October 26, 2006

In this Issue...

Defining Cholesterol Cutoff Values for Adolescents
by Julie McDowell

In 1992, the National Cholesterol Education Program (NCEP) published cutpoints for children and adolescents to identify those who are at high risk for developing cardiovascular-related diseases. However, many clinicians are dissatisfied with these guidelines, because they don’t take into account how cholesterol levels fluctuate as a natural consequence of puberty. Here, Strategies examines recent attempts to create age- and gender-specific cholesterol cutpoints for adolescents between the ages of 12 and 19, and what the clinical laboratory needs to know about issues relating to cholesterol levels and youth.

Overt cardiovascular disease (CVD) is uncommon among children. However, the process of CVD begins in childhood with the development of atherosclerosis, whose progression is related to lipoprotein concentrations. Therefore, it’s vital to track abnormal levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) from childhood into adulthood, as these values can help identify high-risk CVD patients at an early stage.

To identify children at risk, the NCEP classified cutpoints for TC and LDL into three categories—acceptable, borderline, and high (http://www.americanheart.org/presenter.jhtml?identifier=4499), which have been endorsed by the American Heart Association. In addition, the guideline states that HDL levels should be greater than or equal to 35 mg/dL and TG should be less than or equal to 150 mg/dL.

But many clinicians criticize these cutpoints for ignoring the variability of cholesterol and blood fat levels in children and adults caused by normal puberty and growth development. “When you look at these cutpoints for children and adolescents, they use the same threshold to define risk, regardless of age,” said Ian Janssen, PhD, Professor at Queen’s University’s Department of Community Health and Epidemiology in Ontario, Canada. “One year a child might be below the risk cutpoint, and the next year, they might be higher, even though their cholesterol level is changing as it should be.”

To more accurately quantify risk and cholesterol levels for this population, Janssen and a colleague developed age- and gender-specific cutpoints for TC, LDL-C, HDL-C, and TG for adolescents age 12-19 (Circulation 2006; 114;1056-1062). The cutpoint tables and related data figures are online at http://circ.ahajournals.org/cgi/content/full/114/10/1056. “We wanted to take into consideration the age of the child and link the thresholds used in childhood to those used in adulthood, which are used to predict risk,” said Janssen.

Janssen developed the age-specific cutpoints using growth curve modeling. The data came from the National Health and Nutrition Examination Surveys (NHANES). Specifically, the data used was collected from 1988-1994 (NHANES III), 1999-2000, and 2001-2002. “Essentially what we did was create growth charts for cholesterol and blood fat levels, similar to what has been done for height and weight,” said Janssen. “We can monitor or track the progress over time and we created these charts that define the at-risk level. If you are above the line for a given age, it means you are at risk. If you fall below the lines, you are in the healthy range.”

Questions about Cutpoints

Since the 1992 NCEP guidelines were published, the obesity rates in the U.S.—particularly among children and adolescents—have skyrocketed. But the guidelines don’t address some of the lipid-related problems that have emerged because of obesity. “The kids who are overweight have different types of lipid problems than kids who have high cholesterol due to genetic issues,” explained Samuel S. Gidding, MD, Director, Outreach Services, Nemours Cardiac Center, A.I. duPont Hospital for Children (Wilmington, Del.). “The guidelines need to be updated to encompass the problems related to overweight.”

Gidding has mixed feelings about Janssen’s cutpoints, as detailed in an accompanying editorial (Circulation 2006: 114:989-991, http://circ.ahajournals.org/cgi/content/full/114/10/989). On the one hand, it’s beneficial for pediatricians to have age-specific values to look at how patients compare to the population. It could also be useful in alerting parents to potential problems. “I think having these values is useful so parents know if their children have cholesterol levels that are unhealthy,” he explained. “If it’s related to weight, it could wake parents up to realizing that their child is facing some health problems.”

But Gidding isn’t sure of the medical importance of the revised cutpoints. Prior to the obesity epidemic, the vast majority of children had cholesterol levels well below the threshold associated with heart disease. This means that unless the high cholesterol is related to a genetic disorder, the child and parents really just need advice about diet and exercise. “Since we know that we need to have an LDL level of at least 100, if not 110, to put the patient at risk for heart disease, it’s unclear whether you really need to label someone who has levels below that, even if it’s a high percentile, as having high cholesterol,” said Gidding.

Whatever the issues are related to the specifics of cardiovascular risk and adolescence, Janssen wants clinical laboratorians to be aware of the role of age when looking at cholesterol values. “What I want clinical laboratorians to understand is that the age of the child does matter,” he explained. “The threshold that you use to define high risk for a 19 year old should not be the same as the threshold you use for a 12 year old.”

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