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.

Effect of specific lipoprotein(a) apheresis on coronary atherosclerosis regression assessed by quantitative coronary angiography.

AIM: To evaluate the effect of specific lipoprotein(a) [Lp(a)] apheresis on coronary atherosclerosis progression in coronary heart disease (CHD) patients with elevated Lp(a) levels. METHODS: A total of 30 subjects (mean age 53.5 ± 8.3 years, 70% male) with CHD verified by angiography, Lp(a) > 50 mg/dL, and low density lipoprotein cholesterol (LDL-C) ≤ 2.5 mmol/L on chronic statin treatment were prospectively evaluated for 18 months. Patients were allocated to receive specific Lp(a) apheresis, which was carried out weekly with Lp(a) Lipopak(®) columns (POCARD Ltd., Russia) (n = 15), or atorvastatin only (n = 15). Blinded quantitative coronary angiography analyses of percent diameter stenosis and minimal lumen diameter (MLD) were performed at baseline and after the 18-month treatment period. RESULTS: By the single specific Lp(a) apheresis procedure, Lp(a) level decreased by an average of 73 ± 12% to a mean of 29 ± 16 mg/dL, and mean Lp(a)-corrected LDL-C decreased by 7% to a mean of 1.4 mmol/L. Median percent diameter stenosis was reduced by -2.0 (95% confidence interval [CI], -5.0-0.0) with apheresis (p < 0.01 in comparison with baseline), and increased by 3.5 (0.0-6.9) with atorvastatin (p < 0.001 between the groups). The effect on MLD was more favorable with apheresis than with atorvastatin: 0.20 ± 0.39 mm, as compared with 0.01 ± 0.34 mm, p = 0.04. Lp(a) apheresis had greater efficacy regarding the amount of regressed/stabilized coronary segments than atorvastatin alone in the majority of patients (chi-square test 13.61, p < 0.005). CONCLUSION: Specific Lp(a) apheresis for 18 months produced coronary atherosclerosis regression in stable CHD patients with high Lp(a) levels and reached LDL-C goals.