0437 Obstructive Sleep Apnea Symptom Subtypes and Hypoxic Burden Independently Predict Distinct Cardiovascular Outcomes

Abstract

Abstract Introduction Studies on heterogeneity of obstructive sleep apnea (OSA) have identified clinically relevant symptom-based subtypes and novel OSA-specific nocturnal hypoxemia measures. Evidence suggests that moderate-severe OSA patients with the excessively sleepy subtype have increased risk of incident major adverse cardiovascular events (MACE; composite of coronary heart disease, heart failure, stroke, or cardiovascular mortality) and that OSA-specific hypoxic burden (HB) is associated with increased risk of cardiovascular disease (CVD) mortality. However, no study has comprehensively examined their combined impact. This study provides a systematic assessment of the individual and combined contribution of these factors on incident CVD risk, addressing an important gap in evidence. Methods Participants from the Sleep Heart Health Study with high-quality oxygen saturation, OSA severity quantified by apnea-hypopnea index (AHI), and symptom data were included. Latent class analysis on 14 symptoms was used to classify participants with moderate-severe OSA (AHI≥15) into subtypes. HB was calculated from respiratory event-related hypoxia and sleep time. Cox proportional hazards models were used to assess the relative contributions of OSA symptom subtypes and HB (natural log transformed) on risk for CVD mortality and MACE, adjusted for demographic and CVD risk factors. Analyses were performed in both CVD-free participants and all participants (adjusted for CVD at baseline). Results A total of 5,027 participants were analyzed, with median follow-up of 11.6 years (CVD mortality) and 11.3 years (MACE). HB was independently associated with CVD mortality in all participants (HR[95% CI] = 1.44 [1.06-1.97]; p=0.021) and CVD-free participants (1.62 [1.12-2.35]; p=0.010) controlling for symptom subtype. Conversely, symptom subtypes were independently associated with MACE incidence among CVD-free participants, controlling for HB, with the excessively sleepy participants having nearly two-fold higher risk (HR[95% CI] = 1.98 [1.26-3.10]; p=0.003) compared to those without OSA. Conclusion OSA symptom subtypes and HB are independently associated with distinct CVD-related endpoints. Higher HB was associated with cardiovascular mortality, controlling for symptom subtype. The excessively sleepy subtype was at higher risk of new MACE, controlling for HB. Thus, both factors are important for understanding OSA-related CVD risk. Support (if any) AHA (20CDA35310360), NIH (P01HL094307, U01HL53916, U01HL53931, U01HL53934, U01HL53937, U01HL53938, U01HL53940, U01HL53941, U01HL64360 R24 HL114473, 75N92019R002).