Lp(a) correlates with PCSK9 levels only in patients with the low molecular weight apo(a) phenotype, a study of 205 patients with suspected familial hypercholesterolaemia (Atherosclerosis 2018)

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

Atherosclerosis · 1 October 2018 · 6

Afanasieva OI, Ezhov MV, Razova OA, Afanasieva MI, Utkina EA, Pokrovsky SN

This study by Afanasieva, Ezhov, Razova, Afanasieva, Utkina and Pokrovsky examined the relationship between Lp(a) and PCSK9 concentrations according to apolipoprotein(a) [apo(a)] phenotype in 205 patients with potential familial hypercholesterolaemia (32 with ischaemic heart disease, 64 on statins), divided into high molecular weight (HMW, n=145) and low molecular weight (LMW, n=60) apo(a) phenotype groups. Across the whole cohort, PCSK9 correlated with age, statin use, Lp(a), total cholesterol and triglycerides, but a correlation between Lp(a) and PCSK9 was found only in the LMW apo(a) phenotype group, independent of statin use (r=0.46, P<0.001). The Lp(a)-PCSK9 complex also correlated with large intermediate-density and low-density lipoprotein subfractions (r=0.30 for both, P<0.05), more strongly in the LMW group (r=0.59, P<0.005 and r=0.40, P<0.05). The findings show apo(a) phenotype, specifically the LMW form, determines the correlation between Lp(a) and PCSK9 in patients with suspected familial hypercholesterolaemia.

Original abstract

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.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.