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 int...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.037356 |
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| author | Zheng‐Wei Chen Wei‐Kai Wu Jiun‐Yang Chiang Nai‐Chen Cheng Jen‐Kuang Lee Ming‐Shiang Wu |
| author_facet | Zheng‐Wei Chen Wei‐Kai Wu Jiun‐Yang Chiang Nai‐Chen Cheng Jen‐Kuang Lee Ming‐Shiang Wu |
| author_sort | Zheng‐Wei Chen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5510f5e899004532a68f63c2ac29eead |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-5510f5e899004532a68f63c2ac29eead2025-08-20T07:25:00ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-08-01141610.1161/JAHA.124.037356Microbiota γ‐Butyrobetaine Is Associated With Increased Risk of Major Adverse Limb Events in People With Lower Extremity Arterial Disease Undergoing Endovascular TherapyZheng‐Wei Chen0Wei‐Kai Wu1Jiun‐Yang Chiang2Nai‐Chen Cheng3Jen‐Kuang Lee4Ming‐Shiang Wu5Division of Cardiology, Department of Internal Medicine National Taiwan University College of Medicine and Hospital Taipei TaiwanDepartment of Medical Research National Taiwan University Hospital Taipei TaiwanDivision of Cardiology, Department of Internal Medicine National Taiwan University College of Medicine and Hospital Taipei TaiwanDivision of Plastic Surgery, Department of Surgery National Taiwan University College of Medicine and Hospital Taipei TaiwanDivision of Cardiology, Department of Internal Medicine National Taiwan University College of Medicine and Hospital Taipei TaiwanDivision of Gastroenterology and Hepatology, Department of Internal Medicine National Taiwan University College of Medicine and Hospital Taipei TaiwanBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.124.037356major adverse cardiovascular eventsmajor adverse limb eventsperipheral artery diseasetrimethylamine N‐oxideγ‐Butyrobetaine |
| spellingShingle | Zheng‐Wei Chen Wei‐Kai Wu Jiun‐Yang Chiang Nai‐Chen Cheng Jen‐Kuang Lee Ming‐Shiang Wu Microbiota γ‐Butyrobetaine Is Associated With Increased Risk of Major Adverse Limb Events in People With Lower Extremity Arterial Disease Undergoing Endovascular Therapy Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease major adverse cardiovascular events major adverse limb events peripheral artery disease trimethylamine N‐oxide γ‐Butyrobetaine |
| title | Microbiota γ‐Butyrobetaine Is Associated With Increased Risk of Major Adverse Limb Events in People With Lower Extremity Arterial Disease Undergoing Endovascular Therapy |
| title_full | Microbiota γ‐Butyrobetaine Is Associated With Increased Risk of Major Adverse Limb Events in People With Lower Extremity Arterial Disease Undergoing Endovascular Therapy |
| title_fullStr | Microbiota γ‐Butyrobetaine Is Associated With Increased Risk of Major Adverse Limb Events in People With Lower Extremity Arterial Disease Undergoing Endovascular Therapy |
| title_full_unstemmed | Microbiota γ‐Butyrobetaine Is Associated With Increased Risk of Major Adverse Limb Events in People With Lower Extremity Arterial Disease Undergoing Endovascular Therapy |
| title_short | Microbiota γ‐Butyrobetaine Is Associated With Increased Risk of Major Adverse Limb Events in People With Lower Extremity Arterial Disease Undergoing Endovascular Therapy |
| title_sort | microbiota γ butyrobetaine is associated with increased risk of major adverse limb events in people with lower extremity arterial disease undergoing endovascular therapy |
| topic | major adverse cardiovascular events major adverse limb events peripheral artery disease trimethylamine N‐oxide γ‐Butyrobetaine |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.037356 |
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