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Cited by 29Lipoproteins and Cardiovascular HealthLipid metabolism and disordersDiabetes, Cardiovascular Risks, and Lipoproteins

Altered composition of triglyceride-rich lipoproteins and coronary artery disease in a large case–control study

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Hopkins, Paul N., Nanjee, M. Nazeem, Wu, Lily L., McGinty, Michael G., Brinton, Eliot A., Hunt, Steven C., Anderson, Jeffrey L.·2009·Atherosclerosis
DOI 10.1016/j.atherosclerosis.2009.05.016PMC PMC2787968
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Abstract

Background Traditional beta-quantification of plasma lipoproteins by ultracentrifugation separates triglyceride-rich lipoproteins (TGRL) from higher density lipoproteins. The cholesterol in the TGRL fraction is referred to as measured very low-density lipoprotein cholesterol (VLDL-C) recognizing that other TGRL may be present. The measured VLDL-C to total plasma triglyceride (VLDL-C/TG) has long been considered an index of average TGRL composition with abnormally high VLDL-C/TG ratios (>or=0.30 with TG>150mg/dL) indicative of atherogenic remnant accumulation (type III hyperlipidemia). However, virtually no reports are available which examine potential associations between CAD and VLDL-C/TG at the lower end of the spectrum. Methods and results We performed ultracentrifugation in 1170 cases with premature-onset, familial CAD and 1759 population-based controls and examined the VLDL-C/TG ratio as an index of TGRL composition. As expected, we found very high CAD risk associated with severe type III hyperlipidemia (OR 10.5, p=0.02). Unexpectedly, however, we found a robust, graded, and independent association between CAD risk and lower than average VLDL-C/TG ratios (p<0.0001 as ordered categories or as a continuous variable). Among those in the lowest VLDL-C/TG category (a ratio <0.12), CAD risk was clearly increased (OR 4.5, 95% CI 2.9-6.9) and remained significantly elevated in various subgroups including those with triglycerides below 200mg/dl, in males and females separately, as well as among those with no traditional CAD risk factors (OR 5.8, 95% CI 1.5-22). Significant compositional differences by case status were confirmed in a subset whose samples were re-spun with measurement of lipids and apolipoprotein B (apo B) in each subfraction. Conclusions We found a strong, graded, independent, and robust association between CAD and lower VLDL-C/TG ratios. We consider this a novel, hypothesis-generating observation which will hopefully generate additional future studies to provide confirmation and further insight into potential mechanisms.

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  • Familial dysbetalipoproteinemia (FD) is a highly atherogenic, prevalent, genetically based lipid disorder.

    “Familial dysbetalipoproteinemia (FD) is a highly atherogenic, prevalent genetically based lipid disorder.”

    From Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia (2024) · cites this paper as [13]

    The Introduction and Results link type III hyperlipidemia (dysbetalipoproteinemia) to atherogenic remnants and substantially increased coronary artery disease risk; the Discussion also describes genetic variants associated with its manifestation. But the Discussion calls type III hyperlipidemia infrequent, contrary to the claim that it is prevalent. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Authors
Hopkins, P. N., Nanjee, M. N., Wu, L. L., McGinty, M. G., Brinton, E. A., Hunt, S. C., & Anderson, J. L.
Affiliations
  • University of Utah (US)
  • Intermountain Healthcare (US)
Corresponding author
Hopkins, Paul N.
ORCID
Venue
Atherosclerosis
Publisher
Elsevier BV
Published
2009-12
Volume
207
Issue
2
Pages
559-566
ISSN
0021-9150 (ISSN-L)
DOI
10.1016/j.atherosclerosis.2009.05.016
PMC
PMC2787968
OpenAlex
W2107874108
Cited by
29
References
8
Citations by year
2024: 3 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 1 · 2013: 1
FWCI
0.34
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Atherosclerosis (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Utah
  • National Institute on Aging (AG18734, R01AG018734)
  • National Heart, Lung, and Blood Institute (HL71878, R01HL021088, R01HL047651, HL21088, R01HL071878, R01HL047466)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
triglyceride-rich lipoproteins, coronary artery disease, type III hyperlipidemia, apolipoprotein B, lipoprotein composition, triglycerides
MeSH terms
Adult, Aged, Coronary Artery Disease, Female, Genetic Testing, Humans, Hyperlipidemias, Lipoproteins, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Risk Factors, Triglycerides, Ultracentrifugation, Cholesterol, VLDL, Biomarkers, Logistic Models, Odds Ratio, Case-Control Studies, Age of Onset, Risk Assessment, Lipoproteins, IDL

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