title: Clinical, biochemical, and genetic predictors of coronary artery bypass graft failure.
abstract: OBJECTIVE
  To identify novel predictors for coronary artery bypass grafting failure, we probed for associations with known clinical and biochemical risk factors for atherosclerosis. We also used microarray analysis to identify novel single nucleotide polymorphisms to better understand the genetics and pathogenesis of graft occlusion.
  
  
  METHODS
  The present study was a nested case-control substudy of the Radial Artery Patency Study 5-year follow-up data. From 1996 to 2001, 87 patients underwent coronary artery bypass grafting. Of these, 26 patients (29.9%) had an occluded study graft (saphenous vein or radial artery) at 8.0 ± 1.1 years. The clinical parameters, late angiography, blood biomarker levels, and surgical outcomes data were included in a multivariate analysis to determine the independent predictors of graft failure.
  
  
  RESULTS
  The risk factors of graft failure were fibrinogen (odds ratio [OR], 3.94; 95% confidence interval [CI], 1.33-11.63; P = .01), creatinine (OR, 1.06; 95% CI, 1.02-1.10; P = .006), and diabetes mellitus (OR, 5.15; 95% CI, 1.08-24.59; P = .04). High-density lipoprotein (OR, 0.74; 95% CI, 0.53-1.02; P = .06) was weakly protective; however, low-density lipoprotein and total cholesterol were not predictors. We then identified the association of several human single nucleotide polymorphisms with graft failure, including mutations in glutathione-S-transferase α3. Human coronary arteries and bypass grafts demonstrated increased protein expression of glutathione-S-transferase α3, a known cardioprotective factor, in the atherosclerotic regions and surrounding adventitial tissues.
  
  
  CONCLUSIONS
  We identified diabetes as a potential clinical predictor and plasma fibrinogen, creatinine, and high-density lipoprotein as potential novel biomarkers. These might help risk stratify patients for the development of graft failure. We also demonstrated a novel association between glutathione-S-transferase α3 and graft failure.
authors: Division of Cardiac Surgery, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Bobby
authors: B
authors: Yanagawa
authors: Division of Cardiac Surgery, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; King Fahad Cardiac Center, King Saud University, Riyadh, Saudi Arabia.
authors: Khaled D
authors: KD
authors: Algarni
authors: Hamilton Health Sciences Centre, Hamilton, Ontario, Canada.
authors: Steve K
authors: SK
authors: Singh
authors: Division of Cardiac Surgery, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Saswata
authors: S
authors: Deb
authors: Division of Cardiac Surgery, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Jessica
authors: J
authors: Vincent
authors: Division of Cardiac Surgery, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Randi
authors: R
authors: Elituv
authors: Penn Heart and Vascular Center, Perelman Center for Advanced Medicine, Philadelphia, Pa.
authors: Nimesh D
authors: ND
authors: Desai
authors: Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, British Columbia, Canada.
authors: Karthikeyan
authors: K
authors: Rajamani
authors: Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, British Columbia, Canada.
authors: Bruce M
authors: BM
authors: McManus
authors: Division of Cardiology, Toronto General Hospital, Toronto, Ontario, Canada.
authors: Peter P
authors: PP
authors: Liu
authors: Division of Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Eric A
authors: EA
authors: Cohen
authors: Division of Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Sam
authors: S
authors: Radhakrishnan
authors: Division of Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors: James D
authors: JD
authors: Dubbin
authors: Division of Cardiology, Toronto General Hospital, Toronto, Ontario, Canada.
authors: Leonard
authors: L
authors: Schwartz
authors: Division of Cardiac Surgery, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address: stephen.fremes@sunnybrook.ca.
authors: Stephen E
authors: SE
authors: Fremes
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood*; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005982:Glutathione Transferase / Q000235:genetics*; D006083:Graft Occlusion, Vascular / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017211:Treatment Failure; D014654:Vascular Patency / Q000235:genetics
chemical_list: D015415:Biomarkers; D008075:Lipoproteins, HDL; D005340:Fibrinogen; D003404:Creatinine; D005982:Glutathione Transferase