The Long-Term Influence of Tissue Inhibitor of Matrix Metalloproteinase-1 in Patients with Mild to Moderate Coronary Artery Lesions in a Chinese Population: A 7-Year Follow-Up Study

Abstract

Objectives: Matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and their ratio (MMP-9/TIMP-1) are involved in multiple processes that are associated with coronary heart disease and are especially associated with cardiovascular events. However, few long-term population-based clinical studies have evaluated the role of these factors in cardiovascular events in a Chinese population. Methods: A prospective study was performed on 560 patients with mild to moderate coronary artery lesions. MMP-9, TIMP-1 and their ratio were determined. Results: A total of 522 of patients completed the follow-up. The median follow-up time was 64 months. Kaplan-Meier analysis demonstrated a clear increase of the incidence of major adverse cardiac events (MACEs) during the follow-up period in subjects with above-median levels of TIMP-1 (p = 0.033), whereas there was no association with either MMP-9 (p = 0.199) or MMP-9/TIMP-1 (p = 0.631). Multivariate Cox proportional hazards analysis showed the same results after further adjustment for covariates. Patients with above-median levels of TIMP-1 were more likely to suffer from adverse outcomes than patients with below-median levels of TIMP-1. However, the lack of relationship of MACEs with MMP-9 and MMP-9/TIMP-1 remained. Conclusions: Higher circulating TIMP-1 concentrations were associated with cardiovascular events during long-term follow-up of Chinese patients with mild to moderate coronary artery lesions.

MMP-9 and Its Regulators TIMP-1 and EMMPRIN in Patients with Acute ST-Elevation Myocardial Infarction: A NORDISTEMI Substudy

“…MMP-9 levels have previously been associated with clinical events in numerous reports [25,28], although some of these are contradictory [29]. In our study, circulating MMP-9 levels and the MMP-9/TIMP-1 ratios were numerically, but not significantly, higher in patients experiencing clinical events during follow-up.…”

“…We have previously shown that genetically determined high circulating levels of MMP-9 were associated with new clinical events in patients with stable coronary artery disease and the metabolic syndrome [30]. TIMP-1 has previously been associated with clinical outcome in Caucasians with AMI and in a Chinese population with coronary artery lesions [15,29]. …”

“…The observed high MMP-9/TIMP-1 ratio post-AMI may indicate an imbalance between the markers, possibly leading to vulnerable plaques and future cardiovascular events, to our knowledge, only rarely and contradictorily reported [29]. …”

Tissue Inhibitor of Metalloproteinase-1: Actions beyond Matrix Metalloproteinase Inhibition

“…In the manuscript that is the focus of this editorial, Wang and colleagues investigated whether plasma MMP-9 and TIMP-1 levels as well as the MMP-9/TIMP-1 ratio could be used as biomarkers to predict future cardiovascular events in Chinese patients with mild to moderate coronary artery stenosis [3]. Immediately after diagnosis, plasma levels of MMP-9 and TIMP-1 were measured, and the patients were followed for a median of 64 months.…”

“…Of note, TIMP-1 suppresses microvascular endothelial cell migration through both MMP-dependent and MMP-independent mechanisms [11]. The MMP independent roles of TIMP-1 may, at least partially, explain why TIMP-1, but not MMP-9, independently predicted MACEs risk in the Wang et al study [3]. …”