Cited by 847Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsCholesterol and Lipid Metabolism

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Association of Small Low-Density Lipoprotein Particles With the Incidence of Coronary Artery Disease in Men and Women

Gardner, Christopher D.·1996·JAMA: The Journal of the American Medical Association

DOI 10.1001/jama.1996.03540110029028

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Abstract

OBJECTIVE: To investigate the prospective association of low-density lipoprotein (LDL) particle diameter with the incidence of fatal and nonfatal coronary artery disease (CAD). DESIGN: A nested case-control study. SETTING: Cases and controls were identified from a population-based sample of men and women combining all of the 5 cross-sectional surveys conducted from 1979 to 1990 of the Stanford Five-City Project (FCP). PARTICIPANTS: Incident CAD cases were identified through FCP surveillance between 1979 and 1992. Controls were matched by sex, 5-year age groups, survey time point, ethnicity, and FCP treatment condition. The sample included 124 matched pairs: 90 pairs of men and 34 pairs of women. MAIN OUTCOME MEASURES: LDL peak particle diameter (LDL size) was determined by gradient gel electrophoresis on plasma samples collected during the cross-sectional surveys (stored at 70 degrees C for 5-15 years). Established CAD risk-factor data were available from FCP baseline measurements. RESULTS: LDL size was smaller among CAD cases than controls (mean +/- SD) (26.17 +/- 1.00 nm vs 26.68 +/- 0.90 nm; P<.001). The association was graded across control quintiles of LDL size. The significant case-control difference in LDL size was independent of levels of high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C), triglyceride, smoking, systolic blood pressure, and body mass index, but was not significant after adjusting for the ratio of total cholesterol (TC) to HDL-C (TC:HDL-C). Among all the physiological risk factors, LDL size was the best differentiator of CAD status in conditional logistic regression. However, when added to the physiological parameters above, the TC:HDL-C ratio was found to be a stronger independent predictor of CAD status. CONCLUSION: LDL size was significantly smaller in CAD cases than in controls in a prospective, population-based study. These findings support other evidence of a role for small, dense LDL particles in the etiology of atherosclerosis.

