Metabolomic profile associated with coronary artery disease: a higher level of indoleamine 2,3-dioxygenase activity and lower tryptophan concentrations predict a worse prognosis.

Abstract

Introduction: Metabolites can lead to novel discoveries in cardiovascular disease (CVD).

Objectives: The aim of the study was to investigate whether a metabolomic profile is associated with mortality in patients with coronary artery disease (CAD).

Methods: The study group consisted of 170 participants with CAD who were hospitalized due to acute coronary syndrome or elective percutaneous coronary intervention 12-26 months before evaluation (mean[SD] months, 16.3 [2.2]). A total of 132 metabolites were profiled by liquid chromatography-tandem mass spectrometry, and sums/ratios of 102 metabolite concentrations were calculated. Dates of death from all causes were obtained from the Polish Ministry of Digital Affairs.

Results: The median age of the group was 62 years (IQR 58-66), 68.8% (n=117) were male. The median follow-up time was 6.4 years (IQR 5.5-6.5). After adjustment for CVD risk factors affecting survival in the population analyzed (i.e. age, statin dose, current smoking, estimated glomerular filtration rate, and high-sensitivity C-reactive protein) with Bonferroni's correction, tryptophan (Trp) was negatively associated with death (HR = 0.558, 95%CI = 0.38-0.82, P = 0.003), whereas indoleamine 2,3-dioxygenase (IDO) activity level was positively associated with death (HR = 2.925, 95%CI = 1.71-5.01, P <0.001). Survival analysis showed that patients with IDO activity levels above he median had statistically worse survival than patients with lower activity levels (log-rank test, P = 0.009). In contrast, patients with Trp concentration below the median had worse survival than those with higher levels (log-rank test,  P = 0.03).

Conclusions: In patients with CAD, the increased IDO activity level predicts a worse long-term prognosis independently of known CVD risk factors.