Trimethylamine N-Oxide, a Gut Microbiota-Dependent Metabolite, is Associated with Frailty in Older Adults with Cardiovascular Disease

Wei He,1,2 Yao Luo,1 Jun-Peng Liu,1 Ning Sun,1 Di Guo,1 Ling-Ling Cui,1 Pei-Pei Zheng,1 Si-Min Yao,1 Jie-Fu Yang,1,2 Hua Wang1,2 1Department of Cardiology, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 2Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Hua Wang; Jie-Fu YangDepartment of Cardiology, Beijing Hospital, National Center of Gerontology, No. 1, Dahua Road, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel +86 13911680467; +86 13601292259Fax +86 10-58115035Email wanghua2764@bjhmoh.cn; yangjiefu2011@126.comObjective: Our study aimed to explore the association between trimethylamine N-oxide and frailty in older adults with cardiovascular disease.Patients and Methods: This cross-sectional study analyzed a total of 451 people aged 65 years or older who underwent comprehensive geriatric assessments. Frailty status was determined using a frailty index constructed with 48 variables according to the cumulative deficits model. Physical frailty and cognitive frailty were also assessed in detail. Fasting plasma TMAO was measured by mass spectrometry.Results: The proportion of frail subjects was 29.9% (135/451). Plasma TMAO levels were significantly higher in frail patients than in nonfrail individuals (4.04 [2.84– 7.01] vs 3.21 [2.13– 5.03] μM; p< 0.001). Elevated plasma TMAO levels were independently associated with the likelihood of frailty (OR 2.12, 95% CI 1.01– 4.38, p=0.046). Dose–response analysis revealed a linear association between the TMAO concentration and the OR for frailty. A 2-unit increase in TMAO was independently correlated with physical frailty (OR 1.23, 95% CI 1.08– 1.41, p for trend 0.002) and cognitive frailty (OR 1.21, 95% CI 1.01– 1.45, p for trend 0.04).Conclusion: Elevated circulating TMAO levels are independently associated with frailty among older adults with cardiovascular disease.Keywords: older adults, frailty, TMAO, cardiovascular disease, physical frailty, cognitive frailty