AUTHOR=Wang Shuai , Fu Di , Liu Huixing , Peng Daoquan 

TITLE=Independent association of PCSK9 with platelet reactivity in subjects without statin or antiplatelet agents

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.934914

DOI=10.3389/fcvm.2022.934914

ISSN=2297-055X

ABSTRACT=Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels could predict cardiovascular event in patients with well-controlled LDL-C levels, suggesting an LDL-independent mechanism of PCSK9 on cardiovascular system. Accumulating evidence suggest PCSK9 might be associated with increased platelet reactivity. This study aimed to assess the relationship between PCSK9 levels and platelet reactivity in subjects not taking statins or antiplatelet agents.
Methods A cross-sectional study was conducted to investigate the independent contribution of PCSK9 to platelet activity by controlling for the potential confounding factors. The study population included 89 subjects from health examine center who underwent routine annual healthy check-up or did examination before selective operation. Subjects taking statins or antiplatelet agents were excluded. Adenosine diphosphate (ADP)-induced platelet aggregation was determined by PL-11 platelet analyzer using impedance aggregometry and plasma PCSK9 levels were determined using an ELISA. Serum Lipid profile was assessed by measuring the concentration of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG), with low-density lipoprotein cholesterol (LDL-C) being directly measured using enzymatic techniques. The association between PCSK9 and platelet reactivity was investigated.
Results The study subjects were composed of 53 male and 36 female with an average of 55 (±11) years old. The univariate correlation analysis showed significant correlation between ADP-induced maximal aggregation rate (MAR) and PCSK9 (r=0.55, p<0.001) as well as TC (r=0.23, p=0.028), LDL-C (r=0.27, p<0.001), PLT (r=0.31, p=0.005). Male (41.2% vs 46.6, p=0.04) and smoking (37.4% vs 46.2%, p=0.016) were associated with lower ADP-induced MAR than female and non-smoking. However, there is no correlation between PCSK9 and AA-induced platelet maximal aggregation rate (r=0.17, p=0.12). Multiple regression analysis suggested that PCSK9 contributed independently to ADP-induced maximal aggregation rate (β=0.08, p=0.004) after controlling for the effect of TC, LDL-C, PLT, male and smoking.
Conclusions PCSK9 is positively associated with platelet reactivity, which may partly account for the beneficial effect of PCSK9 inhibition in reducing the risk of major adverse cardiovascular events after acute coronary syndrome (ACS).