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Rethinking good cholesterol: a clinicians' guide to understanding HDL
Angie S Xiang1, Bronwyn A Kingwell1
1Metabolic and Vascular Physiology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Central Clinical School, Monash University, Melbourne, VIC, Australia.
The Lancet. Diabetes & Endocrinology
|March 27, 2019
Summary
Low high-density lipoprotein (HDL) cholesterol is common in type 2 diabetes. While HDL cholesterol is a risk factor for cardiovascular disease, its therapeutic value is debated, necessitating a re-evaluation of its clinical use.
Area of Science:
- Cardiovascular Medicine
- Metabolic Disorders
- Lipidology
Background:
- Low high-density lipoprotein (HDL) cholesterol dyslipidemia is prevalent in type 2 diabetes, a significant risk factor for atherosclerotic cardiovascular disease.
- The traditional view of HDL cholesterol as "good cholesterol" is challenged by recent drug trial outcomes, creating a clinical paradox regarding its value as a biomarker and therapeutic target.
Purpose of the Study:
- To resolve the paradox surrounding HDL cholesterol's role in cardiovascular disease by examining the historical context and the distinction between HDL and HDL cholesterol.
- To explore the compositional complexity and diverse functions of HDL particles beyond cholesterol content, including their impact on glucose metabolism.
Main Methods:
- Historical review of the HDL hypothesis and its evolution.
- Analysis of HDL particle composition and function, focusing on lipid transport and novel roles.
- Discussion of evidence linking HDL functions to glucose metabolism and implications for type 2 diabetes.
Main Results:
- The clinical paradox stems from conflating HDL particles with HDL cholesterol, overlooking HDL's complex composition and functions.
- HDL particles possess multifaceted roles in lipid transport and glucose metabolism, extending beyond their cholesterol content.
- HDL cholesterol remains a valuable, albeit imperfect, biomarker for cardiovascular disease risk prediction, especially in type 2 diabetes.
Conclusions:
- HDL cholesterol is an imperfect marker for the complex HDL system; novel, more causally linked HDL markers are needed for clinical application.
- The "good cholesterol" label for HDL cholesterol is misleading and should be abandoned to prevent prognostic overgeneralizations.
- Despite limitations, HDL cholesterol retains value in cardiovascular disease risk prediction models, particularly for individuals with type 2 diabetes.