The lipoprotein Lp(a) is strongly associated with measures of atherosclerosis and cardiovascular disease. In several studies, primarily of white populations, Lp(a) was found to be the strongest correlate with disease. The unique apolipoprotein, apo(a), must play an essential role in the association because it is the only lipoprotein component that distinguishes Lp(a) from low-density lipoprotein (LDL). Lp(a) exhibits extremely wide ranges of variation between individuals in serum concentrations and in the sizes of apo(a), but both are quite constant during an individual's lifetime. Apo(a) size phenotypes show significant differences among populations, including blacks and whites. We hypothesize that apo(a) size variation is correlated with extent and severity of arteriosclerotic lesions. We plan to test this hypothesis using serum samples taken at autopsy of young persons, 15-34 years of age, who have died of external causes. These samples come from the multicenter study funded by two initiatives entitled Pathobiological Determinants of Atherosclerosis in Youth (PDAY) and Risk Factors in Early Human Atherosclerosis (RFEHA). In the proposed study we will measure apo(a) phenotypes in serum samples from approximately 715 PDAY-RFEHA cases. The end point in this study will be the measures of extent and severity of atherosclerosis as determined by pathologists in the study.
The Specific Aims are as follows: 1) to determine apo(a) isoform phenotypes (molecular weights) in serum samples from approximately 715 PDAY-RFEHA cases; 2) to quantitate relative amounts of each band for all samples with two distinguishable apo(a) isoform bands; 3) to determine the association of apo(a) molecular weight with extent and severity of lesions after accounting for the effects of Lp(a), lipoprotein cholesterol, smoking, race, gender, and age; and 4) to determine the effects of race and gender on the association of apo(a) molecular weight with extent and severity of lesions. The results of this study will be used to test the hypothesis that variation in apo(a) size phenotype is associated with prevalence of atherosclerotic lesions. The potential long-term benefit to human health will be the identification of high risk phenotypes that warrant clinical intervention.
