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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>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\u2009years [hazard ratio (HR) 1.37\u20131.51, P\u2009\u2264\u20090.019). 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\u2009&amp;lt;\u20090.001), 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\u20133.43, P\u2009&amp;lt;\u20090.001] compared to patients with lower than median levels either before or after treatment (HR 1.13, 95% CI 0.63\u20132.04, P\u2009=\u20090.684 and HR 1.14, 95% CI 0.64\u20132.03, P\u2009=\u20090.662, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1338","type":"journal-article","created":{"date-parts":[[2018,10,29]],"date-time":"2018-10-29T07:44:26Z","timestamp":1540799066000},"page":"877-886","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Association with Outcomes and Response to Treatment of Trimethylamine N-Oxide in Heart Failure: Results from BIOSTAT-CHF"],"prefix":"10.1093","volume":"21","author":[{"given":"Toru","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Leicester, NIHR Leicester Biomedical Research Centre , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Yazaki","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of 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Leicester Biomedical Research Centre , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Division of Cardiology and Metabolism \u2013 Heart Failure, Cachexia & Sarcopenia, Department of Cardiology (CVK); and Berlin-Brandenburg Center for Regenerative Therapies (BCRT); Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung (DZHK) Berlin, Charit\u00e9 Universit\u00e4tsmedizin Berlin ,","place":["Germany"]},{"name":"Department of Cardiology and Pneumology, University Medical Center G\u00f6ttingen (UMG) , G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Cleland","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[{"name":"University of Bergen , Bergen ,","place":["Norway"]},{"name":"Stavanger University Hospital , Stavanger ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens, School of Medicine, Department of Cardiology, Heart Failure Unit, Athens University Hospital Attikon , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans L.","family":"Hillege","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chim C.","family":"Lang","sequence":"additional","affiliation":[{"name":"School of Medicine Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Ninewells Hospital & Medical School , Dundee ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"Department of Heart Diseases, Wroclaw Medical University, Poland, and Cardiology Department, Military Hospital , Wroclaw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh J.","family":"Samani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Leicester, NIHR Leicester Biomedical Research Centre , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, 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