Matrix metalloproteinases and their inhibitors have been implicated in both vascular and ventricular remodeling, and in atherosclerotic plaque rupture. The prognostic value of plasma tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in patients with established or suspected coronary artery disease is unknown.Methods
Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 (MMP-9) levels, along with a number of other established biomarkers, were measured in 389 male patients undergoing coronary angiography at a Veterans Administration Medical Center. The patients were then followed prospectively for the occurrence of all-cause mortality, cardiac mortality, and myocardial infarction (MI).Results
Follow-up data at 24 months were available for 97% of the patients. For the entire cohort of patients, TIMP-1 was the only biomarker to independently predict all-cause mortality and MI. In addition, the ratio of TIMP-1 to matrix metalloproteinase-9 was independently predictive of cardiac mortality at 24 months. The 24-month survival rates for patients in the lower quartile (<66.5 ng/mL), interquartile (66.5–100 ng/mL), and upper quartile (>100 ng/mL) of plasma TIMP-1 values were 95.3%, 89.3%, and 72.2%, respectively (P < .001). Furthermore, when patients with chest pain were risk stratified into those with and without an acute coronary syndrome, TIMP-1 remained an independent predictor of all-cause mortality in both subgroups.Conclusions
In a cohort of male patients undergoing coronary angiography, a single baseline determination of plasma TIMP-1 is independently predictive of the subsequent risk of death and MI.