Association of muscle wasting with mortality risk among adults: A systematic review and meta‐analysis of prospective studies

Abstract

The relationship between muscle wasting and mortality risk in the general population remains unclear. Our study was conducted to examine and quantify the associations between muscle wasting and all‐cause and cause‐specific mortality risks. PubMed, Web of Science and Cochrane Library were searched until 22 March 2023 for main data sources and references of retrieved relevant articles. Prospective studies investigating the associations of muscle wasting with risks of all‐cause and cause‐specific mortality in the general population were eligible. A random‐effect model was used to calculate the pooled relative risk (RR) and 95% confidence intervals (CIs) for the lowest versus normal categories of muscle mass. Subgroup analyses and meta‐regression were performed to investigate the potential sources of heterogeneities among studies. Dose–response analyses were conducted to evaluate the relationship between muscle mass and mortality risk. Forty‐nine prospective studies were included in the meta‐analysis. A total of 61 055 deaths were ascertained among 878 349 participants during the 2.5‐ to 32‐year follow‐up. Muscle wasting was associated with higher mortality risks of all causes (RR = 1.36, 95% CI, 1.28 to 1.44, I2 = 94.9%, 49 studies), cardiovascular disease (CVD) (RR = 1.29, 95% CI, 1.05 to 1.58, I2 = 88.1%, 8 studies), cancer (RR = 1.14, 95% CI, 1.02 to 1.27, I2 = 38.7%, 3 studies) and respiratory disease (RR = 1.36, 95% CI, 1.11 to 1.67, I2 = 62.8%, 3 studies). Subgroup analyses revealed that muscle wasting, regardless of muscle strength, was significantly associated with a higher all‐cause mortality risk. Meta‐regression showed that risks of muscle wasting‐related all‐cause mortality (P = 0.06) and CVD mortality (P = 0.09) were lower in studies with longer follow‐ups. An approximately inverse linear dose–response relationship was observed between mid‐arm muscle circumference and all‐cause mortality risk (P < 0.01 for non‐linearity). Muscle wasting was associated with higher mortality risks of all causes, CVD, cancer and respiratory disease in the general population. Early detection and treatment for muscle wasting might be crucial for reducing mortality risk and promoting healthy longevity.

Musculoskeletal Pain, Physical Activity, Muscle Mass, and Mortality in Older Adults: Results from the Korean Longitudinal Study on Health and Aging (KLoSHA)

“…A recent review indicates that muscle mass in individuals aged 75 years or older declines at a rate of 0.64–0.70% per year in women and 0.80–0.98% per year in men, which is greater compared to younger age groups [ 60 ]. This age-related decline in muscle mass compromises physical performance [ 61 ], elevates the risk of physical disability in later life [ 62 ], and increases the overall mortality risk [ 63 ]. Additionally, levels of inflammatory cytokines are elevated in older adults compared to younger individuals [ 64 ].…”

Leucine Supplementation Prevents the Development of Skeletal Muscle Dysfunction in a Rat Model of HFpEF

“…The abnormalities observed in the SKM of HFpEF patients or experimental models of the disease include the following: decreased muscle mass [ 8 , 10 ]; a reduced type I-to-type-II fiber ratio as well as a reduced capillary-to-fiber ratio [ 7 , 11 , 12 ]; abnormal fat infiltration into the thigh SKM [ 13 , 14 ]; increased levels of atrophy genes and proteins [ 8 , 15 ]; reduction in mitochondrial function and content [ 16 , 17 , 18 ]; and rapid depletion of high-energy phosphate during exercise with markedly delayed repletion of high-energy phosphate during recovery [ 19 ]. Since exercise intolerance is associated with reduced quality of life and increased mortality [ 20 , 21 , 22 ], the search for therapeutic options to improve exercise capacity and the translation to the clinical scenario is performed with great effort. So far, exercise training [ 23 , 24 ] and sodium–glucose cotransporter 2 inhibitors (SGLTi) [ 25 ] have demonstrated positive effects with respect to improved quality of life and reduced mortality.…”

β2-Adrenoceptors activation regulates muscle trophic-related genes following acute resistance exercise in mice

“…This tissue is fundamental for locomotion, breathing, thermogenesis, energy expenditure, and glycemic control ( Pedersen, 2013 ; Schnyder and Handschin, 2015 ). Due to these important functions, muscle wasting and weakness have been associated with reduced quality of life and higher mortality risks of all causes, cancer, chronic obstructive pulmonary disease (COPD) and aging ( Mathur et al, 2014 ; Santana et al, 2019 ; Zhou et al, 2023 ). Despite these alarming findings, there is no effective pharmacological treatment for preventing muscle atrophy in such conditions.…”