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Table 1 Characteristics of included studies. (placed in the section of “result”, the first paragraph of “Characteristics of included studies”)

From: Trimethylamine-N-oxide has prognostic value in coronary heart disease: a meta-analysis and dose-response analysis

Study

Country

Age

(mean ± SD)

Gender

(% male)

Follow up

(years)

Popula-

tion

Samp-

le size

TMAOa

(μmol/L)

TMAO type

Fast-

ing

Quantification of TMAO

Collection time

HR

(95% CI)

Outcomes

Model charac-

ter

Adjust-

ed

NOS

Selecti-

on

Compar-ability

Outco-me

Total

stars

Tang WH 2013 [5]

USA

63 ± 11

64

3

Chronic CHD

4007

3.7

(2.4–6.2)

plasma

+

LC/MS/MS

Time of cardiac catheterize-

tion

1.30 (1.20–1.4, P < 0.001)

MACE

Per SD

+b

***

*

***

7

Lever M

2014 D [6]

New Zealand

74 ± 6.7

73

4.8

ACS

74

7.5

(4.4–12.1)

plasma

HPLC-MS/MS

Fourth-month post-discharge outpatient clinic visit

2.0 (1.1–3.6)

All cardiovascul-

ar events

Tertile

***

*

**

6

Lever M

2014 UD [6]

New Zealand

68 ± 6.3

73

5.0

ACS

381

4.8

(3.0–9.1)

plasma

2.7 (1.6–4.8)

Death

Tertile

****

*

**

7

Senthong V 2016 [7]

USA

63 ± 11

71

5

Chronic CHD

2235

3.8

(2.5–6.5)

plasma

+

LC/MS/MS

Time of cardiac catheterize-

tion, immediately prior to heparin injection and catheterizetion procedure

1.71 (1.11–2.61, P < 0.0138)

All-cause mortality

Quartile

+c

****

**

**

8

Suzuki T 2017 [8]

UK

67 ± 3.3

70

2

ACS

1079

3.7

(4.6–6.4)

plasma

LC-ToF-MRM

Days 1, 3 and 5 after admission

1.40 (1.26–1.55, P < 0.0005)

Death/MI

Per SD

****

**

***

9

CC

Li XS

2017 [9]

USA

62.4±

13.9

57.5

7

ACS

530

4.28

(2.55–7.91)

plasma

LC/MS/MS

On presentation

to the emergency room (baseline) and 4, 8 and 16 h later

1.81 (1.04–3.15,

P < 0.05)

All-cause mortality

Quartile

+d

****

*

***

8

SC

Li XS

2017 [9]

Swiss Confede-ration

63.9±

12.4

77.8

1

ACS

1683

2.87

(1.94–4.85)

plasma

Average time from the onset of chest pain to blood draw was 4.0 h

1.57

(1.03–2.41, P < 0.05)

MACE

Quartile

+e

***

*

***

7

Xu K-Z

2018 [10]

China

67.4±

12.8

44

in-

hospital

ACS

200

5.9 ± 1.9

plasma

HPLC-MS/MS

At hospital admission or the next morning in fasting state

OR: 6.01 (2.03–17.73, P < 0.05)

MACE

Quartile

+e

***

**

***

8

Matsuzawa Y 2019 [11]

Japan

63.0±

2.5

88.0

5.4

ACS

112

5.63 (3.20–10.38)

plasma

LC-MS

At hospital admission before primary percutaneous coronary intervention

1.72 (0.63–4.92, P = 0.29)

cardiovascul-

ar events

Above vs. below

+f

***

**

***

8

  1. ACS acute coronary syndrome, CHD coronary heart diseases, CC Cleveland acute coronary syndrome cohort, CI confidence interval, D patients with diabetes, F female, HR hazard ratio, HPLC-MS/MS high performance liquid chromatography- tandem mass spectrometry, LC-MS liquid chromatography-mass spectrometry, LC/MS/MS stable isotope dilution high-performance liquid chromatography with on line electrospray ionization tandem mass spectrometry, LC-ToF-MRM stable-isotope dilution-hydrophilic interaction liquid chromatography-time of flight mass spectrometry with multiple reaction monitoring, M male, MACE major adverse cardiovascular event, MImyocardial infarction, NOS the Newcastle-Ottawa scale, P P-value, SC Swiss ACS cohort, SD standard deviation, TMAO trimethylamine-N-oxide, UD patients without diabetes, UK United Kingdom, USA United States of America
  2. aConcentration of TMAO are presented as median (interquartile range) or mean ± standard deviation
  3. bAdjusted for age, sex, smoking status, systolic blood pressure, low-density lipoprotein cholesterol level, high-density lipoprotein, cholesterol level, and status with respect to diabetes mellitus, and other baseline covariates
  4. cAdjusted for age, sex, systolic blood pressure, diabetes mellitus, LDL, HDL, and smoking status, high sensitivity C reactive protein, estimated glomerular filtration rate, B-type natriuretic peptide, myeloperoxidase, number of diseased vessels, and medications
  5. dAdjusted for age, gender, HDL, LDL, smoking, presence or absence of a history of diabetes mellitus, hypertension, hyperlipidemia, revascularization or coronary artery disease, C-reactive protein level, estimated glomerular filtration rate, initial troponin T level and diagnosis of either acute ST-segment elevation myocardial infarction (STEMI), non-STEMI or unstable angina
  6. eAdjusted for age, left ventricular end-diastolic diameter, left ventricular ejection fraction, cardiac troponin I, high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide and diabetes mellitus
  7. fAdjusted for age, sex, hypertension, diabetes, dyslipidemia, smoking habits, systolic and diastolic blood pressure, triglycerides, high- and low-density lipoprotein cholesterol, glucose, hemoglobin A1c, estimated glomerular filtration rate, B-type natriuretic peptide, C-reactive protein, anterior myocardial infarction, atrial fibrillation, and medications on discharge