Small, dense cholesterol particles worse for your heart

November 29, 1994

By David Gilbert,

BERKELEY--New studies on low-density lipoprotein (LDL)--the so-called "bad" cholesterol particle--by researchers at Lawrence Berkeley Laboratory (LBL) indicate that bigger is better and small is not beautiful.

Using data from a broad medical study of male physicians, the researchers have linked LDL particle size to the subsequent development of heart disease. The research was presented at the American Heart Association's 67th Scientific Sessions in Dallas on November 16.

"Since heart attacks often occur in people whose total cholesterol levels put them at only moderate risk--those with readings in the 200-240 milligrams per decimeter (mg/dl) range--it is hard to pick out the person who's going to get heart disease," says Dr. Ronald M. Krauss, head of the Department of Molecular Medicine at LBL. "That's why it is important to look at other factors such as LDL that might aid in that prediction."

Lipoproteins transport cholesterol in the blood and are classified according to their density. LDL is known as the "bad cholesterol" because high levels are associated with increased heart disease risk. But even within the category of LDL, not all particles are created equal.

LBL scientists were the first to establish a link between a predominance of smaller, denser LDL particles and heart disease. However, those studies looked at people who had already developed the disease. In contrast, the studies presented today examined healthy people to determine if the dense LDL trait is associated with later development of disease. Krauss says these types of studies are considered more convincing.

Krauss and his associates worked with researchers at Brigham and Women's Hospital in Boston to analyze statistics collected in the Harvard-based Physicians' Health Study, which has followed nearly 15,000 male doctors for several years. The researchers matched 312 of the subjects who had heart attacks during a 7 1/2 year period by age and smoking status with 312 health control subjects.

The researchers then determined each person's LDL particle-size profile and divided the subjects into five groups (quintiles). The lowest quintile--those with the smallest and most dense LDL particles--had more than three times the risk of heart attack as the quintile with the largest LDL particles.

The trend held true even after the researchers adjusted for other risk factors such as the ratio of total cholesterol to high-density lipoprotein (the so-called "good" cholesterol, which helps clear LDL from the blood), body mass index (a measure of obesity), diabetes, high blood pressure and physical activity level.

The tendency toward small, dense LDL particles--a profile called pattern B--is a common trait affecting an estimated 25-35 percent of healthy men and 40-50 percent of heart disease patients. The size and density of LDL particles, Krauss' previous studies have shown, reflect elevated levels of blood triglycerides, another type of blood fat linked to heart disease.

"These observations reinforce the value of using these LDL size and triglyceride level measurements to sharpen our focus in identifying high risk individuals and institute appropriate interventions to prevent heart attacks," Krauss says.

Krauss' collaborators include Patricia J. Blanche and Laura G. Holl, of LBL; and Drs. Meir J. Stampfer, Jing Ma, and Charles Hennekens, of Brigham and Women's Hospital.

LBL is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California.