Association of trimethylamine N-Oxide with cardiovascular and all-cause mortality in hemodialysis patients.

ABSTRACT

BACKGROUND: Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. METHODS: Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. RESULTS: We recruited 252 patients and divided them into a high-TMAO group (>4.73 µg/mL) and a low-TMAO group (≤4.73 µg/mL). The median follow-up time was 73.4 months (interquartile range 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank p = 0.006) and all-cause death (Log-Rank p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable HR 1.18, 95%CI 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable HR 3.44, 95%CI 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable HR 1.14, 95%CI 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable HR 2.54, 95%CI 1.71, 3.76, p < 0.001). CONCLUSIONS: High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.