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dc.contributor.authorSuzuki, T-
dc.contributor.authorYazaki, Y-
dc.contributor.authorVoors, AA-
dc.contributor.authorJones, DJL-
dc.contributor.authorChan, DCS-
dc.contributor.authorAnker, SD-
dc.contributor.authorCleland, JG-
dc.contributor.authorDickstein, K-
dc.contributor.authorFilippatos, G-
dc.contributor.authorHillege, HL-
dc.contributor.authorLang, CC-
dc.contributor.authorPonikowski, P-
dc.contributor.authorSamani, NJ-
dc.contributor.authorvan Veldhuisen, DJ-
dc.contributor.authorZannad, F-
dc.contributor.authorZwinderman, AH-
dc.contributor.authorMetra, M-
dc.contributor.authorNg, LL-
dc.identifier.citationEur J Heart Fail, 2018en
dc.descriptionThe file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.en
dc.description.abstractAIMS: 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 2234 patients with new-onset or progressively worsening HF showed strong associations with adverse events (mortality and/or rehospitalisation) at 1, 2 and 3 years [hazard ratio (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 (BNP) 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% confidence interval (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 pharmacological treatment in contrast to BNP levels which did as expected. Lower TMAO levels were associated with favourable outcome regardless of treatment.en
dc.description.sponsorshipBIOSTAT-CHF was supported by the European Commission[FP7-242209-BIOSTAT-CHF; EudraCT 2010- 020808-29]. Thepresent analysis was supported by the following funding to T.S.:the Practical Research Project for Life-Style related Diseasesincluding Cardiovascular Diseases and Diabetes Mellitus fromJapan Agency for Medical Research and Development (AMED)(17ek0210011h0005), the Japan Heart Foundation, the Universityof Tokyo, the John and Lucille van Geest Foundation, and theNational Institute for Health Research, Leicester BiomedicalResearch Centre.en
dc.publisherOxford University Press (OUP)en
dc.rightsCopyright © 2018, The Authors. Deposited with reference to the publisher’s open access archiving policy. (
dc.subjectGut microbiomeen
dc.subjectHeart failureen
dc.subjectOutcome studyen
dc.titleAssociation with outcomes and response to treatment of trimethylamine N-oxide in heart failure (from BIOSTAT-CHF)en
dc.typeJournal Articleen
dc.type.subtypeJournal Article-
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCESen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicineen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Cancer Research Centreen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciencesen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themesen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themes/Canceren
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themes/Cardiovascularen
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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