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J Am Soc Nephrol. 2017 Jan;28(1):321-331. doi: 10.1681/ASN.2016030374. Epub 2016 Jul 19.

Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis Patients.

Author information

1
Department of Medicine and tshafi@jhmi.edu.
2
Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
3
Department of Medicine, University of California, San Francisco, California.
4
Department of Medicine, Palo Alto Veterans Affairs Health Care System and Stanford University, Palo Alto, California.
5
Department of Medicine and.
6
Department of Medicine, Case Western University School of Medicine, Cleveland, Ohio.
7
Departments of Medicine and Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, New York; and.
8
Departments of Epidemiology and Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Abstract

Cardiovascular disease causes over 50% of the deaths in dialysis patients, and the risk of death is higher in white than in black patients. The underlying mechanisms for these findings are unknown. We determined the association of the proatherogenic metabolite trimethylamine N-oxide (TMAO) with cardiovascular outcomes in hemodialysis patients and assessed whether this association differs by race. We measured TMAO in stored serum samples obtained 3-6 months after randomization from a total of 1232 white and black patients of the Hemodialysis Study, and analyzed the association of TMAO with cardiovascular outcomes using Cox models adjusted for potential confounders (demographics, clinical characteristics, comorbidities, albumin, and residual kidney function). Mean age of the patients was 58 years; 35% of patients were white. TMAO concentration did not differ between whites and blacks. In whites, 2-fold higher TMAO associated with higher risk (hazard ratio [95% confidence interval]) of cardiac death (1.45 [1.24 to 1.69]), sudden cardiac death [1.70 (1.34 to 2.15)], first cardiovascular event (1.15 [1.01 to 1.32]), and any-cause death (1.22 [1.09 to 1.36]). In blacks, the association was nonlinear and significant only for cardiac death among patients with TMAO concentrations below the median (1.58 [1.03 to 2.44]). Compared with blacks in the same quintile, whites in the highest quintile for TMAO (≥135 μM) had a 4-fold higher risk of cardiac or sudden cardiac death and a 2-fold higher risk of any-cause death. We conclude that TMAO concentration associates with cardiovascular events in hemodialysis patients but the effects differ by race.

KEYWORDS:

cardiovascular events; epidemiology and outcomes; hemodialysis

PMID:
27436853
PMCID:
PMC5198291
DOI:
10.1681/ASN.2016030374
[Indexed for MEDLINE]
Free PMC Article

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