Abstract
BACKGROUND: Obstructive sleep apnea syndrome (OSAS) elevates the risk of major adverse cardiovascular events (MACEs), though the underlying mechanisms are not fully elucidated. This study investigated the correlations between bone metabolism markers, inflammatory cytokines, and MACEs in OSAS patients. METHODS: A retrospective study was conducted on patients diagnosed with OSAS between March 2019 and March 2022, alongside baseline characteristics - matched controls without OSAS. The cohort comprised 496 OSAS patients and 545 controls. Based on the occurrence of major adverse cardiovascular events (MACEs), the entire cohort (n=1041) was segregated into a MACE group (n=120) and a non-MACE group (n=921). Clinical data collected included demographic information, polysomnography results, bone metabolism markers (β-CrossLaps [β-CTX], total procollagen type I N-terminal propeptide [TPINP]), and inflammatory cytokines (interleukin-1 beta [IL-1β], interleukin-6 [IL-6], C-reactive protein [CRP], tumor necrosis factor-alpha [TNF-α], interleukin-10 [IL-10], interferon-gamma [IFN-γ]). Statistical analyses included independent t tests, Pearson correlation coefficients, logistic regression, and structural equation modeling. RESULTS: OSAS patients showed significantly higher β-CTX (0.49±0.15 vs 0.43±0.14 ng/mL; P<0.001) and lower TPINP (103.81±37.57 vs 118.19±41.20 ng/mL; P<0.001) than controls. Levels of IL-6, TNF-α, and IL-1β were also elevated in the OSAS group (all P<0.01). MACEs were more frequent in OSAS patients (P=0.002). Multivariate analysis identified severe OSAS (OR=2.771, P<0.001), elevated IL-6 (OR=1.114, P=0.013), elevated IL-1β (OR=1.598, P=0.033), and increased β-CTX (OR=3.386, P<0.001) as independent MACE predictors. SEM revealed OSAS directly associated with MACEs (β=0.18) and indirectly via inflammatory and bone metabolism pathways. CONCLUSION: Altered bone metabolism markers and elevated pro-inflammatory cytokines are associated with an increased risk of MACEs in OSAS patients, suggesting their role in the pathophysiology of OSAS-related cardiovascular morbidity. Monitoring these markers could aid in risk stratification.