Study Links Fat in Arteries of Boys to Heart Attacks

SAN ANTONIO — Scientists Monday reported the first direct evidence that fat deposits in the arteries of teen-age boys turn into heart-attack-causing lesions by the time they reach their early 30s.

In a study presented here at the American Heart Assn. science writers forum, researchers also reported evidence of a genetic predisposition in some people that may account for why some fat streaks become lesions and some don’t. The preliminary findings come from autopsies of 300 males aged 15 to 34.

If the results in the nationwide study hold up after all 1,800 planned autopsies are completed, physicians might be able to give children and teen-agers a simple blood test to tell them whether they are at high or low risk for heart disease. Confirmation of the findings would also effectively quash a longstanding controversy over whether some children should be fed the same lower-fat diets recommended for adults.

The results show that the area of the coronary artery with the highest incidence of fatty streaks up to age 24 is the same general area where lesions most commonly appear 10 years later, reported Dr. Henry C. McGill Jr., scientific director of the Southwest Foundation for Biomedical Research, a private research center here.

McGill said these early results represent what appears to be the best direct evidence of what most cardiologists already have concluded from more indirect data--that fat deposits acquired during childhood lead to heart-attack-causing lesions later in life.

By age 30 to 34, a quarter of white males have raised lesions in their coronary artery, which nourishes the heart with blood, the early data on about 500 males shows. As expected, fatty streaks and lesions are most likely in smokers and in people who have the highest levels of cholesterol in their blood.

But the findings would appear to have the most practical impact for children.

“Children should be able to eat at the same table as their parents who are observing a low-fat, low-cholesterol diet,” McGill said. “My personal opinion is that children deserve the benefits of the good advice given to adults by the Heart Assn.”

The Heart Assn. and the National Heart Lung and Blood Institute have endorsed diets in which fat accounts for no more than 30% of calories for adults and for children over age 2. But the American Academy of Pediatrics has urged caution, warning that too little fat in a child’s diet before age 5 could stunt growth, particularly of the brain and nervous system.

The early results reported Monday also indicate that differences in the body’s genetic code for producing a specific molecule influence whether fatty streaks will form in arteries, said James Hixson, a colleague of McGill at the Southwest Foundation. An individual is coded to produce the fat-protein molecule, called apolipoprotein E, in one of three forms.

Among the 213 blood samples studied so far, the researchers found that people who produce the most common form of the molecule have a 28% risk of developing fatty streaks in their abdominal aorta. Those who produce one genetic variation of the protein have a higher risk--33%--while those that produce the third type have only a 20% risk, Hixson said.

Apolipoprotein E, which helps remove cholesterol from the blood, has been known for about a decade to come in varying forms, Hixson said. However, if the statistical link holds up in the larger, 1,800-person study, it would probably provide reason for physicians to act on those differences--by screening patients’ blood for the genetic variations to identify those most likely to develop cardiovascular disease.

“This difference could even be determined from examination of a few drops of blood at birth, and these highly susceptible individuals could be advised early in life to avoid certain habits,” McGill said.

Such genetically based tests currently are expensive and tedious to perform, but automation of the process--being hotly pursued by industry--eventually could make the tests as widespread as routine cholesterol monitoring is today, experts say.

The results that McGill reported were obtained as part of a continuing national study involving researchers from all over the United States, called Pathobiological Determinants of Atherosclerosis in Youth (PDAY). Blood and artery samples are being collected during legally required autopsies of males between the ages of 15 and 34 who die of violent or accidental causes.

The blood is analyzed for cholesterol levels, genetic and other molecular data, and levels of tobacco smoke products and excess glucose, which would indicate whether the person was a smoker or diabetic. Both conditions are associated with increased cardiovascular disease.

Key arteries are also collected and their internal structure photographed. These are then converted into standardized digital images that can be mapped into computer images that are color-coded to reflect the varying incidence of fatty streaks or lesions. This allows scientists to compare images of the teen-age group’s fatty streaks, for instance, to those of persons 10 or 15 years older.

J. Fredrick Cornhill, an Ohio State University professor who is overseeing the digitization, said that just as important as the location of the lesions are the places where they do not appear.

Often, the pictures show that an area that was moderately affected by fatty streaks later does not become the site of a lesion, he noted.

“The question is, are all fatty streaks created equal? Why do some apparently not progress?” Cornhill asked. While genetic variations may account for part of the difference, they do not explain all of them.

Equally puzzling is the observation that an area with a 60% chance of lesions may be directly adjacent to a site with only a 10% chance, he said.

PDAY is just now beginning studies of cellular characteristics around such sites to try to find a reason. Other studies will investigate the hypothesis that, like sand in a riverbed, cholesterol is deposited in areas where the blood forms eddies or slows. This would explain why lesions are most often seen at bends or branch points in arteries, he noted.

Scientists first began to suspect that the genesis of atherosclerosis is in childhood when autopsies of young Korean War casualties showed lesions in their arteries. However, a direct link has been slow to be found.

Last year, a long-term Louisiana study, using only 50 children and young adults, showed an association between high levels of “bad” LDL cholesterol and early signs of atherosclerosis.

HYPOTHESIS OF GENETIC FACTOR IN HEART DISEASE

Accumulations of fat called fatty streaks appear in the arteries of children as young as 3 years old and increase through their teen-age and young adult years. No one knows why, but some fatty streaks (top) regress or fail to grow. But, by age 20, scientists reported Monday, a few have converted into raised lesions, or plaques. Fat-loaded cells accumulate in the smooth muscle layer and emit substances causing the plaque on the arterial wall to grow further. If a blood clot forms in the coronary artery, it causes a heart attack. If the clot forms in the carotid artery, a stroke occurs.