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Association of Small Low-Density Lipoprotein Particles With the Incidence of Coronary Artery Disease in Men and Women
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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“the reduction in ratio of total to HDL cholesterol, which has been identified as a predictor of coronary heart disease (35), was not significantly different between the 2 diets.”
From Effects of Low-Carbohydrate Diets Versus Low-Fat Diets on Metabolic Risk Factors: A Meta-Analysis of Randomized Controlled Clinical Trials (2012) · cites this paper as [35]
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Should we measure routinely the LDL peak particle size?
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“It has been reported that LDL size was the best predictor of coronary artery disease [ 34 ,35] and the increase in cardiovascular risk, attributable to lipid factors, was significantly modulated by variations in LDL particle size [32,36].”
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“On the other hand, the accumulated evidence of a number of studies suggests that low-density lipoprotein (LDL) particle size is a risk factor for CAD [9–12].”
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Background
Metadata
- Authors
- Gardner, C. D.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- 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
- 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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