Dataset Information

Microbiota-derived Trimethylamine N-oxide Predicts Cardiovascular Risk After STEMI.

ABSTRACT: Trimethylamine N-oxide (TMAO), a metabolite derived from the gut microbiota, is proatherogenic and associated with cardiovascular events. However, the change in TMAO with secondary prevention therapies for ST-segment elevation acute myocardial infarction (STEMI) remains unclear. The purpose of this study was to investigate the sequential change in TMAO levels in response to the current secondary prevention therapies in patients with STEMI and the clinical impact of TMAO levels on cardiovascular events We included 112 STEMI patients and measured plasma TMAO levels at the onset of STEMI and 10 months later (chronic phase). After the chronic-phase assessment, patients were followed up for cardiovascular events. Plasma TMAO levels significantly increased from the acute phase to the chronic phase of STEMI (median: 5.63 to 6.76??M, P?=?0.048). During a median period of 5.4 years, 17 patients experienced events. The chronic-phase TMAO level independently predicted future cardiovascular events (adjusted hazard ratio for 0.1 increase in log chronic-phase TMAO level: 1.343, 95% confidence interval 1.122-1.636, P?=?0.001), but the acute-phase TMAO level did not. This study demonstrated the clinical importance of the chronic-phase TMAO levels on future cardiovascular events in patients after STEMI.

SUBMITTER: Matsuzawa Y

PROVIDER: S-EPMC6690996 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Microbiota-derived Trimethylamine N-oxide Predicts Cardiovascular Risk After STEMI.

Matsuzawa Yasushi Y Nakahashi Hidefumi H Konishi Masaaki M Sato Ryosuke R Kawashima Chika C Kikuchi Shinnosuke S Akiyama Eiichi E Iwahashi Noriaki N Maejima Nobuhiko N Okada Kozo K Ebina Toshiaki T Hibi Kiyoshi K Kosuge Masami M Ishigami Tomoaki T Tamura Kouichi K Kimura Kazuo K

Scientific reports 20190812 1

Trimethylamine N-oxide (TMAO), a metabolite derived from the gut microbiota, is proatherogenic and associated with cardiovascular events. However, the change in TMAO with secondary prevention therapies for ST-segment elevation acute myocardial infarction (STEMI) remains unclear. The purpose of this study was to investigate the sequential change in TMAO levels in response to the current secondary prevention therapies in patients with STEMI and the clinical impact of TMAO levels on cardiovascular ...[more]

PMID: 31406181

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Project description:Objective- Gut microbiota-dependent metabolites, in particular trimethylamine N-oxide (TMAO), have recently been reported to promote atherosclerosis and thrombosis. Here, we examined for the first time the relation of TMAO and the risk of incident cardiovascular events in patients with recent first-ever ischemic stroke in 2 independent prospective cohorts. Moreover, the link between TMAO and proinflammatory monocytes as a potential contributing factor for cardiovascular risk in stroke patients was studied. Approach and Results- In a first study (n=78), higher TMAO plasma levels were linked with an increased risk of incident cardiovascular events including myocardial infarction, recurrent stroke, and cardiovascular death (fourth quartile versus first quartile; hazard ratio, 2.31; 95% CI, 1.25-4.23; P<0.01). In the second independent validation cohort (n=593), high TMAO levels again heralded marked increased risk of adverse cardiovascular events (fourth quartile versus first quartile; hazard ratio, 5.0; 95% CI, 1.7-14.8; P<0.01), and also after adjustments for cardiovascular risk factors including hypertension, diabetes mellitus, LDL (low-density lipoprotein) cholesterol, and estimated glomerular filtration rate (hazard ratio, 3.3; 95% CI, 1.2-10.9; P=0.04). A significant correlation was also found between TMAO levels and percentage of proinflammatory intermediate CD14++CD16+ monocytes ( r=0.70; P<0.01). Moreover, in mice fed a diet enriched with choline to increase TMAO synthesis, levels of proinflammatory murine Ly6Chigh monocytes were higher than in the chow-fed control group (choline: 9.2±0.5×103 per mL versus control: 6.5±0.5×103 per mL; P<0.01). This increase was abolished in mice with depleted gut microbiota (choline+antibiotics: 5.4±0.7×103 per mL; P<0.001 versus choline). Conclusions- The present study demonstrates for the first time a graded relation between TMAO levels and the risk of subsequent cardiovascular events in patients with recent prior ischemic stroke. Our data support the notion that TMAO-related increase of proinflammatory monocytes may add to elevated cardiovascular risk of patients with increased TMAO levels.

