Although the latest high-density lipoprotein (HDL) clinical trials have not shown protection against cardiovascular disease, HDL research needs to continue, according to Alan T. Remaley, MD, PhD, one of the presenters for Saturday afternoon’s symposium The Atherogenic Dyslipidemia Complex—New Biomarkers and Therapies Beyond LDL
“There’s a lot of pessimism now about HDL. Drug companies have spent billions of dollars, mostly related to CETP [cholesteryl ester transfer protein] inhibitors, and it could have been that it was a fundamentally flawed strategy,” said Dr. Remaley, Senior Investigator in the Lipoprotein Metabolism Section at the National Institutes of Health. “It could also be that the HDL cholesterol (HDL-C) focus led us astray.”
Dr. Remaley discuss HDL as a therapeutic target and a diagnostic test. To date, the studies haven’t shown that the drugs under investigation increase HDL-C, but Dr. Remaley noted that HDL-C is just part of the HDL’s diverse lipid and protein composition. HDL-C may have been the wrong target, and he proposes that other measures of HDL composition and function, such as cholesterol efflux capacity, may provide a better measure of HDL’s atheroprotective properties.
“I think there’s a tendency when you name something that you think you understand it,” Dr. Remaley said. “People are calling this HDL cholesterol, and it’s not really synonymous with all the other components of HDL. We’ve had a too simplistic view of HDL, and I think that’s led to some of these disappointing failures in clinical trials.”
Christie M. Ballantyne, MD
Also during the session, Christie M. Ballantyne, MD, discuss whether novel biomarkers and testing can help unravel the atherogenic dyslipidemia complex and guide therapy.
Dr. Ballantyne, Chief of Cardiology and Cardiovascular Research and Director of the Maria and Alando J. Ballantyne, M.D. Atherosclerosis Clinical Research Laboratory at Baylor College of Medicine and Director of the Center for Cardiovascular Disease Prevention at Methodist DeBakey Heart and Vascular Center, focus on the biomarkers and lab tests that physicians tend to rely on for patients at risk. He examine the best strategies to assess risk and review the benefits of several clinical options, including apolipoprotein B, low-density lipoprotein (LDL) particle concentration, remnant lipoprotein cholesterol (RLP-C), and triglycerides.
“Although overall LDL cholesterol is a pretty reasonable surrogate for measurement of atherogenic lipoproteins in patients who have metabolic syndrome and diabetes, you may miss people who are high risk,” Dr. Ballantyne said. “Therefore, it’s important for people who are treating such individuals to also consider other parameters.”
Dr. Ballantyne also reviewed a new analysis of data from the Atherosclerosis Risk in Communities (ARIC) study. Dr. Ballantyne and his colleagues measured both RLP-C and LDL triglycerides and discovered that LDL triglycerides were a better risk predictor for atherosclerosis than RLP-C.
Henry N. Ginsberg, MD, the Irving Professor of Medicine at Columbia University College of Physicians and Surgeons, opened the symposium with an update on the atherogenic dyslipidemia complex.
Patients with type 2 diabetes have a dyslipidemia characterized by high levels of plasma triglycerides, low HDL, and increased LDL, which together increase the risk for atherosclerotic cardiovascular disease. Treatment of these patients is focused first on achieving goal levels of LDL cholesterol with a statin, Dr. Ginsberg said. Ezetimibe can be added, and then PCSK9 inhibitors can be added if the patient has very high levels of LDL cholesterol. Secondary goals of reducing triglycerides and increasing HDL cholesterol are best achieved through lifestyle changes, Dr. Ginsberg added.
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