Table 1 The characteristics of the studies included in the systematic review of the association between TMAO and stroke
first author | Year/ country | Disease status | Total Num. of participants | Num. of categories/ num. Each group | Design | Sample source | TMAO μmol/ lit | Age range (y) | Male % | Main Results | Adjustments |
|---|---|---|---|---|---|---|---|---|---|---|---|
Zheng L et al. [16] | 2019/ North Korea | Community based general population | 192 | 4/86 | Nested case-control | Serum TMAO | CVD: 1.57 (0.79–2.29) μmol/L versus Control: 0.68 (0.23–1.40) μmol/L | ≥ 35 | 35.41 | The odds of CVD (defined as CHD+ stroke) at highest TMAO quartile was significantly higher than the lowest (OR 2.73 CI: 1.32–5.63) | SBP, BMI, use of anti-HTN, smoking, drinking, T2DM, TC, TG, HDL-C, eGFR |
Winther SA et al. [35] | 2019/ Denmark | Type1 Diabetes | 1159 | 4/ 290 | Cohort/ median 15 years follow-up | Plasma TMAO | 5.7 (3.8–9.9) | 46 ± 13 | 58% | The HR of relation between incident stroke and TMAO was 1.08 (0.93–1.27) P = 0.33 | age, sex, DM duration, HbA1c, SBP, TC, smoking, UAER |
Stubbs JR et al. [21] | 2019/ Baseline data of EVOLVE trial of 22 countries | Patients receiving maintenance hemodialysis | 1243 | 5/ 248 | Cross-sectional | Serum TMAO | 2.5–1103.1 | 54 ± 14 (50–60) | 60% | Higher prevalence of stroke in highest (11%) versus lowest (9%) TMAO quintiles; the HR/SHR of the plasma TMAO and stroke was OR:1.20 (CI: 0.88 to 1.64) | age, sex, BMI, SBP, albumin, race, dialysis-duration, smoking, CVD, history of coronary intervention, stroke, MI, BUN |
Rexidamu M et al. [20] | 2019/ China | Patients with first acute ischemic stroke | 510 | 2/ 255 | Case- control | Serum TMAO | Mean: 0.5–18.3 μM, Median: 5.8 (IQR: 3.3–10.0) | 65 (IQR: 57–71) | 53.3 | Mean serum TMAO in patients stroke was higher than controls (P < 0.001). The odds of severe stroke with TMAO levels was 1.22 CI:1.08–1.32) (P < 0.001) | Age, CRP, HCY and other factors |
Liang Z et al. [36] | 2018/ China | Patients with arterial fibrillation | 179 | 2 (68/111) | Case-control | Plasma TMAO | Stroke versus non-stroke (8.25 ± 1.58 μM versus 2.22 ± 0.09) | Stroke versus non stroke (68.0 ± 9.6; 64.1 ± 13.3) | 58.10 | Significantly higher plasma TMAO in stroke versus non-stroke; the odds ratio of association between TMAO and stroke was 4.934 (P < 0.001) | – |
Wu C et al. [9] | 2018/ China | Patient’s with CAS | 268 | 2 (117/ 151) | Cohort / 30 day follow up for developing new lesions | Plasma TMAO | New lesions versus non-new lesions median 5.2 versus 3.2 μmol/L | 64.4 | 56.7 | Higher risk of new ischemic brain lesions in highest versus lowest TMAO quartiles (OR: 3.85 (1.37–7.56) (P < 0.001) | Age, sex, symptomatic CAS%, CAS, SBP, FSG, LDL-C, HDL-C, hcys, % aortic arch III |
Nie J et al. [7] | 2018/ China | Incident stroke and matched control, using data from the CSPPT | 1244 | 2/ 622 | Nested case-control | Serum TMAO | Stroke: 2.5 (1.6–4.0) control: 2.3 (1.4–3.7) | (45–75) | 47% | Higher serum TMAO in patients with stroke compared with controls (2.5 versus 2.3 μmol/L) and higher odds of stroke in highest versus lowest TMAO tertile (OR:1.43 (1.02–2.01) P = 0.04 | SBP, BMI, FSG, TC, eGFR, hcys, folate, smoking, time-averaged SBP in treatment period, choline, L carnitine |
