Lipoprotein(a) in Familial Hypercholesterolemia

Background Low density lipoprotein (LDL) and Lipoprotein(a) (Lp(a)) are pro-atherogenic apolipoprotein (apo) B-containing members of the non-high-density lipoprotein (non-HDL) family of particles. Elevated plasma levels of LDL cholesterol (C), non-HDL-C and apo B are defining features of heterozygous familial hypercholesterolemia (HeFH), but reports of elevated plasma Lp(a) concentration are inconsistent. Methods We performed retrospective chart reviews of 256 genetically characterized patients with hypercholesterolemia and 272 control subjects from the Lipid Genetics Clinic at University Hospital in London, Ontario. We evaluated pairwise correlations between plasma levels of Lp(a) and those of LDL-C, non-HDL-C and apo B. Results Mean Lp(a) levels were not different between individuals with hypercholesterolemia and control subjects. No correlations were found between Lp(a) and LDL-C or non-HDL-C levels in control or hypercholesterolemia patients; all R-values < 0.079 and all P-values > 0.193. Borderline weak correlations between Lp(a) and apo B were identified in patients r=0.103, P=0.112) and controls (r = 0.175, P=0.005). Results were similar across genotypic subgroups. Conclusions Lp(a) levels are independent of LDL-C and non-HDL-C; in particular Lp(a) levels are not increased in patients with hypercholesterolemia and molecularly proven HeFH. Apo B was only weakly associated with Lp(a). Elevated Lp(a) does not cause FH in our clinic patients. Genetic variants causing HeFH that raise LDL-C do not affect Lp(a), confirming that these lipoproteins are metabolically distinct. Lp(a) cannot be predicted from LDL-C and must be determined separately to evaluate its amplifying effect on atherosclerotic risk in patients with hypercholesterolemia.