Cholesterol Drugs Address Childhood Disorder

Early Studies Provide Hopeful News

For some unlucky people, high cholesterol is passed from one generation to the next, but children who inherit the disorder may benefit from cholesterol-lowering drugs known as statins, according to a report in the Journal of the American Medical Association.

Children who have this inherited disorder, known as familial hypercholesterolemia, are at great risk of having a heart attack as early as their mid-20s.

"They develop coronary artery disease at a relatively young age," explains Dr. Albert Wiegman, a pediatric cardiologist at the Academic Medical Center in Amsterdam, the Netherlands.

But the class of cholesterol-lowering medications called statins holds promise for these children.

Statins lower cholesterol by slowing down the production of cholesterol and by increasing the liver's ability to remove the LDL-cholesterol already in the blood.

Study Looks At One Statin Medication

Under normal conditions, people inherit two genes responsible for making LDL receptors - the "fishing rods," as Dr. Wiegman describes them - that remove cholesterol from the blood.

But in people with familial hypercholesterolemia, an abnormal gene is passed along.

As a result, half of their LDL receptors are defective or missing, according to the organization called MEDPED (Make Early Diagnosis to Prevent Early Death), a Salt Lake City-based nonprofit organization that works to help families with inherited high cholesterol disorders.

The condition results in abnormally elevated levels of LDL cholesterol beginning at birth.

An estimated 10 million people worldwide suffer from the condition, resulting in premature heart disease and death if not diagnosed and treated properly, says MEDPED.

"You have to prevent this disorder as early as possible, in my opinion," Dr. Wiegman says.

The two-year study found that children who took the medication pravastatin had significant improvement in the thickness of the walls of their carotid arteries, which supply blood to the brain. They also had sharply reduced levels of low-density lipoprotein (LDL) cholesterol, the "bad" kind that clogs vessels.

In addition, the medication worked without any apparent adverse effects on the children's growth, sexual maturation, hormone levels, or liver or muscle tissue - at least over the period of the study.

"It seems to be safe and it works," says Dr. Wiegman, lead author of the study. "It makes the vessel walls thinner, and perhaps they [will] have a normal life expectancy."

In an editorial in the same journal, cardiologist and statin expert Dr. Antonio M. Gotto Jr., dean of the Weill Medical College of Cornell University in New York City, concludes the benefit of treating high-risk youngsters with statins exceeds the potential risk.

"In the case of familial hypercholesterolemia," Dr. Gotto writes, "the promise of reducing future cardiovascular morbidity and mortality, as well as future demands on acute care and more expensive medical approaches, would make aggressive treatment of high-risk youth patients a worthwhile long-term initiative."

Study Findings Were Significant

The study involved 214 children, ages eight to 18, who were followed for two years. The researchers encouraged every participant to exercise and eat a fat-restricted diet. Half of the children were given either 20 milligrams or 40 milligrams of pravastatin, depending on the child's age, and the other half received a placebo (inactive substance).

Before-and-after ultrasound images were taken to measure the change in the thickness of the walls of patients' carotid arteries, a marker for the fatty plaque build-up that leads to atherosclerosis.

After two years, children on the placebo had increased arterial wall thickness, while children on pravastatin showed significant regression.

LDL cholesterol levels dropped 24.1 percent in the statin group but rose 0.3 percent in the placebo group.

"That's promising because the LDL cholesterol-lowering, we could expect, but it's important that it does something to the vessel walls," Dr. Wiegman notes.

Although the study is believed to be the most extensive yet, longer studies are needed to demonstrate the long-term safety and efficacy of statin therapy in children, the authors said.

Always consult your child's physician for more information.

Online Resources

American Academy of Pediatrics

American Heart Association

Centers for Disease Control and Prevention (CDC)

Centers for Disease Control and Prevention (CDC) 5 A Day

National Health and Nutrition Examination Survey

National Institute of Child Health & Human Development

National Institutes of Health (NIH)

US Food and Drug Administration

September 2004

Cholesterol Drugs Address Childhood Disorder

Study Looks At One Statin Medication

Study Findings Were Significant

Cholesterol Goals

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Cholesterol Goals

According to the National Institutes of Health (NIH), to reach an LDL-cholesterol goal of less than 100 mg/dL, a person may need to take a cholesterol-lowering medicine in addition to making life habit changes.

Heart disease patients and those at high risk for developing heart disease need to lower their LDL more than other people.

As a result, medications are more often used by patients with heart disease and those at high risk than by those who do not have heart disease or who have a lower risk of developing it.

If an individual has an LDL level of 130 mg/dL or greater, an LDL-lowering medicine is often recommended, the NIH states.

If the LDL level is 100 to 129 mg/dL, a physician will consider all the facts of a case in deciding whether to prescribe medication for further LDL lowering or for high triglycerides and/or low HDL if they are present.

If a person has been hospitalized for a heart attack, a physician will likely start a patient on a medication at discharge if LDL-cholesterol is 130 mg/dL or greater.

If LDL-cholesterol is between 100 and 129 mg/dL during hospitalization, the physician may choose to start you on an LDL-lowering medication before discharge.

Also, if LDL-cholesterol is far above the goal level of less than 100 mg/dL when first measured, the physician may choose to start a cholesterol-lowering medication together with diet and physical activity right from the beginning of treatment.

The NIH points out that if a physician prescribes medication, a person most likely will need to:

• Follow a cholesterol-lowering diet.
  
  
• Be more physically active.
  
  
• Lose weight if overweight.
  
  
• Control all of other heart disease risk factors, including smoking, high blood pressure, and diabetes.
  

Taking all these steps together may lessen the amount of medicine needed or make the medicine work better - and that reduces risk for a heart attack.

There are currently five statin drugs on the market in the US used for adults:

• lovastatin
• simvastatin
• pravastatin
• fluvastatin
• atorvastatin

The major effect of the statins is to lower LDL-cholesterol levels, and they lower LDL-cholesterol more than other types of drugs. Statins inhibit an enzyme, HMG-CoA reductase, that controls the rate of cholesterol production in the body.

These medications lower cholesterol by slowing down the production of cholesterol and by increasing the liver's ability to remove the LDL-cholesterol already in the blood.

The statins are usually given in a single dose at the evening meal or at bedtime. It is important that these medications be given in the evening to take advantage of the fact that the body makes more cholesterol at night than during the day.

A person often sees results from the statins after several weeks, with a maximum effect in four to six weeks. After about six to eight weeks, a physician can do the first check of LDL-cholesterol while a person is on the medication. A second measurement of LDL-cholesterol level will have to be averaged with the first for a physician to decide whether a dose of medication should be changed to help meet a goal.

Always consult your child's physician for more information.