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. 2020 Nov;42(1):1004-1014.
doi: 10.1080/0886022X.2020.1822868.

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

Pan Zhang  1   2   3   4   5 , Jian-Zhou Zou  1   2   3   4   5 , Jun Chen  6 , Xiao Tan  1   2   3   4   5 , Fang-Fang Xiang  1   2   3   4   5 , Bo Shen  1   2   3   4   5 , Jia-Chang Hu  1   2   3   4   5 , Jia-Lin Wang  1   2   3   4   5 , Ya-Qiong Wang  1   2   3   4   5 , Jin-Bo Yu  1   2   3   4   5 , Yu-Xin Nie  1   2   3   4   5 , Xiao-Hong Chen  1   2   3   4   5 , Jia-Wei Yu  1   2   3   4   5 , Zhen Zhang  1   2   3   4   5 , Wen-Lv Lv  1   2   3   4   5 , Ye-Qing Xie  1   2   3   4   5 , Xue-Sen Cao  1   2   3   4   5 , Xiao-Qiang Ding  1   2   3   4   5
Affiliations

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

Pan Zhang et al. Ren Fail. 2020 Nov.

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.

Keywords: Uremic toxins; all-cause mortality; cardiovascular mortality; hemodialysis; trimethylamine N-oxide.

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Conflict of interest statement

The results presented in this paper have not been published previously in whole or part, except an abstract of this manuscript was presented earlier in ASN’s Kidney Week 2019 in Washington, DC (NO. 3236604).

Figures

Figure 1.
Figure 1.
Kaplan-Meier survival curves of cardiovascular death during follow-up of HD patients stratified by the TMAO level.
Figure 2.
Figure 2.
Kaplan-Meier survival curves of all-cause death during follow-up of HD patients stratified by the TMAO level.
See this image and copyright information in PMC

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