Received on November 12, 2003
Accepted on December 30, 2003

Lipids, Lipoproteins, and Cardiovascular Risk Factors

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

¹ Research Department, R & D Center, 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 MRC 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
⁶ Cardiovascular Biochemistry Unit, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London, UK, and Current address: Molecular Pathology Laboratory, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy

^* To whom correspondence should be addressed. 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--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--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--HDL was assayed by crossed immunoelectrophoresis.

Results: Cases had lower HDL-cholesterol (-23%), total apolipoprotein A-I (-26%), and pre--HDL (-55%; all P <0.001) concentrations; lower pre--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--HDL concentrations. On ROC analysis, pre--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--HDL increased by 47 (5)% in controls, but was unchanged in cases (group difference, P <0.001).

Conclusions: Our results suggest that inefficient RCT, secondary to a low pre--HDL concentration and production rate in plasma, contributes to premature CHD in Japanese men with low HDL-cholesterol.