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“A change in LDL subfraction profiles associated with the accumu lation of denser particles is associated with an in creased risk of ischemic heart disease in non-renal popu lations and should be added to the list of poten tially atherogenic disturbances of the lipoprotein me ta bolism associated with uremia (31, 32).”
Background
Impact of lipid ratio as an objective indicator of mental health status in Indian Individuals with Diabetes mellitus: an observational pilot study
Roy, A., Singh, P. K., Saha, S., Das, A., & Naithani, M. (2022) · Journal of Public Health · doi:10.1007/s10389-022-01702-6 · Cited by 4
“Thus, it may be used to predict levels of small, dense LDL, which is linked to coronary artery disease (Gardner et al. 1996).”
Background
value of ldl particle number and size as predictors of coronary artery disease in apparently healthy men and women. The epic-norfolk prospective population study
Harchaoui, A. K. E., van der Steeg, W. A., Stroes, E. S. G., Kuivenhoven, J. A., Otvos, J. D., Wareham, N. J., Hutten, B. A., Jp, J., Khaw, K., & Boekholdt, S. M. (2007) · Cited by 4
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“多くのアテローム発生を促す傾向があることを示唆する研究もある(11)。しかし、Moraらが指摘するように(22)、いかなる濃度でもLDLの粒径と粒子数は逆相関の関係にあるため、Otvos”
Small Dense Low-Density Lipoprotein for Risk Prediction of Acute Coronary Syndrome
Singh, A., Puhan, R., Pradhan, A. K., Ali, W., & Sethi, R. (2021) · Cardiology Research · doi:10.14740/cr1254 · Cited by 4
“Hence, this study was conducted to: 1) investigate the association of sd-LDL as a risk factor in ACS patients; 2) correlate the presence of sd-LDL with severity of CAD as determined by coronary angiography; and 3) to correlate the presence of sd-LDL with short-term outcomes.”
BackgroundInfluential
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Targeting triglycerides as prognostic indicators and determining lowest values for patient benefit
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Lipoprotein subclasses—A changing landscape
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“The accumulation of smaller, denser LDL particles in the vessel wall is considered to be a key pathophysiological mechanism responsible for the development of atherosclerosis and cardiovascular disease (Coresh and Kwiterovich, 1996; Gardner et al., 1996; Lamarche et al., 1997).”
Background
Association between Lp(a) and small dense LDL in menopausal women without metabolic syndrome
Gentile, M., Iannuzzo, G., Mattiello, A., Marotta, G., Rubba, F., Iannuzzi, A., Panico, S., & Rubba, P. (2018) · Acta cardiologica. Supplementum · doi:10.1080/00015385.2018.1481599 · Cited by 4
Comparison of Low-Density Lipoprotein Size by Polyacrylamide Tube Gel Electrophoresis and Polyacrylamide Gradient Gel Electrophoresis
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Zeng, Y., Lin, L., Zheng, W., & Chen, G. (2025) · PLoS ONE · doi:10.1371/journal.pone.0332376 · Cited by 3
“Low HDL-C levels fail to effectively clear oxidative byproducts, worsening vascular damage [36,37].”
A Non-Atherogenic and Atherogenic Lipoprotein Profile in Individuals with Dyslipoproteinemia
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“…density lipoproteins (IDL1, IDL2), and especially, by the presence of small dense low-density lipoproteins (sdLDL), which form LDL 3-7 subfractions, and which are strongly atherogenic (Lamarche et al. 1997; Gardner et al. 1996; Rajman et al. 1996; Halle et al. 1998, Austin et al. 1994).”
Association between postprandial lipoprotein subclasses and Framingham cardiovascular disease risk stratification
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Lipoprotein particle alterations due to androgen therapy in individuals with dyskeratosis congenita
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“The relationship between small, dense LDL and CHD risk has been described in a range of different situations 17-20 , and HDL sub-fractions are among the new emerging CAD risk factors, and in particular HDL 2b has been shown to be linked to cardiovascular risk 21 .”
Background

Authors: Gardner, C. D.
Affiliations: Stanford Medicine (US)
Corresponding author: Gardner, Christopher D.
ORCID: Gardner, Christopher D.
Venue: JAMA: The Journal of the American Medical Association
Publisher: American Medical Association (AMA)
Published: 1996-09-18
Volume: 276
Issue: 11
Pages: 875
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.1996.03540110029028
OpenAlex: W2050758709
Cited by: 843
References: 53
Citations by year: 2026: 3 · 2025: 4 · 2024: 5 · 2023: 10 · 2022: 10 · 2021: 16 · 2020: 23 · 2019: 14 · 2018: 7 · 2017: 16 · 2016: 10 · 2015: 23 · 2014: 14 · 2013: 33 · 2012: 22
FWCI: 37.88
Type: journal article
Language: en
Open access: closed
Locations: JAMA (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p01hl018574-26, 5r01hl021906-19)
National Heart, Lung, and Blood Institute (T32HL007034, HL21906, HL-18574, 5 T32 HL07034)
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 particle size, coronary artery disease, atherosclerosis, cardiovascular risk factors, TC/HDL-C ratio, HDL cholesterol, non-HDL cholesterol, triglycerides, sex differences
MeSH terms: Adult, Aged, Coronary Disease, Cross-Sectional Studies, Electrophoresis, Polyacrylamide Gel, Female, Humans, Lipids, Lipoproteins, LDL, Male, Middle Aged, Prospective Studies, Risk Factors, Body Mass Index, Incidence, Linear Models, Logistic Models, Case-Control Studies

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Association of Small Low-Density Lipoprotein Particles With the Incidence of Coronary Artery Disease in Men and Women

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