Lp (a) concentration and Apo(a) isoform size - Relation to the presence of coronary artery disease in familial hypercholesterolemia

Abstract

We studied the relation between the concentration of lipoprotein(a) [Lp(a)] in plasma, apolipoprotein (a) [apo(a)] phenotype, and the clinical expression of coronary artery disease (CAD) in a previously described cohort of patients with familial hypercholesterolemia (FH) and an appropriate population of control subjects. The plasma concentration of Lp(a) was markedly skewed in both the FH and control populations; however, the distribution was less skewed in FH (50% greater than 300 mg/L) compared with control subjects (27% greater than 300 mg/L). Patients with FH had significantly higher median and mean log Lp(a) levels compared with control subjects. There was no difference in the level of Lp(a) between men and women in both the control and FH groups. Frequency distribution analysis of the major apo(a) isoform size for each subject showed that, in contrast to the near-normal distribution seen in control subjects, two major subpopulations were apparent in the FH cohort, based on apo(a) isoform size >700 kD or ≤700 kD. There was no correlation between Lp(a) plasma concentration and apo(a) isoform size in either population. FH subjects with smaller apo(a) isoforms were more likely to have a history of, signs of, or symptoms of CAD than those with larger isoforms. These data illustrate that on the basis of Lp(a) plasma concentration alone, there is no significant difference between FH patients with and without signs or symptoms of CAD. In the control population the smaller apo(a) isoforms were associated with higher Lp(a) levels, whereas in the FH population both small and large apo(a) isoforms were associated with higher Lp(a) levels. The combination of high serum Lp(a) levels and small apo(a) isoform size portends the greatest risk for FH patients developing CAD. We speculate that specific differences in Lp(a) metabolism in patients with FH lead to differences in both apo(a) isoform size distribution and Lp(a) plasma con-centration compared with control subjects.