Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis Patients

Tariq Shafi, Neil R. Powe, Timothy W. Meyer, Seungyoung Hwang, Xin Hai, Michal L. Melamed, Tanushree Banerjee, Josef Coresh, Thomas H. Hostetter

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)321-331
Number of pages11
JournalJournal of the American Society of Nephrology : JASN
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Renal Dialysis
Sudden Cardiac Death
Cause of Death
trimethyloxamine
Random Allocation
Proportional Hazards Models
Comorbidity
Dialysis
Albumins
Cardiovascular Diseases
Odds Ratio
Demography
Confidence Intervals
Kidney
Serum
hydroquinone

Keywords

  • cardiovascular events
  • epidemiology and outcomes
  • hemodialysis

ASJC Scopus subject areas

  • Nephrology

Cite this

Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis Patients. / Shafi, Tariq; Powe, Neil R.; Meyer, Timothy W.; Hwang, Seungyoung; Hai, Xin; Melamed, Michal L.; Banerjee, Tanushree; Coresh, Josef; Hostetter, Thomas H.

In: Journal of the American Society of Nephrology : JASN, Vol. 28, No. 1, 01.01.2017, p. 321-331.

Research output: Contribution to journalArticle

Shafi, T, Powe, NR, Meyer, TW, Hwang, S, Hai, X, Melamed, ML, Banerjee, T, Coresh, J & Hostetter, TH 2017, 'Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis Patients', Journal of the American Society of Nephrology : JASN, vol. 28, no. 1, pp. 321-331. https://doi.org/10.1681/ASN.2016030374
Shafi, Tariq ; Powe, Neil R. ; Meyer, Timothy W. ; Hwang, Seungyoung ; Hai, Xin ; Melamed, Michal L. ; Banerjee, Tanushree ; Coresh, Josef ; Hostetter, Thomas H. / Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis Patients. In: Journal of the American Society of Nephrology : JASN. 2017 ; Vol. 28, No. 1. pp. 321-331.
@article{cc5f036a16f7443a82f0392a9e3a74d7,
title = "Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis Patients",
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",
author = "Tariq Shafi and Powe, {Neil R.} and Meyer, {Timothy W.} and Seungyoung Hwang and Xin Hai and Melamed, {Michal L.} and Tanushree Banerjee and Josef Coresh and Hostetter, {Thomas H.}",
year = "2017",
month = "1",
day = "1",
doi = "10.1681/ASN.2016030374",
language = "English (US)",
volume = "28",
pages = "321--331",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "1",

}

TY - JOUR

T1 - Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis Patients

AU - Shafi, Tariq

AU - Powe, Neil R.

AU - Meyer, Timothy W.

AU - Hwang, Seungyoung

AU - Hai, Xin

AU - Melamed, Michal L.

AU - Banerjee, Tanushree

AU - Coresh, Josef

AU - Hostetter, Thomas H.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - cardiovascular events

KW - epidemiology and outcomes

KW - hemodialysis

UR - http://www.scopus.com/inward/record.url?scp=85021849955&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021849955&partnerID=8YFLogxK

U2 - 10.1681/ASN.2016030374

DO - 10.1681/ASN.2016030374

M3 - Article

VL - 28

SP - 321

EP - 331

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 1

ER -