Lp(a) is a lipoprotein which is strongly associated with an increased risk of premature atherosclerotic cardiovascular disease. The protein which identifies this unique lipoprotein is apo(a), which has high homology with plasminogen. Apo(a) is polymorphic, with many different sizes of this protein in the population. This size polymorphism is genetically determined, and in turn, is a major determinant of the plasma level of Lp(a). However, other factors also strongly influence Lp(a) levels but are very poorly understood. We have established that in individuals with the same apo(a) isoform but widely different levels of Lp(a), variation in the production rate of Lp(a) is the cause of the variation in plasma Lp(a) levels. This directs attention to the genetic factors distinct from apo(a) isoform which affect apo(a) production. A detailed study of the effect of apo(a) isoprotein size on the density of Lp(a) demonstrated that the larger the apo(a) isoform, the more dense the Lp(a) particle. Heterozygotes for two forms of apo(a) have two distinct populations of Lp(a) that can be preparatively separated based on their different densities. Ongoing studies are focused on the mechanism by which the apo(a) isoprotein size influences plasma Lp(a) levels. These studies included subjects of age 19 to 46 years. 38% of the subjects were women. The studies included one Asian subject.
