Microbiota γ‐Butyrobetaine Is Associated With Increased Risk of Major Adverse Limb Events in People With Lower Extremity Arterial Disease Undergoing Endovascular Therapy
Journal
Journal of the American Heart Association
Journal Volume
14
Journal Issue
16
ISSN
2047-9980
Date Issued
2025-08-19
Author(s)
Abstract
Background: Peripheral artery disease (PAD), a significant contributor to both acute and chronic illnesses, indicates a grave prognosis, but it is often unrecognized and receives inadequate treatment. γ-Butyrobetaine, formed during gut microbial metabolism of L-carnitine, acts as a proatherogenic intermediate in the production of trimethylamine N-oxide (TMAO). While TMAO has been linked to a heightened risk of cardiovascular mortality of individuals with PAD, the impact of γ-butyrobetaine remains unclear. The objective of this study was to examine the prognostic value of serum γ-butyrobetaine for patients with PAD.
Methods: We prospectively enrolled 395 patients with symptomatic PAD. Comprehensive medical histories, encompassing demographic and medication data, were collected, and serum biochemistry data, including TMAO and γ-butyrobetaine, were obtained. These patients, with a mean age of 72.2 years (61% men), were followed for an average of 1.5 years. They were categorized into 2 groups: 165 patients with intermittent claudication and 230 patients with critical limb-threatening ischemia. The primary outcome studied was major adverse limb events (MALE), which included lower-limb revascularization and amputation. MALE developed in 89 (22.5%) patients. Following adjustment for confounding factors in the multivariate Cox proportional hazards model, γ-butyrobetaine was significantly associated with MALE (hazard ratio, 1.93 [95% CI, 1.35-2.76]). By contrast, TMAO did not show a significant association with the risk of MALE.
Conclusions: While both TMAO and γ-butyrobetaine were linked to increased major adverse cardiovascular events in patients with PAD, only γ-butyrobetaine was associated with an elevated risk of MALE.
Subjects
major adverse cardiovascular events
major adverse limb events
peripheral artery disease
trimethylamine N‐oxide
γ‐Butyrobetaine
SDGs
Publisher
Ovid Technologies (Wolters Kluwer Health)
Type
journal article