Risk Factors for Cardiovascular Mortality in Patients With Obstructive Sleep Apnea
Wojciech Kuczyński, Karol Pierzchała, Zuzanna Boczar, Aleksandra Kudrycka, Piotr BiałasiewiczAbstract
Study Objectives
Obstructive sleep apnea (OSA) is associated with increased cardiovascular mortality, but the relative contributions of OSA-specific parameters versus classical cardiometabolic risk factors remain poorly defined.
Methods
We conducted a retrospective cohort study of 4,368 consecutive adults referred for diagnostic polysomnography at a tertiary sleep center and followed for up to 20 years. The primary outcome was cause-specific cardiovascular mortality ascertained by national death registry linkage. Analyses integrated cause-specific Cox regression, Fine-Gray subdistribution hazard models, and a random survival forest (RSF) competing-risk model (1000 trees; 70/30 train-test split). Gower-distance-based hierarchical clustering of RSF-predicted cumulative incidence identified patient phenotypes.
Results
Over a median follow-up of 8.6 years (interquartile range 6.7-12.5), 335 cardiovascular deaths occurred. Heart failure (30.4%), chronic ischemic heart disease (14.0%), and acute myocardial infarction (11.6%) were the leading causes. Independent predictors were age (hazard ratio 1.08, 95% confidence interval 1.07-1.10, per year), male sex (1.68, 1.29-2.18), active smoking (1.68, 1.30-2.15), hypertension (1.73, 1.29-2.33), atrial fibrillation (2.16, 1.56-2.98), prior myocardial infarction (1.71, 1.25-2.35), and diabetes (1.37, 1.06-1.76). Nocturnal desaturation lost significance after multivariable adjustment. Among patients with an apnea-hypopnea index ≥15 events/h, a good continuous positive airway pressure (CPAP) response was associated with lower cardiovascular mortality (0.72, 0.55-0.96). The RSF C-index was 0.80. Six phenotypes showed cardiovascular mortality of 2.9% to 14.4%.
Conclusions
Cardiovascular mortality in OSA was driven predominantly by classical cardiometabolic risk factors rather than by nocturnal hypoxemic burden or CPAP response. Comorbidity-targeted prevention should be prioritized, and phenotype-aware stratification may identify subgroups warranting intensified cardiovascular surveillance.