Coronary Heart Disease Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, 100037, Beijing, China.
Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Rd, Shenzhen, 518000, China.
Cardiovasc Diabetol. 2022 May 20;21(1):80. doi: 10.1186/s12933-022-01519-3.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular outcomes in stable coronary artery disease with diabetes. We aimed to assess the relationship between PCSK9 and major adverse cardiovascular events (MACEs) in ST-segment elevation myocardial infarction (STEMI) patients with or without diabetes, as well as the relationships between PCSK9 and metabolism, inflammation and platelet activation markers.
A total of 1027 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) and without prior lipid-lowering therapy were consecutively enrolled and the baseline plasma PCSK9 levels were determined by ELISA. Patients were divided into high and low PCSK9 groups according to PCSK9 median. All patients were followed up for the occurrence of MACEs. The associations of PCSK9 with metabolism, inflammation and platelet activation markers and MACEs were evaluated.
PCSK9 levels were positively correlated with triglycerides, high-sensitivity C reactive protein, soluble CD40 ligand and soluble P-selectin levels, and the correlations were stronger in diabetic patients than in non-diabetic patients. In diabetic patients receiving ticagrelor, PCSK9 levels were positively correlated with maximal platelet aggregation measured by light transmittance aggregometry and maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots measured by thrombelastography in the maintenance phase of treatment, whereas no correlations were found in non-diabetic patients. During a median follow-up of 2.0 years, 155 (15.1%) MACEs occurred. The Kaplan-Meier analysis displayed that the patients with high PCSK9 levels had lower event-free survival rate than those with low PCSK9 levels (P = 0.030). When participants were categorized into 4 subgroups according to PCSK9 levels and diabetes status, high PCSK9 levels plus diabetes subgroup had the lowest cumulative event-free survival rate (P = 0.043). Multivariable Cox regression analysis revealed that high PCSK9 levels were independently associated with MACEs in diabetic patients (hazard ratio 2.283, 95% confidence interval: 1.094-4.764, P = 0.028), but not in the whole cohort or non-diabetic patients.
The study showed that high PCSK9 levels were independently associated with MACEs in STEMI patients with diabetes undergoing primary PCI, and the association may be due to stronger correlations of PCSK9 with inflammation and platelet activation markers in diabetic patients.
前蛋白转化酶枯草溶菌素 9（PCSK9）已被证明可预测合并糖尿病的稳定型冠状动脉疾病患者的心血管结局。我们旨在评估 PCSK9 与 ST 段抬高型心肌梗死（STEMI）患者合并或不合并糖尿病患者的主要不良心血管事件（MACE）之间的关系，以及 PCSK9 与代谢、炎症和血小板激活标志物之间的关系。
连续纳入 1027 例接受直接经皮冠状动脉介入治疗（PCI）且无降脂治疗的 STEMI 患者，通过 ELISA 测定基线血浆 PCSK9 水平。根据 PCSK9 中位数将患者分为高 PCSK9 组和低 PCSK9 组。所有患者均进行 MACE 随访。评估 PCSK9 与代谢、炎症和血小板激活标志物以及 MACE 的相关性。
PCSK9 水平与甘油三酯、高敏 C 反应蛋白、可溶性 CD40 配体和可溶性 P-选择素水平呈正相关，且在糖尿病患者中的相关性强于非糖尿病患者。在接受替格瑞洛治疗的糖尿病患者中，在治疗维持阶段，通过光透射聚集仪测量的最大血小板聚集和通过血栓弹力图测量的二磷酸腺苷诱导的血小板-纤维蛋白凝块的最大振幅，PCSK9 水平与这些参数呈正相关，而非糖尿病患者中则无相关性。在中位随访 2.0 年期间，有 155 例（15.1%）发生了 MACE。Kaplan-Meier 分析显示，高 PCSK9 水平组患者的无事件生存率低于低 PCSK9 水平组（P=0.030）。当根据 PCSK9 水平和糖尿病状态将参与者分为 4 个亚组时，高 PCSK9 水平+糖尿病亚组的累积无事件生存率最低（P=0.043）。多变量 Cox 回归分析显示，高 PCSK9 水平与糖尿病患者的 MACE 独立相关（风险比 2.283，95%置信区间：1.094-4.764，P=0.028），但在整个队列或非糖尿病患者中则无相关性。
本研究表明，在接受直接 PCI 的 STEMI 合并糖尿病患者中，高 PCSK9 水平与 MACE 独立相关，这种相关性可能是由于糖尿病患者中 PCSK9 与炎症和血小板激活标志物的相关性更强。