Haghikia A et al. [37] | 2018/ Germany | Patients with incident stroke | 78 | 4/20 | Cohort / 1 year follow-up | Plasma TMAO | – | 59 ± 14 | 69% | Higher odds of incident CVD event (including stroke) in highest versus lowest TMAO quartile OR: 2.31; 95% CI, 1.25–4.23; P < 0.01 | Age, sex, HTN, T2DM, LDL-C, smoking |
Haghikia A et al. [37] | 2018/ Germany | Patients with incident stroke | 593 | 4/148 | Cohort / 1 year follow-up | Plasma TMAO | – | 67 ± 13 | 61% | Higher odds of incident CVD event (including stroke) in highest versus lowest TMAO quartile OR: 3.3; 95% CI, 1.2–10.9; P = 0.04) | age, sex, HTN, T2DM, LDL, smoking |
Tang WHW et al. [32] | 2017/ USA | Patients with T2DM | 1216 | 3 /401 | Cohort / 5 years follow-up | Plasma TMAO | 4.4 (2.8–7.7) | 64.4 ± 10.2 | 58% | Significantly higher prevalence of stroke history in highest versus lowest TMAO tertiles (12% versus 5%; P = 0.002). Increased odds of major adverse cardiac risk including stroke in highest versus lowest TMAO tertiels (OR: 1.94 (1.23–3.05) P < 0.001) | Age, gender, history of CVD, history of HF, SBP, LDL-C, HDL-C, smoking, BMI, hsCRP, HbA1C, eGFR. |
Li X et al. [38] | 2017/ USA | Patinets with CVD (Cleveland acute coronary syndrome cohort) | 530 | 2 (220/ 310) | Cohort /7 years follow-up | Plasma TMAO | 4.28 (2.55–7.91) | 62.4 ± 13.9 | 57.5 | Higher plasma TMAO in patients with adverse cardiac events (including stroke) compared without (5.09 versus 3.73); P < 0.001 | Age, gender, HDL-C, LDL-C, smoking, history of DM, HTN, CAD, CRP, eGFR, troponin T, STEMI, NSTEMI or unstable angina |
Li X et al. [38] | 2017/ USA | Patients with CVD (Swiss ACS cohort) | 1683 | 2 (190/ 1493) | Cohort/ 7 years follow-up | Plasma TMAO | 2.87 (1.94–4.85) | 63.9 ± 12.4 | 77.8 | Higher plasma TMAO in patients with adverse cardiac events (including stroke) compared without (3.75 versus 2.80); P < 0.001 | Age, gender, HDL-C, LDL-C, smoking, history of DM, HTN, revas-cularization or CAD, CRP, eGFR, troponin T, STEMI, NSTEMI or unstable angina |
Guasch-Ferre M et al. [22] | 2017/ USA | Patients with CVD | 980 | 4/ 245 | Case-cohort | Plasma TMAO | – | 55–80 | 46.12 | No significant association between HR of stroke in TMAO tertiels (P = 0.31) | Age, sex, family history of CVD, smoking, BMI, PA, HTN, T2DM |
Mafune A et al. [13] | 2016/ Japan | Patients underwent CVD surgeries | 227 | 4/ 56–57 | Cross-sectional | Serum TMAO | 0.09 to 141.2 | 68 | 70 | No significant difference in prevalence of stroke between quartiles of TMAO (P = 0.49) | – |
Yin J et al. [15] | 2015/ China | Patients with ischemic or TIA stroke | 551 | 2 (322/ 231) | Case- control | Plasma TMAO | Stroke versus controls (2.70; 1.91) | 18–80 | 63.70 | Plasma TMAO was lower in patients with stroke compared with controls (P < 0.001) | – |
Tang WHW et al. [39] | 2013/ USA | Patients underwent CABG | 4007 | 2 (513/3494) | Cohort/ 3 years follow-up | Plasma TMAO | 3.7 (2.4–6.2) | 63 | 64 | Plasma TMAO was significantly higher in patients with adverse events (including stroke) compared with controls (P < 0.001); increased odds of events in forth quartiles versus first (1.43 (1.05–1.94)) | Age, sex, smoking status, SBP, LDL-C, HDL-C, DM, hs-CRP, myeloperoxidase level, eGFR, WBC-count, BMI, medications (aspirin, statin, ACE inhibitor, ARB, or beta-blocker, extent of disease |