Sorathia Nilofer, Al-Rubaye Hussein, Zal Benham
Medipathways College London London, UK.
University of Buckingham Buckingham, UK.
Eur Cardiol. 2019 Jul 11;14(2):123-129. doi: 10.15420/ecr.2019.9.2. eCollection 2019 Jul.
Acute coronary syndrome (ACS) is characterised by increased effector cells and decreased regulatory T-cells (Tregs). Statins have been shown to be clinically beneficial in ACS patients. This effect could be mediated via the induction of Tregs in ACS patients. The aim of this systemic review and meta-analysis was to evaluate whether statin therapy enhances the frequency of Tregs determined by CD4+CD25+FOXP3+ in this subset of patients. A comprehensive search of PubMed and Embase was performed. Studies were restricted to randomised controlled trials that quantified CD4+CD25+FOXP3+ cell frequency by flow cytometric analysis before and after statin treatment in adults diagnosed with ACS. A minimum of at least two of the conventional markers to identify Tregs was compulsory. Four randomised controlled trials studies (439 participants) were included, all with low-to-moderate risk of bias. Pooled data showed a significant increase in Treg frequency after statin therapy in ACS patients. A further meta-regression and subgroup analysis also showed a negative dose-related effect, and a statin type-related effect (rosuvastatin versus atorvastatin), respectively. The results confirmed that statins positively alter the frequency of Tregs, which may indicate a potential mechanism of their therapeutic effect. However, there was a risk of information bias due to the markers used to identify Tregs, which was not fully explored, therefore, further randomised controlled trials should utilise markers of Tregs, such as the FOXP3 locus (Treg-specific demethylated region), for identification.
急性冠状动脉综合征（ACS）的特征是效应细胞增加和调节性T细胞（Tregs）减少。他汀类药物已被证明对ACS患者具有临床益处。这种作用可能是通过诱导ACS患者的Tregs来介导的。本系统评价和荟萃分析的目的是评估他汀类药物治疗是否能提高该亚组患者中由CD4 + CD25 + FOXP3 +确定的Tregs频率。对PubMed和Embase进行了全面检索。研究仅限于随机对照试验，这些试验通过流式细胞术分析对诊断为ACS的成年人在他汀类药物治疗前后的CD4 + CD25 + FOXP3 +细胞频率进行量化。必须至少使用两种传统标志物来识别Tregs。纳入了四项随机对照试验研究（439名参与者），所有研究的偏倚风险均为低到中度。汇总数据显示，ACS患者接受他汀类药物治疗后Tregs频率显著增加。进一步的荟萃回归和亚组分析分别显示出与剂量相关的负效应和与他汀类药物类型相关的效应（瑞舒伐他汀与阿托伐他汀）。结果证实，他汀类药物能积极改变Tregs的频率，这可能表明其治疗作用的潜在机制。然而，由于用于识别Tregs的标志物存在信息偏倚风险，且未得到充分探讨，因此，进一步的随机对照试验应使用Tregs的标志物，如FOXP3基因座（Treg特异性去甲基化区域）进行识别。
