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

OBJECTIVE: 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.