Interventions for lowering cardiovascular disease risk markers in Chronic Obstructive Pulmonary Disease patients and apparently healthy smokers

Abstract

Cardiovascular disease (CVD) is a leading cause of death worldwide. Disease prevention is a fundamental element in tackling CVD, which includes lifestyle modification. Physical activity (PA) is a beneficial modifiable risk factor for individual health. Higher levels of PA are associated with a lower risk of CVD and all-cause mortality. While CVD prevention is essential for every individual, it is more critical for those who are at higher CVD risk such as smokers and people with chronic obstructive pulmonary disease (COPD). This thesis consists of three studies and one study protocol designed to tackle CVD risk. First, using two, 2-day conditions (control, exercise) in a randomised crossover design, this thesis examined the effects of acute running exercise for attenuating postprandial lipaemia (PPL) and other CVD risk markers in 12 healthy young male smokers and 12 matched male non-smokers. The findings revealed that C-reactive protein (CRP) and fasted triacylglycerol and low density lipoprotein cholesterol concentrations were significantly higher in smokers than non-smokers while high density lipoprotein cholesterol concentrations were lower in smokers than non-smokers. The postprandial lipaemic response to a high-fat meal was higher in smokers than non-smokers and was attenuated to a similar extent the day after exercise in smokers and non-smokers. Exercise also lowered plasma insulin and resting arterial blood pressure responses and increased CRP concentrations in smokers and non-smokers. C-reactive protein concentrations were increased to a similar extent in both groups in response to acute exercise and C-reactive protein concentrations were also elevated in control conditions in smokers. These findings highlight the ability of an acute bout of exercise to augment the postprandial metabolic health of cigarette smokers and non-smokers.Second, a robust protocol that accounts for the control condition and replicates both control and intervention conditions was used to test the reproducibility and true interindividual variability of PPL, arterial stiffness, systolic and diastolic blood pressure responses to acute exercise and high-fat meals. This study revealed promising results where PPL and arterial stiffness responses to acute exercise were reproducible in some of the healthy young male participants, and most participants replicated their responses after the two exercise conditions. Although the findings revealed that acute exercise with high-fat meal ingestion attenuated next day blood pressure, the blood pressure responses showed a large participant variability demonstrated by graph visualisation. Further research with a larger sample size is needed to expand knowledge about the reproducibility and individual variability of CVD risk marker responses to acute exercise. Third, a secondary analysis was conducted on a dataset from four studies to investigate the effectiveness of home based and centre based pulmonary rehabilitation (PR) in people with COPD by stratifying responders (change in PA ≥ 1000 steps/day or change in incremental shuttle walk test (ISWT) performance ≥ 40 m or both) and non-responders (PA change ≤ 1000 steps/day and ISWT change ≤39 m) for each intervention. The baseline characteristics for each response group were compared and tested (using linear regression) as predictors for the improvements in PA. The study revealed that centred-based PR was more effective than home-based PR and usual care in increasing the proportion of responders (PA ≥ 1000 steps/day or ISWT ≥ 40 m or both) and group average ISWT performance. Baseline ISWT performance was shown to predict the change in PA level after PR. People with COPD who had better ISWT performance at baseline were more likely to improve their PA level after PR.Fourth, a robust randomised control study protocol was designed to tackle CVD risk in people with COPD, which included three arms. The first arm is PR, where people with COPD will be enrolled in a gold standard PR programme. The second arm involves a PA intervention where people with COPD will be coached remotely, and a step target will be set weekly to improve their PA. The third arm is usual care where people with COPD will have their routine disease management programme without any exercise intervention. This protocol was approved by the National Health Services ethical committee: REC Reference: 18/EM/0270, IRAS Project ID: 232477 on the 2nd of November 2018, data collection was started but not completed, partly due to COVID-19.Collectively, the information presented in this thesis extends knowledge on the importance of exercise interventions for lowering CVD risk in apparently healthy smokers and in people with COPD. Furthermore, this thesis demonstrates the feasibility of a new technique for examining the reproducibility of acute exercise for modifying PPL and other CVD risk markers in healthy men. Finally, this thesis expands upon existing work employing chronic exercise interventions in people with COPD to improve exercise capacity and PA levels, which could result in a lowering of CVD risk in this diseased population. Exercise and PA interventions should be translated into clinical settings to tackle CVD in smokers and people with COPD. Smokers should engage in regular exercise to improve their postprandial metabolic health and attenuate their CVD risk. Researchers and clinician should use exercise intervention approach to lower the adverse effect of smoking in CV health. Pulmonary rehabilitation programme should be offered to all people with COPD to improve CVD risk markers such as physical inactivity and exercise intolerance. Other strategies to deliver PR should be considered for patients who cannot attend centre-based PR such as home-based PR. Finally, individual response differences after interventions, especially exercise interventions, do exist which may be undesirable for some individuals. Future research should focus on individual responses to exercise interventions to determine the best exercise mode, duration, intensity, frequency, and intervention length of exercise for each individual. Therefore, there is a need in future research and clinical settings to investigate individual responses, and to implement adjunctive interventions (such as weight loss programme) for an optimal response. Postprandial lipaemic response and arterial stiffness measurement was shown to be reproducible in this thesis and could be used to assess the effectiveness of exercise programmes on attenuating CVD risk.