LP(A) LEVELS AND ATHEROSCLEROTIC VASCULAR-DISEASE IN A SAMPLE OF PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA SHARING THE SAME GENE DEFECT

There is considerable variation in the severity of cardiovascular dise ase among patients with familiar hypercholesterolemia (FH). Some repor ts have suggested that plasma lipoprotein(a) [Lp(a)] levels may explai n such variation and that FH subjects deficient in LDL receptors, espe cially those with coronary heart disease, tend to have elevated Lp(a) levels. We have investigated the possible role of the LDL receptor in determining plasma Lp(a) levels in a genetically homogeneous FH popula tion and the contribution of Lp(a) to cardiovascular risk. A total of 98 FH subjects and 66 healthy first- and second-degree relatives from 30 families with FH due to the French-Canadian >10-kilobase deletion o f the LDL receptor gene were studied. A reference group of 392 normoli pidemic French-Canadian participants in a Heart Health Survey was used for comparison. FH subjects were subdivided into subsets of 63 indivi duals free from atherosclerotic vascular disease (AVD) and 35 individu als with AVD. A complete cardiovascular evaluation was performed, and plasma lipid, lipoprotein, and Lp(a) levels were measured in all subje cts in the absence of medication. Apolipoprotein (a) [apo(a)] phenotyp e was deter-mined in 112 of FH and non-FH subjects. The log-transforme d values for plasma Lp(a) were not significantly different among the t hree groups: 0.98 +/- 0.54 (mean +/- SD) in FH subjects with AVD, 0.89 +/- 0.51 in FH subjects without AVD, and 0.82 +/- 0.64 in their relat ives. The distribution of the apo(a) phenotypes did not differ between the FH and non-FH groups. Comparison of two age- and sex-matched subg roups of FH subjects, with and without AVD, failed to show any differe nces in Lp(a) level. However, mean Lp(a) log values in the reference g roup (n=392) were significantly lower than values obtained for the tot al FH group (0.79 +/- 0.57 versus 0.92 +/- 0.52, respectively; P<.05) but were not different from those of the unaffected family members. Th us, in our sample, the LDL receptor appears not to influence plasma Lp (a) levels; rather, these levels reflect shared apo(a) genes. The card iovascular risk in this group of subjects with FH was related to age, male sex, total and LDL cholesterol, and higher apoB but not Lp(a) lev els.