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 Screening for Lipid Disorders  



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USPSTF Issues Statement Regarding Routine Screening for Lipid Disorders in Young People CME/CE

News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD
Disclosures
Release Date: July 9, 2007; Valid for credit through July 9, 2008
Credits Available

Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)â„¢ for physicians;
Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians;
Nurses - 0.25 nursing contact hours (None of these credits is in the area of pharmacology)

July 9, 2007 — The potential harms and benefits of routinely screening for lipid disorders in children, adolescents, or adults as old as 20 years are not clear, according to the US Preventive Services Task Force (USPSTF) statement published in the July issue of Pediatrics. Although no recommendations for or against screening can be determined based on currently available evidence, the statement offers some clinical considerations about screening this population.

"The relationship between childhood and adult dyslipidemia, increasing prevalence of related CHD [coronary heart disease] risk factors in children (eg, obesity and diabetes), and continued emphasis on a primary prevention approach for CHD has raised interest in screening children for dyslipidemia," write Elizabeth M. Haney, MD, from Oregon Health and Science University in Portland, and colleagues. "Identifying children with dyslipidemia could lead to interventions or treatments that could prevent or delay adult dyslipidemia and CHD. ...Clinic-based screening, neonatal screening, community-based screening, and other prevention strategies have been proposed, but most recommendations support selective strategies to test children who have family members with dyslipidemia or premature CHD and those with unknown family histories."

This systematic evidence review from the USPSTF aimed to synthesize the published evidence regarding the effectiveness of selecting, testing, and treating children and adolescents with dyslipidemia in the course of routine primary care.

The panel conducted literature searches to identify published articles addressing 10 key questions:

1. Is screening for dyslipidemia in children and adolescents effective in delaying the onset and reducing the incidence of CHD-related events?

2. What is the accuracy of screening for dyslipidemia in identifying children and adolescents at increased risk for CHD-related events and other outcomes?

3. What are the adverse effects of screening, such as false-positive and false-negative results and labeling?

4. In children and adolescents, what is the effectiveness of drug, diet, exercise, and combination therapy in reducing the incidence of adult dyslipidemia and delaying the onset and reducing the incidence of CHD-related events, including optimal age for initiation of treatment?

5 - 8. What is the effectiveness of drug, diet, exercise, and combination therapy for treating dyslipidemia in children and adolescents?

9. What are the adverse effects of drug, diet, exercise, and combination therapy in children and adolescents?

10. Does improving dyslipidemia in childhood reduce the risk for dyslipidemia in adulthood?

The review notes that normal values for lipids for children and adolescents are defined based on population levels (percentiles), but that age, sex, racial differences, and temporal trends may affect these statistical cut points. An estimated 40% to 55% of children with increased total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels will continue to have increased lipid levels on follow-up.

Current screening recommendations, which are based on family history, will fail to detect a significant proportion (30% to 60%) of children with elevated lipid levels. In children, drug treatment of dyslipidemia has been proven to be effective only for suspected or confirmed familial monogenic dyslipidemias.

Although intensive dietary counseling and follow-up may help normalize lipid levels in the short term, lipid levels typically increase when the intervention is stopped. There have been only a few trials of exercise, and these are of fair to poor quality, showing little or no improvements in lipid levels for children without monogenic dyslipidemias. Reported adverse events were not serious, but these trials were mostly small and of insufficient duration to determine the long-term effects of either short-term or long-term use.

"Several key issues about screening and treatment of dyslipidemia in children and adolescents could not be addressed because of lack of studies, including effectiveness of screening on adult coronary heart disease or lipid outcomes, optimal ages and intervals for screening children, or effects of treatment of childhood lipid levels on adult coronary heart disease outcomes," the authors write.

Many studies have described various features of dyslipidemia, but there is still a paucity of evidence to answer the key questions about screening. Data are lacking regarding efficacy of screening children and adolescents for dyslipidemia in delaying the onset and lowering the incidence of CHD-related events; efficacy of drug, dietary, exercise, and combination therapies in lowering the incidence of adult dyslipidemia or delaying the onset and reducing the risk for CHD-related events; and whether improving dyslipidemia in children and adolescents lowers the risk for adult dyslipidemia.

Risk factors that might be useful to construct a risk-assessment tool have not been studied adequately, family history questions are not standardized and have limited diagnostic accuracy, and the potential impact of incorporating overweight into a screening strategy for dyslipidemia is unknown. Other risk factors including diet, physical inactivity, and aerobic capacity/fitness have not been evaluated sufficiently to determine their usefulness as screening tools either alone or in combination.

There is limited compliance by parents and children for currently recommended screening strategies, as well as low adherence by providers. To date, no studies have compared strategies by location, venue, age, or provider; none have evaluated the frequency and optimal age for testing or adverse effects of screening for dyslipidemia.

