Department of Medicine, Division of Cardiology (Z.A., J.H.K., M.G., K.M., B.L., A.M., A.J.S., M.S.H., V.V., A.A.Q.), Emory University School of Medicine, Atlanta, GA.
Department of Epidemiology (Z.A., J.H.K., M.G., K.M., B.L., S.S., J.A., A.J.S., B.D.P., V.V.), Rollins School of Public Health, Emory University, Atlanta, GA.
Arterioscler Thromb Vasc Biol. 2021 Nov;41(11):2814-2822. doi: 10.1161/ATVBAHA.121.316574. Epub 2021 Sep 23.
Circulating progenitor cells possess immune modulatory properties and might mitigate inflammation that is characteristic of patients with coronary artery disease. We hypothesized that patients with fewer circulating progenitor cells (CPCs) will have higher inflammatory markers and worse outcomes.
Patients with stable coronary artery disease were enrolled in a prospective study enumerating CPCs as CD (cluster of differentiation)-34-expressing mononuclear cells (CD34+) and inflammation as levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein) levels. Patients were followed for 5 years for the end points of death and myocardial infarction with repeat inflammatory biomarkers measured after a median of 2 years. In the entire cohort of 392 patients, IL-6 and high-sensitivity CRP levels remained unchanged (0.3+/-2.4 pg/mL and 0.1+/-1.0 mg/L; P=0.45) after 2 years. CPC counts (log-transformed) were inversely correlated with the change in IL-6 levels (r, -0.17; P<0.001). Using linear regression, IL-6 and high-sensitivity CRP levels declined by -0.59 (95% CI, -0.90 to -0.20) pg/mL and -0.13 (-0.28 to 0.01) mg/L per 1 log higher CPC counts after adjustment for the demographic and clinical variables, as well as medications. Using Cox models adjusted for these risk factors, a rise in 1 pg/mL of IL-6 was associated with a 11% (95% CI, 9-13) greater risk of death/myocardial infarction. We found that the change in IL6 level partly (by 40%) mediated the higher risk of adverse events among those with low CPC counts.
Reduced cardiovascular regenerative capacity is independently associated with progressive inflammation in patients with coronary artery disease that in turn is associated with poor outcomes.
循环祖细胞具有免疫调节特性，可能减轻冠心病患者特有的炎症。我们假设循环祖细胞（CPCs）较少的患者炎症标志物水平较高，预后较差。
稳定型冠心病患者参与了一项前瞻性研究，该研究通过 CD（分化簇）-34 表达的单核细胞（CD34+）计数来评估 CPCs，并通过白细胞介素（IL）-6 和高敏 C 反应蛋白（hsCRP）水平来评估炎症。中位随访 2 年后，在 392 例患者中，有 5 年的死亡和心肌梗死终点事件，再次测量炎症生物标志物。在整个队列中，IL-6 和 hsCRP 水平在 2 年后保持不变（0.3±2.4 pg/mL 和 0.1±1.0 mg/L；P=0.45）。CPC 计数（对数转换）与 IL-6 水平变化呈负相关（r，-0.17；P<0.001）。使用线性回归，在调整了人口统计学和临床变量以及药物治疗后，每增加 1 个对数 CPC 计数，IL-6 和 hsCRP 水平分别下降-0.59（95%CI，-0.90 至-0.20）pg/mL 和-0.13（-0.28 至 0.01）mg/L。使用 Cox 模型在这些危险因素调整后，IL-6 水平升高 1 pg/mL 与死亡/心肌梗死风险增加 11%（95%CI，9-13）相关。我们发现，IL6 水平的变化部分（40%）介导了 CPC 计数较低的患者不良事件风险的增加。
心血管再生能力下降与冠心病患者进行性炎症独立相关，而炎症又与不良预后相关。
