Risks For Heart Disease Associated With Size Of LDL Particles

March 26, 1999

Researchers at the University of Washington School of Public Health and Community Medicine have produced new analyses predicting the risk of heart disease among diverse population groups -- younger women, middle-aged men and older Japanese-American men.

The findings are being presented on March 26 at the 39th Annual American Heart Association (AHA) Conference on Cardiovascular Disease Epidemiology and Prevention in Orlando, Florida.

The analyses are based on results from several studies showing that for every nanometer decrease in low-density lipoprotein (LDL) particle diameter or size, heart disease risk increases from 30 to 230 percent, depending on the population studied.

LDL particles carry the "bad cholesterol" through the bloodstream. Smaller LDL particles may more easily become trapped in blood vessel walls than larger ones, possibly increasing risk for atherosclerosis. LDL particle size is determined using a technique called gradient gel electrophoresis that separates LDL particles obtained from blood samples by their diameter and shape.

The UW researchers have analyzed data from three different population groups. In a case-control study of 231 primarily Caucasian women aged 20-44 in Western Washington, blood samples from women with heart disease had smaller LDL size than control women in the same age group. A one-nanometer decrease in LDL size was associated with a more than two-fold risk for heart disease. The relationship remained after taking into account smoking, diabetes, hypertension and LDL cholesterol level, but was reduced substantially after taking into account triglycerides (another form of fat carried in the bloodstream) or high-density lipoprotein (HDL) cholesterol, known as the "good cholesterol".

"Many people think heart disease occurs mainly in men, but heart disease is also the number-one cause of death among women in this country," says Dr. Melissa Austin, professor of epidemiology. "We need more data to better understand heart disease risk in women."

"The association between small LDL and heart disease may involve genetic predisposition," she adds. "If we can find the genes involved, and how they interact with environmental and behavioral factors, we can find new ways to prevent heart disease."

Small-particle LDL has also been shown to be a risk factor among middle-aged to older Caucasian men, based on data from the Physician's Health Study, the Stanford Five-City Project and the Quebec Cardiovascular Study. However, these studies all reported the results differently. To pinpoint the strength of the association, Austin's team applied semi-quantitative methods of meta-analysis to the combined data from these studies, which included 960 men. It was found that a one-nanometer decrease in LDL size predicted a 60 percent increase in heart disease risk. After controlling for blood levels of triglycerides and HDL cholesterol, the risk was still 30 percent greater.

Among a third group studied earlier -- more than 400 Japanese-American men with an average age of 65 -- the association was also found but was not as strong. A one-nanometer decrease in LDL size predicted a 30 percent increase in risk of heart disease, and was not present after taking triglyceride and HDL cholesterol into account. The study was in collaboration with the National Heart, Lung and Blood Institute's (NHLBI) Honolulu Heart Program.

Other studies will be needed to determine whether this difference is attributable to age or ethnicity. "The magnitude of the association between small LDL and heart disease varies from group to group, but the risk is always there," says Austin.

The study on heart disease risk among younger women is being presented by Alisa Kamigaki, an MPH student in epidemiology, while the results in the middle-aged men are a poster presentation by Austin's group at the meeting.

The research was sponsored by grants from the NHLBI and the AHA.
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University of Washington

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