Abstract 12428: Matrix Metalloproteinase-9/Tissue Inhibitor of Matrix Metalloproteinase-1 Ratio is Associated with the Severity and Major Adverse Cardiovascular Event in Patients with Systolic Heart Failure
INTRODUCTION: Matrix metalloproteinase (MMP) species are upregulated in the failing human heart and influenced ventricular remodeling. We assessed the hypothesis that disparity between MMP-9 and tissue inhibitors of MMP-1 (TIMP-1) is associated with the clinical manifestation and is related to prognostic risk in patients with systolic heart failure.
METHODS: Circulating levels of MMP-9, TIMP-1 and B-type natriuretic peptide were measured in 173 heart failure patients with reduced left ventricular ejection fraction<50% and New York Heart Association class I-IV. Major adverse cardiovascularc event (MACE) was assessed during the follow-up period (average of 88 ± 49 months).
RESULTS: MMP-9/TIMP-1 ratio increased with the severity of New York Heart Association functional class (rs = 0.28, P = 0.003). Patients who had MACE had higher values of MMP-9/TIMP-1 (0.62 ± 0.19 versus 0.32 ± 0.04, P = 0.033). During the follow-up period, 44 patients had MACE. Kaplan-Meier analysis demonstrated a higher probability of MACE in the high values (>0.30) of MMP-9/TIMP-1 group (P = 0.016). Risk ratio of increased MMP-9/TIMP-1 ratio was 2.22 (95% CI 1.24-3.98) for MACE compared with low MMP-9/TIMP-1 ratio group. In the setting of combination of MMP-9/TIMP-1 ratio and B-type natriuretic peptide, even in lower B-type natriuretic peptide (<240 pg/mL) group, the risk ratio of high MMP-9/TIMP-1 ratio was 2.70 (95% CI 1.22-5.99) for MACE compared with low B-type natriuretic peptide and low MMP-9/TIMP-1 ratio group.
CONCLUSIONS: MMP-9/TIMP-1 ratio positively correlates with the severity of New York Heart Association class and the high value of MMP-9/TIMP-1 is associated with MACE in heart failure. MMP-9/TIMP-1 ratio allows further risk stratification, suggesting the disparity between MMP-9 and TIMP-1 contribute to the occurrence of MACE in patients with heart failure and systolic dysfunction.
- © 2011 by American Heart Association, Inc.