Microbiota γ-Butyrobetaine Is Associated With Increased Risk of Major Adverse Limb Events in People With Lower Extremity Arterial Disease Undergoing Endovascular Therapy.

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.