Editorial

Abstract

IT HAS been well established that the lipids in plasma do not circulate free but combine in orderly arrangements with protein. Most of the lipid is combined with two major proteins, the a and ,3 polypeptides, to form lipoproteins that extend over a wide density range, from greater than 1.21 to that of fat itself, about 0.9 Gm. per ml. Changes in this lipoprotein spectrum occur in many diseases. In many instances the lipoprotein abnormality appears to be the primary expression of a biochemical defect. These disorders are usually familial, relatively common, and of particular interest in relation to atherogenesis and coronary heart disease. Despite their relative importance, the present understanding of these hereditary defects is meager and their classification chaotic. For the determination and study of such abnormalities a number of methods have been available for some time. The minimum is a determination of plasma cholesterol and glyc-eride content. The maximum in resolving power is offered by the ultracentrifuge, which is capable of measuring changes within small increments of the density spectrum. When one is concerned particularly with familial hyperlipoproteinemia, necessitating screening of large kindreds, neither of these approaches has proved ideal. Measurement of triglyc-Circulation, Volume XXXI, March 1965 erides is tedious. Furthermore, even after considerable experience, knowledge of both cholesterol and triglyceride concentrations is inadequate for distinguishing all of the familial syndromes. The ultracentrifugal technics also do not meet current needs because they are time-consuming, costly, and not sufficiently available to clinicians. In the present state of knowledge of fat transport, most clinical stutdies require only rough quantitation of four groups of lipopro-teins known to be related to independent metabolic processes and therefore possibly subject to specific inborn errors. These are the soluble alpha and beta lipoproteins and the two groups of lipoproteins or particles that transport, respectively, glycerides of ex-ogenous or dietary origin (chylomicrons) and of endogenous, mainly hepatic, origin (pre-beta lipoproteins). These lipoprotein groups can be separated by a rapid and simple method, a modification' of established technics for paper electro-phoresis. By its application to a large number of subjects with familial hyperlipoproteinemia, we have so far been able to detect what appear to be five different phenotypes, more than have been seriously considered in the past.3 It has also been possible to follow such patients through various dietary and metabolic studies much more easily than heretofore. Of particular value has been the ability to make a tentative diagnosis of fat or carbo