Different Cholesterol Predicts Heart Risk Too, New Target for Drugs?

Non-high density lipoprotein cholesterol (non-HDL-C) may help predict heart problems in people who have heart disease, according to a report in today's Circulation: Journal of the American Heart Association.

Reducing low-density lipoprotein (LDL) cholesterol has long been the goal of medications and other cholesterol-lowering treatments. But researchers are finding that other lipoproteins appear to be involved in developing heart disease. These include some very low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL) -- which are types of non-HDL cholesterol.

Studies have shown that the general category of "non-HDL" cholesterol, is a strong predictor of heart disease in people who have not yet developed signs of heart problems. As a result, the latest version of the National Cholesterol Education Program (NCEP) guidelines recommends that doctors first target LDL cholesterol, but also pay attention to non-HDL cholesterol.

"LDL cholesterol, even though it is a 'bad' cholesterol, tells only part of the story," says lead author Vera Bittner, M.D., MSPH, professor of medicine in the division of cardiovascular diseases at the University of Alabama at Birmingham. "We found that while LDL cholesterol is important, the non-HDL cholesterol is the more important predictor -- at least in this group of people with heart disease."

The researchers studied data compiled previously during the Bypass Angioplasty Revascularization Investigation (BARI) trial, a study that followed 1,514 heart patients (73 percent male, average age 61 years) for five years, taking their cholesterol levels throughout the study period and recording their health histories. The study authors found that non-HDL cholesterol is a strong and independent predictor of non-fatal heart attack and angina (chest pain or discomfort) at five years, even after considering other risk factors, such as age and smoking.

"Our data suggest that non-HDL cholesterol is an appropriate treatment target among patients with coronary disease," the authors say.

Specifically, they found that non-HDL was the strongest lipoprotein indicator for non-fatal heart attack and angina among total cholesterol, LDL, triglycerides (a blood fat) and HDL. There was a 4.9 percent increase in risk of heart attack for every 10 milligram per deciliter (mg/dL) increase in non-HDL cholesterol, versus a 4.3 percent increase in risk for every 10 mg/dL of total cholesterol, and a 1.6 percent increase in risk with each 10 mg/dL rise in triglycerides. The increased risk associated with increased LDL levels was not significant. They also found that non-HDL cholesterol had the most profound affect on angina, with a 4.9 percent increased risk for every 10mg/dL rise in non-HDL.

One possible reason that the LDL levels were insignificant in this study, Bittner says, is that many patients with heart disease are already on medications to lower their LDL levels.

"What we have done is purely focused on the LDL and ignored these other particles. This study tells the consumer and physician to look at the entire picture and treat both," she says.

Medications traditionally used to lower LDL, such as statins, tend to affect other lipoproteins only in part, Bittner says. Niacin and some other medications might better treat these particles that have higher triglycerides. Often patients require a combination of medications for the best results.

In an accompanying editorial, Scott M. Grundy, M.D., Ph.D., director of the departments of internal medicine and clinical nutrition at the University of Texas Southwestern Medical Center at Dallas, agrees that non-HDL cholesterol is an important part of the treatment picture. But, he says, it should be a secondary target of therapy until more evidence shows that it's more important than LDL. Currently, LDL is the main target of cholesterol treatment.

"I think the study shows that non-HDL cholesterol increasingly appears to be a useful predictor of coronary outcomes, and the findings of this study support the NCEP's new emphasis of non-HDL as a secondary target of treatment after LDL cholesterol," he says.

Co-authors of the study include Regina Hardison; Sheryl F. Kelsey, Ph.D.; Bonnie H. Weiner, M.D.; Alice K. Jacobs, M.D.; and George Sopko, M.D.