Cited by 241Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsCholesterol and Lipid Metabolism

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Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal

Sacks, Frank M., Campos, Hannia·2003·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2003-030636

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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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Authors: Sacks, F. M., & Campos, H.
Affiliations: Harvard University (US)
Corresponding author: Sacks, Frank M.
ORCID: Sacks, Frank M.
Campos, Hannia
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
DOI: 10.1210/jc.2003-030636
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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Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal

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