Value of High-Density Lipoprotein (HDL) Subpopulations in Predicting Recurrent Cardiovascular Events in the Veterans Affairs HDL Intervention Trial
Abstract
Objective— To test the hypothesis whether determination of high-density lipoprotein (HDL) subpopulations provides more power to predict recurrent cardiovascular disease (CVD) events (nonfatal myocardial infarction, coronary heart disease death, and stroke) than traditional risk factors in the Veterans Affairs HDL Intervention Trial (VA-HIT). Methods and Results— Apolipoprotein A-I (apoA-I)–containing HDL subpopulations were quantitatively determined by nondenaturing 2D gel electrophoresis. Hazard ratios of recurrent CVD events were calculated by comparing VA-HIT subjects with (n=398) and without (n=1097) such events. Subjects with new CVD events had significantly lower HDL-C, apoA-I, and large cholesterol-rich HDL particle (α-1, α-2, pre–α-1, and pre–α-2) levels, significantly higher triglyceride, and small poorly lipidated HDL particle (pre–β-1 and α-3) levels than subjects without such events. Multivariate analyses indicated that α-1 and α-2 particle levels were significant negative risk factors, whereas α-3 level was a significant positive risk factor for new CVD events. Pre–β-1 level was a significant risk factor for new CVD events only in univariate analysis. A forward selection model indicated that α-1 was the most significant risk factor for recurrent CVD events among HDL particles. Conclusions— An altered HDL subpopulation profile marked with low α-1 and α-2 levels and a high α-3 level in coronary heart disease patients indicated an elevated risk for new CVD events. Moreover, α-1 and α-2 levels were superior to HDL-C levels in risk assessment in patients with low HDL-C in VA-HIT.
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Prebeta-1 HDL levels positively associate with increased risk of new CVD events, with ischemic heart disease, and with both coronary artery disease and myocardial infarction.
“Prebeta-1 HDL levels positively associate with increased risk of new CVD events,34 with ischemic heart disease,35 and with both coronary artery disease and myocardial infarction.36”
From Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function (2014) · cites this paper as [34]
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Self-citationHDL and atherosclerosis: Insights from inherited HDL disorders
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Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency
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Relation of Increased Prebeta-1 High-Density Lipoprotein Levels to Risk of Coronary Heart Disease
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Prebeta-1 HDL and coronary heart disease
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HDL Atheroprotection by Aerobic Exercise Training in Type 2 Diabetes Mellitus
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HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity
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High-Density Lipoprotein Particles, Cell-Cholesterol Efflux, and Coronary Heart Disease Risk
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Self-citationRelationship between the concentration and antiatherogenic activity of high-density lipoproteins
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Self-citationLipid and lipoprotein profiles and prevalence of dyslipidemia in Mexican adolescents
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Self-citationPolyacrylamide Gradient Gel Electrophoresis of Lipoprotein Subclasses
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Self-citationFenofibrate, HDL, and cardiovascular disease in Type-2 diabetes: The DAIS trial
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High-density lipoprotein subpopulation profiles in lipoprotein lipase and hepatic lipase deficiency
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Self-citationInfluence of HDL particles on cell-cholesterol efflux under various pathological conditions
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Lipid efflux mechanisms, relation to disease and potential therapeutic aspects
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Self-citation
- Authors
- Asztalos, B. F., Collins, D., Cupples, L. A., Demissie, S., Horvath, K. V., Bloomfield, H. E., Robins, S. J., & Schaefer, E. J.
- Affiliations
- Boston University (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2005-10
- Volume
- 25
- Issue
- 10
- Pages
- 2185-2191
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2160230170
- Cited by
- 268
- References
- 35
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 12 · 2017: 10 · 2016: 8 · 2015: 12 · 2014: 14 · 2013: 22 · 2012: 17
- FWCI
- 24.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 64738, R01HL064738)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- HDL subpopulations, apolipoprotein A-I, HDL particle size, cardiovascular risk prediction, recurrent cardiovascular events, coronary artery disease, myocardial infarction, stroke, HDL cholesterol, triglycerides, veterans
- MeSH terms
- Aged, Cardiovascular Diseases, Coronary Disease, Follow-Up Studies, Humans, Lipoproteins, LDL, Male, Middle Aged, Myocardial Infarction, Predictive Value of Tests, Recurrence, Risk Factors, United States, United States Department of Veterans Affairs, Biomarkers, Proportional Hazards Models, Stroke
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