Document Detail


High pre-beta1 HDL concentrations and low lecithin: cholesterol acyltransferase activities are strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol.
MedLine Citation:
PMID:  20511449     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 >or=735 mg/L; men >or=619 mg/L) or low HDL-C (n = 42; women <or=387 mg/L; men <or=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-beta(1) 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-beta(1) 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) micromol x L(-1) x h(-1); P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) micromol x L(-1) . h(-1); P = 0.03] HDL-C groups. ROC curves for pre-beta(1) 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-beta(1) HDL was observed (r(2) = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r(2) = 0.56; P < 0.0001). CONCLUSIONS: IHD was associated with high pre-beta(1) 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-beta(1) HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease.
Authors:
Amar A Sethi; Maureen Sampson; Russell Warnick; Nehemias Muniz; Boris Vaisman; Børge G Nordestgaard; Anne Tybjaerg-Hansen; Alan T Remaley
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-28
Journal Detail:
Title:  Clinical chemistry     Volume:  56     ISSN:  1530-8561     ISO Abbreviation:  Clin. Chem.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-29     Completed Date:  2010-07-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421549     Medline TA:  Clin Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1128-37     Citation Subset:  IM    
Affiliation:
NIH, National Heart Lung and Blood Institute, Lipoprotein Metabolism Section, Bethesda, MD, USA. amars@pacbio.com
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MeSH Terms
Descriptor/Qualifier:
Biological Markers / blood
Cholesterol, HDL / blood*
Female
High-Density Lipoproteins, Pre-beta / blood*
Humans
Lecithins / blood*
Male
Middle Aged
Myocardial Ischemia / blood*,  diagnosis
Risk Factors
Sterol O-Acyltransferase / blood*
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Cholesterol, HDL; 0/High-Density Lipoproteins, Pre-beta; 0/Lecithins; EC 2.3.1.26/Sterol O-Acyltransferase

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