TABLE 3.
HRs (95% CIs) for stroke and nonstroke cases by baseline and 1-y changes in plasma metabolites (tryptophan, kynurenine, kynurenic acid, 3-HAA, and quinolinic acid) as continuous and categorical variables1
| Tryptophan | Kynurenine | Kynurenic acid | 3-HAA | Quinolinic acid | |
| Stroke | |||||
| Baseline2 | |||||
| Model 1, metabolite as continuous variable, per SD | |||||
| HR (95% CI) | 0.97 (0.76, 1.24) | 0.97 (0.79, 1.20) | 1.05 (0.87, 1.26) | 0.78 (0.61, 0.98) | 0.91 (0.72, 1.15) |
| P | 0.81 | 0.79 | 0.65 | 0.04 | 0.42 |
| Metabolite in Q categories as compared with Q1 (reference) | |||||
| Q2 | 0.68 (0.38, 1.22) | 0.87 (0.49, 1.54) | 1.43 (0.79, 2.61) | 0.67 (0.37, 1.21) | 0.81 (0.45, 1.46) |
| Q3 | 0.61 (0.34, 1.10) | 0.80 (0.46, 1.40) | 1.00 (0.54, 1.86) | 0.69 (0.37, 1.30) | 0.95 (0.55, 1.65) |
| Q4 | 0.95 (0.54, 1.66) | 0.89 (0.50, 1.57) | 1.16 (0.61, 2.18) | 0.63 (0.34, 1.17) | 0.96 (0.54, 1.72) |
| P-trend | 0.77 | 0.62 | 0.94 | 0.18 | 0.97 |
| Model 2, metabolite as continuous variable, per SD | |||||
| HR (95% CI) | 0.98 (0.71, 1.35) | 1.02 (0.82, 1.26) | 1.06 (0.83, 1.37) | 0.76 (0.57, 1.01) | 1.05 (0.81, 1.37) |
| P | 0.89 | 0.89 | 0.63 | 0.06 | 0.72 |
| Metabolite in Q categories as compared with Q1 (reference) | |||||
| Q2 | 0.73 (0.38, 1.41) | 1.22 (0.65, 2.30) | 1.43 (0.72, 2.82) | 0.56 (0.28, 1.12) | 0.93 (0.49, 1.75) |
| Q3 | 0.52 (0.25, 1.09) | 0.90 (0.48, 1.67) | 1.07 (0.52, 2.18) | 0.87 (0.42, 1.80) | 1.09 (0.58, 2.05) |
| Q4 | 0.96 (0.43, 2.16) | 1.13 (0.60, 2.12) | 1.19 (0.55, 2.61) | 0.52 (0.24, 1.12) | 1.26 (0.65, 2.47) |
| P-trend | 0.74 | 0.96 | 0.85 | 0.23 | 0.43 |
| 1-y changes3 | |||||
| Model 1, metabolite as continuous variable, per SD | |||||
| HR (95% CI) | 0.89 (0.70, 1.12) | 0.88 (0.66, 1.17) | 0.90 (0.71, 1.15) | 1.27 (0.93, 1.72) | 0.87 (0.69, 1.10) |
| P | 0.32 | 0.37 | 0.41 | 0.14 | 0.24 |
| Metabolite in Q categories as compared with Q1 (reference) | |||||
| Q2 | 1.51 (0.79, 2.90) | 0.64 (0.33, 1.26) | 0.46 (0.22, 0.99) | 1.65 (0.63, 4.31) | 1.11 (0.54, 2.27) |
| Q3 | 0.88 (0.43, 1.80) | 0.44 (0.20, 0.98) | 0.83 (0.41, 1.68) | 1.90 (0.68, 5.31) | 1.10 (0.54, 2.25) |
| Q4 | 0.84 (0.41, 1.70) | 0.67 (0.34, 1.31) | 0.59 (0.28, 1.23) | 1.79 (0.65, 4.92) | 0.85 (0.43, 1.70) |
| P-trend | 0.35 | 0.16 | 0.40 | 0.25 | 0.66 |
| Model 2, metabolite as continuous variable, per SD | |||||
| HR (95% CI) | 0.91 (0.70, 1.19) | 0.85 (0.63, 1.16) | 0.97 (0.72, 1.29) | 1.24 (0.90, 1.72) | 0.85 (0.66, 1.09) |
| P | 0.49 | 0.31 | 0.81 | 0.19 | 0.20 |
| Metabolite in Q categories as compared with Q1 (reference) | |||||
| Q2 | 1.60 (0.82, 3.16) | 0.59 (0.28, 1.25) | 0.44 (0.18, 1.04) | 1.30 (0.46, 3.74) | 1.03 (0.46, 2.29) |
