Beyond HDL:
New Insights into HDL Function in Cardiovascular Disease By: Mark Houston, MD and Sara Gottfried, MD The following article is not endorsed and/or supported by The American Academy of Anti-Aging Medicine. The purposes of this publication do not imply endorsement and/or support of any author, company or theme related to this article.
INTRODUCTION
High-density lipoprotein (HDL) plays a vital role in lipid biology and coronary heart disease (CHD) pathophysiology. However, a major paradigm shift is happening in the medical community regarding the role of HDL-cholesterol (HDL-C) in dyslipidemia and dyslipidemia-induced cardiovascular disease, especially CHD and myocardial infarction (MI). HDL are complex nanoparticles with more than 80 associated proteins, phospholipids, cholesterol, and cholesteryl esters. HDL is best known for its ability to scavenge for and ferry low-density lipoprotein cholesterol (LDL-C) away from the arteries and back to the liver for redistribution, metabolism, and elimination, as well as for its anti-inflammatory, antithrombotic, anti-immune and antioxidative activity. The prevailing dogma for the past 30 years was that high total HDL-C (a lab measure reflecting the amount of cholesterol carried by the HDL particles) was cardioprotective, because it reflected better clearance of cholesterol. However, the emerging narrative is that the HDL particle is far more heterogeneous than previously understood. In order for HDL
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to be cardioprotective, it must be functional.1 Furthermore, there are genomic, proteomic, and other compositional considerations. The main takeaway is that because of the heterogeneity of HDL, measurement of HDL-C alone does not provide a complete picture of the protective qualities of HDL vis-à-vis cardiovascular disease.
HDL: THE PARADIGM SHIFT ABOUT THE ROLE OF HDL LDL is essentially a “garbage” type of particle that deposits cholesterol in cells all over the body, while HDL is like a garbage collector. It literally takes excess cholesterol out of tissue to remove it from the body, usually through the liver. Epidemiological studies, ranging from the Framingham Study and continuing through to the Atherosclerosis Risk in Communities (ARIC) Study, demonstrated that HDL-C is inversely associated with CHD and MI.2,3 Specifically, as the calculation was extended, CHD risk increases by 3% in men and 2% in women for every 1 mg/dL decrement in HDL-C.4 Put
ANTI-AGING MEDICAL NEWS
• SUMMER 2020
