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Association of Coronary Heart Disease with Pre-ß-HDL Concentrations in Japanese Men

¹ Department of Advanced Medical Technology and Development, BML, Kawagoe, Saitama, Japan.² Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.³ Third Department of Internal Medicine, Fukui Medical University, Fukui, Japan.⁴ Medical Research Council Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, London, UK.⁵ Cardiovascular Biochemistry Unit, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London, UK.

^aAddress correspondence to this author at: Metabolism Research Laboratory, Department of Cardiovascular Genetics, University of Utah College of Medicine, Rm. 218, 410 Chipeta Way, Salt Lake City, UT 84108. Fax 801-581-6862; e-mail nazeem{at}ucvg.med.utah.edu.

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-ß-HDLs. These are generated during remodeling of -HDLs, which account for almost all HDL-cholesterol. We studied the strength of the association of CHD with pre-ß-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-ß-HDL was assayed by crossed immunoelectrophoresis.

Results: Cases had lower HDL-cholesterol (-23%), total apolipoprotein A-I (-26%), and pre-ß-HDL (-55%; all P <0.001) concentrations; lower pre-ß-HDL:-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-ß-HDL concentrations. On ROC analysis, pre-ß-HDL concentration discriminated between cases and controls better than any other lipoprotein measurement. When plasma was incubated for 16 h at 37 °C, mean (SD) pre-ß-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-ß-HDL concentration and production rate in plasma, contributes to premature CHD in Japanese men with low HDL-cholesterol.

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				M. Suzuki, H. Wada, S. Maeda, K. Saito, S. Minatoguchi, K. Saito, and M. Seishima Increased Plasma Lipid-Poor Apolipoprotein A-I in Patients with Coronary Artery Disease Clin. Chem., January 1, 2005; 51(1): 132 - 137. [Abstract] [Full Text] [PDF]