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

INTRODUCTION

Metabolite profiling can lead to novel discoveries in cardiovascular disease (CVD) physiology.

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 hospitalized for acute coronary syndrome or elective percutaneous coronary intervention 12-26 months (mean [SD], 16.3 [2.2] months) before evaluation. 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 a registry of the Polish Ministry of Digital Affairs.

RESULTS

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

CONCLUSIONS

In patients with CAD, increased IDO activity predicts worse long‑term prognosis independently of known CVD risk factors.