Abstract
We aimed to investigate a causal effect of functional sarcopenia status, including poor handgrip strength and slow walking pace, on cardiovascular diseases. This study was an observational cohort study including observational analysis and Mendelian randomization. We studied the UK Biobank prospective cohort (n = 324,486) for observational analysis with poor handgrip strength or self-reported slow walking pace as the exposures, investigating risk of myocardial infarction or mortality. Genetic instruments for the exposures were developed in 337,138 individuals of white British ancestries, and coronary artery disease outcome (60,801 cases/123,504 controls) from the independent CARDIoGRAMplustC4D cohort was studied by two-sample Mendelian randomization. The findings were replicated by one-sample analysis by polygenic risk score analysis within the UK Biobank. Both slow walking pace and poor handgrip strength were significantly associated with higher risks of incident myocardial infarction and mortality, particularly from cardiovascular deaths, in the observational investigation. Genetically predicted poor handgrip strength (odds ratio: 1.128 [1.041 to 1.222]) and slow walking pace (odds ratio: 1.171 [1.022 to 1.342]) showed causal effects on the coronary artery disease risks in the independent cohort. The results were again identified by the one-sample Mendelian randomization, as the higher polygenic risk score for poor handgrip strength and slow walking pace was associated with a higher risk of mortality. In conclusion, this study supports the causal effects of slow walking pace and poor handgrip strength on the risks of cardiovascular disease and mortality. The functional sarcopenia status are targetable causative factors for interventions aiming to reduce risks of cardiovascular disease or mortality.</p>