Table 3.
Survival analysis for HFrH, the composite HFrH and/or CV death event and all-cause death
| Unadjusted model | Fully adjusted model | |||
|---|---|---|---|---|
| HR (95%CI) | P-value | HR (95%CI) | P-value | |
| Cause-specific HM for HFrH | ||||
| Carnitine | 1.20 [1.05; 1.37] | 0.0065 | 1.13 [0.99; 1.29] | 0.061 |
| Betaine | 1.34 [1.20; 1.50] | < 0.0001 | 1.11 [0.97; 1.27] | 0.13 |
| Choline | 1.35 [1.20; 1.52] | < 0.0001 | 0.94 [0.82; 1.08] | 0.39 |
| TMAO* | 1.32 [1.16; 1.50] | < 0.0001 | 1.09 [0.94; 1.26] | 0.24 |
| TMA | 1.01 [0.89; 1.15] | 0.86 | 0.98 [0.86; 1.13] | 0.78 |
| Cysteine | 1.38 [1.21; 1.58] | < 0.0001 | 1.10 [0.95; 1.28] | 0.20 |
| Homocysteine | 1.28 [1.17; 1.39] | < 0.0001 | 1.05 [0.91; 1.21] | 0.49 |
| Methionine | 1.02 [0.89; 1.18] | 0.73 | 1.06 [0.93; 1.22] | 0.38 |
| Cause-specific HM for HFrH and/or CV death | ||||
| Carnitine | 1.12 [1.01; 1.25] | 0.037 | 1.06 [0.95; 1.17] | 0.32 |
| Betaine | 1.27 [1.16; 1.40] | < 0.0001 | 1.04 [0.93; 1.17] | 0.46 |
| Choline | 1.28 [1.17; 1.42] | < 0.0001 | 0.91 [0.82; 1.02] | 0.093 |
| TMAO* | 1.31 [1.19; 1.45] | < 0.0001 | 1.10 [0.98; 1.23] | 0.11 |
| TMA | 1.02 [0.93; 1.13] | 0.65 | 0.99 [0.89; 1.10] | 0.81 |
| Cysteine | 1.31 [1.17; 1.46] | < 0.0001 | 1.04 [0.92; 1.18] | 0.49 |
| Homocysteine | 1.28 [1.20; 1.37] | < 0.0001 | 1.08 [0.97; 1.21] | 0.16 |
| Methionine | 0.96 [0.85; 1.08] | 0.46 | 1.00 [0.89; 1.11] | 0.93 |
| Cause-specific HM for all-cause death | ||||
| Carnitine | 1.05 [0.95; 1.15] | 0.32 | 1.01 [0.92; 1.11] | 0.84 |
| Betaine | 1.28 [1.18; 1.39] | < 0.0001 | 1.07 [0.97; 1.18] | 0.20 |
| Choline | 1.26 [1.16; 1.38] | < 0.0001 | 0.94 [0.85; 1.04] | 0.23 |
| TMAO* | 1.20 [1.10; 1.31] | < 0.0001 | 1.03 [0.94; 1.14] | 0.52 |
| TMA | 1.05 [0.97; 1.14] | 0.26 | 1.01 [0.93; 1.10] | 0.83 |
| Cysteine | 1.34 [1.22; 1.48] | < 0.0001 | 1.08 [0.97; 1.20] | 0.15 |
| Homocysteine | 1.30 [1.23; 1.38] | < 0.0001 | 1.16 [1.06; 1.27] | 0.0011 |
| Methionine | 0.96 [0.87; 1.06] | 0.37 | 0.98 [0.89; 1.07] | 0.66 |
*TMAO was natural-log transformed before standardization. Cause-specific hazard models were fitted using two adjustment models, unadjusted and fully adjusted. Covariates added in the fully adjusted models were age, sex, history of CAD, log transformed NT-proBPNP, eGFR and log transformed uACR. The nutritional biomarkers were tested separately from each other in the different adjustment models. All HR are given per 1 SD of the given parameter
Abbreviations: CV: cardiovascular; eGFR: estimated glomerular filtration rate calculated with the CKD-EPI 2009-formula; HFrH: Heart Failure requiring Hospitalization, defined as the first occurrence of acute HF leading to hospitalization and/or death; HM: Hazard model; HR: Hazard-ratio; NT-proBNP: N-terminal prohormone of brain natriuretic peptide; TMA: trimethylamine; TMAO: trimethylamine N-oxide; uACR: urine albumin/creatinine ratio