The Association of Plasma Trimethylamine N-Oxide with Coronary Atherosclerotic Burden in Patients with Type 2 Diabetes Among a Chinese North Population

Figures & data

Figure 1 Flowchart of coronary atherosclerosis screening and quantification in T2D patients.

Abbreviations: T2D, type 2 diabetes; CAG, coronary arteriography; CABG, coronary artery bypass grafting; PCI, percutaneous transluminal coronary intervention; CAD, coronary artery disease; SVD, single-vessel disease; DVD, dual-vessel disease; TVD, triple-vessel disease.

Table 1 Baseline Characteristics of the Study Participants Associated with Plasma Levels of TMAO (Distribution in Tertiles)

Variables	All n = 349	Tertiles of TMAO			P-value
		Tertile 1	Tertile 2	Tertile 3
		(TMAO <1.96μM)	(1.96 ≤TMAO <4.38μM)	(TMAO ≥4.38μM)
		n = 115	n = 117	n = 117
Age (y)	65.3 ± 10.4	64.7 ± 11.6	65.5 ± 9.4	65.6 ± 10.2	0.801
Sex, male (n)	220 (63.0%)	68 (59.1%)	76 (65.0%)	76 (65.0%)	0.570
BMI (kg/m^2)	26.1 ± 3.6	25.8 ± 3.5	26.2 ± 3.6	26.4 ± 3.7	0.320
Active smoking (n)	169 (48.4%)	55 (47.8%)	57 (48.7%)	57 (48.7%)	0.988
Hypertension (n)	256 (73.6%)	79 (69.3%)	79 (67.5%)	98 (83.8%)	0.009
Hyperlipidemia (n)	265 (76.1%)	91 (79.8%)	85 (72.6%)	89 (76.1%)	0.441
Diabetes duration (y)	10.4 ± 8.9	8.6 ± 8.3	10.9 ± 9.3	11.6 ± 8.8	0.018
FBG (mmol/L)	8.64 ± 4.81	8.78 ± 6.73	8.66 ± 3.42	8.49 ± 3.71	0.654
HbA1c (%)	7.5 ± 1.4	7.4 ± 1.4	7.6 ± 1.4	7.6 ± 1.4	0.125
TC (mmol/L)	3.92 ± 1.07	3.99 ± 1.07	3.95 ± 1.16	3.84 ± 0.98	0.771
LDL-C (mmol/L)	2.24 ± 0.82	2.26 ± 0.84	2.27 ± 0.90	2.18 ± 0.73	0.924
HDL-C (mmol/L)	0.97 ± 0.25	1.04 ± 0.29	0.97 ± 0.21	0.91 ± 0.21	<0.001
TG (mmol/L)	1.87 ± 1.32	1.83 ± 1.53	1.90 ± 1.15	1.88 ± 1.27	0.528
eGFR (mL/min/1.73 m^2)	74.44 ± 21.65	81.36 ± 16.34	79.32 ± 15.58	62.80 ± 26.31	<0.001
TMAO (μM)	2.83 [1.65–5.39]	1.22 [0.60–1.64]	2.83 [2.31–3.48]	6.93 [5.39–9.31]	<0.001
CAD (n)	279 (79.9%)	89 (77.4%)	99 (84.6%)	91 (77.8%)	0.301
TVD (n)	94 (26.9%)	25 (21.7%)	28 (23.9%)	41 (35.0%)	0.049
SYNTAX score >22 (n)	90 (25.8%)	23 (20.0%)	24 (20.5%)	43 (36.8%)	0.004

Note: Continuous data are presented as means ± SD or medians (interquartile ranges), and categorical variables are presented as counts (%).

Abbreviations: BMI, body mass index; FBG, fasting blood glucose; HbA1c, hemoglobin A1c; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TG, triglyceride; eGFR, estimated glomerular filtration rate; TMAO, trimethylamine N-Oxide; CAD, coronary artery disease; TVD, triple vessel disease.

Figure 2 Plasma levels of TMAO in different subgroups divided by the presence of CAD (A), the number of diseased coronary arteries (B) and the SYNTAX score (C).

Abbreviation: CAD, coronary artery disease.

