Department of Internal Medicine IV, Saarland University Medical Center, Homburg/Saar, Germany.
J Am Coll Cardiol. 2012 Oct 16;60(16):1512-20. doi: 10.1016/j.jacc.2012.07.019. Epub 2012 Sep 19.
The aim of this study was to analyze the yet ill-defined relationship of distinct human monocyte subsets with cardiovascular outcomes in a broad patient population at cardiovascular risk.
Monocytes, the most abundant immune cell type found in atherosclerotic plaques, are crucial promoters of atherogenesis. Three distinct human monocyte subsets exist: classical CD14++CD16-, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes. Immunomodulation of distinct monocyte subsets has recently been discussed as a new therapeutic avenue in atherosclerosis.
Cardiovascular events in 951 subjects referred for elective coronary angiography were prospectively analyzed. Monocyte subset analysis was performed using flow cytometry, blinded to patients' clinical characteristics, and patients were categorized according to quartiles of total monocyte and monocyte subset counts. The primary endpoint was defined a priori as the first occurrence of cardiovascular death, acute myocardial infarction, or nonhemorrhagic stroke. Endpoint adjudication was done blinded to monocyte subset distribution.
During a mean follow-up period of 2.6 ± 1.0 years, 93 patients experienced the primary endpoint. In univariate Kaplan-Meier analysis, counts of total (p = 0.010), classical CD14++CD16- (p = 0.024), and intermediate CD14++CD16+ (p < 0.001) monocytes predicted the primary endpoint, whereas nonclassical monocytes did not (p = 0.158). After full adjustment for confounders, CD14++CD16+ monocytes remained the only monocyte subset independently related to cardiovascular events (fourth vs. first quartile: hazard ratio: 3.019; 95% confidence interval: 1.315 to 6.928; p = 0.009).
CD14++CD16+ monocytes independently predicted cardiovascular events in subjects referred for elective coronary angiography. Future studies will be needed to elucidate whether CD14++CD16+ monocytes may become a target cell population for new therapeutic strategies in atherosclerosis.
本研究旨在分析在心血管风险患者中广泛人群中，不同的人单核细胞亚群与心血管结局之间尚未明确的关系。
单核细胞是动脉粥样斑块中最丰富的免疫细胞类型，是动脉粥样形成的关键促进者。存在三种不同的人单核细胞亚群：经典 CD14++CD16-，中间 CD14++CD16+和非经典 CD14+CD16++单核细胞。最近，人们讨论了对不同单核细胞亚群进行免疫调节作为动脉粥样硬化的一种新的治疗途径。
前瞻性分析了 951 例因选择性冠状动脉造影而转介的患者的心血管事件。使用流式细胞术进行单核细胞亚群分析，分析过程对患者的临床特征进行盲法处理，并根据总单核细胞和单核细胞亚群计数的四分位数将患者进行分类。主要终点预先定义为首次发生心血管死亡、急性心肌梗死或非出血性中风。终点裁决对单核细胞亚群分布进行盲法处理。
在平均 2.6±1.0 年的随访期间，93 例患者发生了主要终点。在单变量 Kaplan-Meier 分析中，总计数（p=0.010）、经典 CD14++CD16-（p=0.024）和中间 CD14++CD16+（p<0.001）单核细胞计数预测了主要终点，而非经典单核细胞则没有（p=0.158）。在充分调整混杂因素后，CD14++CD16+单核细胞仍然是唯一与心血管事件独立相关的单核细胞亚群（第四与第一四分位：风险比：3.019；95%置信区间：1.315 至 6.928；p=0.009）。
在因选择性冠状动脉造影而转介的患者中，CD14++CD16+单核细胞独立预测了心血管事件。未来的研究将需要阐明 CD14++CD16+单核细胞是否可能成为动脉粥样硬化新治疗策略的靶细胞群。
