High-density lipoproteins: A consensus statement from the National Lipid Association
Abstract
For >4 decades it has been recognized that elevated serum levels of high-density lipoprotein cholesterol (HDL-C) are associated with reduced risk of cardiovascular disease (CVD) and its sequelae. Many prospective observational studies performed around the world have confirmed an inverse relationship between HDL-C and cardiovascular risk in people irrespective of sex, race, or ethnicity. Consequently, it was assumed that, by extension, raising HDL-C through lifestyle modification and pharmacologic intervention would reduce risk of CVD. Animal studies are consistent with this assumption. Lipid treatment guidelines around the world promoted the recognition of HDL-C as a therapeutic target, especially in high-risk patients. Some post hoc analyses from randomized controlled trials also suggest that raising HDL-C beneficially affects the risk of CVD. However, a number of recent randomized studies putatively designed to test the "HDL hypothesis" have failed to show benefit. The results of these trials have caused many clinicians to question whether HDL-C is a legitimate therapeutic target. In response to the many questions and uncertainties raised by the results of these trials, the National Lipid Association convened an expert panel to evaluate the current status of HDL-C as a therapeutic target; to review the current state of knowledge of HDL particle structure, composition, and function; and to identify the salient questions yet to be answered about the role of HDL in either preventing or contributing to atherosclerotic disease. The expert panel's conclusions and clinical recommendations are summarized herein. The panel concludes that, although low HDL-C identifies patients at elevated risk, and much investigation suggests that HDL may play a variety of antiatherogenic roles, HDL-C is not a therapeutic target at the present time. Risk stratified atherogenic lipoprotein burden (low-density lipoprotein cholesterol and non-HDL-C) should remain the primary and secondary targets of therapy in patients at risk, as described by established guidelines. The National Lipid Association emphasizes that rigorous research into the biology and clinical significance of low HDL-C should continue. The development of novel drugs designed to modulate the serum levels and functionality of HDL particles should also continue. On the basis of an enormous amount of basic scientific and clinical investigation, a considerable number of reasons support the need to continue to investigate the therapeutic effect of modulating HDL structure and function.
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HDL-C plays an anti-atherosclerotic role, and increased serum HDL-C concentrations are strongly inversely related to the risk of atherosclerotic CVD.
“HDL-C is well known to play an anti-atherosclerotic role by protecting against the development of CVD; indeed, increased serum concentrations of HDL-C are strongly inversely related to the risk of atherosclerotic CVD [6,7].”
High-density lipoprotein cholesterol is a strong, consistent, and independent predictor of cardiovascular events.
“High-density lipoprotein cholesterol (HDL-C) is a strong, consistent, and independent predictor of cardiovascular events”
From Effects of aerobic exercise on lipids and lipoproteins (2017) · cites this paper as [2]
HDL particles drive reverse cholesterol transport and may exert a variety of anti-atherogenic effects.
“This is biologically plausible since HDL particles drive reverse cholesterol transport and may exert a variety of anti-atherogenic effects3.”
From Is Isolated Low High-Density Lipoprotein Cholesterol a Cardiovascular Disease Risk Factor?: New Insights From the Framingham Offspring Study (2016) · cites this paper as [3]
Low HDL-C has long been viewed as a robust and independent CVD risk factor.
“For many decades, a low level of HDL-C has been viewed as a robust and independent CVD risk factor1-4.”
From Is Isolated Low High-Density Lipoprotein Cholesterol a Cardiovascular Disease Risk Factor?: New Insights From the Framingham Offspring Study (2016) · cites this paper as [3]
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“HDL-C is well known to play an anti-atherosclerotic role by protecting against the development of CVD; indeed, increased serum concentrations of HDL-C are strongly inversely related to the risk of atherosclerotic CVD [6,7].”
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- Authors
- Toth, P. P., Barter, P. J., Rosenson, R. S., Boden, W. E., Chapman, M. J., Cuchel, M., D'Agostino, R. B., Davidson, M. H., Davidson, W. S., Heinecke, J. W., Karas, R. H., Kontush, A., Krauss, R. M., Miller, M., & Rader, D. J.
- Affiliations
- CGH Medical Center (US)
- The Heart Research Institute (AU)
- Icahn School of Medicine at Mount Sinai (US)
- Albany Medical College (US)
- Inserm (FR)
- University of Pennsylvania (US)
- University of Chicago (US)
- University of Cincinnati (US)
- University of Washington (US)
- Tufts University (US)
- University of California, San Francisco (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- Toth, Peter P.
- ORCID
- Venue
- Journal of Clinical Lipidology
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 7
- Issue
- 5
- Pages
- 484-525
- ISSN
- 1876-4789 (ISSN-L)
- 1933-2874
- OpenAlex
- W2106601510
- Cited by
- 336
- References
- 282
- Citations by year
- 2026: 6 · 2025: 21 · 2024: 10 · 2023: 21 · 2022: 34 · 2021: 24 · 2020: 38 · 2019: 25 · 2018: 28 · 2017: 26 · 2016: 19 · 2015: 41 · 2014: 41 · 2013: 2
- FWCI
- 33.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of clinical lipidology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL112625)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- HDL cholesterol, cardiovascular risk, atherosclerosis, LDL cholesterol, non-HDL cholesterol, risk stratification
- MeSH terms
- Animals, Cardiovascular Diseases, Humans, Lipoproteins, HDL, Risk Factors, Societies, Scientific, Consensus, Molecular Targeted Therapy
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