Table 3 Summary of selected literature relevant to trimethylamine-N-oxide in all-cause mortality prediction
First author, year, reference | Marker | Study type | Study population | Key findings | Limitations |
|---|---|---|---|---|---|
Tang et al.., 2015, [102] | TMAO | Single-center, prospective observational cohort-study (5-year follow-up) | 112 adults with stable but symptomatic chronic systolic HF (left ventricular ejection fraction ≤35 %) (Cleveland Clinic) | - After adjustment for age, eGFR, and NT-proBNP levels, higher TMAO levels were associated with poor prognosis (death/transplantation) (HR 1.46; 95 % CI 1.03-2.14; p = 0.03) | - Single-center study |
- Selection bias | |||||
- TMAO levels were higher in subjects with higher plasma NT-proBNP levels and NYHA functional class III or IV (p = 0.02) | |||||
Tang et al.,, 2013, [103] | TMAO | Single-center, prospective interventional study (9-day follow-up) | 40 healthy adults without chronic illnesses, active Infections or antibiotic therapy (Cleveland Clinic) | - Increasing plasma levels of TMAO after oral phosphatidylcholine challenge | - Small study population |
- Only healthy adults included | |||||
- In 6 adults, plasma levels of TMAO were markedly suppressed after a weekly therapy with broad-spectrum antibiotics and reappeared after withdrawal of antibiotics. | |||||
Tang et al., 2013, [103] | TMAO | Single-center, prospective observational cohort-study (3-year follow-up) | 4,007 adults undergoing elective diagnostic cardiac catheterization without evidence of an ACS (Cleveland Clinic) | - Elevated plasma levels of TMAO were associated with a higher risk of a major cardiovascular event after adjustment for traditional risk factors (p < 0.001) | - Single-center study |
- Selection bias | |||||
- Prognostic value of elevated plasma levels of TMAO remained significant in low-risk subgroups | |||||
Tang et al.., 2014, [101] | TMAO | Single-center, prospective observational cohort study (5-year follow-up) | 720 subjects with a history of HF (Cleveland Clinic) | - Subjects with HF (5.0 μmol) had higher median TMAO levels than subjects without HF (3.5 μmol; p < 0.001) | - Single-center study |
- Selection bias | |||||
- TMAO levels were predictive of 5-year mortality risk after adjustments for traditional risk factors, BNP levels and eGFR (HR 1.75; 95 % CI 1.07–2.86; p < 0.001) | |||||
Tang et al.., 2015, [100] | TMAO | Single-center, prospective observational cohort-study (5-year follow-up) | 521 subjects with CKD (eGFR < 60 mL/min) and 3,166 non-CKD subjects (Cleveland Clinic) | - TMAO levels were increased in CKD subjects (median, 7.9 μmol/L) compared with non-CKD subjects (median, 3.4 μmol/L), p < 0.001 | - No specific results for CKD stage 1-2 |
- Single-center study | |||||
- Higher TMAO levels (quartiles 4 versus 1) were associated with an increase in 5-year all-cause mortality in CKD subjects (HR 1.93; 95 % CI 1.13–3.29; p < 0.05) and non-CKD subjects after adjustment for traditional CVD risk factors and eGFR (HR 1.47; 95 % CI 1.02–3.29; p < 0.05) |