TY - JOUR
T1 - Association with outcomes and response to treatment of trimethylamine N-oxide in heart failure (from BIOSTAT-CHF)
AU - Suzuki, Toru
AU - Yazaki, Yoshiyuki
AU - Voors, Adriaan A.
AU - Jones, Donald J. L.
AU - Chan, Daniel C. S.
AU - Anker, Stefan D.
AU - Cleland, John G.
AU - Dickstein, Kenneth
AU - Filippatos, Gerasimos
AU - Hillege, Hans L.
AU - Lang, Chim C.
AU - Ponikowski, Piotr
AU - Samani, Nilesh J.
AU - van Veldhuisen, Dirk J.
AU - Zannad, Faiez
AU - Zwinderman, Aeilko H.
AU - Metra, Marco
AU - Ng, Leong L.
PY - 2019/7
Y1 - 2019/7
N2 - 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 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.
AB - 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 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85055727026&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30370976
U2 - https://doi.org/10.1002/ejhf.1338
DO - https://doi.org/10.1002/ejhf.1338
M3 - Article
C2 - 30370976
SN - 1388-9842
VL - 21
SP - 877
EP - 886
JO - European journal of heart failure
JF - European journal of heart failure
IS - 7
ER -