Andrew Maxwell, M.D.

From: hwrc@galegroup.com
Sent: Thursday, November 20, 2003 2:18 PM
To: amaxwell@heartofthevalley.us
Subject: HWRC Document: Cholesterol Screening in Children and Adolescents.

HWRC Document

Cholesterol Screening in Children and Adolescents.

THOMAS B. NEWMAN, ALAN M. GARBER. Pediatrics. March 2000 v105 i3 p637.

Abstract:

Most children do not need to have their cholesterol levels checked. The Committee on
Nutrition of the American Academy of Pediatrics recommends screening for children with a
family history of high blood cholesterol or premature cardiovascular disease. However, the
American College of Physicians
(ACP) does not recommend cholesterol screening in children. The ACP guideline is based on
45 clinical trials and 8 meta-analyses of cholesterol reduction. The Committee on
Nutrition statement is based on 5 clinical trials. The impact of high cholesterol levels
in childhood is minimal.

Full Text: COPYRIGHT 2000 American Academy of Pediatrics

ABBREVIATIONS. ACP, American College of Physicians; CHD, coronary heart disease.

The Committee on Nutrition of the American Academy of Pediatrics recently reiterated its
recommendation that children and adolescents with a family history of high blood
cholesterol or premature cardiovascular disease should be screened for high blood
cholesterol.[1] In contrast, the American College of Physicians (ACP) does not recommend
cholesterol screening in adults who may have familial hypercholesterolemia or other risk
factors for coronary heart disease (CHD) until at least 25 to 30 years old in men and 35
to 40 years old in women.[2] Why the discrepant recommendations, and which ones should
clinicians follow?

A review of the 2 sets of recommendations and their supporting documentation reveals a

difference in the quality and quantity of evidence cited to support them. The ACP
guideline is based on an exhaustive review of 45 clinical trials and 8 meta-analyses of
cholesterol reduction. It includes projections of costs and of numbers-needed-to-treat to
prevent 1 death in different risk groups? In contrast, the Committee on Nutrition
statement primarily cites studies of cholesterol and arteriosclerosis in animals (7
references), cross-national comparisons (15 references), and studies of familial
aggregation and tracking of cholesterol levels (16 references). The Committee on Nutrition
does not quantify the costs or estimate the effects of the interventions it recommends--
precisely the numbers on which the ACP statement focuses. This turns out to be a key
omission.

The Committee on Nutrition statement cites only 5 clinical trials of cholesterol-lowering

interventions.[4-8] One trial, discussed below, was in children,[8] the other 4[4-7] were
studies of thousands of high-risk, middle-aged adults. Two of the adult trials[4,5]
studied interventions that the committee recommends for children. The first trial, the
Multiple Risk Factor Intervention Trial,[4] tested a multifactorial intervention that
included a cholesterol-lowering diet, blood pressure control, and smoking cessation
counseling. Although this multifactorial intervention would likely overestimate benefits
of dietary counseling alone, after 10.5 years the observed difference in CHD deaths was
still small and not statistically significant (3.1% vs 3.4%; 2-tailed, P = .24). The
second trial, the Lipid Research Clinics Coronary Primary Prevention Trial,[5-9] studied

1
cholestyramine, a bile acid-binding resin recommended by the committee for treating
children [is greater than] 10 years old with persistent high cholesterol levels. In the
Lipid Research Clinics Coronary Primary Prevention Trial, the difference in CHD events
approached statistical significance (2-tailed, P = .094). Even in these high-risk middle-
aged men, however, the effect size was modest: it took an estimated 11 tons of
cholestyramine to prevent 1 CHD death.[10]

The single clinical trial in children cited in the Committee on Nutrition statement is
the Dietary Intervention Study in Children.[8] The Committee devoted one half of its
section on clinical trials to this study, without mentioning the magnitude of the effort
required for the intervention or the size of its effect on blood cholesterol levels. To
identify the 663 children that participated in the trial, the investigators needed to
screen [is greater than] 44 000 children.[8] For each enrolled child, the dietary
intervention included 27 to 31 individual and group visits with nutritionists,
behaviorists, and health educators and monthly telephone follow-up for 3 years. Despite
this intensive effort, the observed difference in low-density lipoprotein-cholesterol
levels between intervention and control groups, although statistically significant, was
only 3.2 mg/dL.

