Letters to the Editor
Importance of Dyslipidemia Screening in Children and Adolescents
Am Fam Physician. 2019 Oct 1;100(7):391-392.
Original Article: Right Care for Children: Top Five Do's and Don'ts
Issue Date: March 15, 2019
See additional reader comments at: https://www.aafp.org/afp/2019/0315/p376.html
To the Editor: Familial hypercholesterolemia (FH) is present in approximately one out of 250 children, resulting in lifelong elevated cholesterol and premature coronary artery disease (CAD). FH triples the likelihood of CAD at any given low-density lipoprotein cholesterol (LDL-C) level. FH can be easily identified in childhood by simple lipid screening.1–5 Some guidelines recommend universal lipid screening in children and adolescents nine to 11 years and 17 to 21 years.1,2,4
In this article by Dr. Schefft and colleagues, routine testing for dyslipidemia in children and adolescents is listed as a top five “don't” for the right care for children, implying that physicians screening for dyslipidemia are providing the wrong care. The safety of statin therapy in children is also questioned. This statement contradicts the 2016 U.S. Preventive Services Task Force report, which acknowledges the importance of early detection of FH and multifactorial dyslipidemias, leaving the decision about screening to clinical judgment, despite evidence that cholesterol screening in childhood is insufficient to assess the balance of benefits and harms.5
Many levels of evidence support screening and early treatment of severe hypercholesterolemia, including FH. There is a significant linear relationship between cholesterol-years of exposure and the risk of future CAD. For every mmol per L (38 mg per dL) of lifelong genetically elevated LDL-C, the risk of CAD is increased by 50%. FH-associated mutation triples the risk of CAD at any level of cholesterol. Lowering LDL-C early in life can alter this relationship. FH registry studies and meta-analyses of randomized trials demonstrate that patients with the highest cholesterol levels who are treated early benefit the most from treatment, with as much as a 75% risk reduction in event rates in young patients with FH.1–3
There are no published studies suggesting harm from statin treatment, and there are no data reports of adverse events in children. Current data actually suggest that statins may be better tolerated when prescribed at younger ages.1,2,4,5
Family physicians are uniquely positioned to screen for, detect, and treat prevalent genetic conditions such as FH that affect families across many generations. Similar to monogenic causes of cancer, FH has a Tier 1 recommendation for testing of first-degree relatives of affected patients issued by the Centers for Disease Control and Prevention.2 Lipid screening should be one of the “do's” of right care for children, not one of the “don'ts.”
Author disclosure: Dr. Gidding is the medical director of the FH Foundation. He receives research funding from the National Institute of Diabetes and Digestive and Kidney Diseases as a consultant for the TODAY studies. He was a coauthor of the 2011 National Heart, Lung, and Blood Institute Cardiovascular Risk Reduction in Childhood and Adolescence guideline. Dr. Wójcik has no relevant financial affiliations.
Referencesshow all references
1. Wiegman A, Gidding SS, Watts GF, et al.; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36(36):2425–2437....
2. Gidding SS, Champagne MA, de Ferrant SD, et al.; American Heart Association Atherosclerosis, Hypertension, and Obesity in Young Committee of Council on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and Council on Lifestyle and Cardiometabolic Health. The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association [published correction in Circulation. 2015;132(25):e397]. Circulation. 2015;132(22):2167–2192.
3. Khera AV, Won HH, Peloso GM, et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67(22):2578–2589.
4. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Circulation. 2019;139(25):e1082–e1143.
5. Lozano P, Henrikson NB, Morrison CC, et al. Lipid screening in childhood and adolescence for detection of multifactorial dyslipidemia: evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2016;316(6):634–644.
In Reply: We appreciate the thoughtful response by Drs. Wójcik and Gidding to our article and thank them for their numerous contributions surrounding the management of familial hypercholesterolemia (FH). We agree that early diagnosis and initiation of lipid-lowering medications for children with FH are important for their longevity and quality of life. As the authors state, the U.S. Preventive Services Task Force chose not to recommend for or against routine lipid screening in children, a position supported by the American Academy of Family Physicians.1 The National Heart, Lung, and Blood Institute (NHLBI) panel's basis for universal screening is the suggestion that obtaining family history is insensitive for the detection of children at high risk of FH. However, the studies cited to support this concern used family history as a screen for high lipid levels, not FH. The LDL-C thresholds used in these studies were surprisingly low (some as low as 135 mg per dL [3.50 mmol per L]).2 Therefore, an otherwise healthy nine year old with no family history of cardiovascular disease and a borderline elevated LDL level would theoretically be “missed.” An estimated 200,000 children and adolescents could qualify for statin therapy if universal screening was widely implemented.3
Although existing data suggest a low rate of adverse events, the long-term consequences of lipid-lowering medications for children are a significant concern. The data supporting the safety of statins in children are almost entirely industry sponsored, short in time horizon, and exclusively in children with FH.4 The safety and effectiveness of statins in the population most impacted by universal screening, otherwise healthy children with common comorbidities such as obesity, have not been studied. Additionally, there is evidence that cholesterol levels among adolescents have decreased over time without screening or treatment.5
Half of the NHLBI expert panel had conflicts of interest related to 16 pharmaceutical and biotechnology companies.6 We recognize the important role that the pharmaceutical industry plays in bringing innovative medications to market; however, the potential for these relationships to influence guideline development cannot be ignored.
Under the premise that “do no harm” should be the fundamental starting point in health care, we disagree that universal lipid screening should be considered a top five “do” for the right care for children. Although identifying and treating patients with FH are important, the net benefits of screening all children, especially children without a family history of cardiovascular disease, are uncertain. We hope that research in this area continues to better inform clinical decision-making.
Author disclosure: No relevant financial affiliations.
Referencesshow all references
1. American Academy of Family Physicians. Lipid disorders. Accessed May 10, 2019. https://www.aafp.org/patient-care/clinical-recommendations/all/lipid-disorders.html...
2. Haney EM, Huffman LH, Bougatsos C, et al. Screening and treatment for lipid disorders in children and adolescents: systematic evidence review for the US Preventive Services Task Force. Pediatrics. 2007;120(1):e189–214.
3. Psaty BM, Rivara FP. Universal screening and drug treatment of dyslipidemia in children and adolescents. JAMA. 2012;307(3):257–258.
4. Schroeder AR, Redberg RF. Cholesterol screening and management in children and young adults should start early-NO! Clin Cardiol. 2012;35(11):665–668.
5. Kit BK, Carroll MD, Lacher DA, et al. Trends in serum lipids among US youths aged 6 to 19 years, 1988–2010. JAMA. 2012;308(6):591–600.
6. Newman TB, Pletcher MJ, Hulley SB. Overly aggressive new guidelines for lipid screening in children: evidence of a broken process. Pediatrics. 2012;130(2):349–352.
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