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 -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.