Vascular Dysfunction and Chronic Obstructive Pulmonary Disease

Abstract

Chronic obstructive pulmonary disease is characterized by low pulmonary function, inflammation, free-radical production, vascular dysfunction and subsequently a greater incidence of cardiovascular disease. By administering an acute oral antioxidant cocktail to patients with chronic obstructive pulmonary disease (n=30) and controls (n=30), we sought to determine the role of redox balance in the vascular dysfunction of these patients. Using a double blind, randomized, placebo controlled, crossover design, patients with chronic obstructive pulmonary disease and controls ingested placebo or the antioxidant cocktail (Vitamin-C, Vitamin-E, α-lipoic acid) after which brachial artery flow mediated dilation and carotid-radial pulse wave velocity were assessed using ultrasound Doppler. The patients exhibited lower baseline antioxidant levels (Vitamin-C and superoxide dismutase activity) and higher levels of oxidative stress (Thiobarbituic acid reactive species) in comparison to controls. The patients also displayed lower basal flow mediated dilation (p<0.05), which was significantly improved with antioxidant cocktail (3.1±0.5 vs. 4.7±0.6 %, p<0.05, placebo vs. antioxidant cocktail), but not controls (6.7±0.6 vs. 6.9±0.7 %, p>0.05, placebo vs. antioxidant cocktail). The antioxidant cocktail also improved pulse wave velocity in the patients (14±1 vs. 11±1 m·s−1, p<0.05, placebo vs. antioxidant cocktail), while not affecting controls (11±2 vs. 10±1 m·s−1, p>0.05, placebo vs. antioxidant). Patients with chronic obstructive pulmonary disease exhibit vascular dysfunction, likely mediated by an altered redox balance, which can be acutely mitigated by an oral antioxidant. Therefore, free radically-mediated vascular dysfunction may be an important mechanism contributing to this population’s greater risk and incidence of cardiovascular disease.

Airflow Limitation and Endothelial Dysfunction. Unrelated and Independent Predictors of Atherosclerosis

“…Specifically, a study that used the gold standard method to assess endothelial function (invasive measurement of forearm vasoreactivity to intraarterial infusion of vasodilators) did not identify an association between airflow limitation and endothelial function (30). In contrast, others have reported statistically significant associations between airflow limitation and endothelial function, although with large differences in effect size (6)(7)(8)(9)(10)(11). For example, there was a greater than 10-fold difference in the magnitude of change in endothelial function per unit change in FEV 1 between two studies (b = 0.22 vs. 0.019; both P , 0.05) (6,10).…”

“…Prior studies that have investigated the relationship between airflow limitation and endothelial function, however, have produced inconsistent results (6)(7)(8)(9)(10)(11)30). Specifically, a study that used the gold standard method to assess endothelial function (invasive measurement of forearm vasoreactivity to intraarterial infusion of vasodilators) did not identify an association between airflow limitation and endothelial function (30).…”

“…Some studies excluded women (8); current smokers (9,11); those treated with statins or antihypertensive medication (6,10); and those with a history of coronary, cerebrovascular, or peripheral artery disease (30) or heart failure (8). In one study only 13% of eligible participants met inclusion criteria (6).…”

“…Prior studies have examined the relationship between expiratory airflow and endothelial dysfunction but have produced inconsistent results (6)(7)(8)(9)(10)(11). Because these studies did not assess atherosclerosis per se, it remains unknown if endothelial dysfunction mediates the association between FEV 1 and atherosclerosis.…”

“Radical” Link Between Chronic Obstructive Pulmonary Disease and Cardiovascular Disease?

“…Importantly, in a study of 60 subjects with COPD, FEV1 and major indicators of inflammation such as leukocyte count or C-reactive protein were identified as major independent predictors of endothelial dysfunction. 4,5 In the current issue of Hypertension, Ives et al 6 show that vascular endothelial function is impaired and vascular stiffness is increased in patients with COPD. Importantly, they demonstrate that free radical production may be involved in mediating the link between COPD and vascular dysfunction, as oral antioxidant cocktail administration acutely restored vascular function back to that of controls.…”