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PEDIATRICS Vol. 113 No. 6 June 2004, pp. 1723-1727

Usefulness of the American Academy of Pediatrics Recommendations for Identifying Youths With Hypercholesterolemia

Jennifer O’Loughlin, PhD*,{ddagger}, Beatrice Lauzon, BSc*, Gilles Paradis, MD*,{ddagger},§, James Hanley, PhD{ddagger}, Emile Lévy, PhD||,¶, Edgar Delvin, PhD,# and Marie Lambert, MD**,{ddagger}{ddagger}

* Direction de santé publique de Montréal-Centre, Montreal, Quebec, Canada
{ddagger} Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada
§ Division of Preventive Medicine, McGill University Health Center, Montreal, Quebec, Canada
|| Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
Research Center, Ste-Justine Hospital, Montreal, Quebec, Canada
# Department of Clinical Biochemistry, Ste-Justine Hospital and University of Montreal, Montreal, Quebec, Canada
** Division of Medical Genetics, Ste-Justine Hospital, Montreal, Quebec, Canada
{ddagger}{ddagger} Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Objective. To determine the usefulness of parent history of hypercholesterolemia and cardiovascular disease as a screening criterion for hypercholesterolemia in youths.

Methods. Data were available from a population-based survey of 3665 Quebec youths aged 9, 13, and 16 years (81.2% of eligible subjects). Blood specimens were collected from 2475 subjects (54.8% of those eligible), and questionnaire data were obtained from 3048 parents (67.5% of those eligible). Lipids were measured in a Centers for Disease Control and Prevention standardized laboratory. Usefulness of parent history in identifying borderline/high low-density lipoprotein cholesterol (LDL-C) (≥2.8 mmol/L [≥110 mg/dL]) and high LDL-C (≥3.4 mmol/L [≥130 mg/dL]) was assessed according to test performance statistics (sensitivity, specificity, positive predictive value, and negative predictive value).

Results. The prevalence of a positive parent history was 25.6%; 18.3% of subjects had borderline/high LDL-C, and 4.8% had high LDL-C. Sensitivity, specificity, positive predictive value, and negative predictive value of parent history were 33.1%, 76.0%, 23.7%, and 83.5%, respectively, for identifying borderline/high LDL-C; they were 40.7%, 75.1%, 7.7%, and 96.1% for identifying high LDL-C. Test performance statistics were not improved in subgroups defined according to age, gender, parent education, household income, family status, and family origin (French Canadian, other); neither were they improved by adding screening criteria (parent history of diabetes or hypertension, or youth overweight).

Conclusion. Parent history screening criteria offer little improvement over random population screening in identifying youths with hypercholesterolemia.

Key Words: screening • children • adolescent • cholesterol • family history • sensitivity • specificity • positive predictive value • negative predictive value

Abbreviations: CVD, cardiovascular disease • AAP, American Academy of Pediatrics • LDL-C, low-density lipoprotein cholesterol • PPV, positive predictive value • QCAHSS, Quebec Child and Adolescent Health and Social Survey • CV, coefficient of variation • TC, total cholesterol • TG, triglycerides • NPV, negative predictive value

Cardiovascular disease (CVD) represents an immense public health burden, accounting for 15 million deaths worldwide each year, or ~30% of all mortality.1 Studies have linked blood cholesterol, atherosclerosis, and CVD mortality/morbidity, establishing hypercholesterolemia as a risk factor for CVD.2–4 There is evidence that atherosclerosis begins in childhood and adolescence5,6 and that CVD risk factors track from childhood into adulthood.7–10

To reduce the burden of CVD, the American Academy of Pediatrics (AAP) recommends cholesterol screening in childhood and adolescence,11 with accompanying recommendations for the management of hypercholesterolemia cases identified through screening. The 1998 AAP recommendations state that youths aged 2 years or older should be screened for high cholesterol if they have a family history of premature CVD (≤55 years of age) or a parent history of hypercholesterolemia (240 mg/dL [6.2 mmol/L] or higher). For youths whose family history is not available and/or for those with other CVD risk factors, screening is recommended at the physician’s discretion. In the AAP recommendations, hypercholesteremia in screened youths is defined by blood low-density lipoprotein cholesterol (LDL-C) level; LDL-C levels ≥2.8 mmol/L (110 mg/dL) and <3.4 mmol/L (130 mg/dL) are defined as borderline. LDL-C levels ≥3.4 mmol/L (130 mg/dL) are defined as high.

