| Variable | Odds Ratio (95% CI) for Quartiles of Metabolites Concentration | P for trend | Odds Ratio (95% CI) per 1-SD increment |
|---|
| 1 | 2 | 3 | 4 |
|---|
| Betaine |
| No. of controls | 62 | 62 | 61 | 62 | … | … |
| No. of cases | 59 | 45 | 53 | 97 | … | … |
| Model 1 a | Ref. | 0.69 (0.40–1.18) | 0.84 (0.50–1.43) | 1.43 (0.87–2.34) | 0.07 | 1.11(0.93–1.33) |
| Model 2 b | Ref. | 0.62 (0.35–1.07) | 0.76 (0.44–1.31) | 1.43 (0.87–2.36) | 0.07 | 1.12(0.93–1.35) |
| Model 3 c | Ref. | 0.63 (0.36–1.09) | 0.78 (0.45–1.34) | 1.41 (0.85–2.34) | 0.08 | 1.12(0.93–1.34) |
| Choline |
| No. of controls | 62 | 62 | 61 | 62 | … | … |
| No. of cases | 35 | 28 | 27 | 164 | … | … |
| Model 1 a | Ref. | 0.82 (0.44–1.53) | 0.70 (0.37–1.31) | 4.36 (2.61–7.38) | < 0.001 | 1.85(1.52–2.28) |
| Model 2 b | Ref. | 0.79 (0.42–1.47) | 0.58 (0.30–1.11) | 3.91 (2.33–6.65) | < 0.001 | 1.79(1.47–2.21) |
| Model 3 c | Ref. | 0.73 (0.39–1.39) | 0.55 (0.29–1.06) | 3.72 (2.21–6.34) | < 0.001 | 1.77(1.44–2.18) |
| TMA |
| No. of controls | 62 | 62 | 61 | 62 | … | … |
| No. of cases | 70 | 49 | 59 | 76 | … | … |
| Model 1 a | Ref. | 1.41 (0.85–2.34) | 0.94 (0.56–1.58) | 0.67 (0.39–1.15) | 0.02 | 1.11(0.92–1.34) |
| Model 2 b | Ref. | 1.53 (0.92–2.57) | 1.09 (0.64–1.85) | 0.76 (0.44–1.32) | 0.07 | 1.05(0.87–1.27) |
| Model 3 c | Ref. | 1.71 (1.01–2.91) | 1.26 (0.73–2.17) | 0.80 (0.46–1.40) | 0.09 | 1.10(0.90–1.33) |
| TMAO |
| No. of controls | 62 | 62 | 61 | 62 | … | … |
| No. of cases | 85 | 62 | 42 | 65 | … | … |
| Model 1 a | Ref. | 0.79 (0.47–1.35) | 0.95 (0.57–1.60) | 1.25 (0.75–2.08) | 0.37 | 0.87(0.72–1.05) |
| Model 2 b | Ref. | 0.70 (0.40–1.20) | 0.91 (0.54–1.53) | 1.01 (0.60–1.70) | 0.76 | 0.84(0.69–1.02) |
| Model 3 c | Ref. | 0.71 (0.41–1.23) | 0.94 (0.56–1.59) | 1.09 (0.64–1.85) | 0.56 | 0.80(0.65–0.97) |
| Metabolite Score |
| No. of controls | 62 | 62 | 61 | 62 | … | … |
| No. of cases | 41 | 26 | 59 | 128 | … | … |
| Model 1 a | Ref. | 1.10(0.60–2.03) | 1.65(0.93–2.97) | 3.65(2.14–6.32) | < 0.001 | 1.96(1.49–2.59) |
| Model 2 b | Ref. | 1.00(0.54–1.86) | 1.39(0.77–2.52) | 3.26(1.90–5.67) | < 0.001 | 1.85(1.40–2.45) |
| Model 3 c | Ref. | 1.00(0.54–1.86) | 1.35(0.75–2.46) | 3.18(1.85–5.54) | < 0.001 | 1.80(1.37–2.40) |
| Betaine/choline ratio |
| No. of controls | 62 | 62 | 61 | 62 | … | … |
| No. of cases | 160 | 39 | 24 | 31 | … | … |
| Model 1 a | Ref. | 0.23(0.14–0.39) | 0.16(0.09–0.29) | 0.19(0.11–0.31) | < 0.001 | 0.46(0.37–0.57) |
| Model 2 b | Ref. | 0.24(0.14–0.39) | 0.17(0.09–0.30) | 0.20(0.12–0.35) | < 0.001 | 0.48(0.39–0.59) |
| Model 3 c | Ref. | 0.24(0.14–0.41) | 0.17(0.09–0.30) | 0.21(0.12–0.36) | < 0.001 | 0.49(0.39–0.60) |
- The inverse normal transformation was applied to the raw values of metabolites. To build the score, we applied a weighted sum of concentrations of 4 metabolites in the choline pathway (betaine, choline, TMA, and TMAO). The ratio of betaine/choline was calculated by dividing the raw values and then applying the inverse normal transformations
- TMA trimethylamine, TMAO trimethylamine N-oxide. Ref., i.e., reference group, and we used participants assigned to the first quartile of the concentrations of each metabolite, the metabolite score and betaine to choline ratio, as the reference group in each model
- a in model 1, odds ratio was adjusted for age, sex, smoking index and body mass index;
- b in model 2, odds ratio was adjusted for all factors in model 1, plus history of the disease (i.e., hypertension, diabetes mellitus and hyperlipidemia);
- c in model 3, odds ratio was adjusted for all factors in model 2, plus kidney function measured by eGFR
