Statin Reverses Carotid Atherogenesis, Exercise Improves Vascular Function in Children

Charlene Laino

November 13, 2003

Nov. 13, 2003 (Orlando) — Two new studies presented here this week at the American Heart Association Scientific Sessions point to the importance of early preventive intervention in children at high risk of heart disease.

In a randomized, double-blind, placebo-controlled trial, statin therapy safely reversed carotid atherogenesis in children with familial hypercholesterolemia, reported Albert Wiegman, MD, a pediatrician at the Academic Medical Center in Amsterdam, the Netherlands.

A second study showed that exercise can improve vascular function in obese children.

For the first study, 211 children, aged eight to 18 years, were randomized to pravastatin or placebo. Children under 14 years were given a 20-mg dose, while teens received the 40-mg adult dose daily, Dr. Wiegman said.

All of the children had low-density lipoprotein (LDL) cholesterol levels above 4.0 mmol/L and had been on a lipid-lowering diet for at least three months before starting the medication.

By the end of two years, ultrasound measurements showed that mean carotid intima-media thickness had decreased about 0.010 mm in the pravastatin group, while increasing 0.005 mm in the placebo group ( P = .019).

In addition, mean LDL cholesterol levels dropped 25% in those who received pravastatin, but mean LDL cholesterol levels stayed the same in those receiving placebo ( P < .0001). High-density lipoprotein levels increased 7% in the pravastatin group and 2% in the placebo group ( P = .09).

"There was normal growth and maturation in both groups," Dr. Wiegman said, with no changes in creatinine phosphokinase, aspartate amino transferase, or amino alanine transferase.

Pharmacokinetic studies performed after completion of the trial suggest that children can be safely started on a full dose at age 12 years, he said.

Vinay Nadkarni, MD, associate professor of anesthesia and pediatrics at the University of Pennsylvania in Philadelphia, said the findings are "remarkable.

"Intervention in highly motivated children can not only halt the progression of plaque, but reverse it," said Dr. Nadkarni, who moderated a discussion of the findings.

An autosomal dominant disorder, familial hypercholesterolemia affects 1 in 400 births. But not all children at high risk of heart disease should be started in statin therapy, Dr. Wiegman said.

"I would not translate these findings to the general population," he told Medscape. "This is for children with a genetic defect that makes them handle lipids abnormally."

For obese children or children with other risk factors, diet and exercise should be prescribed, he said. A second study bears him out.

In the second study, Australian researchers showed that a simple exercise program can improve vascular function.

"This is the first study in at-risk children to show that the progression of atherosclerosis that begins early on can be reversed," said Daniel Green, PhD, from the University of Western Australia in Nedlands.

Dr. Green studied 35 obese children aged six to 16 years who performed a program of weight-resistance exercise, three times a week, for eight weeks.

Although their total body weight didn't change, the adolescents shed an average of three pounds of body fat, Dr. Green said.

In the younger children, "it was a little bit trickier because they don't want to push weights in a gym. They want to run around in a field," he said.

So that's what they did, Dr. Green said. "It was essentially fun and games."

By the end of the eight-week program, endothelial function had improved in both groups of children, he reported.

Flow-mediated dilation (FMD) of the brachial artery, a measure of vascular function and an early index of atherosclerosis, was significantly impaired at baseline in the obese children: 5.5% compared with 8.7% in a group of 21 age-matched controls.

By the end of the exercise program, FMD had reverted to normal levels: 8.2% ( P < .005). But what happened when they stopped exercising?

Two months later, "all the improvements had reverted back," Dr. Green said. "You have to keep on doing it."

AHA 2003 Scientific Sessions: Abstract 2406, presented Nov. 11, 2003; abstract 3487, presented Nov. 12, 2003.

Reviewed by Gary D. Vogin, MD