Project description:IntroductionTrimethylamine-N-oxide (TMAO) is a circulating biomarker associated with cardiovascular disease (CVD). Production of TMAO is facilitated by gut microbiota and dependent on micronutrients such as choline, betaine, and L-carnitine, present in foods such as red meat and eggs.HypothesisWe sought to predict serum TMAO quartile levels among healthy individuals at increased risk of CVD using clinical data via an ordinal logistic model.MethodsData from participants (n = 127) enrolled in a longitudinal observational study on CVD were used to build a predictive model for TMAO using ordinal logistic regression with demographic variables and 40 other variables considered related to CVD risk. First, univariate models for each covariate were tested (with serum TMAO quartiles as the dependent variable), and only variables with P < 0.30 were evaluated further. Second, demographic variables (age, gender, white vs. non-white race) were included in a multivariable model with each previously identified independent variable controlling for potential confounding. Last, the final model included fixed demographics and candidates from the confounder-adjusted model with P < 0.10.ResultsEight candidate variables were included in the final model, with only transferrin, high-density lipoprotein cholesterol (HDL-C) and race (white vs. non-white) showing significant associations with TMAO. Participants had 0.16 (Q2), 0.31 (Q3), and 0.20 (Q4) odds of being in a higher TMAO quartile compared with participants in the lowest transferrin quartile. Non-white participants had 2.92 times higher odds of being in the highest TMAO quartile compared to white individuals. Participants in the second quartile of HDL-C had 2.68 times higher odds of being in a higher TMAO quartile compared with participants in the lowest HDL-C quartile.ConclusionsTransferrin demonstrated a significant predictive association with TMAO and may represent a novel potential biomarker of increased CVD risk worthy of further study. These results warrant further examination of iron, metabolism, homeostasis, and gut microbiome to better understand and mitigate known increased CVD risk.

Project description:Systemic levels of trimethylamine N-oxide (TMAO), a pro-atherogenic and pro-thrombotic metabolite produced from gut microbiota metabolism of dietary trimethylamine (TMA)-containing nutrients such as choline or carnitine, predict incident cardiovascular event risks in stable primary and secondary prevention subjects. However, the prognostic value of TMAO in the setting of acute coronary syndromes (ACS) remains unknown.We investigated the relationship of TMAO levels with incident cardiovascular risks among sequential patients presenting with ACS in two independent cohorts. In the Cleveland Cohort, comprised of sequential subjects (n?=?530) presenting to the Emergency Department (ED) with chest pain of suspected cardiac origin, an elevated plasma TMAO level at presentation was independently associated with risk of major adverse cardiac events (MACE, including myocardial infarction, stroke, need for revascularization, or death) over the ensuing 30-day (4th quartile (Q4) adjusted odds ratio (OR) 6.30, 95% confidence interval (CI), 1.89-21.0, P?<?0.01) and 6-month (Q4 adjusted OR 5.65, 95%CI, 1.91-16.7; P?<?0.01) intervals. TMAO levels were also a significant predictor of the long term (7-year) mortality (Q4 adjusted HR 1.81, 95%CI, 1.04-3.15; P?<?0.05). Interestingly, TMAO level at initial presentation predicted risk of incident MACE over the near-term (30 days and 6 months) even among subjects who were initially negative for troponin T (< 0.1?ng/mL) (30 days, Q4 adjusted OR 5.83, 95%CI, 1.79-19.03; P?<?0.01). The prognostic value of TMAO was also assessed in an independent multicentre Swiss Cohort of ACS patients (n?=?1683) who underwent coronary angiography. Trimethylamine N-oxide again predicted enhanced MACE risk (1-year) (adjusted Q4 hazard ratios: 1.57, 95% CI, 1.03-2.41; P?<0.05).Plasma TMAO levels among patients presenting with chest pain predict both near- and long-term risks of incident cardiovascular events, and may thus provide clinical utility in risk stratification among subjects presenting with suspected ACS.

Dataset Information

Microbiota-derived Trimethylamine N-oxide Predicts Cardiovascular Risk After STEMI.

Publications

Microbiota-derived Trimethylamine N-oxide Predicts Cardiovascular Risk After STEMI.

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