The relation of serum lipoprotein (a) concentration and apolipoprotein (a) phenotype with preclinical atherosclerosis

Lipoprotein (a) [Lp(a)] is a plasmatic lipoprotein, comprising a low density lipoprotein-like particle with the addition of an apolipoprotein (a) molecule, covalently bonded to apolipoprotein B100. High levels of Lp(a) have been linked to an increased risk of cardiovascular events. Lp(a) levels are mostly attributed to genetic determinants within the apolipoprotein(a) gene (LPA). We examined whether Lp(a) plasma levels, isoforms and polymorphisms are associated with early atherosclerosis by measuring intima-media thickness (IMT) in an asymptomatic population. We assessed data for 60 adult subjects from our Lipid Clinic, in primary prevention and with Lp(a) levels >35 mg/dL. We collect data for Lp(a) concentrations in plasma, LPA kringle IV type 2 (KIV-2) sums of repeats (affecting isoform size), and carrier status for the LPA single-nucleotide polymorphisms (SNP) rs10455872 and rs3798220. Lp(a) was quantified by ELISA test and isoform size by electrophoresis (SDS-PAGE). Isoforms were classified as F, B, S1, S2, S3, S4 based on electrophoretic mobility compared with apoB100. LPA genotype was assessed using a Human CVD BeadChip. Lp(a) mean plasma level was 117 mg/dL (range 36-375 mg/dL). Small isoform apo(a) size (F,B,S1,S2) was present in the 80% of subjects and confirm the inverse relation with plasmatic Lp(a) concentration. Genetic analysis revealed that 26% of subjects carries SNP rs10455872, while 17% carries rs3798220, which are associated with increased Lp(a) levels in carriers versus non-carriers. Finally the carotid IMTs were determined to analyze the association of Lp(a) and with IMT and we found that IMT increased with increase in quartiles of IMT (p<0.05) confirming a relationship between Lp(a) and development of atherosclerosis.