Protective association of renin-angiotensin system inhibitor use with skeletal muscle wasting in diabetic heart failure.

AIMS: Muscle wasting is common in heart failure (HF) patients, particularly those with diabetes mellitus (DM). Renin-angiotensin system inhibitors (RASI) may have muscle-protective effects, but their association with muscle wasting in diabetic HF patients remains unclear. We investigated whether the association between RASI use and muscle wasting differs by DM status and plasma 3-methylhistidine (3-Me-His) levels, a muscle protein breakdown biomarker. MATERIALS AND METHODS: We performed a cross-sectional analysis of 384 hospitalized HF patients (mean age 71 ± 14 years, 41% female, 38% with DM). Muscle wasting was defined by dual-energy X-ray absorptiometry according to the Asian Working Group for Sarcopenia criteria. Associations between RASI use and muscle wasting were evaluated using logistic regression with inverse probability of treatment weighting. Interaction analyses assessed effect modification by DM status and 3-Me-His levels. RESULTS: Muscle wasting prevalence was 58%. DM was an independent risk factor for muscle wasting (adjusted odds ratio [OR] 2.07, 95% confidence interval [CI] 1.27-3.38, P = 0.004). RASI were prescribed in 52% of patients. After adjustment, a significant interaction with DM was observed (P = 0.033). Among DM patients, RASI use was associated with lower muscle wasting (OR 0.33, 95% CI 0.14-0.76, P = 0.010), while no association was found in non-DM patients. Within the DM subgroup, the association was more evident in patients with lower 3-Me-His levels (OR 0.12, 95% CI 0.03-0.52, P = 0.005). CONCLUSIONS: RASI use was associated with significantly lower muscle wasting in HF patients with DM, particularly those with lower 3-Me-His levels. These findings suggest a potential therapeutic window and warrant prospective investigation.