Correlation between serum levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and atherogenic lipoproteins in patients with coronary artery disease

Abstract

BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of serum low-density lipoprotein (LDL) cholesterol levels. Recently, PCSK9 has additionally been related to metabolic risk factors such as the levels of triglycerides, apolipoprotein B (apoB), insulin, and glucose, as well as body mass index. The purpose of this study was to investigate correlations between serum levels of PCSK9 and apoB-containing atherogenic lipoproteins in patients with coronary artery disease (CAD).MethodsSerum levels of PCSK9 and lipoprotein(a) [Lp(a)]; small, dense LDL; and oxidized LDL were measured in 101 patients with CAD who were not receiving lipid-lowering therapy.ResultsSerum hetero-dimer PCSK9 levels were positively correlated with serum levels of Lp(a) (r = 0.195, p = 0.05); small, dense LDL (r = 0.336, p = 0.0006); and oxidized LDL (r = 0.268, p = 0.008). Multivariate regression analyses showed that serum hetero-dimer PCSK9 was a significant predictor of serum levels of Lp(a) (β = 0.235, p = 0.01); small, dense LDL (β = 0.143, p = 0.03); and oxidized LDL (β = 0.268, p = 0.008).ConclusionsSerum PCSK9 levels were positively correlated with serum levels of Lp(a); small, dense LDL; and oxidized LDL in patients with CAD. This suggests that the interaction between serum PCSK9 and apoB-containing lipoproteins plays a role in establishing the atherosclerotic status of patients.Trial registrationUMIN Clinical Trials Registry, UMIN ID: C000000311.

Lipid Lowering Therapy and Circulating PCSK9 Concentration

“…Lakoski et al also reported that changes in plasma PCSK9 level did not correlate with the magnitude of the LDL-C lowering response achieved with 10 mg of simvastatin 21 ) . Consistent with these reports, we previously showed that the percentage change in PCSK9 level did not correlate with the LDL-C reduction observed after statins therapy 48 ) . Furthermore, although the reduction in LDL-C was greater with pitavastatin than with pravastatin, the level of increase in PCSK9 did not differ between these statins 48 ) .…”

Association between proprotein convertase subtilisin/kexin 9 (PCSK9) and lipoprotein subclasses in children with type 1 diabetes mellitus: Effects of glycemic control

“…This association remained significant in a multivariate analysis (Table 3). Available literature data indicate that plasma sdLDL particles are positively related to the levels of PCSK9, at least in patients with CVD [9,10]. The observed reciprocal association between PCSK9 and sdLDL in our study could be assigned to the effects of insulin administration, since insulin increases PCSK9, but lowers sdLDL [27].…”

“…So far, a link between PCSK9 and sdLDL particles has been scarcely investigated. A positive correlation was reported in patients with CVD [9,10], whereas no association was found in healthy subjects [11,12]. Hence, it is possible that the relationship between circulating PCSK9 and sdLDL particles varies in health and diseases.…”

Fetal gender and gestational age differentially affect PCSK9 levels in intrauterine growth restriction

“…Since its discovery in 2003 PCSK9 has emerged as a significant modulator of LDL metabolism [10, 11]. Loss of function mutations of PCSK9 are associated with low plasma LDL-C levels [12, 13].…”