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Cited by 91Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthParaoxonase enzyme and polymorphisms

High Pre-β1 HDL Concentrations and Low Lecithin: Cholesterol Acyltransferase Activities Are Strong Positive Risk Markers for Ischemic Heart Disease and Independent of HDL-Cholesterol

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Sethi, Amar A, Sampson, Maureen, Warnick, Russell, Muniz, Nehemias, Vaisman, Boris, Nordestgaard, Børge G, Tybjærg-Hansen, Anne, Remaley, Alan T·2010·Clinical Chemistry
DOI 10.1373/clinchem.2009.139931PMC PMC4763716
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Abstract

Background: We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors. Methods: Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women ≥735 mg/L; men ≥619 mg/L) or low HDL-C (n = 42; women ≤387 mg/L; men ≤341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (<1600 mg/L) and triglyceride (<1500 mg/L), and none were treated with lipid-lowering medications. Pre-β1 HDL and phospholipid transfer protein concentrations were measured by using commercial kits and lecithin:cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay. Results: Pre-β1 HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P < 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) μmol · L−1 · h−1; P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) μmol · L−1 · h−1; P = 0.03] HDL-C groups. ROC curves for pre-β1 HDL in the high–HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61–0.81) for predicting IHD, which increased to 0.92 (0.87–0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-β1 HDL was observed (r2 = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r2 = 0.56; P < 0.0001). Conclusions: IHD was associated with high pre-β1 HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-β1 HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease.

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Authors
Sethi, A. A., Sampson, M., Warnick, R., Muniz, N., Vaisman, B., Nordestgaard, B. G., Tybjærg-Hansen, A., & Remaley, A. T.
Affiliations
  • National Institutes of Health (US)
  • National Institutes of Health Clinical Center (US)
  • Berkeley HeartLab, Burlingame, CA
  • Quantimetrix, Redondo Beach, CA
  • Herlev Hospital (DK)
  • Copenhagen City Heart Study, and
Corresponding author
Sethi, Amar A
ORCID
Venue
Clinical Chemistry
Publisher
Oxford University Press (OUP)
Published
2010-07-01
Volume
56
Issue
7
Pages
1128-1137
ISSN
  • 0009-9147 (ISSN-L)
  • 1530-8561
DOI
10.1373/clinchem.2009.139931
PMC
PMC4763716
OpenAlex
W2160623724
Cited by
91
References
2
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 10 · 2016: 4 · 2015: 10 · 2014: 7 · 2013: 11 · 2012: 7
FWCI
10.12
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Clinical Chemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • National Heart, Lung, and Blood Institute
  • NIH
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
Keywords
HDL dysfunction, lecithin:cholesterol acyltransferase, ischemic heart disease, HDL cholesterol, phospholipid transfer protein, cardiovascular risk markers, dyslipidemia, HDL particle size, HDL3, HDL4, HDL5, HDL2a
MeSH terms
Sterol O-Acyltransferase, Female, Humans, Cholesterol, HDL, Male, Middle Aged, Risk Factors, Biomarkers, Myocardial Ischemia, High-Density Lipoproteins, Pre-beta, Lecithins

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