Cholesterol drugs for kids debated


The Atlanta Journal-Constitution
Published on: 07/13/08

Last week's recommendation by the American Academy of Pediatrics —- that some children as young as 8 with high cholesterol be prescribed statins —- has spurred much public debate.

But among members of the committee that authored the report, there's little doubt that the recommendation is not only sound, it's justified.

"Everyone agreed this was a step in the right direction," said Dr. Jatinder J.S. Bhatia, a member of the AAP Committee on Nutrition and professor of pediatrics at the Medical College of Georgia. "It will only apply to kids who don't respond to the usual measures."

With the incidence of childhood obesity skyrocketing, the likelihood of those children having heart disease in adulthood also will rise, the doctors said. In Georgia, an estimated 24 percent of third-grade children are obese, according to 2005 data from the Department of Human Resources.

The updated report —- on lipid screening and cardiovascular health in childhood —- says drug therapy should be considered only after diet and lifestyle changes fail in children with LDL, or so-called "bad," cholesterol levels of 190 milligrams per deciliter or greater. The average 12- to 19-year-old has an LDL level of 90.5 mg/dL, according to federal health surveys.

"It's very important to recognize that the percentage of adolescents expected to receive [statin] drugs is very small," said Dr. Darwin Labarthe, director of the division for heart disease and stroke prevention at the Centers for Disease Control and Prevention.

The majority of people who start statins in childhood will not realize the ultimate benefit of cholesterol control —- a decreased risk of heart attack and stroke —- until mid-adulthood.

Cholesterol is a fatty substance found in many foods and naturally made by the body. While its bad effect of causing heart disease is well known, cholesterol is an essential building block for cell membranes, bile, hormones and vitamin D. It travels through the body by joining with proteins and other substances to form lipoproteins. Low-density lipoprotein (LDL), or "bad cholesterol," tends to thicken and eventually clog the arteries, increasing the risk of heart attacks and stroke; high-density lipoprotein (HDL), or "good cholesterol," is associated with a decreased risk of heart attack. Many believe this may be from removing excess cholesterol from blood vessels and carrying cholesterol back to the liver, where it's then removed from the circulation.

A strong criticism of the latest recommendation for children —- for whom cholesterol is essential for growth during puberty —- is the lack of scientific evidence backing it up.

"We don't have long-term studies of statins in children, but we do know they reduce heart disease in adults," said Dr. Janet Silverstein, a pediatric endocrinologist in Gainesville, Fla., and a member of the AAP Committee on Nutrition. "The children for whom statins are recommended are at very high risk for developing early heart disease and stroke."

Reported side effects of the drugs in adults include depression, muscle weakness and pain, and possibly long-term complications such as liver damage and stomach cancer.

Of course, there are risks, said Miriam Vos, a pediatric hepatologist at Children's Healthcare of Atlanta and assistant professor of pediatrics at Emory. "All medications have side effects, and there certainly are challenges in prescribing medications for long-term diseases."

A Food and Drug Administration spokesperson said the agency has noted the AAP's new recommendations and will track the use of statins in children and monitor for adverse events. Doctors also should follow their patients on statins, especially their liver function, the spokesperson said.

Dr. William Mahle, a pediatric cardiologist at Children's Healthcare of Atlanta and associate professor of pediatrics at Emory, has studied statin use in preventing coronary artery disease in pediatric heart-transplant patients as young as 2 years old and says the drugs are "remarkably well-tolerated."

In more than 100 patients he's dealt with, Mahle said, there have been no severe side effects.

Still, some are skeptical of the recommendation.

"In adults, we don't jump to medical treatment if the 10-year risk of a cardiac event is low. Using this same measure of absolute risk, I'd step back from these guidelines and be cautious of recommending early medical treatment in an 8-year-old, whose 10-year risk is extremely low, regardless of other risk factors," said Dr. Laurence Sperling, director of preventive cardiology and an associate professor of medicine at Emory.

Some question the motives behind the guidelines.

