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.     

Cholesterol screening by primary care pediatricians: a study of attitudes and practices in the Minneapolis-St Paul metropolitan area.

A telephone survey of the 197 board-certified pediatricians actively engaged in primary care in the Minneapolis-St Paul metropolitan area was conducted to assess their cholesterol screening practices and hypercholesterolemia management. The response rate was 95%. Nearly all the pediatricians (90%) do some cholesterol screening, with the majority (58%) screening only children with a strong family history of coronary heart disease. Though only 33% screen all their patients, 66% advocate universal pediatric screening. Most of the pediatricians indicated they would manage hypercholesterolemia patients themselves, nearly always with dietary means. Despite their strong support for screening, the pediatricians expressed skepticism about the significance of childhood cholesterol level as a predictor of adult cardiovascular disease and doubted their effectiveness in getting patients to adopt a cholesterol-reducing diet. Their definition of elevated total cholesterol level in childhood was consistent with published recommendations, but only 29% could define elevated low-density lipoprotein cholesterol level. The pediatricians expressed strong opposition to pediatric cholesterol screening in schools or in any setting other than clinics and hospitals.     

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.     

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.     

Screening programme for hyperlipidemia in children and adolescents. Prophylactic aspects of atherosclerosis

Atherosclerotic cardiovascular diseases (CVD), mainly coronary heart disease (CHD) remain the leading cause of death in adult populations of many countries. The following risk factors for atherosclerosis were identified: hypercholesterolemia, hypertension, cigarette smoking and obesity. Scientific reports and epidemiological studies have shown that atherosclerosis begins in childhood. Therefore consensus was obtained that the earlier the prevention begins the better results are achieved. But there are many controversies around early identification of hypercholesterolemia in children. Three options were considered: cholesterol mass screening, selective cholesterol screening and no screening at all. The most acceptable is selective screening performed in children of high risk families (CVD or hypercholesterolemia in the family). It is recommended by the US Expert Panel for the National Cholesterol Education Program for Children and Adolescents (NCEP-Peds). According to the NCEP-Peds, screening should include the following groups: I) children whose parents or grandparents have a history of CVD (under the age of 55 years), 2) children whose parents have a raised blood cholesterol concentration (above 240 mg/dl), 3) children with negative or unknown family history, but having other risk factors (hypertension, obesity, cigarette smoking, high-fat diet). The experts recommend that the examination should be performed in children after the age of 2 years. The NCEP-Peds guidelines set total cholesterol levels in serum for children and adolescents from families at risk, below 170 mg/dl, as acceptable. Total cholesterol level between 170 and 199 mg/dl is classified as borderline and 200mg/dl and above--as high.     

Usefulness of serum apolipoprotein B levels for screening children with primary dyslipoproteinemias.

OBJECTIVE--To assess the use of serum apolipoprotein B levels for screening children with primary dyslipoproteinemia (those with elevated levels of low-density lipoprotein cholesterol [LDL-C]) and to know the types of dyslipoproteinemias we can identify. DESIGN--Criterion standard. SETTING--Referral center. PARTICIPANTS--We have studied 267 children. Of these, 31 had parents with dyslipoproteinemia, 38 had parents with ischemic heart disease, and 43 had hypercholesterolemia detected by routine analyses. One hundred fifty-five were considered healthy children and comprised the control group. INTERVENTIONS--None. MEASUREMENTS AND MAIN RESULTS--Sensitivity was 87% for total serum cholesterol levels and 73% for serum apolipoprotein B levels. Of the children studied, 31 had elevated levels of serum LDL-C. The types of dyslipoproteinemia in children with both elevated levels of serum LDL-C and apolipoprotein B consisted of heterozygous familial hypercholesterolemia, found in 12 (50%) of 24 patients; familial combined hyperlipidemia, found in 11 (46%) of 24 patients; and polygenic hypercholesterolemia, found in one (4%) of 24 patients. CONCLUSIONS--Serum apolipoprotein B level appears to be a good tool for screening children with elevated levels of LDL-C and is equivalent to using total serum cholesterol levels. In children with elevated serum LDL-C and apolipoprotein B levels, we can identify not only patients with heterozygous familial hypercholesterolemia but also those with familial combined hyperlipidemia or polygenic hypercholesterolemia.     

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.     

