Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institute, IRCCS Tradate, Varese, Italy.
Clin Chem Lab Med. 2021 Nov 1;60(1):118-126. doi: 10.1515/cclm-2021-0817. Print 2022 Jan 26.
CD40 ligand (CD40L), a transmembrane glycoprotein belonging to the tumor necrosis factor family and expressed by a variety of cells, is involved in the basic mechanisms of inflammation, atherosclerosis and thrombosis. Some studies suggest that the soluble form of CD40L (sCD40L) is a predictor of major cardiovascular events and mortality in a variety of clinical settings, but data from literature are conflicting.
We studied consecutive patients with acute (ACS) or chronic (CCS) coronary syndrome who underwent percutaneous coronary artery intervention (PCI). Blood samples for sCD40L dosage were taken at baseline immediately before PCI. We tested the relation between sCD40L and pre-specified outcome measures consisting of new ACS, clinical restenosis and all-cause mortality. We recruited 3,841 patients (mean age 64 ± 11 years, 79% men) with ACS (n=2,383) or CCS (n=1,458).
During a mean follow-up of two years (±0.6 years), 642 patients developed ACS, 409 developed restenosis (≥70% of at least one of the previously treated coronary segments) and 175 died. For each 1-standard deviation increase in sCD40L (0.80 ng/mL), the hazard ratios (HRs) for ACS, restenosis, and mortality were 1.11 (95% confidence interval [CI]: 1.05 to 1.18, p<0.0001), 1.10 (95% CI: 1.02 to 1.19, p=0.010), and 1.00 (95% CI: 0.86 to 1.16, p=0.983), respectively. In multivariable Cox regression models with adjustment for several potential confounders including age, acute or chronic coronary syndrome, multi-vessel disease, stent placement, diabetes, previous coronary events and dyslipidemia, sCD40L remained an independent predictor of ACS and coronary restenosis. There were no interactions between sCD40L and acute or chronic coronary syndrome or stent placement.
Among patients with ACS or CCS who undergo PCI, higher levels of sCD40L predict an increased risk of acute coronary events and coronary restenosis, but not of mortality.
CD40 配体（CD40L）是一种跨膜糖蛋白，属于肿瘤坏死因子家族，由多种细胞表达，参与炎症、动脉粥样硬化和血栓形成的基本机制。一些研究表明，可溶性 CD40L（sCD40L）是多种临床情况下主要心血管事件和死亡率的预测因子，但文献中的数据存在矛盾。
我们研究了接受经皮冠状动脉介入治疗（PCI）的急性（ACS）或慢性（CCS）冠状动脉综合征的连续患者。在 PCI 前即刻采集基线血样，用于 sCD40L 测定。我们检测了 sCD40L 与新 ACS、临床再狭窄和全因死亡率等预定义结局指标之间的关系。我们招募了 3841 例 ACS（n=2383）或 CCS（n=1458）患者（平均年龄 64±11 岁，79%为男性）。
在平均 2 年（±0.6 年）的随访期间，642 例患者发生 ACS，409 例发生再狭窄（≥70%的至少一个之前治疗的冠状动脉节段），175 例死亡。sCD40L 每增加 1 个标准差（0.80ng/mL），ACS、再狭窄和死亡率的风险比（HRs）分别为 1.11（95%置信区间[CI]：1.05 至 1.18，p<0.0001）、1.10（95%CI：1.02 至 1.19，p=0.010）和 1.00（95%CI：0.86 至 1.16，p=0.983）。在多变量 Cox 回归模型中，调整了年龄、急性或慢性冠状动脉综合征、多血管疾病、支架置入、糖尿病、既往冠状动脉事件和血脂异常等多种潜在混杂因素后，sCD40L 仍然是 ACS 和冠状动脉再狭窄的独立预测因子。sCD40L 与急性或慢性冠状动脉综合征或支架置入之间无交互作用。
在接受 PCI 的 ACS 或 CCS 患者中，较高水平的 sCD40L 预示着急性冠状动脉事件和冠状动脉再狭窄的风险增加，但不预示死亡率增加。
