A longitudinal evaluation of novel outcome measures in chronic obstructive pulmonary disease

Background Chronic obstructive pulmonary disease (COPD) is a multimorbidity disease associated with increased risk of cardiovascular events, arterial stiffness and changes in body composition, potentially features of premature ageing and frailty. The aim of this thesis was to assess the change in aortic pulse wave velocity (PWV) over two years and its contributing factors in COPD. In addition, this thesis also aimed to examine the concept of frailty in patients with COPD and its change over a two-year follow-up. Methods Aortic stiffness and frailty were assessed cross-sectionally in 500 patients with COPD and 150 comparators using aortic PWV and frailty index (FI). Other assessments included spirometry, body composition, handgrip strength, Timed Up and Go test (TUG) and systemic inflammatory biomarkers. After two years, 143 consecutive patients were reassessed to examine the changes in aortic PWV and FI. Results In the cross-sectional data, patients with COPD had greater aortic PWV than comparators similar in age, gender and BMI, independent of traditional risk factors. After two years, the patients demonstrated a significant increase in aortic stiffness, independent of age, lung function, blood pressure and inflammation. In addition, a subset of patients was identified to have an accelerated aortic stiffness by 1.6 m/s. At the initial visit, the patients were more frail than comparators similar in age and gender. After two years, the patients had an increase in the FI, independent of lung function and inflammation. The progression of frailty was related to loss of muscle mass and strength, and prolonged TUG time. Conclusion The longitudinal findings of this thesis suggest that COPD is associated with a rapid increase in aortic stiffness, independent of conventional risk factors. Frailty is a clinical feature of COPD and its progression is dependent on loss of musculoskeletal mass and strength and prolonged TUG time.