Relation of Lipoprotein Subclasses as Measured by Proton Nuclear Magnetic Resonance Spectroscopy to Coronary Artery Disease

From the Division of Nutrition, Centers for Disease Control and Prevention, Atlanta, Ga (D.S.F.); the Department of Biochemistry, North Carolina State University, Raleigh (J.D.O., E.J.J.); the Milwaukee Veterans Administration Medical Center, Milwaukee, Wis (J.J.B.); and St. Luke's Hospital, Milwaukee, Wis (A.J.A., J.A.W.).

Correspondence to David S. Freedman, CDC MS–K26, 4770 Buford Hwy, Atlanta, GA 30341-3724. E-mail Dxf1{at}cdc.gov

Abstract—Although each of the major lipoprotein fractions is composed of various subclasses that may differ in atherogenicity, the importance of this heterogeneity has been difficult to ascertain owing to the labor-intensive nature of subclass measurement methods. We have recently developed a procedure, using proton nuclear magnetic resonance (NMR) spectroscopy, to simultaneously quantify levels of subclasses of very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins; subclass distributions determined with this method agree well with those derived by gradient gel electrophoresis. The objective of the current study of 158 men was to examine whether NMR-derived lipoprotein subclass levels improve the prediction of arteriographically documented coronary artery disease (CAD) when levels of lipids and lipoproteins are known. We found that a global measure of CAD severity was positively associated with levels of large VLDL and small HDL particles and inversely associated with intermediate size HDL particles; these associations were independent of age and standard lipid measurements. At comparable lipid and lipoprotein levels, for example, men with relatively high (higher than the median) levels of either small HDL or large VLDL particles were three to four times more likely to have extensive CAD than were the other men; the 27 men with high levels of both large VLDL and small HDL were 15 times more likely to have extensive CAD than were men with low levels. In contrast, adjustment for levels of triglycerides or HDL cholesterol greatly reduced the relation of small LDL particles to CAD. These findings suggest that large VLDL and small HDL particles may play important roles in the development of occlusive disease and that their measurement, which is not possible with routine lipid testing, may lead to more accurate risk assessment.

Key Words: nuclear magnetic resonance spectroscopy • coronary disease • angiography • lipoproteins • lipoprotein subfractions

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