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Cited by 66Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismParaoxonase enzyme and polymorphisms

Apolipoprotein A-II influences apolipoprotein E-linked cardiovascular disease risk in women with high levels of HDL cholesterol and C-reactive protein

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Corsetti, James P., Bakker, Stephan J. L., Sparks, Charles E., Dullaart, Robin P. F.·2012·PLoS ONE
DOI 10.1371/journal.pone.0039110PMC PMC3377620
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Abstract

BACKGROUND: In a previous report by our group, high levels of apolipoprotein E (apoE) were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP) in the setting of both low (designated as HR1 subjects) and high (designated as HR2 subjects) levels of high-density lipoprotein cholesterol (HDL-C). To assess whether apolipoprotein A-II (apoA-II) plays a role in apoE-associated risk in the two female groups. METHODOLOGY/PRINCIPAL: Outcome event mapping, a graphical data exploratory tool; Cox proportional hazards multivariable regression; and curve-fitting modeling were used to examine apoA-II influence on apoE-associated risk focusing on HDL particles with apolipoprotein A-I (apoA-I) without apoA-II (LpA-I) and HDL particles with both apoA-I and apoA-II (LpA-I:A-II). Results of outcome mappings as a function of apoE levels and the ratio of apoA-II to apoA-I revealed within each of the two populations, a high-risk subgroup characterized in each situation by high levels of apoE and additionally: in HR1, by a low value of the apoA-II/apoA-I ratio; and in HR2, by a moderate value of the apoA-II/apoA-I ratio. Furthermore, derived estimates of LpA-I and LpA-I:A-II levels revealed for high-risk versus remaining subjects: in HR1, higher levels of LpA-I and lower levels of LpA-I:A-II; and in HR2 the reverse, lower levels of LpA-I and higher levels of LpA-I:A-II. Results of multivariable risk modeling as a function of LpA-I and LpA-I:A-II (dichotomized as highest quartile versus combined three lower quartiles) revealed association of risk only for high levels of LpA-I:A-II in the HR2 subgroup (hazard ratio 5.31, 95% CI 1.12-25.17, p = 0.036). Furthermore, high LpA-I:A-II levels interacted with high apoE levels in establishing subgroup risk. CONCLUSIONS/SIGNIFICANCE: We conclude that apoA-II plays a significant role in apoE-associated risk of incident CVD in women with high levels of HDL-C and CRP.

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  • Rasmussen et al. showed that adjustment for C-reactive protein did not have any impact on the risk between plasma levels of apoE and ischemic heart disease.

    “The importance of high C-reactive protein levels has been investigated by some studies, however Rasmussen et al. showed that adjustment for C-reactive protein did not have any impact on the risk between plasma levels of apoE and ischemic heart disease [44,116,121,122].”

    From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [122]

    The Study Populations section (page unavailable) reports that apoE predicted cardiovascular disease risk in women with high CRP. The Statistical Analyses section lists CRP among potential adjustment variables, but neither passage says CRP adjustment left the apoE risk association unchanged. The cited paper also does not establish the claim about Rasmussen et al. or specifically ischemic heart disease. (LLM, conf=0.82)

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Cited by

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Authors
Corsetti, J. P., Bakker, S. J. L., Sparks, C. E., & Dullaart, R. P. F.
Affiliations
  • University of Rochester Medicine (US)
  • University Medical Center Groningen (NL)
Corresponding author
Corsetti, James P.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-06-18
Volume
7
Issue
6
Pages
e39110
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0039110
PMC
PMC3377620
OpenAlex
W2104159077
Cited by
66
References
0
Citations by year
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FWCI
3.92
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
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
apolipoprotein A-II, apolipoprotein E, cardiovascular risk, women, HDL cholesterol, C-reactive protein, apolipoprotein A-I, HDL particles, incident cardiovascular disease, gene-gene interaction, lipoprotein composition
MeSH terms
Adult, Aged, Apolipoproteins E, C-Reactive Protein, Cardiovascular Diseases, Female, Humans, Cholesterol, HDL, Male, Middle Aged, Risk, Biomarkers, Apolipoprotein A-II

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