John, Michelle
(2014)
The extra-pulmonary effects of chronic obstructive pulmonary disease (COPD).
PhD thesis, University of Nottingham.
Abstract
Rationale
Cardiovascular disease (CVD) is a leading cause of mortality in patients with COPD. Aortic stiffness, measured using aortic pulse wave velocity (PWV), an independent, non-invasive, predictor of CV risk; and inflammatory markers are increased in COPD. Screening tools for community based identification of increased CVD risk, and a proactive approach to addressing primary prevention of CVD is needed. Statins modulate aortic stiffness and are anti-inflammatory, but are not currently used for primary prevention in COPD.
Objectives
Proof of principle double-blind Randomised Control Trial (RCT) to determine if six weeks simvastatin 20mg od reduces aortic stiffness, systemic and airway inflammation in COPD. Cross-sectional pilot study comparing a non-invasive measure of oxidative stress (skin “AGE”) in COPD and controls, to lung function and aortic stiffness.
Methods
Stable patients (n=70) were randomised to simvastatin or placebo treatment. Pre- and post-treatment aortic stiffness, blood pressure, spirometry, circulating inflammatory mediators and lipids were measured; airway inflammatory markers were performed where possible. Predefined subgroup analysis was performed where baseline aortic PWV >10m/s. For the cross-sectional study stable COPD patients (n=84) and controls (n=36) had lung function, arterial stiffness and skin AGE measured.
Results
In the RCT the active group achieved significantly lower total cholesterol, but no significant drop in aortic PWV compared to placebo group: -0.7(95%CI -1.8,0.5)m/s, p=0.24; or inflammatory markers. In those with higher baseline aortic PWV, n=22, aortic PWV improved in the active group compared to placebo: -2.8(-5.2,-0.3)m/s,
p=0.03.
Skin AGE was increased in COPD compared to controls, inversely related to lung function, and directly related to aortic stiffness.
Conclusions
We could not detect any significant difference in the change in aortic PWV in patients with COPD taking simvastatin compared to placebo. We did, however, report a significant and clinically relevant reduction in aortic PWV in those with high baseline aortic stiffness, suggesting a potential for statins to reduce CV morbidity in high risk individuals. The pilot cross-sectional study suggests there is an indication to assess the potential role of skin AGE in patients with COPD as a non-invasive measure of CV risk.
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