HDL does not predict heart attack risk after dramatic statin therapy: Study

People with high levels of "good cholesterol," HDL-C, tend to have fewer heart attacks, but HDL-C may offer little protection to people who take statins to lower harmful LDL cholesterol, researchers reported July 21. At Brigham and Women's Hospital in Boston, Dr. Paul Ridker and colleagues analyzed a large study of healthy people who took the statin CRESTOR® (rosuvastatin calcium) to prevent heart attacks. They found that in this group, having high HDL-C was a bad predictor of heart attack risk.

"HDL is a very powerful predictor of future risk [of heart disease]," said Ridker, whose results were published in The Lancet. "[But] once we get LDL into these very low ranges with very potent statins, HDL no longer predicts future risk of heart disease."

"The results of Ridker's study are very interesting, but do not question the use of HDL-raising drugs as protection against heart disease," says Dr. Amar Sethi, VP of Science and Technology at Pacific Biomarkers, Inc., a provider of biomarker laboratory services. "The questions it does pose however are: Does statin treatment over time change the composition and overall function of the HDL particle in the patients investigated by Dr. Ridker?

Dr. Sethi has a highly informed perspective on Ridker's result; he recently identified two potential markers for cardiovascular disease, an advance that was published in the July issue of Clinical Chemistry.

Dr. Sethi observed that in ischemic heart disease patients untreated with statins, there is indeed a difference in the way bad cholesterol is removed from the body by the HDL particle. They found that a particle called pre-β1 HDL is increased, while LCAT—the enzyme that packs cholesterol into the core of the HDL particle—is reduced. The authors thus suggested that these patients develop ischemic heart disease due to a malfunction in the cholesterol removal process, which is one of the major functions of the HDL particle.

"Since our study used subjects that were matched by HDL-C levels, we can conclude that HDL-C levels cannot be used as a measure of predicting ischemic heart disease—just as in Ridker's study," says Sethi. He adds, "Perhaps measuring proteins or enzymes involved in the HDL maturation process in Ridker's study would give a better understanding of why HDL didn't predict heart attack risk after dramatic statin therapy."