| Q3 | 0.90 (0.42, 1.92) | 0.51 (0.23, 1.14) | 0.86 (0.38, 1.92) | 1.42 (0.41, 4.85) | 1.08 (0.49, 2.36) |
| Q4 | 0.89 (0.42, 1.92) | 0.56 (0.26, 1.18) | 0.71 (0.31, 1.58) | 1.55 (0.53, 4.56) | 0.78 (0.37, 1.63) |
| P-trend | 0.46 | 0.12 | 0.78 | 0.43 | 0.54 |
| Nonstroke | |||||
| Baseline4 | |||||
| Model 1, metabolite as continuous variable, per SD | |||||
| HR (95% CI) | 0.78 (0.63, 0.97) | 1.03 (0.85, 1.26) | 1.24 (1.02, 1.51) | 0.85 (0.69, 1.06) | 1.17 (0.92, 1.47) |
| P | 0.03 | 0.74 | 0.03 | 0.14 | 0.20 |
| Metabolite in Q categories as compared with Q1 (reference) | |||||
| Q2 | 1.20 (0.67, 2.16) | 0.80 (0.43, 1.50) | 1.50 (0.73, 3.09) | 1.04 (0.56, 1.91) | 1.05 (0.57, 1.95) |
| Q3 | 0.78 (0.42, 1.44) | 1.03 (0.58, 1.85) | 1.90 (0.96, 3.76) | 0.53 (0.26, 1.10) | 1.00 (0.54, 1.86) |
| Q4 | 0.58 (0.30, 1.11) | 0.94 (0.52, 1.71) | 2.02 (1.02, 3.97) | 0.74 (0.40, 1.40) | 1.48 (0.80, 2.73) |
| P-trend | 0.05 | 0.94 | 0.03 | 0.13 | 0.26 |
| Model 2, metabolite as continuous variable, per SD | |||||
| HR (95% CI) | 0.76 (0.54, 1.05) | 1.10 (0.87, 1.39) | 1.46 (1.12, 1.92) | 0.85 (0.66, 1.10) | 1.30 (0.97, 1.73) |
| P | 0.09 | 0.42 | 0.01 | 0.22 | 0.08 |
| Metabolite in Q categories as compared with Q1 (reference) | |||||
| Q2 | 1.16 (0.60, 2.26) | 1.26 (0.60, 2.65) | 1.77 (0.77, 4.08) | 0.99 (0.49, 2.00) | 1.12 (0.54, 2.35) |
| Q3 | 0.69 (0.33, 1.43) | 1.49 (0.75, 2.94) | 2.49 (1.10, 5.66) | 0.81 (0.36, 1.82) | 1.10 (0.53, 2.30) |
| Q4 | 0.52 (0.21, 1.29) | 1.33 (0.65, 2.74) | 2.89 (1.26, 6.65) | 0.74 (0.35, 1.60) | 2.05 (1.00, 4.21) |
| P-trend | 0.10 | 0.39 | 0.01 | 0.39 | 0.07 |
| 1-y changes5 | |||||
| Model 1, metabolite as continuous variable, per SD | |||||
| HR (95% CI) | 0.64 (0.48, 0.86) | 0.82 (0.62, 1.07) | 0.82 (0.65, 1.05) | 1.04 (0.76, 1.42) | 1.03 (0.79, 1.33) |
| P | 0.003 | 0.15 | 0.11 | 0.82 | 0.84 |
| Metabolite in Q categories as compared with Q1 (reference) | |||||
| Q2 | 0.93 (0.47, 1.84) | 0.94 (0.48, 1.81) | 1.69 (0.85, 3.36) | 1.59 (0.62, 4.11) | 0.59 (0.26, 1.37) |
| Q3 | 0.63 (0.31, 1.30) | 0.27 (0.11, 0.68) | 0.79 (0.34, 1.86) | 2.03 (0.76, 5.45) | 0.81 (0.36, 1.83) |
| Q4 | 0.22 (0.08, 0.56) | 0.64 (0.32, 1.28) | 0.79 (0.37, 1.70) | 1.19 (0.44, 3.21) | 0.90 (0.43, 1.88) |
| P-trend | 0.001 | 0.03 | 0.24 | 0.64 | 0.99 |
| Model 2, metabolite as continuous variable, per SD | |||||
| HR (95% CI) | 0.65 (0.46, 0.90) | 0.81 (0.60, 1.09) | 0.85 (0.64, 1.14) | 1.09 (0.78, 1.53) | 0.96 (0.71, 1.30) |
| P | 0.01 | 0.17 | 0.29 | 0.61 | 0.81 |
| Metabolite in Q categories as compared with Q1 (reference) | |||||
| Q2 | 0.84 (0.39, 1.84) | 0.98 (0.48, 2.00) | 2.14 (0.91, 5.04) | 1.30 (0.39, 4.36) | 0.59 (0.22, 1.57) |
