Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Am J Cardiol. 2011 Nov 1;108(9):1362-70. doi: 10.1016/j.amjcard.2011.06.054. Epub 2011 Aug 17.
Inflammation predicts risk for cardiovascular disease (CVD) events, but the relation of drugs that directly target inflammation with CVD risk is not established. Methotrexate is a disease-modifying antirheumatic drug broadly used for the treatment of chronic inflammatory disorders. A systematic review and meta-analysis of evidence of relations of methotrexate with CVD occurrence were performed. Cohorts, case-control studies, and randomized trials were included if they reported associations between methotrexate and CVD risk. Inclusions and exclusions were independently adjudicated, and all data were extracted in duplicate. Pooled effects were calculated using inverse variance-weighted meta-analysis. Of 694 identified publications, 10 observational studies in which methotrexate was administered in patients with rheumatoid arthritis, psoriasis, or polyarthritis met the inclusion criteria. Methotrexate was associated with a 21% lower risk for total CVD (n = 10 studies, 95% confidence interval [CI] 0.73 to 0.87, p <0.001) and an 18% lower risk for myocardial infarction (n = 5, 95% CI 0.71 to 0.96, p = 0.01), without evidence for statistical between-study heterogeneity (p = 0.30 and p = 0.33, respectively). Among prespecified sources of heterogeneity explored, stronger associations were observed in studies that adjusted for underlying disease severity (relative risk 0.64, 95% CI 0.43 to 0.96, p <0.01) and for other concomitant medication (relative risk 0.73, 95% CI 0.63 to 0.84, p <0.001). Publication bias was potentially evident (funnel plot, Begg's test, p = 0.06); excluding studies with extreme risk estimates did not, however, alter results (relative risk 0.81, 95% CI 0.74 to 0.89). In conclusion, methotrexate use is associated with a lower risk for CVD in patients with chronic inflammation. These findings suggest that a direct treatment of inflammation may reduce CVD risk.
炎症可预测心血管疾病 (CVD) 事件的风险，但直接针对炎症的药物与 CVD 风险的关系尚未确定。甲氨蝶呤是一种广泛用于治疗慢性炎症性疾病的疾病修饰抗风湿药物。对评估甲氨蝶呤与 CVD 发生关系的证据进行了系统评价和荟萃分析。如果报告了甲氨蝶呤与 CVD 风险之间的关联，则将队列研究、病例对照研究和随机试验纳入研究。独立裁决纳入和排除标准，并对所有数据进行了重复提取。使用倒数方差加权荟萃分析计算汇总效应。在 694 篇已识别的文献中，有 10 项观察性研究符合纳入标准，这些研究在类风湿关节炎、银屑病或多关节炎患者中使用了甲氨蝶呤。甲氨蝶呤与总 CVD 的风险降低 21%相关（n = 10 项研究，95%置信区间 [CI] 0.73 至 0.87，p <0.001），与心肌梗死的风险降低 18%相关（n = 5 项研究，95%CI 0.71 至 0.96，p = 0.01），且无统计学异质性（p = 0.30 和 p = 0.33）。在探索的预定异质性来源中，在调整潜在疾病严重程度（相对风险 0.64，95%CI 0.43 至 0.96，p <0.01）和其他同时使用的药物（相对风险 0.73，95%CI 0.63 至 0.84，p <0.001）的研究中，相关性更强。发表偏倚可能明显（漏斗图，Begg 检验，p = 0.06）；但是，排除风险估计极端的研究并没有改变结果（相对风险 0.81，95%CI 0.74 至 0.89）。总之，在患有慢性炎症的患者中，使用甲氨蝶呤与 CVD 风险降低相关。这些发现表明，直接治疗炎症可能会降低 CVD 风险。
