Table 1.
Prospective studies about TMAO and adverse outcomes.
| Year | N | Follow-Up | Outcomes | Covariates in the Adjusted Models | Hazard Ratio (95% CI) and p Value | Ref. |
|---|---|---|---|---|---|---|
| Individuals free of known CVD: community-based population | ||||||
| 2013 | 4007 | 3 years | MACE | 1: age, sex, smoking status, SBP, LDLc, HDLc, diabetes, CRP 2: model 1 + myeloperoxidase level, eGFR, total white-cell count, BMI, medication 3: model 2 + extent of the disease |
UA: 2.54 (1.96–3.28) p < 0.001 1: 1.88 (1.44–2.44) p < 0.001 2: 1.49 (1.10–2.03) p = 0.01 3: 1.43 (1.05–1.94) p = 0.02 |
[45] |
| 2021 | 4131 | 15 years | ASCVD | Age, sex, race, study site, education, income, health status, smoking status, alcohol intake, physical activity, BMI, WC, lipid-lowering medication, antihypertensive medication, antibiotics, T2D, HDL-C, LDL-C, TG, CRP, SBP, DBP, diet, eGFR | Adj: 1.07 (0.90–1.27) p = 0.516 Adj: 1.37 (0.98–1.90) p = 0.084 (individuals with eGFR < 60 mL/min 1.73 m2) Adj: 0.98 (0.80–1.20) p = 0.903 (individuals with eGFR ≥ 60 mL/min 1.73 m2) |
[34] |
| 2022 | 5333 | 13.2 years | All-cause mortality Cardiovascular mortality Non-cardiovascular mortality |
1: age, sex, race, and enrollment site 2: model 1 + education, household income, smoking, BMI, physical activity, treated hypertension, instrumental activities of daily living, self-reported health status, systolic blood pressure, HDL cholesterol, prevalent atrial fibrillation, prevalent coronary heart disease, myocardial infarction, prevalent diabetes, prevalent chronic obstructive pulmonary disease, and reported daily intake of eggs, fish, liver, non-processed red meat, processed meat, and total calories 3: model 2 + eGFR |
1: 1.36 (1.24–1.51) p < 0.001 2: 1.30 (1.17–1.44) p < 0.001 3: 1.07 (0.96–1.19) p = 0.51 1: 1.50 (1.27–1.77) p < 0.0001 2: 1.35 (1.14–1.60) p < 0.0001 3: 1.09 (0.91–1.30) p = 0.65 1: 1.29 (1.14–1.46) p < 0.0001 2: 1.27 (1.12–1.44) p = 0.0003 3: 1.06 (0.93–1.21) p = 0.61 |
[32] |
| 2022 | 6393 | 10.5 years | All-cause mortality Cardiovascular mortality Non-cardiovascular mortality |
1: age and sex 2: model 1 + HT, diabetes mellitus, total cholesterol, smoking, BMI, and eGFR |
UA: 3.07 (2.48–3.80) p < 0.001 1: 1.09 (0.88–1.37) p = 0.43 2: 1.11 (0.88–1.40) p = 0.38 UA: 3.75 (2.56–5.49) p < 0.001 1: 1.13 (0.77–1.70) p = 0.54 2: 0.97 (0.65–1.46) p = 0.88 UA: 2.77 (2.14–3.60) p < 0.001 1: 1.07 (0.82–1.40) p = 0.64 2: 1.17 (0.88–1.54) p = 0.28 |
[33] |
| Patients with CVD or CAD | ||||||
| 2015 | 339 | 8 years | MACE | eGFR | UA: 1.01 (0.98–1.04) p = 0.493 Adj: 0.991 (0.98–1.00) p = 0.062 |
[26] |
| 2016 | 2235 | 5 years | All-cause mortality | 1: age, sex, SBP, LDL-C, HDL-C, smoking, and diabetes mellitus 2: model 1 + hsCRP and eGFR 3: model 2 + medications (angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, β-blocker, aspirin, or statin), number of stenotic vessels, myeloperoxidase, and BNP |
