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HDL-C: Target of Therapy – Steven E. Nissen, MD, MACC, Cleveland Clinic vs Peter Libby, MD, BWH

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 7/29/2018

HDL-C: Is It Time to Stop Calling It the ‘Good’ Cholesterol? – Medscape – Jul 27, 2018.

What triggers dysfunctional HDL? It has long been known that such conditions as acute coronary syndrome,^[15] diabetes, or systemic inflammation can alter HDL from a cardioprotective particle to one that promotes inflammation and LDL oxidation.^[16] Budoff and fellow investigators for the MESA study suggest that the transition to menopause should be added to that list. In the main MESA cohort, HDL-C was inversely associated with CAD and carotid intima-media thickness (cIMT).^[17] In contrast, in almost 1500 postmenopausal women, HDL-C was positively associated with increased cIMT.^[18] NMR analysis suggested that small HDL particles are less susceptible to adverse modification at menopause than larger particles. HDL particles were inversely associated with cIMT for men and women—a relationship that held even after adjustment for atherogenic particles.

What to Measure?

If tests for HDL function are not ready for prime time, could measuring the size of the subfractions be the way to go, because very small cholesterol-depleted HDL particles are the main players in cholesterol efflux?^[19] This, too, is overly simplistic for Rosenson, who cautioned that there are many subclasses of HDL and they’re not just differentiated by density. There are more than 60 different proteins associated with HDL, but most particles will only carry a few. Which proteins confer which properties is not fully understood either. The flaw with HDL-C–raising therapies, he noted, is that loading up the particle with cholesterol led to the loss of some surface proteins important in cardioprotection.

Both Budoff and Rosenson like non–HDL-C because it captures all atherogenic particles. But what about patients with very high levels of potentially dysfunctional HDL-C? Budoff explained that when he has a patient of uncertain risk with high LDL-C and very high HDL-C, he will get the HDL particle number; such tests are commercially available. He might also suggest she (he can’t remember seeing a man with HDL-C > 100 mg/dL) get a calcium score. “If the coronaries are clean, the HDL is working,” he said.

SOURCE

https://www.medscape.com/viewarticle/899791?src=WNL_infoc_180729_MSCPEDIT_card&uac=93761AJ&impID=1696486&faf=1#vp_2

HDL-C – A Solid Prognostic Biomarker

Steven E. Nissen, MD, MACC: I am Steve Nissen, chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic. I am here with Dr Peter Libby, chief of cardiology at the Brigham and Women’s Hospital and professor of medicine at Harvard Medical School. We are going to discuss high-density lipoprotein cholesterol (HDL-C), a topic that has been very controversial recently. Peter, HDL-C has been a pretty good biomarker. The question is whether it is a good target.

Peter Libby, MD: Since the early days in Berkley, when they were doing ultracentrifugation, and when it was reinforced and put on the map by the Framingham Study,^[1] we have known that HDL-C is an extremely good biomarker of prospective cardiovascular risk with an inverse relationship with all kinds of cardiovascular events. That is as solid a finding as you can get in observational epidemiology. It is a very reliable prospective marker. It’s natural that the pharmaceutical industry and those of us who are interested in risk reduction would focus on HDL-C as a target. That is where the controversies come in.

VIEW VIDEO

http://www.medscape.com/viewarticle/834197?nlid=69312_1984&src=wnl_edit_medn_card&uac=93761AJ&spon=2