Understanding the link between physical capability markers, sarcopenia and frailty and adverse health outcomes

Although chronological age is the main determinant of ageing, physical and social environment factors play a crucial role in healthy ageing, even in earlier stages of life. Physical and biological limitations are not, necessarily, restricted to older ages. Therefore, considering the predicted rapid increase in the number of older people worldwide along with its individual and societal burden, research into healthy ageing - including middle-aged and older individuals - is a priority. Physical capability is the ability to perform the basic and instrumental activities of daily living. As the decline in physical function occurs progressively with age, the study of this process should start earlier in life and not only during older age. Low levels of physical capability markers (such as grip strength, muscle mass and physical performance [gait speed]) are strong predictors of future health, including premature mortality, cardiovascular and neurodegenerative diseases in middle-aged and old-aged populations. With age, the decline in physical function could occur in more than one marker. Consequently, the study of combined physical capability markers and their clinical combinations 'sarcopenia' and 'frailty' needs to be further explored using prospective data with common and non-common adverse health outcomes. Considering the associations of physical capability, sarcopenia, and frailty with adverse health outcomes are not fully understood (both investigated in isolation and as the combined effect), the main aim of this thesis was to determine the associations between measures of physical capability, sarcopenia, and frailty and a range of health outcomes, including mortality, cardiovascular (CVD) and respiratory diseases. To achieve this general aim, seven papers were completed and included in this thesis. Since the overall prevalence of frailty was already estimated using different classifications, the first paper included in this thesis systematically reports and summarises the overall prevalence of sarcopenia (and severe sarcopenia) using different global classifications. Using 6 main classifications, I estimated that the overall prevalence of sarcopenia ranges from 10% to 27% according to the classification used while the prevalence of severe sarcopenia ranges to 2 to 9%. Then, data from the UK Biobank study was used to investigate the association between the exposures and health outcomes. UK Biobank is a general cohort study that recruited over 500,000 participants between 2006 and 2010. Participants aged 37-73 years attended one of the 22 assessment research centres across Scotland, England and Wales at baseline. Using the UK Biobank data, the other six studies were carried out. Across these manuscripts, the associations between different exposures - combinations of sarcopenia, frailty, and individual physical capabilities - and adverse outcomes were determined in each manuscript included: incident and mortality for CVD, respiratory diseases, osteoporosis, cancer, COVID-19, dementia as well as all-cause mortality. In terms of individuals physical capability markers, the strongest association was identified between slow gait speed and incident COPD and respiratory disease as well as all-cause, respiratory and CVD. For incident osteoporosis instead, low muscle mass, followed by slow gait speed, were associated with a higher risk in both sexes. Regarding combinations of physical capability markers, slow gait speed plus low muscle mass, followed for severe sarcopenia, demonstrated the strongest association with incident respiratory disease and all-cause mortality. In terms of osteoporosis, pre-sarcopenic men and sarcopenic women showed a stronger association with incident osteoporosis. The study of the combination between frailty and sarcopenia categories identified that the highest CVD and respiratory risk was identified among frail and sarcopenic individuals. In addition, individuals with more than one clinical condition (frailty, sarcopenia, cachexia, and malnutrition) had almost five times higher risk of dying than those with none (hazard ratio (HR): 4.96 [95% CI: 2.73 to 9.01]). Finally, when frailty was investigated in isolation, I demonstrated that, independently of the frailty classification used, those with pre-frail or frail had a higher risk of severe covid-19. Moreover, pre-frail and frail individuals had an increased risk of all-cause dementia independently of confounder factors such as morbidity (HR pre-frail: 1.21 [95% CI: 1.04 to 1.42] and HR frail: 1.98 [95% CI: 1.47 to 2.67]). Therefore, this thesis demonstrated that individuals with lower physical capability, sarcopenia and/or frailty had a higher risk of adverse health outcomes, including: incidence and mortality for osteoporosis, CVD, respiratory disease, cancer, COVID-19, dementia, and all-cause mortality. These associations remained even after adjustment for a large range of potential confounders and existed both in middle-aged and older adult sub-groups. Considering that the age-related decline in physical capability markers, and therefore sarcopenia and frailty, could be delay and prevented, health interventions to improve physical capability that may reduce the risk of these outcomes are more urgent than ever.