"What we want to show with this paper is that we have a way to treat these children. We must not wait until they are adults. We need to treat them in childhood when they are still healthy. We want them to stay healthy," said Saskia de Jongh, M.D., lead author of the article. Her Dutch team demonstrated that simvastatin treatment restored normal blood vessel response to changes in blood flow in affected children ages 10 to 17 years.

The researchers studied 50 children with familial hypercholesterolemia, 30 of whom were treated with escalating doses of simvastatin for 28 weeks, starting at 10 mg per day and increasing to 40 mg per day. The remaining 20 children were given placebo pills. The study also included 19 siblings who had a normal genotype. Researchers tested the health of all subjects' blood vessels by using ultrasound to measure responses to the release of a blood pressure cuff --- flow-mediated dilation. Endothelial dysfunction is an early sign of atherosclerosis.

At the beginning of the study, the children with familial hypercholesterolemia had total cholesterol levels averaging about 275 mg/dL (approximately 7 mmol/L), almost 100 mg/dL higher than the levels of their healthy siblings. The average flow-mediated dilation test response of the affected children was significantly lower than that of the healthy siblings. "There already is atherosclerosis in these young children," said Dr. de Jongh. By the end of the study, the cholesterol levels in the children receiving simvastatin had dropped an average of more than 80 mg/dl, nearly matching the levels of the healthy siblings. The cholesterols levels of the children on placebo remained virtually unchanged.

More importantly, according to researchers, was the change in flow-mediated dilation. In the children who received simvastatin, the responses changed to match those of their healthy siblings. "The main question was: Are we able to stop the process of atherosclerosis in children with familial hypercholesterolemia? And we showed that we can," de Jongh said.

The ability of statin treatment to restore normal endothelial function prompted the researchers to urge treatment of similar children. "If you wait to treat these children until they are 20 years or older, there is probably an irreversible stage of atherosclerosis. We think we have to start treatment at an early age," she said.

The researchers did not detect any adverse events in a separate evaluation of children treated with simvastatin for a year. Although Dr. de Jongh conceded there are many unknowns about the risks and clinical benefits of life-long statin treatment that begins in childhood, she said the risks of not treating children with familial hypercholesterolemia are clear. "We know if we don't treat them that some of them will be not live beyond 28, 30 or 35; that's what we know. I think the high priority is the children who already lost a father or mother at a young age, because they are most at risk, they already have a positive family history for cardiovascular disease," she said.

Todd Anderson, M.D., who was not part of the research team, said the study results indicate statins can offer benefits to children that are similar to those seen in adults. "Aggressive lipid lowering with statins for children with familial hypercholesterolemia should likely be more widely considered and applied," Anderson said. "Whereas we have been reluctant to use statins in children in the past, this study demonstrates an improvement not only in cholesterol but vascular function."

He noted improvements in endothelial function have not been proven to prevent adverse cardiovascular events, but endothelial dysfunction plays an important role in atherosclerosis, so it is reasonable to infer that improving function may reduce the risk of later problems.