Abstract
BACKGROUND: Low muscle mass (LMM) and mild anemia (MA) are prevalent yet often overlooked conditions in middle-aged and older adults, each independently associated with adverse health outcomes. However, evidence regarding their combined effect on mortality remains limited. This study aimed to investigate the joint association of LMM and MA with all-cause, cardiovascular, and cancer mortality in a national sample of U.S. adults. METHODS: We analyzed data from 10,313 participants aged 45 years and older from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 and 2011-2018, with mortality follow-up through December 2019. LMM was defined using appendicular skeletal muscle mass index (ASM/BMI), and MA was classified based on hemoglobin levels according to WHO criteria. Multivariable Cox proportional hazards models were used to assess individual and joint associations, adjusting for sociodemographic, lifestyle, and clinical factors. RESULTS: Over a median follow-up of 15.3 years, individuals with both LMM and MA had significantly elevated risks of all-cause (HR = 2.43; 95% CI: 1.82-3.26), cardiovascular (HR = 3.57; 95% CI: 2.31-5.52), and cancer mortality (HR = 3.86; 95% CI: 2.22-6.71) compared to those with neither condition. Significant additive and multiplicative interactions were observed between LMM and MA. Subgroup analyses revealed that the combined effect on cancer mortality was particularly pronounced in males and adults aged 65 years or older. CONCLUSIONS: The co-occurrence of LMM and MA is strongly associated with increased risks of all-cause, cardiovascular, and cancer mortality among middle-aged and older adults. These findings highlight the importance of integrated screening and management of both conditions to mitigate mortality risks.