title: The value of N-terminal fragment of brain natriuretic peptide and tissue inhibitor of metalloproteinase-1 levels as predictors of cardiovascular outcome in the LIPID study.
abstract: OBJECTIVE
  We sought to determine the association between two major biomarkers, the inactive N-terminal fragment of brain natriuretic peptide (NT-proBNP) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and long-term cardiovascular outcomes in a cohort of subjects who had a myocardial infarction or unstable angina 3-36 months previously.
  
  
  RESULTS
  Plasma NT-proBNP and TIMP-1 were measured in a nested case control study of 250 randomly matched subject pairs enrolled in the long-term intervention with pravastatin in ischaemic disease (LIPID) and LIPID extended follow-up studies. Cases (n = 250) were defined as those who had a cardiovascular death, non-fatal myocardial infarction or stroke during the studies. Controls (n = 250) remained event-free for the same follow-up duration (average 2.5 years) as the matched cases. The relationships between cases and plasma NT-proBNP and TIMP-1 were adjusted for the LIPID risk score, treatment allocation and other biomarkers (CRP, IL-6 and white cell count), and examined using a multivariable conditional logistic regression model. NT-proBNP levels were significantly higher in the cases than in the controls [389 (152-864) vs. 198 (93-416) pg/mL, median (25%-75% percentiles), P < 0.001]. The odds ratio (OR) of recurrent cardiovascular events in individuals in the highest quartile was three times higher than those in the lowest quartile (95% confidence interval (CI) 1.8-5.1; P < 0.001). Similarly, TIMP-1 levels were significantly higher among cases compared with controls (806 vs. 736 pg/mL, median: highest vs. lowest quartile: OR 2.8, 95% CI 1.6-4.7; P < 0.001). After adjustment for the LIPID risk score, treatment with pravastatin and other biomarkers, both NT-proBNP and TIMP-1 predicted cardiovascular events significantly and independently of each other.
  
  
  CONCLUSIONS
  The study suggests that in subjects with stable ischaemic disease, NT-proBNP and TIMP-1 are independent predictive markers of coronary heart disease outcome.
authors.affiliation: University of Queensland, Brisbane, Australia.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: West
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Nestel
authors.forename: Adrienne C
authors.initials: AC
authors.lastname: Kirby
authors.forename: Renate
authors.initials: R
authors.lastname: Schnabel
authors.forename: David
authors.initials: D
authors.lastname: Sullivan
authors.forename: R John
authors.initials: RJ
authors.lastname: Simes
authors.forename: Christine
authors.initials: C
authors.lastname: Pollicino
authors.forename: Edith
authors.initials: E
authors.lastname: Lubos
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Münzel
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tonkin
authors.forename: Christoph
authors.initials: C
authors.lastname: Bickel
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiret
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
mesh_terms: D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000097:blood* / Q000188:drug therapy; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D017023:Coronary Angiography; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood* / Q000378:metabolism; D017035:Pravastatin / Q000627:therapeutic use; D011379:Prognosis; D012307:Risk Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; C079903:C-reactive protein (164-173); D010446:Peptide Fragments; D019715:Tissue Inhibitor of Metalloproteinase-1; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein; D017035:Pravastatin