As for any systematic screening recommendation, it is important to establish the usefulness of the screening criteria in correctly identifying the individuals targeted.12–14 Costs incurred through unnecessary diagnostic tests for false-positive results and psychological sequelae related to being labeled at risk for CVD as a result of the screening test15,16 must not outweigh the benefits of screening. In addition, misleading reassurance may be associated with false-negative results. Past studies that have used family history screening criteria similar to those recommended by the AAP17–23 suggest that the AAP criteria are not useful in identifying youths with raised blood cholesterol levels. However, few studies were population based, how unknown family history was analyzed varied and was sometimes unspecified, and most studies were published before the 1998 AAP recommendations were released.

The purpose of the present study was to evaluate the usefulness of the 1998 AAP family history criteria to screen youths for raised LDL-C in a representative, population-based sample. Two test performance statistics were considered to be especially important: 1) that family history criteria be better at selectively identifying youths with high LDL-C than simply screening the entire population12 (ie, that the positive predictive value [PPV] be high) and 2) that many more youths with borderline or high LDL-C be identified by the screening criteria than youths with normal LDL-C (ie, that the likelihood ratio be considerably >1). Secondary objectives were to assess the performance of the AAP screening criteria in selected subpopulations12,23,24 and when screening criteria were expanded to include additional risk factors for CVD.25


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Data were drawn from the Quebec Child and Adolescent Health and Social Survey (QCAHSS), a representative cross-sectional survey of Quebec youths. The QCAHSS used a multistage, stratified, cluster-sampling strategy, targeting all youths who were aged 9, 13, and 16 years and attending public or private schools in Quebec. Schools were randomly sampled, with a fixed sample size of 25 subjects in each of 189 schools selected. Subjects within schools were sampled randomly from Ministry of Education enrollment lists. Data collection tools included youth questionnaires, parent questionnaires, anthropometric measures, and blood draw. The Sainte-Justine’s Hospital ethics committee approved the study protocol; written parental consent was obtained separately for self-administered questionnaires and the blood draw. Detailed descriptions of the QCAHSS design and methods are available.26

Of 3665 subjects overall (response proportion: 81.2%), 831 had parent questionnaire data but no lipid data, 258 had lipid data but no parent questionnaire data, and 359 had neither parent nor lipid data. The analysis presented here therefore included 2217 subjects with data from both parent questionnaires and the blood draw.

Parent History
Self-reported parent history of hypercholesterolemia and CVD was obtained in 5 questions asked of the biological parents: 1) Has a doctor, nurse, or other health professional ever said that you have a high cholesterol level? 2) Do you take any medications to lower cholesterol level? 3) Have you ever had a heart attack or angina? 4) Have you ever had a stroke, cerebral vascular disease, or peripheral vascular disease? 5) Do you take any medications for the heart?

Parent history was coded as positive when there was a "yes" response to 1 or more of the 5 questions, for 1 or both biological parents. Parent history was coded as negative when both parents responded "no" to all 5 questions. Parent history was classified as unknown when there were no "yes" responses for either biological parent and when there was at least 1 "don’t know" or 1 missing response. No information was available on grandparent history.

Lipid Measurement
Blood was collected by venipuncture after an overnight fast, in a 1-mg/mL ethylenediaminetetraacetic acid collection tube. Samples were placed on ice, centrifuged on site, frozen on dry ice, and sent within 24 hours to the laboratory, where they were stored at –80°C until analysis. Plasma lipid concentrations were determined on a Synchron Cx7 (Beckman Instruments, Brea, CA) with Beckman Instruments reagents as previously described.26 Standardization was conducted according to the recommendations of the International Federation of Clinical Chemistry. Interassay coefficient of variation (CV) for total cholesterol (TC) measurements with controls at 2.91, 3.98, 5.55, and 7.45 mmol/L ranged from 1.1% to 1.4%; interassay CVs for high-density lipoprotein cholesterol with controls at 0.56 and 1.63 mmol/L were 3.6% and 4.3%, respectively; interassay CVs for triglycerides (TG) with controls at 1.05, 1.40, 2.13, and 5.12 mmol/L ranged from 3.9% to 5.4%. LDL-C concentrations were calculated according to the Friedewald equation.27

