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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

Study design. LEAD indicates lower extremity peripheral artery disease; PAD, peripheral artery disease.
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jah31807-fig-0002: Study design. LEAD indicates lower extremity peripheral artery disease; PAD, peripheral artery disease.

Mentions: Of the 821 subjects included, 371 had diagnosis of CAS confirmed by duplex ultrasonography (83%), magnetic resonance angiography (2.7%), catheter‐based radiocontrast angiography (4.0%), prior endovascular intervention (3.8%), and open carotid endarterectomy (6.5%); 421 patients had LEAD confirmed by the following: ankle–brachial index <0.9 (65.5%), duplex ultrasonography (7.0%), computed tomography angiography (1.5%), magnetic resonance angiography (0.5%), catheter‐based radiocontrast angiography (7.7%), prior endovascular intervention (8.8%), and prior open surgical procedure (9.0%); 15 patients had RAS confirmed by magnetic resonance angiography (20%), catheter‐based radiocontrast angiography (53%), and prior endovascular intervention (27%); 13 patients had upper extremity artery stenosis confirmed by catheter‐based radiocontrast angiography (38.5%), and prior endovascular intervention (61.5%), and 1 patient had MAS confirmed by prior endovascular intervention (Figure 2).


Trimethylamine N ‐ Oxide and Mortality Risk in Patients With Peripheral Artery Disease
Study design. LEAD indicates lower extremity peripheral artery disease; PAD, peripheral artery disease.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

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

jah31807-fig-0002: Study design. LEAD indicates lower extremity peripheral artery disease; PAD, peripheral artery disease.
Mentions: Of the 821 subjects included, 371 had diagnosis of CAS confirmed by duplex ultrasonography (83%), magnetic resonance angiography (2.7%), catheter‐based radiocontrast angiography (4.0%), prior endovascular intervention (3.8%), and open carotid endarterectomy (6.5%); 421 patients had LEAD confirmed by the following: ankle–brachial index <0.9 (65.5%), duplex ultrasonography (7.0%), computed tomography angiography (1.5%), magnetic resonance angiography (0.5%), catheter‐based radiocontrast angiography (7.7%), prior endovascular intervention (8.8%), and prior open surgical procedure (9.0%); 15 patients had RAS confirmed by magnetic resonance angiography (20%), catheter‐based radiocontrast angiography (53%), and prior endovascular intervention (27%); 13 patients had upper extremity artery stenosis confirmed by catheter‐based radiocontrast angiography (38.5%), and prior endovascular intervention (61.5%), and 1 patient had MAS confirmed by prior endovascular intervention (Figure 2).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Production of the proatherogenic metabolite, trimethylamine N&#8208;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&#8208;cause mortality (5&#8208;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&nbsp;&mu;mol/L (interquartile range, 2.9&ndash;8.0&nbsp;&mu;mol/L). Elevated TMAO levels were associated with 2.7&#8208;fold increased mortality risk (fourth versus first quartiles, hazard ratio 2.86, 95% CI 1.82&ndash;3.97, P&lt;0.001). Following adjustments for traditional risk factors, inflammatory biomarkers, and history of coronary artery disease, the highest TMAO quartile remained predictive of 5&#8208;year mortality (adjusted hazard ratio 2.06, 95% CI 1.36&ndash;3.11, P&lt;0.001). Similar prognostic value for elevated TMAO was seen for subjects with carotid artery, non&ndash;carotid artery, or lower extremity PAD. TMAO provided incremental prognostic value for all&#8208;cause mortality (net reclassification index, 40.22%; P&lt;0.001) and improvement in area under receiver operator characteristic curve (65.7% versus 69.4%; P=0.013).

Conclusions: TMAO, a pro&#8208;atherogenic metabolite formed by gut microbes, predicts long&#8208;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&#8208;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