Risk Factors for Cardiovascular Mortality in Patients With Obstructive Sleep Apnea

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.

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.

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%.

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.