UA: 3.90 (2.78–5.48) p < 0.0001 1: 2.61 (1.82–3.76) p < 0.0001 2: 1.95 (1.33–2.86) p = 0.003 3: 1.71 (1.11–2.61) p = 0.0138 |
[36] |
| 2021 | 1287 | 15 years | ASCVD | Age, sex, race, study site, education, income, health status, smoking status, alcohol intake, physical activity, BMI, WC, lipid-lowering medication, antihypertensive medication, antibiotics, T2D, HDL-C, LDL-C, TG, CRP, SBP, DBP, diet, eGFR | 1.10 (0.87–1.39) p = 0.179 | [34] |
| 2021 | 449 | 9 years | All-cause mortality | 1: BMI, diabetes status, eGFR 2: model 1 + age, sex, smoking status, SBP, DBP, hsCRP, HDL-C, LDL-C, white blood cell count, and in LIFE-CAD additionally for presence of CAD |
UA: 1.61 (1.36–1.92) p < 0.001 1: 1.30 (1.07–1.58) p = 0.009 2: 1.24 (1.01–1.51) p = 0.040 |
[35] |
| 2022 | 1726 | 5 years | All-cause mortality Cardiovascular mortality AMI |
1: age, gender, and history of CAD 2: pre-defined patient characteristics, cardiovascular risk factors, and medical history, including age, gender, body mass index, smoking history, positive cardiovascular family history, hypertension, hypercholesterolemia, history of diabetes, history of stroke, history of CAD, previous AMI, history of heart failure and adjudicated functionally relevant coronary artery disease* Both models also adjusted adding Cystatin-C |
UA: 1.42 (1.29–1.58) p < 0.001 1: 1.28 (1.13–1.43) p < 0.001 1 *: 1.16 (1.03–1.30) p = 0.013 2: 1.23 (1.09–1.38) p < 0.001 2 *: 1.11 (0.99–1.26) p = 0.084 UA: 1.60 (1.39–1.84) p < 0.001 1: 1.44 (1.4–1.68) p < 0.001 1 *: 1.28 (1.10–1.48) p < 0.001 2: 1.36 (1.16–1.58) p < 0.001 2 *: 1.19 (1.01–1.40) p = 0.032 UA: 1.38 (1.17–1.65) p < 0.001 1: 1.33 (1.11–1.60) p = 0.002 1 *: 1.22 (1.01–1.48) p = 0.043 2: 1.32 (1.08–1.60) p = 0.006 2 *: 1.17 (0.95–1.45) p = 0.146 |
[46] |
| 2022 | 4132 | 9.8 years | All-cause mortality Cardiovascular mortality Non-cardiovascular mortality |
1: age and sex 2: model 1 + HT, diabetes mellitus, total cholesterol, smoking, BMI, and eGFR |
UA: 2.29 (1.88–2.79) p < 0.001 1: 1.32 (1.08–1.62) p = 0.01 2: 1.07 (0.86–1.32) p = 0.56 UA: 2.73 (2.00–3.72) p < 0.001 1: 1.52 (1.11–2.09) p = 0.01 2: 1.16 (0.83–1.62) p = 0.38 UA: 2.02 (1.57–2.61) p < 0.001 1: 1.20 (0.92–1.56) p = 0.18 2: 1.02 (0.77–1.34) p = 0.90 |
[33] |
| ACS patients | ||||||
| 2017 | 1079 | 2 years | All-cause mortality Death/MI |
Age, sex, SBP, heart rate, past histories of MI/angina, increased BP and diabetes, Killip score, STEMI class, revascularization, and medication | UA: 1.21 (0.98–1.48) p = 0.074 UA: 1.4 (1.26–1.55) p < 0.0005 Adj: 1.21 (1.03–1.439) p = 0.023 |
[37] |
| 2017 |
530 | 30 days 6 months 7 years |
MACE (30 days and 6 months) All-cause mortality (7 years) |
