Association Between Increased Levels of Cystatin C and the Development of Cardiovascular Events or Mortality: A Systematic Review and Meta-Analysis

Abstract Background: Cystatin C seems promising for evaluating the risk of cardiovascular events and mortality. Objective: To evaluate the association between high levels of cystatin C and the development of cardiovascular events or mortality. Methods: The articles were selected in the Medline/PubMed, Web of Science, and Scielo databases. The eligibility criteria were prospective cohort observational trials that assessed the association of high serum levels of cystatin C with the development of cardiovascular events or mortality in individuals with normal renal function. Only studies that evaluated the mortality outcome compared the fourth with the first quartile of cystatin C and performed multivariate Cox’s proportional hazard regression analysis were included in the meta-analysis. A p value < 0,05 was considered significant. Results: Among the 647 articles found, 12 were included in the systematic review and two in the meta-analysis. The risk of development of adverse outcomes was assessed by eight studies using the hazard ratio. Among them, six studies found an increased risk of cardiovascular events or mortality. The multivariate regression analysis was performed by six studies, and the risk of developing adverse outcomes remained significant after the analysis in four of these studies. The result of the meta-analysis [HR = 2.28 (1.70-3.05), p < 0.001] indicated that there is a significant association between high levels of cystatin C and the risk of mortality in individuals with normal renal function. Conclusion: There is a significant association between high levels of cystatin C and the development of cardiovascular events or mortality in individuals with normal renal function.

摘要 背景：胱抑素C（cystatin C）在评估心血管事件及死亡风险方面展现出良好应用前景。目的：评估高浓度胱抑素C与心血管事件发生或死亡风险之间的关联。方法：文献检索范围涵盖Medline/PubMed、Web of Science及Scielo数据库。纳入标准为：针对肾功能正常人群的前瞻性队列观察性研究，用于评估血清高浓度胱抑素C与心血管事件发生或死亡风险的关联；且仅纳入将胱抑素C第四分位数与第一分位数进行对比，并通过多变量Cox比例风险回归分析评估死亡结局的研究。以p值<0.05为差异具有统计学意义。结果：初检出文献共647篇，最终12篇纳入系统评价，2篇纳入荟萃分析。8项研究采用风险比（hazard ratio, HR）评估不良结局发生风险，其中6项研究发现受试者心血管事件或死亡风险升高。6项研究开展了多变量回归分析，其中4项经校正后不良结局发生风险仍具有统计学意义。荟萃分析结果显示[HR=2.28，95%置信区间1.70~3.05，p<0.001]，表明肾功能正常人群中高浓度胱抑素C与死亡风险存在显著关联。结论：肾功能正常人群中，高浓度胱抑素C与心血管事件发生或死亡风险存在显著关联。