Table 2 Association Between Plasma TMAO Levels and Severity of Coronary Atherosclerosis in Multiple Regression Model

Outcome		Non-Adjusted Model		Model I		Model II		Model III
		OR (95% CI)	P-value	OR (95% CI)	P-value	OR (95% CI)	P-value	OR (95% CI)	P-value
CAD	Continuous TMAO (μM)	1.03 (0.98, 1.09)	0.247	1.03 (0.96, 1.08)	0.294	1.01 (0.98, 1.08)	0.785	1.02 (0.95, 1.09)	0.577
	Tertiles of TMAO
	T1	1.00		1.00		1.00		1.00
	T2	1.61 (0.83, 3.13)	0.163	1.53 (0.78, 3.01)	0.220	1.54 (0.79, 3.00)	0.210	1.29 (0.57, 2.91)	0.536
	T3	1.02 (0.55, 1.90)	0.944	0.95 (0.50, 1.78)	0.869	0.75 (0.39, 1.46)	0.399	0.69 (0.29, 1.62)	0.395
TVD	Continuous TMAO (μM)	1.05 (1.02, 1.09)	0.004	1.05 (1.02, 1.09)	0.005	1.01 (0.97, 1.06)	0.506	1.01 (0.96, 1.07)	0.605
	Tertiles of TMAO
	T1	1.00		1.00		1.00		1.00
	T2	1.13 (0.61, 2.09)	0.691	1.09 (0.59, 2.03)	0.783	1.10 (0.59, 2.05)	0.769	0.61 (0.29, 1.30)	0.234
	T3	1.94 (1.08, 3.48)	0.026	1.89 (1.05, 3.40)	0.035	1.23 (0.65, 2.33)	0.527	0.91 (0.41, 2.04)	0.827
SYNTAX score >22	Continuous TMAO (μM)	1.05 (1.02, 1.09)	0.003	1.05 (1.02, 1.09)	0.005	1.01 (0.97, 1.05)	0.526	1.00 (0.95, 1.06)	0.893
	Tertiles of TMAO
	T1	1.00		1.00		1.00		1.00
	T2	1.03 (0.54, 1.96)	0.923	0.99 (0.52, 1.90)	0.985	1.00 (0.52, 1.91)	0.999	1.03 (0.46, 2.31)	0.936
	T3	2.32 (1.29, 4.20)	0.005	2.28 (1.25, 4.16)	0.007	1.52 (0.80, 2.90)	0.201	1.56 (0.67, 3.64)	0.298

Notes: Model I: Adjusted for age and sex. Model II: Adjusted for log-eGFR. Model III: Adjusted for all of these variables, including log-eGFR, age, sex, BMI, active smoking, hypertension, diabetes duration, FBG, HbA1c, LDL-C, HDL-C and TG.

Table 3 Association Between Plasma TMAO and Severity of Coronary Atherosclerosis in Patients with Different eGFR Levels

		Non-Adjusted Model		Adjusted Model		P for Interaction
		OR (95% CI)	P-value	OR (95% CI)	P-value
TVD
eGFR <60 mL/min/1.73 m^2 (n = 80)						<0.001
Tertiles of TMAO	T1-2	1.00		1.00
	T3	4.12 (1.59, 10.64)	0.004	25.28 (2.55, 250.33)	0.006
eGFR ≥60 mL/min/1.73 m^2 (n = 269)
Tertiles of TMAO	T1-2	1.00		1.00
	T3	0.78 (0.39, 1.56)	0.489	0.75 (0.32, 1.78)	0.517
SYNTAX score >22
eGFR <60 mL/min/1.73 m^2 (n = 80)						0.040
Tertiles of TMAO	T1-2	1.00		1.00
	T3	2.99 (1.18, 7.54)	0.021	7.23 (1.51, 34.64)	0.013
eGFR ≥60 mL/min/1.73 m^2 (n = 269)
Tertiles of TMAO	T1-2	1.00		1.00
	T3	1.37 (0.71, 2.64)	0.341	1.23 (0.52, 2.90)	0.635

Note: The adjusted model was adjusted for all of these variables, including age, sex, BMI, hypertension, active smoking, diabetes duration, FBG, HbA1c, LDL-C, HDL-C and TG.