Metabolic profiles predict adverse events after coronary artery bypass grafting.
OBJECTIVE
Clinical models incompletely predict the outcomes after coronary artery bypass grafting. Novel molecular technologies can identify biomarkers to improve risk stratification. We examined whether metabolic profiles can predict adverse events in patients undergoing coronary artery bypass grafting.


METHODS
The study population comprised 478 subjects from the CATHGEN biorepository of patients referred for cardiac catheterization who underwent coronary artery bypass grafting after enrollment. Targeted mass spectrometry-based profiling of 69 metabolites was performed in frozen, fasting plasma samples collected before surgery. Principal components analysis and Cox proportional hazards regression modeling were used to assess the relation between the metabolite factor levels and a composite outcome of postcoronary artery bypass grafting myocardial infarction, the need for percutaneous coronary intervention, repeat coronary artery bypass grafting, and death.


RESULTS
During a mean follow-up period of 4.3 ± 2.4 years, 126 subjects (26.4%) experienced an adverse event. Three principal components analysis-derived factors were significantly associated with an adverse outcome on univariate analysis: short-chain dicarboxylacylcarnitines (factor 2, P = .001); ketone-related metabolites (factor 5, P = .02); and short-chain acylcarnitines (factor 6, P = .004). These 3 factors remained independently predictive of an adverse outcome after multivariate adjustment: factor 2 (adjusted hazard ratio, 1.23; 95% confidence interval, 1.10-1.38; P < .001), factor 5 (odds ratio, 1.17; 95% confidence interval, 1.01-1.37; P = .04), and factor 6 (odds ratio, 1.14; 95% confidence interval, 1.02-1.27; P = .03).


CONCLUSIONS
Metabolic profiles are independently associated with adverse outcomes after coronary artery bypass grafting. These profiles might represent novel biomarkers of risk that can augment existing tools for risk stratification of coronary artery bypass grafting patients and might elucidate novel biochemical pathways that mediate risk.
Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Asad A
AA
Shah
Damian M
DM
Craig
Jacqueline K
JK
Sebek
Carol
C
Haynes
Robert C
RC
Stevens
Michael J
MJ
Muehlbauer
Christopher B
CB
Granger
Elizabeth R
ER
Hauser
L Kristin
LK
Newby
Christopher B
CB
Newgard
William E
WE
Kraus
G Chad
GC
Hughes
Svati H
SH
Shah
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D001026:Coronary Artery Bypass / Q000009:adverse effects* / Q000401:mortality; D003324:Coronary Artery Disease / Q000097:blood / Q000601:surgery*; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007659:Ketones / Q000097:blood; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000209:etiology; D009657:North Carolina; D016017:Odds Ratio; D025341:Principal Component Analysis; D016016:Proportional Hazards Models; D012086:Reoperation; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D007659:Ketones; C116917:acylcarnitine; D002331:Carnitine