Table 3.

Association between trimethylamine N-oxide (TMAO) and all-cause mortality in 5,469 (322 cases) subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study according to quartiles (Q1-Q4) and as continuous variable.

	Q1	Q2	P-value	Q 3	P-value	Q 4	P-value	P-value for trend	TMAO per 1 SD increment	P-Value
Subjects, n	1361	1373		1367		1368
TMAO range, µM	<1.71	≥1.71–3.17		≥3.17–5.70		≥5.70
No. of deaths	55	68		95		104
Crude	(ref)	1.22 [0.86–1.75]	0.27	1.71 [1.23–2.38]	0.002	1.86 [1.34–2.58]	<0.001	<0.001	1.28 [1.15–1.43]	<0.001
Model 1	(ref)	0.98 [0.69–1.40]	0.90	1.05 [0.75–1.47]	0.76	1.37 [0.99–1.90]	0.06	0.01	1.13 [1.01–1.27]	0.03
Model 2	(ref)	1.00 [0.70–1.44]	0.99	1.11 [0.80–1.56]	0.53	1.41 [1.01–1.96]	0.04	0.009	1.15 [1.03–1.29]	0.016
Model 3	(ref)	0.96 [0.67–1.39]	0.85	1.06 [0.75–1.50]	0.72	1.36 [0.97–1.91]	0.07	0.016	1.14 [1.01–1.28]	0.028
Model 4a	(ref)	0.95 [0.66–1.38]	0.80	1.03 [0.73–1.46]	0.86	1.28 [0.91–1.80]	0.15	0.049	1.11 [0.99–1.25]	0.07
Model 4b	(ref)	0.93 [0.64–1.35]	0.71	1.00 [0.70–1.42]	0.98	1.20 [0.84–1.71]	0.32	0.15	1.08 [0.95–1.22]	0.23
Model 4c	(ref)	0.92 [0.64–1.34]	0.68	0.97 [0.68–1.38]	0.87	1.15 [0.81–1.64]	0.44	0.22	1.06 [0.94–1.20]	0.34

Hazard ratios and 95% confidence intervals were derived from Cox proportional hazards regression models. TMAO was logarithmically transformed before analysis. 1 SD change in TMAO corresponds to 2.94 µM (antilog). Model 1: age and sex. Model 2: Model 1 + body mass index and smoking. Model 3: Model 2 + type 2 diabetes mellitus, history of cardiovascular disease, history of cancer, anti-hypertensive medication, lipid lowering drugs, systolic blood pressure, total cholesterol, high density lipoprotein cholesterol and triglycerides. Model 4a: Model 3 + urinary albumin excretion (UAE). Model 4b: Model 3 + eGFR crea-cysC (estimated glomerular filtration rate based on creatinine-cystatin C equation). Model 4c: Model 3 + UAE and eGFR crea-cysC. Statistically significant correlations are shown in bold print.