Wang Shuai, Fu Di, Liu Huixing, Peng Daoquan
Department of Cardiovascular Medicine, Second Xiangya Hospital of Central South University, Changsha, China.
Front Cardiovasc Med. 2022 Oct 17;9:934914. doi: 10.3389/fcvm.2022.934914. eCollection 2022.
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 the cardiovascular system. Accumulating evidence suggests 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.
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 a health examination centre who underwent routine annual health check-ups or had an examination before a 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.
The study subjects were composed of 53 males and 36 females with an average age of 55 (±11) years old. The univariate correlation analysis showed significant correlation between ADP-induced maximal aggregation rate (MAR) and PCSK9 ( = 0.55, < 0.001) as well as TC ( = 0.23, = 0.028), LDL-C ( = 0.27, < 0.001), and PLT ( = 0.31, = 0.005). Being male (41.2% vs. 46.6, = 0.04) and smoking (37.4 vs. 46.2%, = 0.016) were associated with lower ADP-induced MAR than being female and non-smoking. However, there is no correlation between PCSK9 and AA-induced platelet maximal aggregation rate ( = 0.17, = 0.12). Multiple regression analysis suggested that PCSK9 contributed independently to ADP-induced maximal aggregation rate (β = 0.08, = 0.004) after controlling for the effect of TC, LDL-C, PLT, being male, and smoking.
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).
前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）水平可预测低密度脂蛋白胆固醇（LDL-C）水平控制良好的患者发生心血管事件，提示PCSK9对心血管系统存在不依赖LDL的作用机制。越来越多的证据表明，PCSK9可能与血小板反应性增加有关。本研究旨在评估未服用他汀类药物或抗血小板药物的受试者中PCSK9水平与血小板反应性之间的关系。
进行一项横断面研究，通过控制潜在混杂因素来研究PCSK9对血小板活性的独立影响。研究人群包括89名来自健康体检中心的受试者，他们接受了年度常规健康检查或在择期手术前进行了检查。排除服用他汀类药物或抗血小板药物的受试者。使用PL-11血小板分析仪通过阻抗聚集法测定二磷酸腺苷（ADP）诱导的血小板聚集，并使用酶联免疫吸附测定法测定血浆PCSK9水平。通过测量总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）和甘油三酯（TG）的浓度评估血清脂质谱，使用酶法直接测量低密度脂蛋白胆固醇（LDL-C）。研究PCSK9与血小板反应性之间的关联。
研究对象包括53名男性和36名女性，平均年龄为55（±11）岁。单变量相关分析显示，ADP诱导的最大聚集率（MAR）与PCSK9（r = 0.55，P < 0.001）、TC（r = 0.23，P = 0.028）、LDL-C（r = 0.27，P < 0.001）和血小板计数（PLT）（r = 0.31，P = 0.005）之间存在显著相关性。男性（41.2%对46.6%，P = 0.04）和吸烟（37.4%对46.2%，P = 0.016）与女性和不吸烟相比，ADP诱导的MAR较低。然而，PCSK9与花生四烯酸（AA）诱导的血小板最大聚集率之间无相关性（r = 0.17，P = 0.12）。多元回归分析表明，在控制了TC、LDL-C、PLT、男性和吸烟的影响后，PCSK9对ADP诱导的最大聚集率有独立贡献（β = 0.08，P = 0.004）。
PCSK9与血小板反应性呈正相关，这可能部分解释了PCSK9抑制在降低急性冠状动脉综合征（ACS）后主要不良心血管事件风险方面的有益作用。
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