The failure of the Committee to base its screening and treatment recommendations on
estimates of the benefits, risks, and costs of the interventions it recommends may have
harmful consequences. A 1995 survey of primary care physicians found that 76% of
respondents screen at least some children for high blood cholesterol and that 17% screen
all children.[11] A high proportion of these children, especially girls),[12] will have
cholesterol levels exceeding those that the Committee calls acceptable. Among 5- to 9-
year-old girls in the general population, for example, the prevalence of such levels is
nearly 50%.[13] Labeling these children as having high blood cholesterol levels and
instituting a medically supervised treatment program as if they had a disease could
contribute to a distorted view of the importance of childhood cholesterol levels and diet
in determining heart disease risk. The excess risk associated with an elevated cholesterol
level in childhood is small)4 the dietary treatment has little effect on blood cholesterol
levels,[12,15] and the labeling could exacerbate an already high prevalence of eating
disorders and fear of fat.[16-19] In a survey of fourth grade students in rural Iowa (n =
457), 46% of girls reported that they very often wish they were thinner and 21% very often
feel guilty when they eat foods that might make them fat.[18] Among South Carolina middle
school girls (n = 1599), many had tried to lose weight by dieting (43%), fasting (11%),
vomiting (6%), or taking diet pills (4%), laxatives (2%), or diuretics (2%).[16]
Identifying the 25% to 50% of these girls whose cholesterol levels are above the
"acceptable" level and placing them on low-fat, low-cholesterol diets to reduce their risk
of heart disease decades from now is not justified by a careful consideration of the
likely risks and benefits.

How do physicians and parents manage children identified as having high cholesterol
levels? The vast majority of primary care physicians initially recommend dietary
management and follow-up.[11] In most cases, the parents do not comply, and their children
simply do not keep their follow-up appointments.[20-22] However, in a recent survey ~16%
of primary care physicians used drugs to treat high blood cholesterol levels in children.
[11] The long-term safety of these medications is unknown, but we do know that they cause
or promote cancer in rodents at only 2 to 45 times the exposures that humans receive.[23]

In an era when time for office visits and resources for patient care are severely
limited, when no intervention has been shown to be effective and safe for long-term use in
children, and when labeling and medication use can lead to greater harms than benefits,
childhood cholesterol screening is not justified. Clinicians should follow the
recommendations of the ACP (and the US Preventive Health Services Taskforce[24]) and defer
cholesterol screening until adulthood.

THOMAS B. NEWMAN, MD, MPH Departments of Epidemiology and Biostatistics, Pediatrics, and
Laboratory Medicine School of Medicine University of California San Francisco, CA 94143

ALAN M. GARBER MD, PHD Department of Medicine Stanford University School of Medicine and
Veterans Affairs Palo Alto Health Care System Palo Alto, CA 94304

REFERENCES
2
 [1.] American Academy of Pediatrics, Committee on Nutrition. Cholesterol in childhood.
Pediatrics. 1998;101:141-147

[2.] American College of Physicians. Guidelines for using serum cholesterol high-density
lipoprotein cholesterol, and triglyceride levels as screening tests for preventing
coronary heart disease in adults. Ann Intern Med. 1996;124:515-517. Comments

[3.] Garber AM, Browner WS, Hulley SB. Cholesterol screening in asymptomatic adults,
revisited. Ann Intern Med. 1996;124:518-531. Comments

[4.] The Multiple Risk Factor Intervention Trial Research Group. Mortality rates after
10.5 years for participants in the Multiple Risk Factor Intervention
Trial: findings related to a priori hypotheses of the trial. JAMA. 1990;263:1795-1801.
[Published erratum appears in JAMA. 1990;263: 3151]. Comments

[5.] Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary
Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA.
1984;251:351-364

