Independent association of plasma hydroxysphingomyelins with physical function in the Atherosclerosis Risk in Communities (ARIC) study

Background: Plasma metabolites such as phosphatidylcholines and sphingomyelins (SMs) are associated with an age-related cognitive decline. However, their relations to age-related physical function decline remain largely unknown. Methods: We examined the cross-sectional relations of 12 plasma metabolites (including four phosphatidylcholines and four SMs) with physical function in 383 older adults in the At herosclerosis Risk in Communities Study at the fifth exam (2011-2013, mean age [standard deviation (SD)]: 78.0 [5.5], 54.4% women, 28.3% African Americans). Physical function was assessed using grip strength, Short Physical Performance Battery, and 4-m walking speed. Individual metabolites were log-transformed and standardized. Multivariable linear regression was performed to account for demographics, APOE genotype, cardiovascular risk factors, comorbidities, use of antihypertensive and lipid-lowering medications, depressive symptoms, and cognition. Results: Lower concentrations of asymmetric dimethylarginine and higher concentrations of SM (OH) C22:1, SM (OH) C22:2, and SM (OH) C24:1 were associated with physical function measures. In particular, SM (OH) C22:1 and SM (OH) C24:1 were associated with all three measures of physical function: β-coefficients (95% confidence interval) with grip strength were 0.89 kg (0.00, 1.78) and 0.86 kg (0.10, 1.61) per 1 SD higher concentration, respectively; with Short Physical Performance Battery score, were 0.61 (0.34, 0.88) and 0.41 (0.19, 0.63) per 1 SD difference, respectively; with 4-m walking speed were 0.035 m/s (0.013, 0.056) and 0.035 m/s (0.028, 0.047), respectively. Conclusions: Plasma SM (OH)s may be independently associated with physical function in older adults.