"Recommendations like these need to set off an alarm bell that our approach to health care is being dominated by commercial interests," said Dr. John Abramson, clinical instructor at Harvard Medical School and author of the book "Overdosed America."

But Bhatia said the AAP requires its committee members to disclose any conflicts of interest. "None of us, to the best of my knowledge, has any vested interest in companies that make statins," Bhatia said.

A spokesperson for Bristol-Myers Squibb said that the company is not expecting any increased profits from the new recommendations since the patent for its product Pravachol (pravastatin) expired a few years ago and is now available in generic formulation.

Pravastatin is the only statin with FDA approval for use in children as young as 8.

Cholesterol levels can be lowered with diet and physical activity, which are the recommended first lines of treatment.

Getting an accurate assessment of children's cholesterol levels is complicated by natural fluctuations, decreasing dramatically around puberty and increasing afterward.

"In a 9-year-old, the [LDL] cholesterol level is expected to decrease naturally in the next few years. If an individual patient were given medicine to lower cholesterol, it would be difficult to evaluate if a lower level was due to the medication," Labarthe said.

Cholesterol is used by the body to make steroid hormones, which are important during puberty. However, studies of adolescents taking statins for up to two years have not shown any detrimental effects on growth and development, said Dr. Elaine Urbina, associate professor of pediatrics at Cincinnati Children's Hospital Medical Center.

Last year, the American Heart Association released guidelines, co-authored by Urbina, which are similar to those from the AAP. But the AHA did not recommend drug therapy until age 10 for boys or after girls reach puberty. Dr. Stanley Cohen, a pediatric gastroenterologist in Atlanta, says he hopes the new AAP guidelines will raise awareness about childhood obesity.

"Everybody wants a pill to do magic," he said. "It's not about putting someone on a diet or medication —- it's about giving someone a health lifestyle that will sustain them through their lifetime," Cohen said.

Obese children are often evaluated to see whether hormone dysfunction might be the cause. Dr. Eric Felner, a pediatric endocrinologist and associate professor of pediatrics at Emory, says nine out of 10 patients he sees are simply eating unhealthy foods and not exercising. When lifestyle recommendations fall on deaf ears, physicians are left with few options.

"A number of people could be to blame, but if we are going to accept that the problem of obesity is not going away, we can at least treat the symptoms of being obese and help these people live longer by preventing heart disease," Felner said.

Bhatia stressed the importance of family, schools and society in helping overweight children make lifestyle modifications that will have the biggest impact on their health.

"The whole idea is that pediatricians need to become advocates for patients at risk and begin the dialogue to refer them to programs and services that will help them," Bhatia said.

HIGH-RISK LEVELS

What cholesterol levels are "high risk" in children compared to adults

CHILDREN

> Total cholesterol greater than 200 mg/dL

> LDL greater than 130 mg/dL

> HDL less than 35 mg/dL

> Triglycerides greater than 150 mg/dL

ADULTS

> Total cholesterol greater than 240 mg/dL

> LDL greater than 160 mg/dL

> HDL less than 40 mg/dL for men, less than 50 mg/dL for women

> Triglycerides greater than 200 mg/dL

Source: American Heart Association

SUMMARY OF AAP GUIDELINES

> All children older than 2 should follow the Dietary Guidelines for Americans. Children 12 months to 2 years for whom obesity is a concern should drink reduced-fat milk.

> Children between ages 2 and 10 should undergo cholesterol screening if they have any of the following risk factors: are overweight, have diabetes, have high blood pressure, or there's a family history of high cholesterol or early cardiovascular disease.

> Children and adolescents with high LDL and higher risk for heart disease should be individually counseled on nutrition, changes in diet and increased physical activity.

> Overweight or obese patients with high triglycerides or low HDL should improve diet and increase physical activity.

> Consider drug therapy in patients age 8 or older with an LDL level of 190 mg/dL or greater, if there are no other risk factors. The initial goal of therapy is to lower LDL cholesterol to less than 160 mg/dL, but a lower target may be needed if the patient has other risk factors.

Source: American Academy of Pediatrics report titled "Lipid Screening and Cardiovascular Health in Childhood"

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