Pitt Study Offers Insight on Doubts About the “Good” in “Good Cholesterol”

Rachel Mackey, Ph.D.

New research from the University of Pittsburgh suggests that doubts raised recently about the protective effects of high density lipoprotein (HDL), or “good,” cholesterol by a genetic study and several recent clinical trials of HDL-raising drugs could be put to rest by using a better indicator of HDL status.

A national team of researchers led by Pitt’s Graduate School of Public Health (GSPH) analyzed blood samples of 5,598 healthy men and women and found that when assessing coronary heart disease risk, it appears more beneficial to measure – and make treatment decisions – based on HDL particles, not HDL cholesterol. The results will be published in the Aug. 7 print edition of the Journal of the American College of Cardiology.

“We found that higher levels of HDL cholesterol and HDL particles were both associated with less carotid atherosclerosis, and fewer heart attacks and other cardiovascular events,” said Rachel Mackey, Ph.D., assistant professor of epidemiology at GSPH and lead author of the paper. “However, the risk associated with lower HDL cholesterol levels could be explained by other risk factors, such as higher levels of triglycerides. In contrast, after accounting for these other risk factors, higher levels of HDL particles remained strongly associated with lower coronary heart disease risk.”

Like a fleet of ships, HDL particles carry HDL cholesterol, along with proteins and fats, to the liver where the cholesterol is removed from the body. Low-density lipoprotein (LDL) particles carry cholesterol to the arterial wall, causing atherosclerosis. When doctors measure cholesterol and report HDL and LDL levels, they are referring to HDL and LDL cholesterol, not to the particles that carry this cholesterol.

“HDL cholesterol is only one property of HDL particles. It’s like cargo on a ship; one can look at HDL cholesterol, which is one type of the cargo that is carried on the ship, or one can look at the number of ships,” said Samia Mora, M.D., a physician in the Brigham and Women’s Hospital Cardiovascular Division and senior author of the paper. “In our study, we found that the number of HDL particles had stronger cardio-protection than HDL cholesterol.”

Doctors give drugs such as statins to help lower cholesterol levels. Pharmaceutical companies have been developing and testing drugs that raise HDL cholesterol on the theory that more cholesterol will be taken to the liver for removal, rather than for deposition on arterial walls. So far those trials have not borne out that premise.

“HDL particles are known to have a variety of functions, including anti-oxidant, anti-inflammatory and anti-thrombotic properties, in addition to reverse cholesterol transport,” Dr. Mackey said. “Measuring the concentration of HDL particles, rather than their cholesterol content, may better reflect HDL functionality.”

The study used a commercially available NMR spectroscopy technique to measure lipoprotein particle concentrations in blood samples provided by study participants who were followed for an average of six years as part of the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is an observational study initiated, overseen and funded by the National Heart, Lung and Blood Institute (NHLBI), part of the National Institutes of Health (NIH).

“Our study suggests that it’s important to not only measure HDL cholesterol, but to experiment with other ways of measurement, such as HDL particles,” Dr. Mackey said. “Before we lose confidence in the potential of raising HDL to benefit patients, there needs to be more research extending beyond HDL cholesterol measurement.”

Efforts are underway to further evaluate HDL functionality and to determine which aspects of it are causally related to heart disease, and could be modified through lifestyle or therapeutic interventions.

Collaborators on this study include Philip Greenland, M.D., and Donald Lloyd-Jones, M.D., Sc.M., both of Northwestern University Feinberg School of Medicine; David C. Goff, Jr., M.D., Ph.D., Wake Forest University School of Medicine; and Christopher T. Sibley, M.D., National Institutes of Health Clinical Center.

This research was supported by NHLBI contracts N01-HC-95159 through N01-HC-95169, NHLBI grant K08 HL094375, and by an unrestricted grant from LipoScience, Inc.

The University of Pittsburgh Graduate School of Public Health (GSPH), founded in 1948 and now one of the top-ranked schools of public health in the United States, conducts research on public health and medical care that improves the lives of millions of people around the world. GSPH is a leader in devising new methods to prevent and treat cardiovascular diseases, HIV/AIDS, cancer and other important public health problems. For more information about GSPH, visit the school’s Web site at www.publichealth.pitt.edu.

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