Introduction
Obstructive sleep apnea (OSA) is a common condition that is estimated to affect 1 billion adults between the ages of 35–69 years old [1], and this disease is a major public health problem. Patients with OSA commonly experience excessive daytime sleepiness, insomnia, and snoring and are at an increased risk of cardiovascular disease [2]. According to the American Academy of Sleep Medicine (AASM), OSA can be classified according to the apnea–hypopnea index (AHI), which defines mild OSA as ≥5 events/hour, moderate OSA as 5–15 events/hour and severe OSA as ≥30 events/hour [3,4]. OSA consequences are related to the hypoxia-reoxygenation mechanism and sleep fragmentation, which increase the expression of several proinflammatory markers, oxidative stress, endothelial dysfunction and sympathetic activation. Moderate and severe OSA are associated with an increased risk of cardiovascular (CV) events (stroke, unstable angina, heart failure, myocardial infarction (MI) and CV mortality) [5]. In addition to lifestyle interventions, OSA treatment with continuous positive airway pressure (CPAP) is the standard intervention for moderate and severe OSA patients. The efficacy of this therapy is based on improvement in OSA symptoms, changes in sleep architecture and a significant decrease in the AHI. These improvements are associated with a decrease in CIH and ultimately improved CV outcomes [6].Observational studies have reported an increased risk of cardiovascular mortality in patients with moderate to severe OSA who are not being treated. Long-term CPAP usage has been reported to improve CV outcomes in different OSA populations, such as middle-aged men. Marin et al. [7] reported a significant reduction in CV events with an odds ratio of 0.35, and similar findings were observed in other populations, such as women [8] and the elderly population [9]. Despite the results of observational studies, data from randomized controlled trials (RCTs) have shown discordance in relevant outcomes such as CV morbi-mortality, especially in OSA patients with previous cardiovascular events (secondary prevention) [10].
The purpose of this systematic review and meta-analysis is to analyze the current evidence on the efficacy of CPAP as an intervention to prevent cardiovascular events in patients with OSA, focusing on primary and secondary prevention. For this review, we predefined the following PICO question: In patients with OSA, is CPAP therapy more effective for the reduction of major adverse cardiovascular events (MACEs) than placebo or usual care?