Association with outcomes and response to treatment of trimethylamine N‐oxide in heart failure (from BIOSTAT‐CHF)

Suzuki, T. et al. (2019) Association with outcomes and response to treatment of trimethylamine N‐oxide in heart failure (from BIOSTAT‐CHF). European Journal of Heart Failure, 21(7), pp. 877-886. (doi: 10.1002/ejhf.1338) (PMID:30370976)

171084.pdf - Accepted Version



Aims: Association of elevated circulating levels of trimethylamine N-oxide (TMAO) with adverse outcomes in patients with heart failure (HF) has been described. However, response of TMAO levels to treatment and medications has not been investigated. Therefore, we investigated whether TMAO levels are responsive to guideline-recommended treatment and medications, and further reflect changes in outcomes. Methods and Results: TMAO levels were investigated in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF), which addressed response to guideline-recommended pharmacological treatment. TMAO levels in 2,234 patients with new-onset or progressively worsening HF showed strong associations with adverse events (mortality and /or rehospitalisation) at 1,2 and 3 years (HR 1.37–1.51, p≤0.019). Analysis of 972 patients with plasma available at both enrolment and follow-up visit showed reductions of B-type natriuretic peptide levels with guideline-based treatment (p<0.001), but not for TMAO levels. Moreover, patients with higher TMAO levels than median before and after treatment showed increased association with adverse outcomes (HR 2.21, 95% CI: 1.43-3.43, p<0.001) compared to patients with lower than median levels either before or after treatment (HR 1.13, 95% CI: 0.63-2.04, p=0.684 and HR 1.14, 95% CI: 0.64-2.03, p=0.662, respectively). Conclusion: TMAO levels were associated with adverse outcomes (mortality and/or rehospitalisation) in BIOSTAT-CHF, and did not respond to guideline-based pharmaceutical treatment in contrast to BNP levels which did as expected. Lower TMAO levels regardless of treatment were associated with favorable outcome.

Item Type:Articles
Additional Information:BIOSTAT-CHF was supported by the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010- 020808-29]. The present analysis was supported by the following funding to TS: the Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development (AMED) (17ek0210011h0005), the Japan Heart Foundation, the University of Tokyo, the John and Lucille van Geest Foundation and the National Institute for Health Research Leicester Biomedical Research Centre.
Glasgow Author(s) Enlighten ID:Cleland, Professor John
Authors: Suzuki, T., Yazaki, Y., Voors, A. A., Jones, D. J.L., Chan, D. C.S., Anker, S. D., Cleland, J. G., Dickstein, K., Filippatos, G., Hillege, H. L., Lang, C. C., Ponikowski, P., Samani, N. J., Van Veldhuisen, D. J., Zannad, F., Zwinderman, A. H., Metra, M., and Ng, L. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:European Journal of Heart Failure
ISSN (Online):1879-0844
Published Online:29 October 2018
Copyright Holders:Copyright © 2018 The Authors and European Society of Cardiology
First Published:First published in European Journal of Heart Failure 21:877-886
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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