Analysis
All analyses were conducted using data weighted within age groups to ensure that samples were representative of the Quebec population. In addition, given the fixed sample size in each school, the sample was corrected for overweighting of smaller schools. We computed test performance statistics of parent history in identifying subjects with elevated blood cholesterol levels using two cutoffs: 1) ≥2.8 mmol/L and 2) ≥3.4 mmol/L. Test statistics included sensitivity (the proportion of subjects with elevated LDL-C correctly identified by parent history as having elevated LDL-C), specificity (the proportion of subjects without elevated LDL-C [ie, <2.8 mmol/L] correctly identified by parent history as not having elevated LDL-C), PPV (the proportion of subjects who have a positive parent history and elevated LDL-C), negative predictive value (NPV; the proportion of subjects who have a negative parent history and do not have an elevated LDL-C), and finally the likelihood ratio (the ratio of sensitivity to the probability that parent history incorrectly identified youths with normal LDL-C as having elevated LDL-C; this is equivalent to the ratio of sensitivity to 100 – specificity when test statistics are expressed as percentages).

Of 2217 subjects, 176 had responses to the parent questionnaire but were missing data for 1 or more parent history items. There was no substantive difference in the proportion of subjects with missing parent history data with or without lipid data. Subjects with missing parent history data were coded as having unknown parent history. Test performance statistics were computed first excluding subjects with unknown parent history and then including these subjects and treating parent history as negative.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
Half (50.3%) of the subjects were male; 70.3% reported living with both biological (or adoptive) parents. The proportion of parents who had not completed high school was 17.7%, whereas 21.5% of parents had completed university; 9.0% of subjects lived in households with annual revenues of <$15 000 CDN, whereas 16.7% lived in households that earned $80 000 CDN or more. The sample was predominantly French-Canadian (78.7%). Just more than half (58.5%) of subjects lived in urban areas.

Approximately one quarter of parents reported a history of hypercholesterolemia and/or CVD (Table 1). The prevalence of parent history increased with subjects’ age, from 21.5% of parents of 9-year-olds to 29.9% of parents of 16-year-olds. In all ages combined, the prevalence of borderline and high LDL-C was 18.3%; 4.8% of the sample had high LDL-C (Table 2).


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  		TABLE 1. Prevalence of Self-Reported Parent History of Hypercholesterolemia and CVD, QCAHSS 1999 (n = 2217)

 

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  		TABLE 2. Prevalence of Borderline and High LDL-C by Age and Gender, QCAHSS 1999

 
Both sensitivity and specificity for high LDL-C were relatively low: 50.6% and 69.1%, respectively (Table 3). The PPV was 7.7%, only 2.9% higher than the true population prevalence of 4.8%, indicating that the parent history criteria perform only marginally better in identifying youths with high cholesterol than would random population screening. The likelihood ratio of 1.64 also indicates poor test performance: parent history was not able to differentiate true- from false-positive results. Results for subjects with borderline/high LDL-C levels were also poor, with a PPV of 23.7% (compared with the overall sample prevalence of 18.3%) and a likelihood ratio of 1.40. Figure 1 illustrates the minimal gain achieved through screening for family history, relative to random population screening.


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  		TABLE 3. Performance of Parent History in Screening for Borderline or High LDL-C, QCAHSS 1999 (n = 2217)

 

Figure 1
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  		Fig 1. Proportion of subjects identified as having elevated cholesterol (≥2.8 mmol/L) in random population screening or using parent history screening criteria.

 
In secondary analyses, we examined test performance statistics in specific subgroups according to gender, age, parents’ highest level of education, household income, family status (single vs 2-parent), and family origin (French Canadian vs other). Test performance statistics were not improved, with the differences between PPVs and population prevalences ranging from –3.7% to 8.5% (the negative value indicating that random screening would detect more cases than screening using parent history criteria) and likelihood ratios ranging from 0.43 to 2.54. Test performance statistics were especially poor for the lowest category of household income, where PPVs were equal to or lower than the prevalence of raised blood LDL-C and likelihood ratios were <1.

In additional secondary analyses, we examined whether test performance statistics could be improved by adding easily accessible and highly prevalent characteristics of parents and youths to the parent history criteria. These included parent history of diabetes (5.4% of subjects had parents with self-reported diabetes), parent history of hypertension (reported by 17.5% of parents), and youths overweight (15.6% according to body mass index ≥age and gender-specific 85th percentile of the study population). Again, test performance statistics were not improved and in general were made even worse. The maximum difference obtained between population prevalences and PPVs was 5.4%, and the largest likelihood ratio was 1.70.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
The aim of this study was to evaluate the usefulness of the 1998 AAP criteria to screen youths for raised LDL-C in a representative, population-based sample. We used parent self-reports of high cholesterol and CVD as the source of screening criteria information, providing a test of the effectiveness of the AAP recommendations with information of a quality comparable to what would be available in everyday clinical practice.

