TMAO? Interesting.

[Razors Edge ★]

Anyone getting their TMAO levels checked? Is there an easy check? Anyone even heard of TMAO before? Seems like a potentially VERY useful diagnostic tool for heart disease.

Background

Recent studies in animals have shown a mechanistic link between intestinal microbial metabolism of the choline moiety in dietary phosphatidylcholine (lecithin) and coronary artery disease through the production of a proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO). We investigated the relationship among intestinal microbiota-dependent metabolism of dietary phosphatidylcholine, TMAO levels, and adverse cardiovascular events in humans.

Clinical Outcomes

TMAO Levels and Cardiovascular Events

The baseline characteristics of the 4007 participants in the clinical-outcomes study are shown in Table 1, according to whether they had a major adverse cardiovascular event during the 3-year follow-up. The mean age of the participants was 63 years, and two thirds were men; the prevalence of cardiovascular risk factors was high, and many of the participants had at least single-vessel coronary disease. Participants who had incident major adverse cardiovascular events during 3 years of follow-up had higher risk profiles at baseline than those without events, including an older age, higher fasting glucose levels, and higher rates of diabetes, hypertension, and previous myocardial infarction.

Participants who had major adverse cardiovascular events also had higher baseline levels of TMAO, as compared with those who did not have cardiovascular events (median, 5.0 μM [interquartile range, 3.0 to 8.8] vs. 3.5 μM [interquartile range, 2.4 to 5.9]; P<0.001) (Table 1). As compared with participants in the lowest quartile of TMAO levels, those in the highest quartile had a significantly increased risk of an event (hazard ratio, 2.54; 95% confidence interval [CI], 1.96 to 3.28; P<0.001) (Table 2).

After adjustment for traditional risk factors and other baseline covariates, elevated plasma levels of TMAO remained a significant predictor of the risk of major adverse cardiovascular events (Table 2). We observed a graded increase in risk with increasing levels of TMAO, as illustrated in the Kaplan–Meier analysis shown in Figure 2. A similar graded increase in risk was observed when levels of TMAO were analyzed as a continuous variable in increments of 1 SD (unadjusted hazard ratio, 1.40 [95% CI, 1.29 to 1.51; P<0.001]; adjusted hazard ratio, 1.30 [95% CI, 1.20 to 1.41; P<0.001]).

When the components of the major adverse cardiovascular events were analyzed separately, increased levels of TMAO remained significantly associated with an increased risk of death (hazard ratio, 3.37; 95% CI, 2.39 to 4.75; P<0.001) and nonfatal myocardial infarction or stroke (hazard ratio, 2.13; 95% CI, 1.48 to 3.05; P<0.001). The inclusion of TMAO as a covariate resulted in a significant improvement in risk estimation over traditional risk factors (net reclassification improvement, 8.6% [P<0.001]; integrated discrimination improvement, 9.2% [P<0.001]; C statistic, 68.3% vs. 66.4% [P=0.01]). In a separate analysis, we excluded all participants who underwent revascularization within 30 days after enrollment in the study. In this subcohort of 3475 participants, TMAO remained significantly associated with the risk of major adverse cardiovascular events (unadjusted hazard ratio for highest quartile vs. lowest quartile, 2.47 [95% CI, 1.87 to 3.27]; P<0.001).

Cardiovascular Risk in Low-Risk Subgroups

The prognostic value of elevated plasma levels of TMAO for cardiovascular risk remained significant in various subgroups associated with a reduced overall risk of major adverse cardiovascular events (Fig. S3 in the Supplementary Appendix). These subgroups included younger participants (<65 years of age), women, and participants who did not have a known history of coronary artery disease or coronary disease risk equivalents, had low lipid and apolipoprotein levels, had normal blood pressure, did not smoke, and had low levels of other known risk markers, such as C-reactive protein, myeloperoxidase, and white-cell count.

[Prophet Zacharia]

Quote

"ingestion of two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine"

With some gluten free buttered toast and coffee with Oat Milk, that is a breakfast for ambivalent cardiac care patients. 

[Razors Edge ★]

2 minutes ago, Prophet Zacharia said:

With some gluten free buttered toast and coffee with Oat Milk, that is a breakfast for ambivalent cardiac care patients. 

_{I love this tiny font.}

[Kzoo]

2 minutes ago, Razors Edge said:

_{I love this tiny font.}

What.  I can't hear you.

[Prophet Zacharia]

2 minutes ago, Razors Edge said:

_{I love this tiny font.}

It claimed to be twelve, but it does seem smaller. 

[Razors Edge ★]

Just now, Kzoo said:

What.  I can't hear you.

_{Happy belated birthday!}

[Razors Edge ★]

Just now, Prophet Zacharia said:

It claimed to be twelve, but it does seem smaller. 

Have you ever seen a TMAO test? Ever heard of it?  I wonder if @Dottie has with his cardio research.

[Prophet Zacharia]

2 minutes ago, Razors Edge said:

Have you ever seen a TMAO test? Ever heard of it?  I wonder if @Dottie has with his cardio research.

No. So I wonder what's happened with that field of research since 2013.

[Razors Edge ★]

10 minutes ago, Prophet Zacharia said:

No. So I wonder what's happened with that field of research since 2013. 

So did these guys.

Strength and limitations

Our study demonstrated potential prognostic power of TMAO in a variety of populations. To our knowledge, this is the first meta‐analysis that shows a positive correlation between high‐TMAO level and adverse cardiovascular outcome. In this study, we included only prospective cohorts and followed the PRISMA and MOOSE guidelines. Potential sources of heterogeneity were explored using different methods, and trim‐and‐fill strategy was applied to solve the possibility of publication bias. All of the above aspects added to the power of the study. Our study also has potential limitations, which should be considered when interpreting the results. Firstly, studies that did not provide sufficient data for pooling were excluded from the meta‐analysis 14, 23, 24, 25, 26, which may raise risk of bias in the overall effects by TMAO. Considerable risk of publication bias was identified for the association between high TMAO and all‐cause mortality, leading to a dubitative conclusion of the link. Moreover, considerable heterogeneities existed in baseline clinical characteristics including age, gender and race across individual studies. Additionally, uncontrolled cofounding factors including dietary patterns and genetic variation may significantly affect the concentration of TMAO. Inclusion of those studies without comprehensive adjustment may yield inaccurate effects. Moreover, the lack of continuous data made it difficult to draw a quantitative result on the difference of TMAO between subjects with and without events. Finally, results of our meta‐analysis of observational studies could only provide the potential temporal association between increased circulating TMAO and subsequent CVD risk. Whether increased TMAO was causative to poor cardiovascular outcome deserves further investigation.

Conclusion

Participants with higher baseline TMAO were at higher risk for future cardiovascular risk. Further large‐scale prospective cohorts or even interventional studies are warranted to evaluate the diagnostic power of TMAO and its causative role on cardiovascular outcome.