Zhang Quan, Ding Huiqing, Dai Zhongling, Yang Rukai, Zhou Shenghua, Tai Shi
Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
BMC Cardiovasc Disord. 2025 Feb 19;25(1):116. doi: 10.1186/s12872-025-04543-9.
The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway is closely associated with myocardial infarction (MI). Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) is a key component of this pathway; however, there is currently a lack of clinical evidence linking plasma cGAMP levels to MI.
This study utilized clinical data from 270 patients diagnosed with coronary heart disease (CHD) at the Second Xiangya Hospital of Central South University. The outcomes included ST-segment elevation and non-ST-segment elevation MI. Univariate and multivariate logistic regression models were used to explore the relationships between plasma cGAMP levels and MI, while restricted cubic spline (RCS) using logistic regression to explore the dose-response relationship.
Among the 270 patients, the mean plasma cGAMP level was 1352.58 ± 106.02 ng/L and 89 (32.96%) patients were diagnosed with MI. The RCS curves indicated a U-shape association between the cGAMP levels and MI; the risk of MI was negatively correlated with the cGAMP until it hit bottoms at 1352 ng/L. When the cGAMP level exceeded 1352 ng/L, the risk of MI increased significantly (adjusted OR, 1.02; 95% CI: 1.01-1.03). When considering cGAMP as a categorical variable, patients in Tertile 1 and Tertile 3 had a 167% (adjusted OR: 2.67, 95% CI: 1.23-5.78) and 155% (adjusted OR: 2.55, 95% CI: 1.17-5.55) higher risk of MI compared to those in Tertile 2, respectively. These results were consistent across subgroup analyses, notably, a significant interaction by age category was observed in patients with cGAMP ≥ 1352 ng/L, where the positive association was pronounced in the elderly.
A U-shaped association exists between cGAMP and MI in the CHD population, with a cutoff point at the cGAMP of 1352 ng/L. Both excessively high and low cGAMP levels are associated with an increased risk of MI, particularly among the elderly with cGAMP ≥ 1352 ng/L. This is the first clinical evidence of the cGAS-cGAMP-STING pathway in metabolic cardiovascular diseases.
NCT03363035 (Registration date: 2018-01-15).
环磷酸鸟苷 - 环磷酸腺苷合成酶 - 干扰素基因刺激因子（cGAS - STING）信号通路与心肌梗死（MI）密切相关。环磷酸鸟苷 - 环磷酸腺苷（cGAMP）是该通路的关键组成部分；然而，目前缺乏将血浆cGAMP水平与MI相关联的临床证据。
本研究利用了中南大学湘雅二医院270例诊断为冠心病（CHD）患者的临床数据。结局包括ST段抬高型和非ST段抬高型MI。采用单因素和多因素逻辑回归模型探讨血浆cGAMP水平与MI之间的关系，同时使用逻辑回归的受限立方样条（RCS）来探讨剂量反应关系。
在270例患者中，血浆cGAMP平均水平为1352.58±106.02 ng/L，89例（32.96%）患者被诊断为MI。RCS曲线表明cGAMP水平与MI之间呈U形关联；MI风险与cGAMP呈负相关，直到在1352 ng/L时达到最低点。当cGAMP水平超过1352 ng/L时，MI风险显著增加（调整后的OR为1.02；95%CI：1.01 - 1.03）。将cGAMP视为分类变量时，与第二三分位数的患者相比，第一三分位数和第三三分位数的患者发生MI的风险分别高167%（调整后的OR：2.67，95%CI：1.23 - 5.78）和155%（调整后的OR：2.55，95%CI：1.17 - 5.55）。这些结果在亚组分析中是一致的，值得注意的是，在cGAMP≥1352 ng/L的患者中观察到按年龄分类的显著交互作用，其中在老年人中这种正相关关系更为明显。
在冠心病患者中，cGAMP与MI之间存在U形关联，cGAMP的截断点为1352 ng/L。过高和过低的cGAMP水平均与MI风险增加相关，特别是在cGAMP≥1352 ng/L的老年人中。这是cGAS - cGAMP - STING通路在代谢性心血管疾病中的首个临床证据。
NCT03363035（注册日期：2018年1月15日）。
