Despite high levels of the "good" cholesterol known as HDL, some mysteriously go on to develop heart disease. But doctors at UCLA say they have developed a test to identify which patients have dysfunctional HDL and therefore a higher risk for heart attack.
"They exhibit pro-inflammatory HDL, which means not only is it not protective, it contributes to the problem and enhances this damage to the blood vessel wall," said Dr. Ben Ansell, Director of the UCLA Center for Primary Care-Based Cardiovascular Disease Prevention.
He is the first author of a study on HDL published online in Circulation, the Journal of the American Heart Association. The study evaluated several groups of people. The first had symptomatic coronary artery disease despite having levels of HDL that were double the American average. When the researchers ran their blood through assays in a test tube they found that these patients had HDL that increased pro-inflammatory cell activity.
In the arteries, HDL usually counteracts the effects of LDL — the "bad" cholesterol. When LDL gets taken up by the walls of blood vessels it becomes oxidized and leads to a cascade of events that includes inflammation and the formation of plaque. If this plaque grows it can rupture, attracting platelets, which clog the vessel and ultimately lead to a heart attack. Patients with dysfunctional HDL accelerate this process instead of inhibiting it.
Dr. Ansell says there is probably a genetic predisposition to explain why some people have HDL cholesterol that does not behave as "good" cholesterol should.
"Whether it’s interaction with existing plaque or whatever, no one really knows at this point," he said.
The second part of their study looked at patients with risk factors for heart disease such as diabetes, high blood pressure, and peripheral vascular disease who were not taking statins, drugs that lower bad cholesterol. They were compared to a group of controls—similar patients who did not have heart disease.
Dr. Ansell’s team ran their blood samples through an assay to see whether their HDL was anti or pro-inflammatory. Then the testing was repeated in the patients with heart disease after six weeks of a 40-milligram treatment with the statin Zocor.
They found that testing for the type of HDL, rather than measuring total HDL, was a better indicator for distinguishing the patients with heart disease from the control patients.
In addition, the statin drug appeared to change the character of the dysfunctional HDL and reduced inflammation, but not to the levels of the healthy control group. Which, Ansell said, may be why aggressive statin treatment seems to benefit patients with dysfunctional HDL.
The test for HDL type is not available to the public, but Dr. Ansell says it’s probably not too far away. And women in particular may be good candidates for this test since they tend to have high HDL levels.
"This test may be able to identify a group of patients, who despite normal appearing HDL levels will have a significant risk for coronary disease that is not addressed by traditional blood tests," said Dr. Ansell.
The test may also help doctors identify patients in whom the presumption of heart disease risk is low, but actually merit more aggressive drug therapy because of their dysfunctional HDL cholesterol. And Dr. Ansell is confident that new drugs are in the pipeline that will specifically address HDL.