Table 2 Summary of selected literature relevant to biogenic amines in all-cause mortality prediction
First author, year, reference | Marker | Study type | Study population | Key findings | Limitations |
|---|---|---|---|---|---|
Böger et al., 2009, [77] | - ADMA | Observational, prospective cohort study (median follow-up of 10.9-year) | 3,319 middle-aged participants (Framingham Offspring Study) | - ADMA was positively associated with mortality (multivariable-adjusted HR 1.21, 95 % CI 1.07–1.37, p = 0.003) | - Only middle-aged subjects |
- L-arginine | |||||
- Arginin/ADMA-ratio was inversely associated with mortality (HR 0.80, 95 % CI 0.69–0.93, p = 0.004) | |||||
- Higher ADMA levels (p = 0.0002) and lower Arg/ADMA-ratios (p = 0.0005) were associated with elevated mortality in non-diabetic subjects | |||||
Pizzarelli et al., 2013, [78] | - ADMA | Single-center, prospective cohort study (median follow-up of 110 months) | 1,025 randomly selected adults (>65 years) living in Chianti area, Tuscany, Italy | - Plasma ADMA was a strong predictor of all-cause mortality (HR 1.26, 95 % CI 1.10–1.44, p < 0.001) and there was a non-significant trend for cardiovascular mortality (HR 1.22, p = 0.07) after multivariate adjusment | - Single-center study |
- L-arginine | - Only one ethnic population | ||||
- There was no association of ADMA with mortality in subjects with high L-arginine, but an increase in mortality in those with normal to low L-arginine | |||||
Siegerink et al., 2013, [79] | - ADMA | Multicenter, observational, prospective cohort study (median follow-up of 8.1 years) | 1,148 subjects suffering from myocardial infarction/ACS, or undergoing cardiac surgery due to CHD | - After adjustment for confounders higher levels of ADMA (HR 1.15, 95 % CI 0.95–1.37) and SDMA (HR 1.29, 95 % CI 1.09–1.52) were associated with an increase in all-cause mortality | - Selection bias |
- SDMA | - Only two-center study | ||||
(KAROLA Study, Germany) | |||||
Koch et al., 2013, [80] | ADMA | Single-center, observational prospective cohort study (3-year follow-up) | 255 ICU patients and 78 healthy controls living in Germany | - ICU patients had higher serum ADMA levels than healthy controls (median 0.48 vs. 0.36 μmol/L, p < 0.001) | - Short-term intensive care (<72 h) patients were excluded |
- ICU non-survivors had higher ADMA levels compared with ICU survivors (median 0.62 vs. 0.44 μmol/L, p < 0.001) | - Single-center study | ||||
- High ADMA levels predicted all-cause mortality in critically ill patients (p < 0.001) | |||||
- ADMA levels increased during 7 days of ICU therapy (p < 0.001) | |||||
Koch et al., 2013, [81] | SDMA | Single-center, observational prospective cohort study | 247 ICU patients and 84 healthy controls living in Germany | - ICU patients had higher serum SDMA levels than healthy controls (median 0.84 vs. 0.38 μmol/L, p < 0.001) | - Short-term intensive care (<72 h) excluded |
- ICU non-survivors had higher SDMA levels compared with ICU survivors (median 1.33 vs. 0.74 μmol/L, p = 0.001) | - Single-center study | ||||
(3-year follow-up) | - High SDMA levels predicted poorer long-term prognosis in critically ill patients (p < 0.001) | ||||
Gore et al., 2013, [82] | - SDMA | Observational prospective cohort study (median follow-up of 7.4 years) | 3,523 adults aged 30 to 65 years (Dallas Heart Study) | - After adjustment for cardiorenal indices, age, sex, race, NT-proBNP, hsCRP and Troponin, SDMA, but not ADMA, was associated with all-cause mortality (HR 1.86, 95 % CI 1.04–3.30, p = 0.01) | - Single blood sampling |
- ADMA | |||||
Suzuki et al., 2011, [85] | - Kynurenine | Single-center, observational prospective cohort study | 129 Japanese patients with CAP and 64 healthy controls | - CAP patients had elevated levels of Kyn (p < 0.0001) and reduced levels of Trp (p < 0.0001) compared with healthy controls and thus higher Kyn/Trp ratios (p < 0.0001) | - Single-center study |
- Tryptophan | - Small sample size | ||||
- No information about duration of follow-up | |||||
- Increasing severity of sepsis and CAP (PSI and CURB-65 score) was associated with higher Kyn levels, lower Trp levels and higher Kyn/Trp ratios. | |||||
- Non-survivors had higher Kyn levels (p = 0.023) and lower Trp levels (p = 0.032) and as a result, higher Kyn/Trp ratios (p = 0.005) | |||||
Darcy et al., 2011, [86] | - Kynurenine | Single-center, observational prospective cohort study | 50 patients from Australia with severe sepsis (organ dysfunction or shock), 30 with non-severe sepsis and 40 hospital controls | - Sepsis patients had elevated levels of Kyn (p < 0.0001) and reduced levels of Trp (p < 0.0001) and thus higher Kyn/Trp ratios (p < 0.0001) compared with hospital controls. | - Single-center study |
- Tryptophan | - Small sample size | ||||
- Kyn/Trp ratio was increased in severe sepsis compared with non-severe sepsis (p = 0.0006) | |||||
(28-day follow-up) | |||||
- Kyn/Trp ratio did not differ between survivors and non-survivors by day 28 of the study (p = 0.2) | |||||
Huttunen et al., 2010, [87] | - Kynurenine | Single-center, observational prospective cohort study (30-day follow-up) | 132 patients with bacteremia admitted to Tampere University Hospital in Finland | - Maximum Kyn/Trp ratios were significantly elevated in non-survivors (30-day case fatality) compared with survivors (193.7 vs. 82.4 μmol/mmol; p < 0.001) | - Small sample size |
- Tryptophan | - Single-center study | ||||
Qian et al., 2013, [92] | 3-nitrotyrosine | Single-center, observational prospective cohort study (90-day follow-up) | 158 patients with AKI, 12 critically ill patients without AKI, 15 healthy controls | - Patients with AKI had higher 3-NT/Tyr levels than healthy and critically ill controls (p < 0.001) | - Relatively small size study |
- Single-center study | |||||
- High 3-NT/Tyr was associated with higher 90-day mortality (p = 0.025) |