"Drug treatments for dyslipidemia in children have been studied only in children with FH [familial hypercholesterolemia] or FCH [familial combined hyperlipidemia], the population for whom these drugs are Food and Drug Administration–approved and recommended by the NCEP [National Cholesterol Education Program]," the authors conclude. "Statins are effective for reducing TC and LDL-C [low-density lipoprotein cholesterol] levels in children with FH; it is not clear how this efficacy translates to children with milder and/or nonmonogenic dyslipidemia, and it is not known how frequently these medications are used in children without FH in practice. There are no trials with long-term follow-up for adult lipid outcomes or CHD-related events."

This study was conducted by the Oregon Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality. The authors have disclosed no relevant financial relationships.

Pediatrics. 2007;102:e189-e219.
Clinical Context

Dyslipidemias include elevated TC, LDL-C, or triglyceride levels and decreased high-density lipoprotein cholesterol (HDL-C) level. Screening for dyslipidemias could detect 1 of 3 classifications of dyslipidemia: monogenic (eg, familial hypercholesterolemia), secondary (eg, resulting from diabetes, nephrotic syndrome, organ transplant, or hypothyroidism), or multifactorial (risk factor–associated or polygenetic). Whereas dyslipidemia in adults is a risk factor for CHD, the significance of dyslipidemia in children has not been established.

Haney and colleagues reported findings from a systematic review of data on screening and treatment of dyslipidemia in children and adolescents for the USPSTF. They identified 144 articles about screening and testing, 43 about intervention and follow-up of lipid levels, 6 about adverse effects of screening, and 84 about adverse effects of treatment.

The current statement from the USPSTF, in conjunction with information from the current review by Haney and colleagues, summarizes the evidence regarding methods of detection and benefits and harms of detection and treatment of dyslipidemia in children and young people as old as 20 years.
Study Highlights

* Screening:
o TC levels increase from birth to age 2 years, peak before puberty, and decrease during adolescence.
o Common dyslipidemia cut-off values above 95th percentile (TC > 200 mg/dL and LDL-C > 130 mg/dL) can be affected by age, sex, and ethnicity.
o Per American Academy of Pediatrics and NCEP guidelines, children with family history of cholesterolemia or vascular disease can be screened with initial TC level, followed by lipoprotein profile if TC level is elevated.
o 1 study in black adolescents showed the difference between fasting TC and HDL-C levels at the 95th percentile had 88% to 96% sensitivity and 98% specificity in predicting LDL-C level of 130 mg/dL or more.
o 2 or more lipid level measurements are needed to confirm results.
* Family history can be time consuming to obtain, inaccurate, and defined in various ways in studies.
* Screening based on family history missed 30% to 60% of dyslipidemia cases.
* Of children with elevated TC and LDL-C levels, 40% to 55% will have persistent dyslipidemia into adolescence early adulthood.
* The best predictors of adult dyslipidemia were LDL-C level, which also determines treatment, followed by childhood overweight.
* Efficacy of treatment:
o Statins decreased TC level by 24.4% and LDL-C level by 30.8% in monogenic types.
o Bile acid–binding resins decreased lipid levels in monogenic types.
o Diet supplements (psyllium, oat, and sterol margarine) had marginal effect or no effect (garlic extract) on monogenic type.
o Dietary counseling for 3 years led to minimal (8%), but temporary (< 5 years), reduction in LDL-C level in monogenic and multifactorial types.
o Physical activity had no effect on TC level, decreased LDL-C level by only 3.1% in multifactorial type, and has not been studied for monogenic type.
o Combined exercise, diet, and behavior treatment led to 23% increase in HDL-C level vs control group and diet plus behavior treatment.
* Data on adverse effects of screening are of poor quality:
o Statins were associated with elevated creatine kinase level and liver-function tests.
o Bile-acid–binding resins were linked to gastrointestinal tract symptoms and decreased vitamin and mineral absorption.
o Niacin use was linked to increased liver enzymes, hepatotoxicity, headache, abdominal pain, and nausea.
o 3 children with unmonitored diets had growth retardation, but children with monitored low-fat diets had normal growth.
o In 1 small unconfirmed study, increased behavior problems in screened children were noted.
o Increased anxiety or depression was not reported.
o Long-term effects of lipid-lowering medication were not studied.
o Physical activity was linked to exaggerated blood pressure response in monogenic type but no adverse effect in nonmonogenic types.
* Universal screening is not recommended by any professional group.
* NCEP report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents, endorsed by the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists, recommended screening if family history of premature CHD or at least 1 parent with TC level of at least 240 mg/dL.
* Screening could be considered in children at risk because of being overweight or having high-fat diets.
* The American Heart Association recommended screening children older than 2 years with family history of dyslipidemia or premature cardiovascular disease, with unknown family history plus risk factors, or who are overweight.
* No studies assessed the effect of childhood screening on adult lipid or CHD outcomes.

Pearls for Practice

* Available data are inadequate to recommend for or against routine screening for dyslipidemia in children, adolescents, and young adults; treatment of dyslipidemia can improve lipid levels in childhood but has not yet been shown to improve health outcomes in adults.
* Preferred screening tests are fasting or nonfasting TC and HDL-C levels. Nonfasting TC level minus HDL-C level above the 95th percentile is a sensitive, specific test for detecting elevated LDL-C level, but screening per family history could miss as many as 60% of dyslipidemia cases.









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