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Trimethylamine N ‐ Oxide and Mortality Risk in Patients With Peripheral Artery Disease

View Article: PubMed Central - PubMed

ABSTRACT

Background: Production of the proatherogenic metabolite, trimethylamine N‐oxide (TMAO), from dietary nutrients by intestinal microbiota enhances atherosclerosis development in animal models and is associated with atherosclerotic coronary artery disease in humans. The utility of studying plasma levels of TMAO to risk stratify in patients with peripheral artery disease (PAD) has not been reported.

Methods and results: We examined the relationship between fasting plasma TMAO and all‐cause mortality (5‐year), stratified by subtypes of PAD and presence of coronary artery disease in 935 patients with PAD who underwent elective angiography for cardiac evaluation at a tertiary care hospital. Median plasma TMAO was 4.8 μmol/L (interquartile range, 2.9–8.0 μmol/L). Elevated TMAO levels were associated with 2.7‐fold increased mortality risk (fourth versus first quartiles, hazard ratio 2.86, 95% CI 1.82–3.97, P<0.001). Following adjustments for traditional risk factors, inflammatory biomarkers, and history of coronary artery disease, the highest TMAO quartile remained predictive of 5‐year mortality (adjusted hazard ratio 2.06, 95% CI 1.36–3.11, P<0.001). Similar prognostic value for elevated TMAO was seen for subjects with carotid artery, non–carotid artery, or lower extremity PAD. TMAO provided incremental prognostic value for all‐cause mortality (net reclassification index, 40.22%; P<0.001) and improvement in area under receiver operator characteristic curve (65.7% versus 69.4%; P=0.013).

Conclusions: TMAO, a pro‐atherogenic metabolite formed by gut microbes, predicts long‐term adverse event risk and incremental prognostic value in patients with PAD. These findings point to the potential for TMAO to help improve selection of high‐risk PAD patients with or without significant coronary artery disease, who likely need more aggressive and specific dietary and pharmacologic therapy.

No MeSH data available.


Related in: MedlinePlus

Comparison of fasting trimethylamine‐N‐oxide (TMAO) levels between patients with carotid artery stenosis and non–carotid artery stenosis. TMAO concentration was not significantly different between patients with carotid artery stenosis (CAS) and non–carotid artery stenosis (Non‐CAS).
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jah31807-fig-0001: Comparison of fasting trimethylamine‐N‐oxide (TMAO) levels between patients with carotid artery stenosis and non–carotid artery stenosis. TMAO concentration was not significantly different between patients with carotid artery stenosis (CAS) and non–carotid artery stenosis (Non‐CAS).

Mentions: In our study cohort, a total of 935 subjects had reported a history of PAD. Of these, confirmed diagnosis data were not available for 14 patients, and 100 patients with a diagnosis of aortic aneurysm were excluded. Therefore, 821 consecutive patients were included in this study. Baseline characteristics of the 821 participants are shown in Table 2. In our study cohort, the median TMAO level was 4.8 μmol/L (interquartile range 2.9–8.0 μmol/L), which was similar between patients with CAS and non‐CAS (Figure 1). Subjects with elevated plasma TMAO levels were more likely to be older, with diabetes, with elevated hsCRP, as well as with lower eGFR. In contrast, prior history of CAD, smoking status, myeloperoxidase levels, apolipoprotein B levels, and medication use, were similar across TMAO levels.


Trimethylamine N ‐ Oxide and Mortality Risk in Patients With Peripheral Artery Disease
Comparison of fasting trimethylamine‐N‐oxide (TMAO) levels between patients with carotid artery stenosis and non–carotid artery stenosis. TMAO concentration was not significantly different between patients with carotid artery stenosis (CAS) and non–carotid artery stenosis (Non‐CAS).
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121520&req=5

jah31807-fig-0001: Comparison of fasting trimethylamine‐N‐oxide (TMAO) levels between patients with carotid artery stenosis and non–carotid artery stenosis. TMAO concentration was not significantly different between patients with carotid artery stenosis (CAS) and non–carotid artery stenosis (Non‐CAS).
Mentions: In our study cohort, a total of 935 subjects had reported a history of PAD. Of these, confirmed diagnosis data were not available for 14 patients, and 100 patients with a diagnosis of aortic aneurysm were excluded. Therefore, 821 consecutive patients were included in this study. Baseline characteristics of the 821 participants are shown in Table 2. In our study cohort, the median TMAO level was 4.8 μmol/L (interquartile range 2.9–8.0 μmol/L), which was similar between patients with CAS and non‐CAS (Figure 1). Subjects with elevated plasma TMAO levels were more likely to be older, with diabetes, with elevated hsCRP, as well as with lower eGFR. In contrast, prior history of CAD, smoking status, myeloperoxidase levels, apolipoprotein B levels, and medication use, were similar across TMAO levels.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Production of the proatherogenic metabolite, trimethylamine N‐oxide (TMAO), from dietary nutrients by intestinal microbiota enhances atherosclerosis development in animal models and is associated with atherosclerotic coronary artery disease in humans. The utility of studying plasma levels of TMAO to risk stratify in patients with peripheral artery disease (PAD) has not been reported.

Methods and results: We examined the relationship between fasting plasma TMAO and all‐cause mortality (5‐year), stratified by subtypes of PAD and presence of coronary artery disease in 935 patients with PAD who underwent elective angiography for cardiac evaluation at a tertiary care hospital. Median plasma TMAO was 4.8 μmol/L (interquartile range, 2.9–8.0 μmol/L). Elevated TMAO levels were associated with 2.7‐fold increased mortality risk (fourth versus first quartiles, hazard ratio 2.86, 95% CI 1.82–3.97, P<0.001). Following adjustments for traditional risk factors, inflammatory biomarkers, and history of coronary artery disease, the highest TMAO quartile remained predictive of 5‐year mortality (adjusted hazard ratio 2.06, 95% CI 1.36–3.11, P<0.001). Similar prognostic value for elevated TMAO was seen for subjects with carotid artery, non–carotid artery, or lower extremity PAD. TMAO provided incremental prognostic value for all‐cause mortality (net reclassification index, 40.22%; P<0.001) and improvement in area under receiver operator characteristic curve (65.7% versus 69.4%; P=0.013).

Conclusions: TMAO, a pro‐atherogenic metabolite formed by gut microbes, predicts long‐term adverse event risk and incremental prognostic value in patients with PAD. These findings point to the potential for TMAO to help improve selection of high‐risk PAD patients with or without significant coronary artery disease, who likely need more aggressive and specific dietary and pharmacologic therapy.

No MeSH data available.


Related in: MedlinePlus