Age, gender, HDL-C, LDL-C, smoking, presence or absence of a history of diabetes mellitus, HT, hyperlipidemia, revascularization or CAD, CRP level, eGFR, initial cTnT level, diagnosis of either STEMI, nonSTEMI, or unstable angina | UA: 2.29 (1.39–3.79) p < 0.01 Adj: 6.3 (1.89–21.00) p < 0.01 UA: 2.48 (1.51–4.09) p < 0.001 Adj: 5.65 (1.91–16.74) p < 0.01 UA: 3.72 (2.23–6.20) p < 0.001 Adj: 1.81 (1.04–3.15) p < 0.05 |
[38] |
| 2021 | 326 | 9 years | All-cause mortality | 1: BMI, diabetes status, eGFR 2: model 1 + age, sex, smoking status, SBP, DBP, hsCRP, HDL-C, LDL-C, white blood cell count, and in LIFE-CAD additionally for presence of CAD |
UA: 1.39 (0.98–1.97) p = 0.066 1: 1.10 (0.74–1.65) p = 0.638 2: 1.07 (0.70–1.63) p = 0.771 |
[35] |
| 2021 | 292 | 7 years | Cardiovascular mortality | Prior MI, diabetes, age, gender, diabetes, hemoglobin and creatinine levels at admission | UA: 21.33 (4.7–96.5) p < 0.001 Adj: 11.62 (2.3–59.7) p = 0.003 |
[47] |
| 2022 | 309 | 6.7 years | MACE | 1: age, sex, BMI, smoking, HT, dyslipidemia, type 2 diabetes, unstable angina, STEMI, nonSTEMI, statin medication, beta-blockers, oral antidiabetic medication, insulin medication, diuretics, aspirin 2: model 1 + eGFR |
UA: 2.63 (1.69–4.08) p < 0.001 1: 1.83 (1.08–3.09) p = 0.043 2: 1.66 (0.98–2.82) p = 0.119 |
[42] |
| Stable CKD patients | ||||||
| 2015 | 521 | 5 years | All-cause mortality | Age, sex, systolic blood pressure, LDL-C, HDL-C, smoking, diabetes mellitus, hsCRP, and eGFR | UA: 2.76 (1.74–4.37) p < 0.001 Adj: 1.93 (1.13–3.29) p < 0.05 |
[41] |
| 2016 | 2529 | 3 years | Ischemic events | 1: age, sex, race, diabetes and cardiovascular comorbidities at baseline 2: model 1 + traditional cardiovascular risk factors 3: model 2 + chronic kidney disease-specific risk factors 4: Adjusted for all covariates with statically significant association with ischemic events |
UA: 1.45 (1.28–1.64) 1: 1.38 (1.21–1.57) p < 0.0001 2: 1.39 (1.22–1.59) p = 0.0055 3: 1.24 (1.07–1.43) p = 0.065 4: 1.23 (1.06–1.42) p = 0.0059 |
[39] |
| 2016 | 339 | 3.3 years | All-cause mortality | 1: age, race, sex 2: model 1 + SBP, LDL-C, HDL-C, smoking, CRP, eGFR |
1: 2.45 (1.09–5.50) p = 0.02 2: 1.25 (0.48–3.28) p = 0.37 |
[40] |
Adj: adjusted; AMI: acute myocardial infarction; ACS: acute coronary syndrome; BNP: brain natriuretic peptide; BMI: body mass index; CAD: coronary artery disease; CKD: chronic kidney disease; cTnT: cardiac troponin T; CVD: cardiovascular disease; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; HDL-C: high-density lipoprotein cholesterol; HR: hazard ratio; hsCRP: high sensitivity C reactive protein; HT: hypertension; LDL-C: low-density lipoprotein cholesterol; MACE: major adverse cardiovascular event; SBP: systolic blood pressure; STEMI: ST-segment elevation myocardial infarction; TG: triglycerides; UA: unadjusted; WC: waist circumference.