| Q3 | 0.55 (0.24, 1.27) | 0.22 (0.07, 0.64) | 1.08 (0.39, 2.97) | 1.45 (0.40, 5.28) | 0.84 (0.30, 2.35) |
| Q4 | 0.19 (0.06, 0.61) | 0.62 (0.28, 1.36) | 0.98 (0.38, 2.51) | 1.20 (0.37, 3.88) | 0.74 (0.31, 1.77) |
| P-trend | 0.003 | 0.02 | 0.62 | 0.73 | 0.70 |
Model 1 was adjusted for age, sex, family history of coronary artery disease, smoking status, and BMI and was stratified by intervention group. Model 2 was adjusted as for model 1 plus for baseline hypertension, dyslipidemia, diabetes, and scores for BCAAs, acylcarnitines, and ceramides. For change analyses, metabolites were adjusted for baseline values. Q, quartile; 3-HAA, 3-hydroxyanthranilic acid.
Baseline analysis for stroke consisted of 872 participants and 118 cases for tryptophan (n = 36, 23, 24, and 35 cases for Q1–Q4, respectively), kynurenine (n = 33, 28, 26, and 31 cases for Q1–Q4, respectively), kynurenic acid (n = 25, 35, 27, and 31 cases for Q1–Q4, respectively) and quinolinic acid (n = 35, 23, 28, and 32 cases for Q1–Q4, respectively) and 804 participants and 103 cases for 3-HAA (n = 32, 25, 26, and 20 cases for Q1–Q4, respectively). Nonstroke cases are excluded.
One-year change analysis for stroke consisted of 835 participants and 86 cases for tryptophan (n = 19, 29, 20, and 18 cases for Q1–Q4, respectively), kynurenine (n = 28, 19, 14, and 25 cases for Q1–Q4, respectively), kynurenic acid (n = 29, 15, 24, and 18 cases for Q1–Q4, respectively), and quinolinic acid (n = 19, 23, 23, and 21 cases for Q1–Q4, respectively) and 692 participants and 63 cases for 3-HAA (n = 10, 16, 20, and 17 cases for Q1–Q4, respectively). Nonstroke cases are excluded.
Baseline analysis for nonstroke consisted of 868 participants and 113 cases for tryptophan (n = 27, 35, 26, and 25 cases for Q1–Q4, respectively), kynurenine (n = 28, 22, 31, and 32 cases for Q1–Q4, respectively), kynurenic acid (n = 17, 21, 35, and 40 cases for Q1–Q4, respectively) and quinolinic acid (n = 30, 23, 23, and 37 cases for Q1–Q4, respectively) and 800 participants and 100 cases for 3-HAA (n = 25, 33, 18, and 24 cases for Q1–Q4, respectively). Stroke cases are excluded.
One-year change analysis for nonstroke consisted of 825 participants and 76 cases for tryptophan (n = 25, 25, 19, and 7 cases for Q1–Q4, respectively), cases for kynurenine (n = 23, 24, 8, and 19 cases for Q1–Q4, respectively), 75 cases for kynurenic acid (n = 20, 28, 12, and 15 cases for Q1–Q4, respectively), and 74 cases for quinolinic acid (n = 22, 12, 18, and 22 cases for Q1–Q4, respectively) and 687 participants and 59 cases for 3-HAA (n = 12, 15, 20, and 12 cases for Q1–Q4, respectively). Stroke cases are excluded.