祖细胞与急性冠状动脉综合征患者的临床结局。
Progenitor Cells and Clinical Outcomes in Patients With Acute Coronary Syndromes.
机构信息
From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.).
Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.).
出版信息
Circ Res. 2018 May 25;122(11):1565-1575. doi: 10.1161/CIRCRESAHA.118.312821. Epub 2018 Mar 7.
RATIONALE
Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS).
OBJECTIVE
We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS.
METHODS AND RESULTS
In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, =0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS.
CONCLUSIONS
CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.
背景
循环祖细胞（CPCs）在缺血损伤时动员，但它们在急性冠状动脉综合征（ACS）中的预测价值尚不清楚。
目的
我们旨在研究 ACS 患者与稳定型冠状动脉疾病（CAD）患者之间的 CPC 数量、骨髓 PCs 与 CPCs 之间的关系，以及 CPC 计数是否可预测 ACS 患者的死亡率。
方法和结果
在 2028 例患者中，346 例为不稳定型心绞痛，183 例为急性心肌梗死（AMI），其余 1499 例为稳定型 CAD。ACS 患者随访主要终点为全因死亡。通过流式细胞术对单核细胞表达的 CD34+、CD133+、血管内皮生长因子受体 2+或趋化因子（C-X-C 基序）受体 4+进行 CPC 计数。即使在调整年龄、性别、种族、体重指数、肾功能、高血压、糖尿病、高脂血症和吸烟后，AMI 患者的 CPC 计数仍高于稳定型 CAD 患者；与稳定型 CAD 相比，AMI 患者的 CD34+、CD34+/CD133+、CD34+/CXCR4+和 CD34+/VEGFR2+CPC 计数分别高 19%、25%、28%和 142%。20 例 AMI 患者骨髓抽吸物中 CPC 浓度与 PCs 浓度之间存在很强的相关性。在 529 例 ACS 患者为期 2 年（四分位距，1.31-2.86）的随访期间，有 12.4%的患者死亡。在 Cox 回归模型中，调整年龄、性别、体重指数、心力衰竭史、估计肾小球滤过率和 AMI 后，CD34+细胞计数低的患者全因死亡率增加 2.46 倍（95%置信区间，1.18-5.13），=0.01。CD34+/CD133+和 CD34+/CXCR4+，但不是 CD34+/VEGFR2+CPC 计数，与死亡率有类似的相关性。在另一项 238 例 ACS 患者的队列研究中验证了这些结果。
结论
AMI 后患者的 CPC 水平明显高于稳定型 CAD 患者，反映了骨髓 PCs 含量。在 ACS 患者中，造血丰富的 CPC 数量较少与死亡率升高相关。
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