Abstract | BACKGROUND: In individuals heterozygous for ABCA1 transporter mutations, defective reverse cholesterol transport (RCT) causes low HDL-cholesterol and premature coronary heart disease (CHD). However, the extent to which impaired RCT underlies premature CHD in others with low HDL-cholesterol is not known. The primary acceptors of cell cholesterol are a minor subclass of lipid-poor pre-beta-HDLs. These are generated during remodeling of alpha-HDLs, which account for almost all HDL-cholesterol. We studied the strength of the association of CHD with pre-beta-HDL concentrations in Japanese men. METHODS: Blood was collected from 42 men with clinical CHD and 44 healthy controls 40-70 years of age. Pre-beta-HDL was assayed by crossed immunoelectrophoresis. RESULTS: Cases had lower HDL-cholesterol (-23%), total apolipoprotein A-I (-26%), and pre-beta-HDL (-55%; all P <0.001) concentrations; lower pre-beta-HDL:alpha-HDL ratios (-45%; P <0.001); and higher plasma triglycerides (20%; P <0.03) than the controls. On stepwise logistic regression, CHD was associated most strongly with pre-beta-HDL concentrations. On ROC analysis, pre-beta-HDL concentration discriminated between cases and controls better than any other lipoprotein measurement. When plasma was incubated for 16 h at 37 degrees C, mean (SD) pre-beta-HDL increased by 47 (36)% in controls, but was unchanged in cases (group difference, P <0.001). CONCLUSIONS: Our results suggest that inefficient RCT, secondary to a low pre-beta-HDL concentration and production rate in plasma, contributes to premature CHD in Japanese men with low HDL-cholesterol.
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Authors | Hiroaki Hattori, Takeshi Kujiraoka, Tohru Egashira, Eiji Saito, Takayuki Fujioka, Sadao Takahashi, Mayumi Ito, Jackie A Cooper, Irina P Stepanova, M Nazeem Nanjee, Norman E Miller |
Journal | Clinical chemistry
(Clin Chem)
Vol. 50
Issue 3
Pg. 589-95
(Mar 2004)
ISSN: 0009-9147 [Print] England |
PMID | 14726473
(Publication Type: Journal Article)
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Chemical References |
- Apolipoprotein A-I
- High-Density Lipoproteins, Pre-beta
- Lipoproteins, HDL
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Topics |
- Adult
- Aged
- Apolipoprotein A-I
(blood)
- Coronary Disease
(blood, diagnosis)
- High-Density Lipoproteins, Pre-beta
- Humans
- Japan
- Lipoproteins, HDL
(blood)
- Male
- Middle Aged
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