Abstract 5907: Tissue Inhibitors of Metalloproteinases (TIMPs) as Markers of Prognosis After Acute Myocardial Infarction
Background: Alterations in the balance of matrix metalloproteinase (MMP) to tissue inhibitor of metalloproteinase (TIMP) occur post AMI. The aim of this study was to investigate the relationship between TIMPs -1, −2 & −4 and Major Adverse Cardiac Events (MACE - Death, MI or Heart Failure) post AMI.
Methods: We investigated 1313 patients admitted with AMI prospectively. Plasma TIMP levels were measured prior to discharge. Subjects were followed for MACE over a median of 520 days.
Results: TIMPs correlated with age and were inversely correlated with eGFR (p<0.001). Levels were higher in females v males (p<0.001) and in subjects with diabetes (p<0.001) and hypertension (TIMP-1, p=0.031; TIMP-2 & −4 p<0.001). TIMP-1 and TIMP-4 (p<0.001) were higher in subjects with previous MI or Angina. Levels increased with quartiles of GRACE risk score (ANOVA, p<0.001). TIMPs were associated with MACE on uni-variable (logTIMP-1, HR 8.11; logTIMP-2, HR 22.2; logTIMP-4, HR 3.95, all p<0.001) and multi-variable (logTIMP-1, HR 2.2, p=0.017; logTIMP-2, HR 5.57, p<0.001; logTIMP-4, HR 1.85, p=0.011) analysis. The area under the curve of the receiver operator characteristic curve for MACE at 1 year was 0.657 for TIMP-1, 0.619 for TIMP-2 and 0.662 for TIMP-4 (all p<0.001). Combination of TIMPs with GRACE risk score revealed a greater AUC than GRACE score alone (0.722 v 0.694). On Kaplan Meier analysis the risk of MACE increased incrementally with the number of TIMPs above their respective median values (Log Rank:p<0.001 all comparisons - Fig⇓).
Conclusion: TIMPs -1, −2 and −4 are associated with MACE post AMI and give additional prognostic information than obtained from GRACE clinical risk scores alone.