Format

Send to

Choose Destination
Sci Rep. 2019 Oct 30;9(1):15580. doi: 10.1038/s41598-019-52082-z.

Trimethylamine-N-Oxide (TMAO) Predicts Cardiovascular Mortality in Peripheral Artery Disease.

Author information

1
Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA Universidad de Navarra, Pamplona, Spain.
2
CIBERCV, Instituto de Salud Carlos III, Madrid, Spain.
3
IdiSNA, Pamplona, Spain.
4
Departamento de Angiología y Cirugía Vascular, Complejo Hospitalario de Navarra, Pamplona, Spain.
5
Laboratory of Heart Failure, Program of Cardiovascular Diseases, CIMA Universidad de Navarra, Pamplona, Spain.
6
Department of Occupational Medicine, Clínica Universidad de Navarra, Pamplona, Spain.
7
Small Molecules Platform, Program of Molecular Therapies, CIMA Universidad de Navarra, Pamplona, Spain.
8
Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA Universidad de Navarra, Pamplona, Spain. japaramo@unav.es.
9
CIBERCV, Instituto de Salud Carlos III, Madrid, Spain. japaramo@unav.es.
10
IdiSNA, Pamplona, Spain. japaramo@unav.es.
11
Hematology Service, Clínica Universidad de Navarra, Pamplona, Spain. japaramo@unav.es.

Abstract

Peripheral artery disease (PAD) is a major cause of acute and chronic illness, with extremely poor prognosis that remains underdiagnosed and undertreated. Trimethylamine-N-Oxide (TMAO), a gut derived metabolite, has been associated with atherosclerotic burden. We determined plasma levels of TMAO by mass spectrometry and evaluated their association with PAD severity and prognosis. 262 symptomatic PAD patients (mean age 70 years, 87% men) categorized in intermittent claudication (IC, n = 147) and critical limb ischemia (CLI, n = 115) were followed-up for a mean average of 4 years (min 1-max 102 months). TMAO levels were increased in CLI compared to IC (P < 0.001). Receiver operating characteristic (ROC) curves for severity (CLI) rendered a cutoff of 2.26 µmol/L for TMAO (62% sensitivity, 76% specificity). Patients with TMAO > 2.26 µmol/L exhibited higher risk of cardiovascular death (sub-hazard ratios ≥2, P < 0.05) that remained significant after adjustment for confounding factors. TMAO levels were associated to disease severity and CV-mortality in our cohort, suggesting an improvement of PAD prognosis with the measurement of TMAO. Overall, our results indicate that the intestinal bacterial function, together with the activity of key hepatic enzymes for TMA oxidation (FMO3) and renal function, should be considered when designing therapeutic strategies to control gut-derived metabolites in vascular patients.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center