[6.] 4-8 Study Group. Randomised trial of cholesterol lowering in 4444 patients with
coronary heart disease: the Scandinavian Simvastatin Survival Study. Lancet.
1994;344:1383-1389

[7.] Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with
pravastatin in men with hypercholesterolemia. West of

Scotland Coronary Prevention Study Group. N Engl [ Med. 1995;333: 1301-1307. Comments

[8.] DISC Collaborative Research Group. Efficacy and safety of lowering dietary intake of
fat and cholesterol in children with elevated low-density lipoprotein cholesterol. The
Dietary Intervention Study in Children (DISC). ]AMA. 1995;273:1429-1435

[9.] Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary
Prevention Trial results. II. The relationship of reduction in incidence of coronary heart
disease to cholesterol lowering. JAMA. 1984;251:365-374

[10.] Toronto Working Group on Cholesterol Policy. Asymptomatic hypercholesterolemia: a

clinical policy review. J Clin Epidemiol. 1990;43: 1028-1121

[11.] Kimm SY, Payne GH, Stylianou MP, Waclawiw MA, Lichtenstein C. National trends in
the management of cardiovascular disease risk factors in children: second NHLBI survey of
primary care physicians. Pediatrics. 1998;102(5).
URL: http://www.pediatrics.org/cgi/content/ full/102/5/e50

[12.] Newman TB, Garber AM, Holtzman NA, Hulley SB. Problems with the report of the
expert panel on blood cholesterol levels in children and adolescents. Arch Pediatr Adolesc
Med. 1995;149:241-247

[13.] National Cholesterol Education Program. Report of the expert panel on blood
cholesterol levels in children and adolescents. Pediatrics. 1992;89: 515-584

[14.] Newman TB, Browner WS, Hulley SB. The case against childhood cholesterol screening.
JAMA. 1990;264:3039-3043

[15.] Newman TB, Hulley SB. Reducing dietary intake of fat and cholesterol in children. ]
AMA. 1995;274:1424-1425. Letter

[16.] Childress AC, Brewerton TD, Hodges EL, Jarrell MP. The Kids' Eating Disorders
Survey (KEDS): a study of middle school students. J Am Acad Child Adolesc Psychiatry.
1993;32:843-850

[17.] Shapiro S, Newcomb M, Loeb TB. Fear of fat, disregulated-restrained eating, and
body-esteem: prevalence and gender differences among eight- to ten-year-old children. J
3
Clin Child Psychol. 1997;26:358-365

[18.] Gustafson-Larson AM, Terry RD. Weight-related behaviors and concerns of fourth-
grade children. J Am Diet Assoc. 1992;92:818-822

[19.] Kassirer JP, Angell M. Losing weight--an ill-fated New Year's resolution. N Engl J
Med. 1998;338:52-54. Editorial comment

[20.] Lannon CM, Earp J. Parents' behavior and attitudes toward screening children for
high serum cholesterol levels. Pediatrics. 1992:1159-1163

[21.] Bachman RP, Schoen EJ, Stembridge A, Jurecki ER, Imagire RS. Compliance with
childhood cholesterol screening among members of a prepaid health plan. Am J Dis Child.
1993;147:382-385. Comments

[22.] Nader PR, Yang M, Luepker RV, et al. Parent and physician response to children's
cholesterol values of 200 mg/dL or greater: the Child and Adolescent Trial for
Cardiovascular Health Experiment. Pediatrics. 1997; 99(5). URL:
http://www.pediatrics.org/cgi/content/full/99/5/e5

[23.] Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. JAMA. 1996;275:55-60

[24.] US Preventive Health Services Task Force. Guide to Clinical Preventive Services.
2nd ed. Baltimore, MD: Williams & Wilkins; 1996

Received for publication Jun 14, 1999; accepted Nov 15, 1999.

Address correspondence to Thomas B. Newman, MD, MPH, Department of Epidemiology,

University of California San Francisco, Box 0560, San Francisco, CA 94143.
E-mail: newman@itsa.ucsf.edu
Record Number: A60794277

This information is not a tool for self-diagnosis or a substitute for professional care.

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