Treatment of OSA and its Impact on Cardiovascular Disease, Part 2: JACC State-of-the-Art Review

Abstract

Many studies have shown an association of obstructive sleep apnea (OSA) with incident cardiovascular diseases, particularly when comorbid with insomnia, excessive sleepiness, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease. Randomized controlled trials (RCTs) have demonstrated that treatment of OSA with positive airway pressure devices (CPAP) improves systemic hypertension, particularly in those with resistant hypertension who are adherent to CPAP. However, large RCTs have not shown long-term benefits of CPAP on hard cardiovascular outcomes, but post hoc analyses of these RCTs have demonstrated improved hard outcomes in those who use CPAP adequately. In theory, low CPAP adherence and patient selection may have contributed to neutral results in intention-to-treat analyses. Only by further research into clinical, translational, and basic underlying mechanisms is major progress likely to continue. This review highlights the various treatment approaches for sleep disorders, particularly OSA comorbid with various other disorders, the potential reasons for null results of RCTs treating OSA with CPAP, and suggested approaches for future trials.

Keywords: CPAP; OSA; hypoventilation syndrome; noninvasive ventilation; obesity.

CENTRAL ILLUSTRATION. Phenotypic Therapeutic Options in Obstructive Sleep Apnea

The figure depicts various mechanisms which could be target of therapy in obstructive sleep apnea. Although continuous positive airway pressure (CPAP) device is the most effective therapeutic option, other variables could also be targeted as depicted. HGN = hypoglossal nerve.

FIGURE 1. Effect of CPAP Therapy on BP in Patients With Resistant Hypertension

The figure includes the results of the randomized controlled trials published to date. Positive figures mean improvement in blood pressure (BP) level with continuous positive airway pressure (CPAP) treatment (net changes). From Javaheri et al. DBP = diastolic blood pressure; SBP = systolic blood pressure.

FIGURE 2. Prevalence and Evolution of PH in the Pickwick Trial

This figure shows a significant drop in the prevalence of pulmonary hypertension (PH), which was sustained through the 3-year follow-up. Adapted from Masa et al and Mokhlesi et al. CPAP = continuous positive airway pressure; NIV = noninvasive ventilation.

FIGURE 3. CPAP Treatment of OSA in the Overlap Syndrome Improves Survival

Long-term outcome study showing that patients with overlap syndrome and moderate or severe obstructive sleep apnea (OSA) treated with continuous positive airway pressure (CPAP) have similar survival rates to those with chronic obstructive pulmonary disease (COPD) alone, whereas those patients with overlap syndrome (COPD with OSA) not treated with CPAP had higher mortality, especially from cardiovascular disease. Adapted with permission of the American Thoracic Society.

FIGURE 4. Effective Use of CPAP Improves Cerebrocardiovascular Outcomes and All-Cause Mortality

The y-axis shows the risk ratio (RR) with 95% CI; the x-axis shows the different types of individual and composite cardiovascular (CV) events. *P < 0.05. Reprinted with permission of the American Thoracic Society. AMI = acute myocardial infarction; CCVE = cardiocerebrovascular event; CPAP = continuous positive airway pressure; HF = heart failure; MACCE = major adverse cardiocerebrovascular events; TIA = transient ischemic attack.