Abstract 9131: Clinical, Biochemical and Genetic Predictors of Late Coronary Artery Bypass Graft Failure

Abstract

BACKGROUND: We tested the hypothesis that known clinical and biochemical risk factors for atherosclerosis have prognostic promise as novel biochemical markers to predict coronary artery bypass graft (CABG) failure . We also utilized a high-throughput microarray analysis to identify novel single nucleotide polymorphisms (SNPs) genetic predictors of graft failure and to better understand the pathogenesis of graft occlusion. METHODS AND RESULTS: This is a nested case-control sub-study of the Radial Artery Patency Study (RAPS) 5 year follow-up ( NCT00187356 ). Between June 1996 and January 2001, 87 patients underwent CABG. Of these, 26 patients (29.9%) had an occluded study graft (saphenous vein graft or radial artery) at angiographic follow-up (8.0±1.1 years). Clinical parameters as well as late angiography and concurrent blood biomarker analysis and surgical outcomes data were included in a multivariable analysis to determine independent predictors of graft failure. Risk factors of long term graft failure were fibrinogen (OR 3.94; 95%CI [1.33-11.63], p=0.01), creatinine (OR 1.06; 95%CI [1.02-1.10], p=0.006) and diabetes mellitus (OR 5.15; 95%CI [1.08-24.59], p=0.04). Interestingly, HDL (OR 0.74, 95%CI [0.53-1.02], p=0.06) was weakly protective against long term graft failure but other lipid markers, LDL and total cholesterol were not predictors. We identified the association of several human single nucleotide polymorphisms with graft failure including a novel link with mutations in glutathione-s-tranferase α3 . Human coronary arteries and bypass grafts demonstrated increased GSTα3 expression in atherosclerotic plaques and in tissues surrounding occluded saphenous vein grafts. CONCLUSION: We identify diabetes to be a clinical predictor and plasma fibrinogen, creatinine and HDL as potential novel biomarkers which, together may help to risk stratify patients for development of graft failure. We further demonstrate a novel association between GSTα3 and graft failure, a potential pathogenetic mechanism of saphenous vein graft occlusion.