Vitamin D deficiency and subsequent risk of obstructive sleep apnea: a multi-institutional retrospective study

Obstructive sleep apnea (OSA) is a global health concern associated with cardiovascular and metabolic complications. Vitamin D deficiency (VDD) is common and may contribute to OSA pathophysiology; however, most evidence is cross-sectional. This study investigated whether sustained VDD is associated with an increased risk of developing OSA.

This retrospective cohort study utilized data from the TriNetX federated research network (2010-2023) to investigate the relationship between VDD and incident OSA in adults aged ≥ 18 years. Patients were classified based on sustained serum 25-hydroxyvitamin D levels, with deficiency defined as ≤20 ng/mL and sufficiency as ≥30 ng/mL. To ensure an accurate exposure status, all included individuals underwent confirmatory vitamin D measurements within 3-12 months. After 1:1 propensity score matching, patients were followed for up to 5 years for new-onset OSA diagnoses, with a three-month washout period after vitamin D assessment to mitigate reverse causality and enhance causal inference.

Analysis of 126,563 matched pairs demonstrated that OSA risk was significantly higher in the VDD group than in the controls (5.7% vs. 4.4%; HR 1.26, 95% CI 1.21-1.30; p < 0.001). This association demonstrated temporal consistency across 1-, 3-, and 5-year follow-ups. A clear dose-response relationship emerged, with severe VDD [≤10 ng/mL] conferring greater risk (HR 1.39, 95% CI 1.26-1.53; p < 0.001). Subgroup analyses revealed significant effect modification: stronger associations in women versus men (HR 1.32 vs. 1.19; P for interaction: 0.003), younger versus older adults (HR 1.45 vs. 1.15; P for interaction <0.001), and overweight/obese versus normal-weight individuals (HR 1.27 vs. 1.02; P for interaction <0.001).

Sustained VDD was independently associated with OSA risk, with temporal consistency and dose-response relationships supporting potential causality. The effects were most pronounced in women, younger adults, and overweight/obese individuals, suggesting that targeted assessment and intervention strategies may be warranted in these high-risk subgroups.