Introduction
Materials and methods
Measurement of high-sensitivity troponin T (hs-TnT) and high-sensitivity C-reactive protein (hs-CRP)
Liquid chromatography–mass spectrometry (LC–MS) analysis of L-tryptophan (L-Trp) and L-kynurenine (L-Kyn)
Statistical analysis
Results
Recruitment and baseline characteristics
Characteristics | N = 305 |
---|---|
Age (years) | 63.7 ± 10.0 |
Male sex | 187 (61.3%) |
Creatinine (mg/dL) | 1.07 (0.34, 10.15) |
hs-TnT (ng/l) | 13.20 (3.09, 294.20) |
hs-CRP (mg/l) | 1.47 (0.15, 130.05) |
Kynurenine (µM) | 4.94 (0.00, 11,731.00) |
Tryptophan (µM) | 36.99 (0.00, 43,111.29) |
IDO activity | 0.14 (0.00, 4.58) |
Diabetes | 134 (43.9%) |
Hypertension | 272 (89.2%) |
Dyslipidemia | 233 (76.4%) |
Recent ACS | |
STEMI | 31 (10.2%) |
Non STEMI | 53 (17.4%) |
Unstable angina | 14 (4.6%) |
Stable CAD | 114 (37.4%) |
Other (Pre-op valvular HD / HF / Reduced EF) | 93 (30.5%) |
Ischemic stroke | 13 (4.3%) |
Peripheral vascular disease | 14 (4.6%) |
Current medications | |
ASA | 269 (88.2%) |
Plavix | 183 (60.0%) |
Beta blockers | 245 (80.3%) |
Statin | 258 (84.6%) |
Baseline coronary angiography | |
Nonsignificant CAD | 78 (25.6%) |
Single-vessel disease | 81 (26.6%) |
Double-vessel disease | 66 (21.6%) |
Triple-vessel disease | 80 (26.2%) |
Treatment following baseline coronary angiography | |
Medication only | 123 (40.3%) |
PCI | 145 (47.5%) |
CABG | 37 (12.1%) |
Cutoff point of baseline IDO activity, kynurenine, and hs-TnT levels for predicting significant coronary artery disease (CAD)
IDO activity
hs-TnT levels
Clinical endpoints based on baseline demographic and biomarkers
Parameters | Survived (n = 293) | Died (n = 12) | p-value |
---|---|---|---|
All patients (N = 305) | |||
Baseline hs-TnT | 12.96 (3.09, 294.20) | 15.89 (10.41, 61.03) | 0.154 |
Baseline Kynurenine | 5.07 (0.00, 11,731.00) | 0.79 (0.00, 32.84) | 0.082 |
Baseline IDO activity | 0.15 (0.00, 4.58) | 0.02 (0.00, 0.79) | 0.081 |
Insignificant CAD/SVD patients (n = 159) | Survived (n = 155) | Died (n = 4) | |
---|---|---|---|
Baseline hs-TnT | 11.53 (3.09, 141.50) | 13.24 (12.89, 16.92) | 0.492 |
Baseline Kynurenine | 4.68 (0.00, 7892.33) | 0.38 (0.00, 0.82) | 0.037 |
Baseline IDO activity | 0.13 (0.00, 4.13) | 0.01 (0.00, 0.02) | 0.040 |
DVD/TVD patients (n = 146) | Survived (n = 138) | Died (n = 8) | |
---|---|---|---|
Baseline hs-TnT | 15.93 (4.53, 294.20) | 17.63 (10.41, 61.03) | 0.355 |
Baseline Kynurenine | 5.58 (0.00, 11,731.00) | 2.28 (0.39, 32.84) | 0.380 |
Baseline IDO activity | 0.16 (0.00, 4.58) | 0.06 (0.01, 0.79) | 0.380 |
Parameters | No event (n = 274) | Combined events (n = 17) | p-value |
---|---|---|---|
All patients (N = 291) | |||
Baseline hs-TnT | 12.88 (3.09, 294.20) | 16.92 (8.28, 124.90) | 0.038 |
Baseline Kynurenine | 5.23 (0.00, 11,731.00) | 1.97 (0.00, 32.84) | 0.036 |
Baseline IDO activity | 0.15 (0.00, 4.58) | 0.05 (0.00, 2.91) | 0.159 |
Insignificant CAD/SVD patients (n = 152) | No event (n = 146) | Combined events (n = 6) | |
---|---|---|---|
Baseline hs-TnT | 11.59 (3.09, 141.50) | 15.13 (12.89, 124.90) | 0.111 |
Baseline Kynurenine | 4.94 (0.00, 7892.33) | 0.38 (0.00, 4.45) | 0.017 |
Baseline IDO activity | 0.14 (0.00, 4.13) | 0.01 (0.00, 0.14) | 0.023 |
DVD/TVD patients (n = 139) | No event (n = 128) | Combined events (n = 11) | |
---|---|---|---|
Baseline hs-TnT | 15.05 (4.53, 294.20) | 17.13 (8.28, 61.03) | 0.290 |
Baseline Kynurenine | 5.70 (0.00, 11,731.00) | 4.37 (0.38, 32.84) | 0.264 |
Baseline IDO activity | 0.16 (0.00, 4.58) | 0.12 (0.01, 2.91) | 0.767 |
Limitations of IDO in detected significant CAD
Insignificant CAD (n = 78) | Significant CAD (n = 227) | p-value | |
---|---|---|---|
All patients (n = 305) | |||
Baseline Kynurenine | 2.74 (0.00, 70.58) | 5.36 (0.00, 11,731.00) | 0.007 |
Baseline IDO activity | 0.03 (0.00, 3.78) | 0.16 (0.00, 4.58) | 0.001 |
Excluded pre-op for VHD (n = 279) | n = 59 | n = 220 | |
---|---|---|---|
Baseline Kynurenine | 1.00 (0.00, 70.58) | 5.37 (0.00, 11,731.00) | 0.005 |
Baseline IDO activity | 0.02 (0.00, 3.78) | 0.16 (0.00, 4.58) | 0.001 |
In presence of HF (n = 66) | n = 41 | n = 25 | |
---|---|---|---|
Baseline Kynurenine | 4.97 (0.00, 70.58) | 1.21 (0.00, 44.63) | 0.358 |
Baseline IDO activity | 0.09 (0.00, 3.78) | 0.03 (0.00, 1.22) | 0.512 |
Excluded HF (n = 239) | n = 37 | n = 202 | |
---|---|---|---|
Baseline Kynurenine | 0.82 (0.00, 42.74) | 5.62 (0.00, 11,731.00) | 0.002 |
Baseline IDO activity | 0.01 (0.00, 1.28) | 0.17 (0.00, 4.58) | < 0.001 |
In presence of DM (N = 134) | n = 25 | n = 109 | |
---|---|---|---|
Baseline Kynurenine | 4.60 (0.00, 34.41) | 4.90(0.00, 11,731.00) | 0.276 |
Baseline IDO activity | 0.11 (0.00, 0.71) | 0.15 (0.00, 3.71) | 0.107 |
Excluded DM (n = 171) | n = 53 | n = 118 | |
---|---|---|---|
Baseline Kynurenine | 1.84 (0.00, 70.58) | 5.73(0.00, 10,639.00) | 0.009 |
Baseline IDO activity | 0.02 (0.00, 3.78) | 0.16 (0.00, 4.58) | 0.002 |