Comorbid obstructive sleep apnoea and chronic obstructive pulmonary disease and the risk of cardiovascular disease

Abstract

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) syndrome are both highly prevalent, affecting at least 10% of the general adult population, and each has been independently associated with an increased risk of cardiovascular disease. The presence of both disorders together, commonly referred to as the overlap syndrome, is also highly prevalent, although various clinical and pathophysiological factors associated with COPD may increase or decrease the likelihood of OSA. Lung hyperinflation reduces the likelihood of obstructive apnoea, whereas right heart failure increases the likelihood as a result of rostral fluid shift causing upper airway narrowing in the supine position while asleep. Furthermore, upper airway inflammation associated with OSA may aggravate lower airway inflammation in COPD. The proposed mechanisms of cardiovascular disease in each disorder are similar and include systemic inflammation, oxidative stress, and sympathetic excitation. Thus, one could expect that the prevalence of co-morbid cardiovascular disease would be higher in the overlap syndrome but, with the exception of pulmonary hypertension, there are few published reports that have explored this aspect in depth. Hypoxia is more pronounced in patients with the overlap syndrome, especially during sleep, which is likely to be the principal factor accounting for the recognised higher prevalence of pulmonary hypertension in these patients. Cardiac sympathetic activity is increased in patients with the overlap syndrome when compared to each disorder alone, but echocardiographic evidence of left ventricular strain is no greater in overlap patients when compared to COPD alone. While survival might be expected to be worse in overlap patients, recent evidence surprisingly indicates that the incremental contribution of lung function to mortality diminishes with increasing severity of OSA. Identification of co-morbid OSA in patients with COPD has practical clinical significance as appropriate positive airway pressure therapy in COPD patients with co-existing OSA is associated with improved morbidity and mortality.

Keywords: Obstructive sleep apnoea (OSA); cardiovascular disease; chronic obstructive pulmonary disease (COPD); continuous positive airway pressure (CPAP); overlap syndrome.

Figure 1

Interactions between COPD and OSA that may influence the prevalence of the overlap syndrome [reproduced from (9)]. COPD, chronic obstructive pulmonary disease; OSA, obstructive sleep apnoea; BMI, body mass index; REM, rapid-eye-movement.

Figure 2

Different patterns of oxygen desaturation during sleep in patients with (A) COPD, (B) overlap syndrome and (C) OSA. COPD, chronic obstructive pulmonary disease; OSA, obstructive sleep apnoea; SaO₂/SpO₂, oxygen saturation; PtcCO₂, transcutaneous carbon dioxide tension [adapted from (38)].

Figure 3

Interactions of COPD and OSAS in inflammatory mechanisms that predispose to cardiovascular disease. Both COPD and OSAS are associated with elevated levels of CRP and IL-6, in addition to TNF-α and IL-8, and are also associated with oxidative stress. However, cigarette smoking and obesity are confounding variables in these associations. Hypoxia is a key factor in elevated TNF-α production in OSAS, which is particularly relevant to the overlap syndrome. In OSA, and to a lesser extent COPD, the hypoxia is usually intermittent, which is particularly pro-inflammatory. Each inflammatory pathway has been associated with atherogenesis and subsequent cardiovascular disease. COPD, chronic obstructive pulmonary disease; OSA, obstructive sleep apnoea; CRP, c-reactive protein; IL-6, interleukin-6; TNF-α, tumor necrosis factor alpha; IL-8, interleukin-8. Reproduced from (8).

Figure 4

Kaplan-Meier survival curves for outcomes among COPD patients without OSA (COPD group), patients with COPD and coexisting OSA (overlap group), and patients with overlap syndrome treated with CPAP since enrolment (overlap with CPAP group). Percentage survival (A), percentage of severe COPD exacerbation-free survival curves among the three study groups (B). The differences between COPD only and COPD with OSA treated with CPAP are statistically significant from patients with COPD and untreated OSA (P<0.001). COPD, chronic obstructive pulmonary disease; OSA, obstructive sleep apnoea; CPAP, continuous positive airway pressure. Reproduced from (58).