The Association of Sleep Apnea and Cardiorespiratory Fitness With Long-Term Major Cardiovascular Events

Objective: To determine the risk of long-term major adverse cardiovascular events (MACE) when sleep-disordered breathing (SDB) and decreased cardiorespiratory fitness (CRF) co-occur. Methods: We included consecutive patients who underwent symptom-limited cardiopulmonary exercise tests between January 1, 2005, and January 1, 2010, followed by first-time diagnostic polysomnography within 6 months. Patients were stratified based on the presence of moderate-to-severe SDB (apnea/hypopnea index ≥15 per hour) and decreased CRF defined as <70% predicted peak oxygen consumption (VO₂). Long-term MACE was a composite outcome of myocardial infarction (MI), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), stroke or transient ischemic attack (TIA), and death, assessed until May 21, 2018. Cox-proportional hazard models were adjusted for factors known to influence CRF and MACE. Results: Of 498 included patients (60±13 years, 28.1% female), 175 (35%) had MACE (MI=17, PCI=14, CABG=13, stroke=20, TIA=12, deaths=99) at a median follow-up of 8.7 years (interquartile range=6.5 to 10.3 years). After adjusting for age, sex, beta blockers, systemic hypertension, diabetes mellitus, coronary artery disease, cardiac arrhythmia, chronic obstructive pulmonary disease, smoking, and use of positive airway pressure (PAP), decreased CRF alone (hazard ratio [HR]=1.91, 95% confidence interval [CI], 1.15 to 3.18; P=.01), but not SDB alone (HR=1.26, 95% CI, 0.75 to 2.13, P=.39) was associated with increased risk of MACE. Those with SDB and decreased CRF had greater risk of MACE compared with patients with decreased CRF alone (HR=1.85; 95% CI, 1.21 to 2.84; P<.005) after accounting for these confounders. The risk of MACE was attenuated in those with reduced CRF alone after additionally adjusting for adequate adherence to PAP (HR=1.59; 95% CI, 0.77 to 3.31; P=.21). Conclusion: The incidence of MACE, especially mortality, was high in this sample. Moderate-to-severe SDB with concurrent decreased CRF was associated with higher risk of MACE than decreased CRF alone. These results highlight the importance of possibly including CRF in the risk assessment of patients with SDB and, conversely, that of screening for SDB in patients with low peak VO₂.