Author + information
- Received December 2, 2013
- Revision received February 10, 2014
- Accepted February 17, 2014
- Published online November 4, 2014.
- W.H. Wilson Tang, MD∗,†∗ (, )
- Zeneng Wang, PhD∗,
- Yiying Fan, PhD‡,
- Bruce Levison, PhD∗,
- Jennie E. Hazen∗,
- Lillian M. Donahue∗,
- Yuping Wu, PhD‡ and
- Stanley L. Hazen, MD, PhD∗,†
- ∗Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
- †Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
- ‡Department of Mathematics, Cleveland State University, Cleveland, Ohio
- ↵∗Reprint requests and correspondence:
Dr. W.H. Wilson Tang, Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4, Cleveland, Ohio 44195.
Background Altered intestinal function is prevalent in patients with heart failure (HF), but its role in adverse outcomes is unclear.
Objectives This study investigated the potential pathophysiological contributions of intestinal microbiota in HF.
Methods We examined the relationship between fasting plasma trimethylamine-N-oxide (TMAO) and all-cause mortality over a 5-year follow-up in 720 patients with stable HF.
Results The median TMAO level was 5.0 μM, which was higher than in subjects without HF (3.5 μM; p < 0.001). There was modest but significant correlation between TMAO concentrations and B-type natriuretic peptide (BNP) levels (r = 0.23; p < 0.001). Higher plasma TMAO levels were associated with a 3.4-fold increased mortality risk. Following adjustments for traditional risk factors and BNP levels, elevated TMAO levels remained predictive of 5-year mortality risk (hazard ratio [HR]: 2.2; 95% CI: 1.42 to 3.43; p < 0.001), as well as following the addition of estimated glomerular filtration rate to the model (HR: 1.75; 95% CI: 1.07 to 2.86; p < 0.001).
Conclusions High TMAO levels were observed in patients with HF, and elevated TMAO levels portended higher long-term mortality risk independent of traditional risk factors and cardiorenal indexes.
This research was supported by grants from the National Institutes of Health (NIH) and the Office of Dietary Supplements (R01HL103866, P20HL113452). The GeneBank study was supported by NIH grants P01HL076491, P01HL098055, and R01HL103931, and the Cleveland Clinic Clinical Research Unit of the Case Western Reserve University CTSA (UL1TR 000439). Dr. Wang was partially supported by an American Heart Association Scientist Development Grant (12SDG12050473). Dr. Hazen was partially supported by a gift from the Leonard Krieger endowment and the Foundation LeDucq. Dr. Tang has received investigator-initiated research grant support from Abbott Laboratories, with no personal financial payments. Drs. Wang and Levison are named as co-inventors on pending patents held by the Cleveland Clinic relating to cardiovascular diagnostics and have the right to receive royalty payment for inventions or discoveries related to cardiovascular diagnostics from LipoScience, Inc. Dr. Hazen is named as a co-inventor on pending patents held by the Cleveland Clinic relating to cardiovascular diagnostics; has received consulting fees from Abbott Diagnostics, Cleveland Heart Lab, Esperion, Lilly, LipoScience, Inc., Merck & Co., Procter & Gamble, and Pfizer; has received research funds from Abbott Diagnostics, Cleveland Heart Lab, LipoScience, Inc., Procter & Gamble, Pfizer, and Takeda; and has the right to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland Heart Lab, Esperion, Frantz Biomarkers, and LipoScience, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received December 2, 2013.
- Revision received February 10, 2014.
- Accepted February 17, 2014.
- American College of Cardiology Foundation