TMAO levels predict mortality in peripheral arterial disease

Last Updated: 2016-10-20

By Will Boggs MD

NEW YORK (Reuters Health) - Higher plasma levels of trimethylamine N-oxide (TMAO) are associated with increased mortality in patients with peripheral arterial disease (PAD), researchers report.

"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," Dr. W. H. Wilson Tang from Cleveland Clinic in Cleveland, Ohio, told Reuters Health by email.

Gut microbiota metabolism of dietary phosphatidylcholine results in the production of TMAO, which has been associated with the development of atherosclerosis in animals and humans, Dr. Tang and colleagues note in the Journal of the American Heart Association, online October 19.

Increased levels of TMAO have also been associated with worse coronary artery disease and increased risk of major adverse cardiac events in patients undergoing elective coronary angiography, they add.

The team investigated the clinical prognostic value of plasma TMAO levels in a prospective study of 821 patients with PAD, including 371 with carotid artery stenosis (CAS), 421 with lower extremity peripheral arterial disease (LEAD), 15 patients with renal artery stenosis (RAS), 13 with upper extremity artery stenosis, and one patient with mesenteric artery stenosis.

The median TMAO level was 4.8 mcmol/L, which was similar between patients with CAS and non-CAS. Increasing quartiles of TMAO levels were associated with a graded increase in risk for all-cause mortality.

After adjustment for traditional risk factors, high-sensitivity C-reactive protein levels, and estimated glomerular filtration rate, the highest quartile of TMAO levels was associated with a significant 88% increase in risk of five-year all-cause mortality, compared with TMAO levels below 2.94 mcmol/L.

Mortality risks were similar across PAD diagnostic subgroups.

"There is clear separation of unadjusted mortality risk when fasting TMAO levels were in the third or fourth quartile (>4.8 mcM) in our study cohort, although only the fourth quartile (>8 mcM) remained statistically significant after covariate adjustments," Dr. Tang said. "The optimal cut-off value would benefit from further validation for this patient population."

"Future clinical studies are needed to determine if dietary modification can reduce TMAO levels in humans and to identify compounds that may modulate TMA-lyase activity to reduce generation of TMA/TMAO without eliminating the microbes," he added.

SOURCE: http://bit.ly/2evwlu8

J Am Heart Assoc 2016.