Cholesterol screening in childhood: sixteen-year Beaver County Lipid Study experience

To determine the extent to which cholesterol measured in childhood is predictive of values in adulthood, the investigators conducting the second follow-up of the Beaver County Lipid Study tracked the cholesterol values of 295 adults who had initially participated as children (ages 11 to 14 years) in a countywide school screening program. The follow-up study was conducted 16 years after the initial study, when the participants had reached a mean age of 28 years. The overall correlation (r) between baseline (1972-1973) total cholesterol values and the values found at the present follow-up was 0.44 (p less than 0.0001). Women had a higher correlation (r = 0.51) than men (r = 0.38). In addition, the efficacy of childhood screening for cholesterol levels was assessed by considering currently recommended borderline values (greater than 175 mg/dl (4.6 mmol/L) for children and greater than 200 mg/dl (5.2 mmol/L) for adults) as a "positive" test result. The sensitivity of screening at age 12 years for predicting elevated adult total cholesterol concentrations was 63%, specificity was 67%, and the predictive value of a positive test result was 47%. Comparison of false-positive results (above the borderline cutoff point as a child but not as an adult) and false-negative results (below the borderline cutoff point as a child but above it as an adult) showed that male subjects with false-positive results smoked significantly less than those with false-negative results (p less than 0.05) and had a greater improvement during the preceding 7 years in cholesterol-lowering dietary practices (p less than 0.01). Female subjects with false-positive results smoked significantly less than those with false-negative results (p less than 0.05), were less overweight (p less than 0.05), and had a lower prevalence of oral contraceptive use (p less than 0.01). These results support the potential value of screening for hypercholesterolemia in childhood on a population basis. Although some subjects were misclassified as a result of childhood screening, some of this misclassification was associated with adopting changes that a screening and intervention program would be designed to promote--nonsmoking, weight control, and a prudent diet.     

Is Family History of Premature Cardiovascular Diseases Appropriate for Detection of Dyslipidemic Children in Population-Based Preventive Medicine Programs? CASPIAN Study

The objectives of this study were to determine the prevalence of dyslipidemia and the usefulness of self-report family history (FH) of premature cardiovascular disease (CVD) for identifying children with lipid disorders. This study was conducted on a representative, population-based sample of 4811 Iranian children and adolescents (2248 boys and 2563 girls) aged 6–18 years. We compared the obtained serum lipid profile with that of the Lipid Research Clinic (LRC) and calculated the predictive value of FH for detecting those children with dyslipidemia. Overall, for both genders and for age groups, the mean serum triglycerides (TG) and its percentiles were significantly higher, and the mean and percentiles of total, low-density, and high-density cholesterol (TC, LDL-C, and HDL-C respectively) were significantly lower than the LRC values. In total, 45.7% of participants had dyslipidemia; the most frequent ones were low HDL-C (24.8%) and hypertriglyceridemia (24.5%), followed by hypercholesterolemia (6.4%) and high LDL-C (6.3%), respectively. The mean serum lipid levels and the anthropometric measures were not significantly different among those with or without positive FH. The sensitivity, and specificity, positive and negative predictive values for FH in detecting those children with dyslipidemia were 28.4, 70.3. 44.7, and 53.8%, respectively. The usefulness of FH in identifying dyslipidemic children was relatively low. The common lipid disorders in our community were the components of the metabolic syndrome. We suggest that the current guidelines for screening lipid disorders in youths, which are based on cholesterol, should consider such ethnic differences.     

Educating NPs to educate patients: cholesterol screening in pediatric primary care.

INTRODUCTION: This study described practices, knowledge, and attitudes of primary care nurse practitioners (NPs) in Minnesota regarding cholesterol screening in children and adolescents. METHODS: A survey including 22 questions pertaining to cholesterol screening, adapted from a telephone survey used by Arneson, Luepker, Pirie, and Sinaiko (1992), was mailed to pediatric and family NPs. Eighty-three of 221 surveys (38%) were completed, returned, and used for data analysis. RESULTS: Although 96% of the respondents value childhood cholesterol levels as indicators of the risk of developing adult cardiovascular disease, only 64% follow the current recommendation to selectively screen cholesterol levels in patients who have a parent with hypercholesterolemia. Furthermore, only 55% of the respondents screen patients with a family history of premature cardiovascular disease, and only 58% screen patients with other cardiac risk factors. Whereas 57% of respondents correctly identified an acceptable total cholesterol level for children, only 34% correctly identified an acceptable LDL cholesterol level. DISCUSSION: Gaps in knowledge and practice may prevent NPs from implementing recommended guidelines for childhood cholesterol screening. Educating NPs about cholesterol screening is necessary to ensure the comprehensive cardiac health assessment and management of pediatric patients.     

