Circulating PCSK9 levels are positively correlated with NMR-assessed atherogenic dyslipidaemia in patients with high cardiovascular risk

The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene regulates cholesterol homoeostasis by accelerating low-density lipoprotein receptor (LDLR) degradation resulting in the decreased catabolism of low-density lipoprotein (LDL) leading to hypercholesterolaemia. PCSK9 has also been related to other metabolic risk factors such as triglycerides (TGs) and glucose levels and body mass index (BMI). Therefore, our aim was to study the relationship between the PCSK9 and the lipid and lipoprotein profile. We studied 267 diabetic and metabolic syndrome patients who were not receiving any lipid-lowering therapy. We measured circulating lipids, cholesterol in remnant lipoproteins (RLPc) and PCSK9 levels. A detailed lipoprotein profile was determined based on NMR. Plasma PCSK9 levels were significantly and positively correlated with TG (r = 0.136, P = 0.033), total cholesterol (r = 0.219, P < 0.001) and apoB (apolipoprotein B; r = 0.226, P = 0.006) circulating levels and with an atherogenic profile of lipoprotein subclasses. In further detail, circulating PCSK9 levels were positively correlated with large very-low density lipoprotein (VLDL) particles, (r = 0.210, P = 0.001) and with their remnants, the intermediate-density lipoprotein (IDL) particles (r = 0.206, P = 0.001); positively correlated with smaller LDL particles (for small LDL: r = 0.224, P < 0.001; for medium small LDL: r = 0.235, P < 0.001; and for very small LDL: r = 0.220, P < 0.001); and with high-density lipoprotein (HDL) particles (r = 0.146, P < 0.001), which is mainly explained by the PCSK9 correlation with the smallest HDL particles (r = 0.130, P = 0.037). In addition, circulating PCSK9 levels were positively correlated with the pro-atherogenic circulating RLPc levels (r = 0.171, P = 0.006). All of the correlations were adjusted by age, gender and BMI. PCSK9 levels are significantly and positively correlated with atherogenic lipoproteins such as large VLDL, IDL, the smallest LDL, the smallest HDL particles and RLPc levels.