.2%), and in nine of 51 control subjects (17.6%). The difference was significant (p less than 0.01). This finding indicates that APOE4 is associated with hypercholesterolemia in children.

Routine Cholesterol Surveillance in Childhood

To the Editor.— The article by Garcia and Moodie1 on cholesterol screening in childhood is likely to receive considerable attention and may have an impact on pediatric practice. The observation of these authors that the usual high-risk family characteristics may, if used as sole criteria for screening, allow some hypercholesterolemic children to remain undetected is valid. However, their recommedation that "all children older than 3 years of age should have a cholesterol test" cannot go unchallenged.

The child as proband. High prevalence of unrecognized and untreated hyperlipidemia in parents of hyperlipidemic children.

The authors evaluated the lipids of parents of hypercholesterolemic children to assess the prevalence of unrecognized and/or untreated hyperlipidemia. Biologic parents of 34 children had measurements of total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (n = 47) or total cholesterol only (n = 14). Lipid abnormalities were defined according to guidelines established by the National Cholesterol Education Program. Abnormal values were defined as total cholesterol greater than 240 mg/dl, low-density lipoprotein (LDL) cholesterol greater than 160 mg/dl, HDL cholesterol less than 35 mg/dl, and triglycerides greater than 250 mg/dl. Borderline values were defined as total cholesterol between 200 and 240 mg/dl and LDL cholesterol between 130 and 160 mg/dl. Abnormal values were found in 32/61 (52%) and borderline values were found in 12/61 (20%) parents. Of the abnormal parents, 13/32 (41%) had unrecognized or known but untreated hyperlipidemia, and 9/12 (75%) of the borderline parents had unrecognized abnormalities. In all families where both parents were tested, at least 1 had a lipid abnormality. The authors conclude that when children with hypercholesterolemia are identified, parents should also have lipids assessed. Treatment programs for children should also be directed at the parents.

Paediatric guidelines for lipid reduction.

Due to the fact that atherogenesis starts even in early childhood there is no doubt that the primary prevention of atherosclerotic diseases is a paediatric problem and therefore must start as early as possible in childhood. Thus, there is now indeed strong support for increasing efforts toward identifying those subjects with elevated total cholesterol or low density lipoprotein (LDL)-cholesterol levels and for providing appropriate treatment in order to achieve a substantial and pertinent reduction of those levels. Based on the data from the Lipid Research Clinics Program, the diagnosis of hypercholesterolaemia during infancy and childhood can easily be made, using the 95th percentiles for total cholesterol and for LDL-cholesterol. Today there is no doubt that elevated plasma cholesterol levels should be lowered first by dietary modification even in early childhood, beginning at the age of two years. Most authors report an average cholesterol reduction of about 10-15% by a low cholesterol-low fat diet. Our group had the opportunity to study 11 hypercholesterolaemic children consuming a type II diet containing 15-20 g soybean-protein, which resulted in a reduction of 32% in total cholesterol and 37% in LDL-cholesterol. In an individual patient who does not respond adequately to diet, drug treatment should be started. Bile acid-binding resins in a dose of 4-8 g are the drugs of choice at this time. A further 15-20% reduction of total plasma cholesterol can be achieved in most children. It is concluded that detection and adequate treatment of disorders of lipoproteins should be carried out early in childhood, in particular in families with a cardiovascular history.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in plasma lipid and lipoprotein fractions after alteration in dietary cholesterol, polyunsaturated, saturated, and total fat in free-living normal and hypercholesterolemic children

To assess the effects of dietary cholesterol and the amount and type of fat on plasma lipid and lipoproteins, nutrient intakes were altered sequentially over 15 months in 11 normal children and 12 children with heterozygous familial hypercholesterolemia. After a 3-month base-line assessment period, on an ad libitum diet, the following diets were given sequentially for three months each: dietary cholesterol greater than 450 mg/day, total fat less than 35% of total calories, and polyunsaturated fat to saturated fat ratio (P/S) greater than 1.5 (diet 1); dietary cholesterol less than 160 mg/day, total fat less than 35% total calories and P/S greater than 1.5 (diet 2); dietary cholesterol less than 160 mg/day, total fat 40% total calories P/S = 1 (diet 3), and dietary cholesterol greater than 450 mg/day total fat greater than 40% total calories, P/S less than 0.04 (diet 4). In normal and familial hypercholesterolemic children the high dietary P/S ratio lowered total and low-density lipoprotein cholesterol in the presence of high dietary cholesterol; sharp reductions in dietary cholesterol lowered the total and low-density lipoprotein cholesterol slightly in familial hypercholesterolemia subjects when P/S was high. High-density lipoprotein cholesterol was not affected by large changes in dietary cholesterol or amount or type of fat. Sustained dietary alteration which significantly lowers total and low-density lipoprotein cholesterol with commercially available products is achievable and practical in free-living children.