Test performance statistics for family history in previously reported studies in small or select study populations range from 25% to 93% for sensitivity, 21% to 79.7% for specificity, 11.6 to 45% for PPV, 68.6% to 95% for NPV, and 0.91 to 1.64 for likelihood ratios.17–23 The difference between the PPV and the corresponding prevalence of raised blood cholesterol in the general study population ranged between –1.8 and 10.7.

Our results support the previous findings suggesting that self-reported parent history is not useful in identifying children and adolescents with raised LDL-C levels. Many youths with raised LDL-C will not be identified by the 1998 AAP screening criteria; also, many will be identified incorrectly as at risk. Moreover, applying the parent history criteria to identify youths at risk is no more effective than general population screening.

We suggest that the most likely reason for these results is the inaccuracy of parent self-reports of CVD history and hypercholesterolemia. Poor accuracy of self-reports has been found consistently for hypercholesterolemia29–33 and many other health-related variables.33 A recent report on the accuracy of adults’ knowledge of their cholesterol status using National Health and Nutrition Examination Survey data34 showed that 60% of adults 20 years or older with hypercholesterolemia (LDL-C ≥5.2 mmol/L, as detected by measurement of blood lipids) were unaware of their condition, and only 15% were being treated for it. If these findings can be extended to the situation among Quebec parents of youths between 9 and 16 years, then many parents who met the screening criteria would have been unaware of their status, limiting its information value as a screening criterion.

Limitations
Several limitations may have contributed to the poor performance of the 1998 AAP parent history criteria in this study. First, a single measure of LDL-C was used, rather than the average of 2 measures as recommended by the AAP. Second the response to the blood draw was relatively low, although no differences in the response proportion for blood draw were noted according to gender, pubertal status, smoking, weight status, or parent history of CVD or CVD risk factors including smoking, parent education level, household income, and rural or urban status of the school. Third, our family history criteria were not identical to the AAP criteria because the QCAHSS did not collect data on parent age at diagnosis of CVD (to define early CVD) or grandparent history of CVD. However, only 6 of 135 parents with a positive history were aged 55 years or older. It is also unlikely that lack of data on grandparent history influenced the findings. In most clinical situations in which family history is identified, grandparent history is collected from 1 parent or the youth, which would likely reduce its accuracy relative to parent history of CVD. Considering this and that parent history seemed to identify more false positives than true positives, it is doubtful that grandparent history would prove a useful addition to the parent history criteria. Finally, we included the question, "Do you (biological mother and father) take any medications for the heart?" which was not an AAP criterion, to categorize family history. Inclusion of this additional item might have improved test performance statistics.


   CONCLUSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
Parent history performed poorly in identifying youths with high LDL-C. Test performance statistics were not improved in specific subgroups, and incorporating information to the criteria on CVD risk factors such as parental diabetes or hypertension, or youth overweight, did not improve performance. In light of these findings and in the absence of objective measures of parent history, the AAP and other agencies should reconsider the appropriateness of recommending the use of self-reported family history in screening youths for CVD risk. Contrary to recent claims that family history "may be an effective means for predicting our risk of future disease"35 (p 309–310), it is unlikely, unless there is a significant improvement in parents’ reports of their medical history that current recommendations for screening youths using family history criteria will reduce the burden related to raised LDL-C in the general population.


   ACKNOWLEDGMENTS
 
This study was funded by the Ministère de la santé et des services sociaux du Québec, the Bureau of Nutritional Sciences, Health Canada, and a grant from the Canadian Institutes of Health Research (MOP-44027). Dr O’Loughlin is an investigator of the Canadian Institutes of Health Research.


   FOOTNOTES
 
Received for publication Aug 7, 2003; Accepted Jan 9, 2004.

Reprint requests to (J.O.) Direction de santé publique de Montreal-Centre, 1301 Sherbrooke St East, Montreal (Quebec) H2L 1M3. E-mail: jennifer.oloughlin{at}mcgill.ca


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics



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