Routine cholesterol surveillance in childhood

Coronary heart disease is the leading cause of death in the United States, and there is reason to believe that it begins in childhood. Evidence is accumulating that early diagnosis and treatment of hypercholesterolemia, a major coronary risk factor, can markedly reduce the incidence of atherosclerotic heart disease in later life. A pediatric group practice consisting of six pediatricians and a pediatric nurse practitioner performed a cholesterol surveillance study of 6500 children between 3 and 18 years of age. Parents and patients were counseled regarding other coronary risk factors, and the American Heart Association diet was recommended. According to the results of the study, 1251 children (19%) exceeded the acceptable 90th percentile for cholesterol and that 143 of 299 significantly hypercholesterolemic children (48%) had no family history of premature myocardial infarction or known hypercholesterolemia. The current recommendation is that only those children from high-risk families should be screened for an elevated cholesterol level. The authors conclude, as a result of this study, that all children older than 3 years of age should have a cholesterol test and that advice regarding avoidance of high-risk coronary life-style behaviors should be a routine part of pediatric anticipatory guidance.     

Cholesterol screening in children during office visits

Elevated blood cholesterol levels, a major risk for coronary artery disease in adults, has been associated with atherosclerotic disease in children. More than 10% of North American children have blood cholesterol levels higher than the desirable levels for adults. Current guidelines recommend screening only in children who have a family history of hyperlipidemia or myocardial infarction at an early age; however, this method fails to identify most children with hypercholesterolemia. Office-based cholesterol screening is an effective means to identify children and family members for dietary assessment and counseling. Should these measures be insufficient to lower the child's cholesterol level, referral for pharmacologic treatment is indicated.     

Therapeutic approach to childhood hypercholesterolemia

Hypercholesterolemia is associated with increased risk of premature cardiovascular disease in adults, while early atherosclerotic lesions (reversible fatty streaks and non reversible fibrous plaques) are also associated with cardiovascular risk factors including low density lipoprotein-cholesterol (LDL-C). Although LDL-C is a risk factor that should be addressed in high risk children such as those with familial hypercholesterolemia, it is unclear, at present, whether there is a certain plasma LDL-C level that would call for an intervention regardless of the etiology of elevated LDL-C. Therefore, at present, screening the entire population to identify subjects with hypercholesterolemia is not justified. The aims of this review are to familiarize the reader with inherited diseases that are associated with elevated LDL-C and discuss the management of children with elevated LDL-C.     

Management of cardiovascular disease risk factors in children. A national survey of primary care physicians

A national survey of family physicians, general practitioners, and pediatricians revealed substantial physician differences in managing cardiovascular disease risk factors in children aged 2 to 18 years. Pediatricians tended to screen younger children but were more conservative in treatment. General practitioners tended to screen less and to initiate intervention in older children, but were more aggressive in therapy. While only 9% of surveyed physicians measured blood cholesterol levels routinely, 72% screened children with family histories of cardiovascular disease. The majority routinely measured blood pressure, but the ages of first measurements differed among physicians. Surprisingly, of those who had treated children with elevated blood pressure or blood cholesterol, 54% said that they had ever used antihypertensive and 12% used lipid-lowering drugs in children, including angiotensin converting enzyme inhibitors and clofibrate. Half the surveyed physicians felt prepared to provide dietary counseling, but only 14% felt successful with it. When asked what they considered were the major cardiovascular risk factors, less than one third of the physicians cited all three major factors: hypertension, hypercholesterolemia, and smoking.     

What are parents of obese children concerned about in their children?

We retrospectively examined the issues that concern parents of obese children to determine the most effective means of motivating them to seek treatment for obesity in their children. Children with an obesity index > 40%, aged six to 12 years, were screened in Kagoshima City in 1992. Parents were notified if their children needed an evaluation that included a family history and measurements of the blood pressure, total cholesterol, high density lipoprotein (HDL)-cholesterol, atherogenic index (ASI), triglycerides, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Parents were informed of the results of the evaluation and invited to attend a lecture on the treatment of obesity in children. A total of 378 obese children were evaluated. However, the parents of only 39 children attended the lecture. Children whose parents attended had higher mean total levels of cholesterol (190 ± 25 vs 175 ± 28, P < 0.01) and ASI values (3.2 ± 0.9 vs 2.7 ± 0.9, P < 0.02) than those whose parents did not attend. There were no significant differences in other factors. Only 4.2% of parents whose children showed no abnormal values, except for obesity, attended the lecture, compared with 20.3% (P< 0.01) or 16.9% (P< 0.05) of parents whose children had abnormal levels of cholesterol or abnormal ASI. Parents may be more concerned about hypercholesterolemia or arteriosclerosis than obesity per se. We should perhaps use the total cholesterol or ASI values, not just the severity of obesity, to motivate parents to enter their children into treatment programs for obesity.     

