title: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Medicine, State University of New York Health Science Center, Brooklyn, NY 11203-2098, USA.
authors.forename: Erdal
authors.initials: E
authors.lastname: Cavusoglu
authors.forename: Cyril
authors.initials: C
authors.lastname: Ruwende
authors.forename: Vineet
authors.initials: V
authors.lastname: Chopra
authors.forename: Sunitha
authors.initials: S
authors.lastname: Yanamadala
authors.forename: Calvin
authors.initials: C
authors.lastname: Eng
authors.forename: Luther T
authors.initials: LT
authors.lastname: Clark
authors.forename: David J
authors.initials: DJ
authors.lastname: Pinsky
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Marmur
mesh_terms: D000368:Aged; D015331:Cohort Studies; D017023:Coronary Angiography; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000401:mortality*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009026:Mortality; D009203:Myocardial Infarction / Q000209:etiology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9