Thursday, July 7, 2011

Screening Kids for Familial Hypercholesterolemia

From Medscape Pediatrics

Recommendations From the National Lipid Association

Laurie Scudder, DNP, NP; Anne C. Goldberg, MD

Posted: 06/29/2011

Editor's Note: The National Lipid Association (NLA) Expert Panel on Familial Hypercholesterolemia recently issued a clinical guidance document titled Familial Hypercholesterolemia: Screening, diagnosis and management of pediatric and adult patients. In addition to clarification regarding the definition and prevalence of familial hypercholesterolemia (FH), the document called for universal screening in all individuals, regardless of family history, beginning at the age of 9 years. Medscape spoke with Anne C. Goldberg, MD, Associate Professor of Medicine in the Division of Endocrinology, Metabolism and Lipid Research at Washington University School of Medicine and Chairperson of the NLA panel about this recommendation among others and their implications for primary care clinicians.
Medscape: Dr. Goldberg, by considering a broader definition of FH to include other genetic defects associated with lipid anomalies, the expert panel determined that incidence of FH was as high as 1 in 300 to 500 individuals in some populations. Can you tell us which populations are at the highest risk?
Anne C. Goldberg, MD: The incidence figures you cite are actually for the phenotype of FH due to either mutations in the gene for the low-density lipoprotein (LDL) receptor, which accounts for about 80%-85% of this population. About 5%-10% of people with phenotypic FH have mutations in the apolipoprotein B gene that results in an abnormality that prevents interaction with the LDL receptor. A small percentage of patients have gain-of-function mutations in PCSK9, which is a protein that modifies the LDL receptor. Other causes of phenotypic FH are rare.
The phenotype of FH includes all of these patients who present with LDL cholesterol levels that are typically double what is normal. Some populations such as South African Afrikaans, Lebanese Christians, and French Canadians have specific mutations that are enriched in those populations. Approximately 1 in 100 people in these groups are heterozygous for FH.
Homozygous patients are rare, with an incidence of about 1 in 1 million. These individuals have either 2 copies of the same abnormal allele or 2 abnormal mutations, a compound heterozygote. At birth, these children have total cholesterol levels in the range of 600-1000 mg/dL, and they can present with yellow patches on the skin called cutaneous xanthomas. These children have high cholesterol levels for their entire lives. The homozygous patients are at extremely high risk and, untreated, can have vascular disease and heart attacks in childhood and adolescence. Male heterozygous patients may have events starting in their 30s and 40s. In heterozygous women, these sequelae generally occur about a decade later.
Medscape: One of the practice-changing, and potentially controversial, recommendations called for universal screening for FH in all children aged 9-11 years of age. Can you discuss this recommendation and the reasons for a recommendation for screening at this particular age? Can you suggest some best practices for implementation of this recommendation as well as potential barriers?
Dr. Goldberg: The rationale for universal screening for children 9-11 years of age is to identify children with severe cholesterol problems at a time before they start developing significant plaque, which is really about at that time of life. The Bogalusa Heart Study demonstrated that plaque development began in childhood and adolescence.
Screening on the basis of risk factors or family history will miss a very high percentage of children with significant lipid disorders. Universal screening is probably more cost effective. Additionally, cholesterol levels are fairly stable by this age.
There is a wide fluctuation in cholesterol levels that begins just before and continues during puberty. Cholesterol levels do not stabilize for a number of years.
At 9-11 years of age the numbers are still stable.
Additionally, this is a time when prevention should be emphasized
Counseling should focus on preventing initiation of smoking, improving eating habits, preventing excessive weight gain, and development of appropriate exercise patterns.
Interventions focus on earlier risk factor modification using good lifestyle choices.
The primary care provider (PCP) will need to do a lot of this screening. The idea would be to include cholesterol screening as part of a well-child approach along with an assessment of growth, questions about seatbelt wearing, etc.
Medscape: The statement also called for screening beginning as early as 2 years of age for children at high risk. Can you describe some of the risk factors that should prompt consideration of screening of these very young children?
Dr. Goldberg: A positive family history of high cholesterol or premature coronary disease, such as a father with coronary disease in his 30s, should prompt consideration of earlier screening.
Screening should also be considered if the child has hypertension or diabetes.
A child who appears to have FH at 2 years of age should be closely monitored for weight gain, and the family should receive diet counseling that includes education about low saturated fat diets.
Families should also be counseled to not expose the child to secondhand smoke, and physical activity should be emphasized.
It's not that you're going to put 2-year-old children on medication. Rather primordial prevention should be the emphasis.

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