Migraine in children: association with primary and familial dyslipoproteinemias

We studied lipids and lipoprotein cholesterols in 39 children (26 boys, 13 girls) with severe migraine, to examine the hypothesis that primary and familial lipoprotein abnormalities might be associated with or predispose children to the migraine syndrome. Each of the children, 4 to 20 years of age, had severe migraine, leading to pediatric neurologic referral and therapy. Twenty-five of the 39 probands (64%) had a first degree relative with severe migraine, and 18% had a second degree relative with severe migraine. In 11 of the 39 kindreds (28%), there was a family history of premature myocardial infarction and/or cerebral vascular accident (less than age 55 years), involving one grandparent from each of ten kindreds and one parent in the 11th kindred. In nine of the 26 boys, low-density lipoprotein cholesterol (LDL-C) levels were greater than or equal to the age-, sex-, race-specific 90th percentile, and in three of these nine children, there was at least one additional first degree relative also having a primary top decile LDL-C level, consistent with the presumptive diagnosis of familial hypercholesterolemia. The finding of more than three times as many boys with migraine headache having top decile LDL-C than expected (9 v 2.6) was significant (chi 2 = 17.5, P less than .01). Also, there were six boys having bottom decile levels of high-density lipoprotein cholesterol (HDL-C); all six came from kindreds with at least one first degree relative also having bottom decile HDL-C.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Effect of Statins in Children and Adolescents With Familial Hypercholesterolemia: A Systematic Review

IntroductionFamilial hypercholesterolemia (FH) is a genetic disorder that causes elevated low-density lipoprotein–cholesterol (LDL-C) levels. If undiagnosed and untreated in childhood, affected individuals can suffer premature health complications. Statins reduce the risks of complications for adults, but less is known about children. This systematic review examined the effectiveness of statin therapy for lowering LDL-C levels in children with FH.MethodMedline Ovid, Embase, CINAHL, and Allied Health Literature Plus were searched for studies that examined the effectiveness of stains in children ages 1–18 years with heterozygous FH.ResultsOf the 706 articles identified, 10 were included in the review. Statin therapy significantly reduced LDL-C levels in pediatric patients with FH. Statins were safe and well-tolerated with minimal adverse effects.DiscussionPediatric providers should be familiar with diagnosis, treatment, and management of FH to successfully lower LDL-C levels and avoid potential long-term health effects. Evidence suggests statins are safe and effective in children with FH.     

Obesity and lipid profiles in children and adolescents

Childhood obesity is associated with unfavorable lipid profile, suggesting that obese children should be screened for hypercholesterolemia. However, the prevalence of hypercholesterolemia in childhood obesity, and the effect of the degree of obesity on lipid profile, are unknown. Eighty-nine obese children and adolescents (BMI >85%, mean age 10.4 +/- 2.5 years) and 53 non-obese control children matched for age, gender and pubertal stage participated in the study. Early morning blood samples for serum lipids were collected in all children after a 12-h fast. Mean serum cholesterol and triglycerides (TG) levels were significantly higher (p <0.05) among the obese children (cholesterol: 175.2 +/- 31.4 vs 143.3 +/- 24.3 mg/dl; TG: 122.8 +/- 69.7 vs 94.3 +/- 37.8 mg/dl in obese and control children, respectively). Among the obese children, 52% had elevated serum cholesterol levels (>170 mg/dl) compared to 16% in the controls. The degree of obesity (BMI 85-95% vs BMI >95%) had no effect on serum lipids. Unfavorable lipid levels were relatively common among obese children, suggesting that obesity should be considered a risk factor for hypercholesterolemia, and that screening obese children for hypercholesterolemia should be considered.     

Coronary risk factors in children of parents with premature coronary artery disease

In order to assess the value of family history of premature coronary artery disease as a criterion for coronary risk factor screening, a group of 53 children with such a family history was selected. We determined various coronary risk factors in these children in comparison to 33 controls. Statistically significant differences were observed in apoprotein concentrations but not in concentrations of lipids, lipoproteins or glucose, or in blood pressure or body mass index. The ratio between apoprotein B and apoprotein A1 was the best discriminator between the two groups. The predictive value of family history is more reliable for detecting abnormal apoprotein ratio than for detection of hypercholestero-lemia. We conclude that if abnormal apoprotein levels during childhood are found to be a valued predictor of premature coronary artery disease, then family history of premature coronary artery disease can be used to select children for determination and assessment of their coronary risk.     

Lipid screening and cardiovascular health in childhood

This clinical report replaces the 1998 policy statement from the American Academy of Pediatrics on cholesterol in childhood, which has been retired. This report has taken on new urgency given the current epidemic of childhood obesity with the subsequent increasing risk of type 2 diabetes mellitus, hypertension, and cardiovascular disease in older children and adults. The approach to screening children and adolescents with a fasting lipid profile remains a targeted approach. Overweight children belong to a special risk category of children and are in need of cholesterol screening regardless of family history or other risk factors. This report reemphasizes the need for prevention of cardiovascular disease by following Dietary Guidelines for Americans and increasing physical activity and also includes a review of the pharmacologic agents and indications for treating dyslipidemia in children.