Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Am J Cardiol. 2010 Aug 15;106(4):477-82. doi: 10.1016/j.amjcard.2010.03.060.
Alterations in the balance of matrix metalloproteinase to tissue inhibitor of metalloproteinase (TIMP) are seen after acute myocardial infarction (AMI) and are associated with adverse left ventricular remodeling and prognosis in this setting. We aimed to investigate the association between TIMP levels and the occurrence of major adverse cardiac events (MACEs) after AMI. We measured plasma TIMP-1, -2, and -4 levels in 1,313 patients presenting with AMI. Subjects were followed over a median period of 520 days for the occurrence of MACEs. Clinical risk was assessed using the Global Registry of Acute Coronary Events (GRACE) score. All TIMP levels correlated with patient age and inversely with estimated glomerular filtration rate (all p values <0.001). Levels were higher in women versus men (p <0.001) and in subjects with a history of diabetes (TIMP-1, p <0.001; TIMP-2, p = 0.002; TIMP-4, p <0.001) or hypertension (TIMP-1, p = 0.031; TIMP-2, p <0.001; TIMP-4, p <0.001). TIMP-1 and TIMP-4 were higher in subjects with previous MI or angina (p <0.001). TIMP levels increased incrementally with quartiles of GRACE score (p <0.001). All TIMPs showed univariate association with the occurrence of MACEs (p <0.001). Areas under the receiver operator characteristic curve for prediction of MACE at 1 year were 0.61 for TIMP-1, 0.57 for TIMP-2, and 0.64 for TIMP-4. Combination of TIMPs with GRACE risk score revealed a greater area under the curve than GRACE score alone (0.72 vs 0.69, p = 0.0015). On multivariable Cox proportional hazards analysis, GRACE score (p <0.001) and plasma TIMPs (log TIMP-1, p = 0.017; log TIMP-2, p <0.001; log TIMP-4, p = 0.011) independently predicted MACEs. Using Kaplan-Meier analysis, the risk of MACEs increased incrementally with the number of TIMPs above their respective median (p <0.001 for all comparisons, log-rank test). In conclusion, higher plasma TIMP-1, -2, and -4 after AMI are associated with MACEs and provide additional prognostic information to that obtained from GRACE clinical risk scores alone.
心肌梗死后，基质金属蛋白酶（MMP）与组织金属蛋白酶抑制剂（TIMP）的平衡发生改变，与这种情况下的不良左心室重构和预后相关。我们旨在研究 TIMP 水平与心肌梗死后主要不良心脏事件（MACE）发生之间的关系。我们测量了 1313 例心肌梗死患者的血浆 TIMP-1、-2 和-4 水平。在中位时间为 520 天的时间内，对患者进行了 MACE 发生的随访。使用全球急性冠状动脉事件登记处（GRACE）评分评估临床风险。所有 TIMP 水平均与患者年龄相关，与估算肾小球滤过率呈负相关（所有 p 值均<0.001）。女性的水平高于男性（p<0.001），且女性有糖尿病史（TIMP-1，p<0.001；TIMP-2，p=0.002；TIMP-4，p<0.001）或高血压史（TIMP-1，p=0.031；TIMP-2，p<0.001；TIMP-4，p<0.001）。TIMP-1 和 TIMP-4 在有既往 MI 或心绞痛的患者中更高（p<0.001）。TIMP 水平随 GRACE 评分四分位数递增而递增（p<0.001）。所有 TIMP 在单变量分析中均与 MACE 的发生相关（p<0.001）。预测 1 年 MACE 的受试者工作特征曲线下面积为 TIMP-1 为 0.61，TIMP-2 为 0.57，TIMP-4 为 0.64。TIMP 与 GRACE 风险评分的组合比 GRACE 评分单独显示出更大的曲线下面积（0.72 与 0.69，p=0.0015）。多变量 Cox 比例风险分析显示，GRACE 评分（p<0.001）和血浆 TIMP（logTIMP-1，p=0.017；logTIMP-2，p<0.001；logTIMP-4，p=0.011）独立预测 MACE。使用 Kaplan-Meier 分析，MACE 的风险随 TIMP 高于中位数的数量而递增（所有比较的 log-rank 检验均<0.001）。总之，心肌梗死后血浆中较高的 TIMP-1、-2 和-4 与 MACE 相关，并为仅基于 GRACE 临床风险评分获得的预后信息提供了额外的信息。
