The DOI matches its Crossref record; 88 of the 88 references it cites were found in a registry or an index.
Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal
Abstract
The major lipoprotein types, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), are composed of many subgroups (1–3). Classifications are based on size (1), density, or apolipoprotein (apo) content (2), or a combination of these (3), and the subfractions that are isolated have distinct metabolic and other functional properties. Thus, it is entirely reasonable to think that subfractions of the major lipoproteins have diverse relationships to coronary heart disease (CHD). Because the classical lipid risk factors by no means perfectly predict CHD in patients, lipoprotein subfractionation has the potential to improve risk prediction. Among the various lipoprotein subfractionation systems, LDL size and density by far have attracted the most basic, clinical, and population research. Several companies offer LDL size measurements to physicians as a diagnostic test for CHD risk. Several lines of evidence implicate small, dense LDL in the etiology of CHD. Small, dense LDL is often increased in relative proportion or concentration in patients with CHD. Small, dense LDL has several characteristics that are linked to atherogenesis: long residence time in plasma, and enhanced oxidizability, arterial proteoglycan binding, and permeability through the endothelial barrier (4). Together, these findings have led to the hypothesis that small, dense LDL is a potent atherogenic lipoprotein that can be used to improve risk prediction, and evaluate response to lipid therapy (5–7). Furthermore, small, dense LDL is often part of a group of high-risk characteristics including high triglycerides, low HDL, diabetes, insulin resistance, obesity, and the metabolic syndrome (8–10). This has led logically to the concept that it contributes to the high rate of CHD in these groups. Yet, the very association between small, dense LDL and these other high-risk conditions challenges proponents of the hypothesis to show a direct, independent relationship between small, dense LDL and CHD. In this article, we evaluate evidence on LDL subclasses in risk assessment and therapy, reaching the conclusion that LDL subclass measurement does not add independent information to that conferred generically by the LDL concentration along with the other standard risk factors.
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“Neither LDL size nor the concentration of small, dense LDL particles adds to CVD prediction in multiple variable analysis beyond the standard lipid risk factors, although small LDL particles predict cardiovascular risk in univariate analysis (35)(36)(37).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [35]
In the citing paper
“Prospective multivariate studies demonstrate that large LDL predicts atherosclerosis and coronary heart disease (35,38,39).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [35]
Citations
Cites
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944
Low-Density Lipoprotein Subclass Patterns and Risk of Myocardial Infarction
Austin, M. A. (1988) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1988.03410130125037 · Cited by 1,780
Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk
Austin, M. A., King, M. C., Vranizan, K. M., & Krauss, R. M. (1990) · Circulation · doi:10.1161/01.cir.82.2.495 · Cited by 1,411
Stampfer, M. J. (1996) · JAMA · doi:10.1001/jama.1996.03540110036029 · Cited by 1,081
Lamarche, B., Tchernof, A., Moorjani, S., Cantin, B., Dagenais, G. R., Lupien, P. J., & Despre´s, J.-P. (1997) · Circulation · doi:10.1161/01.cir.95.1.69 · Cited by 1,077
Identification of multiple subclasses of plasma low density lipoproteins in normal humans.
Krauss, R. M., & Burke, D. J. (1982) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38178-5 · Cited by 992
Metabolic origins and clinical significance of LDL heterogeneity
Berneis, K. K., & Krauss, R. M. (2002) · Journal of Lipid Research · doi:10.1194/jlr.r200004-jlr200 · Cited by 896
Gardner, C. D. (1996) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1996.03540110029028 · Cited by 843
Ehara, S., Ueda, M., Naruko, T., Haze, K., Itoh, A., Otsuka, M., Komatsu, R., Matsuo, T., Itabe, H., Takano, T., et al. (2001) · Circulation · doi:10.1161/01.cir.103.15.1955 · Cited by 780
Reaven, G. M., Chen, Y. I., Jeppesen, J., Maheux, P., & Krauss, R. M. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116541 · Cited by 687
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Eckel, R. H., Alberti, K., Grundy, S. M., & Zimmet, P. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61794-3 · Cited by 6,317
Eckel, R. H., Grundy, S. M., & Zimmet, P. (2005) · The Lancet · doi:10.1016/s0140-6736(05)66378-7 · Cited by 5,755
Dietary fats and cardiovascular disease: a presidential advisory from the American Heart Association
Sacks, F. M., Lichtenstein, A. H., Wu, J. H. Y., Appel, L. J., Creager, M. A., Kris-Etherton, P. M., Miller, M., Rimm, E. B., Rudel, L. L., Robinson, J. G., et al. (2017) · Circulation · doi:10.1161/cir.0000000000000510 · Cited by 1,386
Self-citationGrundy, S. M. (2010) · Springer eBooks · doi:10.1007/978-1-4419-5839-6_1 · Cited by 1,227
Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline
Berglund, L., Brunzell, J. D., Goldberg, A. C., Goldberg, I. J., Sacks, F., Murad, M. H., & Stalenhoef, A. F. H. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3213 · Cited by 887
Self-citation
Metadata
- Authors
- Sacks, F. M., & Campos, H.
- Affiliations
- Harvard University (US)
- Corresponding author
- Sacks, Frank M.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2003-10
- Volume
- 88
- Issue
- 10
- Pages
- 4525-4532
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2164346577
- Cited by
- 241
- References
- 88
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 9 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 14 · 2015: 8 · 2014: 8 · 2013: 9 · 2012: 10
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- small dense LDL, LDL subclasses, coronary artery disease, cardiovascular risk prediction, atherogenesis, metabolic syndrome, HDL cholesterol, triglycerides
- MeSH terms
- Cardiovascular Diseases, Humans, Cholesterol, LDL, Particle Size
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