Apolipoprotein(a) phenotype determines the correlations of lipoprotein(a) and proprotein convertase subtilisin/kexin type 9 levels in patients with potential familial hypercholesterolemia

Background and aims: The aim of this study is to investigate the relation between lipoprotein(a) [Lp(a)] and proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations, and their complex, in patients with potential familial hypercholesterolemia (FH), depending on apo(a) phenotype. Methods: The study included 205 patients with total cholesterol (TC) > 7.5 mmol/L and/or low density lipoprotein cholesterol (LDL-C)> 4.9 mmol/L, 32 (15%) patients suffered from ischemic heart disease (IHD), 64 were taking statins. The diagnosis of FH was estimated according to the Dutch Lipid Clinics Network criteria. Lipid parameters, apoB-containing lipoprotein subfractions, Lp(a), PCSK9, Lp(a)-PCSK9 complex levels and apo (a) phenotype were determined. Depending on the apo(a) phenotype, all patients were divided into 2 groups: with high molecular weight (HMW) (n=145) and low molecular weight (LMW) (n=60) apo(a) phenotype. Results: The groups were comparable by all major clinical characteristics and biochemical parameters. In the whole group, PCSK9 concentration correlated with age, statins intake, Lp(a), TC and TG levels. Correlation between Lp(a) and PCSK9 levels was found only in the LMW apo(a) phenotype group independently of statins intake (r=0.46, p < 0.001). Associations between Lp(a)-PCSK9 complex and large subfractions of intermediate (r=0.30) and low-density lipoproteins (r=0.30, p < 0.05 for both) were observed, with more significance in group 2 (r=0.59, p < 0.005 and r=0.40, p < 0.05, respectively). Conclusions: In patients with potential familial hypercholesterolemia, positive correlations between concentrations of Lp(a) and PCSK9, as well as of Lp(a)-PCSK9 plasma complex with large subfractions of intermediate and low-density lipoproteins (IDL-1 and LDL-C), were determined by the LMW apo(a) phenotype.