Prospective studies in several countries have demonstrated an inverse association between incidence of ischemic heart disease (IHD) and high-density lipoprotein (HDL) cholesterol concentration. 1~ 2 It is now established that HDL particles exhibit considerable heterogeneity of size, density, and flotation rate, and of lipid and apoprotein composition3 and that the cholesterol content of the entire family is a complex function of the compositions and particle numbers of several subclasses. Because each of these occupies a different place in HDL metabolism, it is possible that some will have a stronger relationship to IHD than others. Comparisons of the relative strengths of the associations of different subclasses with disease are of interest for two reasons. First, the identification of a subclass that is more powerful than HDL cholesterol as a risk factor would have considerable clinical utility if the method of measurement were suitable for routine use. Second, the results of such studies might provide insight into the molecular basis of the link between HDL and IHD.

As an alternative to measuring subclasses, some investigators have explored the associations of HDL apoproteins with disease. This approach has the same potential benefits as subclass analysis, with the added attraction of being technically less demanding. Because the major HDL apoproteins AI and AI1 are confined almost entirely to HDL, they can be quantified in whole plasma. A case for measurement of apoproteins can also be made on theoretical grounds, since the metabolism of lipoproteins is largely determined by their apoprotein content.