Abstract 17793: Apolipoprotein(a) Phenotype Determines the Correlation of Lipoprotein(a) and Protein Convertase Subtilisin-Kexin Type 9 Levels in Patients With Hypercholesterolemia

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Introduction: Mechanism of reducing of plasma Lp(a) concentration by protein convertase subtilisin-kexin type 9 (PCSK9) inhibitors is not clear and is actively studied. The aim of this study was to investigate the relationship between the concentration of Lp(a) and in hypercholesterolemic patients with low (LMW) and high molecular weight (HMW) apo(a) phenotype.

Methods: The study included 215 patients with TC>7.5 mmol/L or LDL-C>4.9 mmol/L (mean age 53±11 years, 83 (39%) male). All patients were evaluated with duplex of carotid arteries, 32 patients had CHD, 64 (30%) took statins. For all patients lipid parameter, Lp(a) and PCSK9 plasma level, apo(a) phenotype were determined in blood serum. Depending on the apo(a) phenotype patients were divided into 3 subgroups: LMW apo(a) phenotype (LMW subgroup, n=60), the HMW apo(a) (HMW subgroup, n=72) and with undetectable phenotype of apo(a) (n=76) due to the low plasma concentration of Lp(a) (level 5.4±2.4 mg/dL).

Results: The subgroups were comparable for all major clinical characteristics, lipids and PCSK9. The plasma Lp(a) level was significantly higher LMW subgroup 69±37 (70;40-97) mg/dL than in the HMW subgroup 35±29 (24; 16-44) mg/dL, p <0.05. In the total group the PCSK9 level correlated with TC (r=0.17), LDL-C (r=0.17), TG (r=0.22, p<0.01 for all). We found the correlation between concentrations of Lp(a) and PCSK9 (r=0.20, p=0.003), which was enhanced in the LMW subgroup (r=0.38, p=0.003) and disappeared in HMW subgroup (r=0.10, p=0.36). In the LMW subgroup the concentrations of Lp(a) (r=0.46, p=0.005) and TG level (r=0.33, p=0.017) were independent predictors of PCSK9 plasma concentration, independent of age, sex, TC, LDL-C and hypolipidemic therapy. Similar results were obtained for the whole group: Lp(a) (r=0.18), TG (r=0.21, p<0.005 for all). In HMW subgroup the level of PCSK9 was associated only with age, TC and statin medication (r=0.28, r=0.32, r=0.36, correspondingly, p <0.05 for all).

Conclusions: The positive relationship between the concentrations of Lp(a) and PCSK9 is due to the presence of the LMW apo(a) phenotype and illustrates the differences in metabolism and pathophysiological properties of Lp(a) with small and large apo(a) isoforms.

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