Restless legs syndrome determines whether periodic limb movements are associated with altered lipid profiles in sleep-disordered breathing

OBJECTIVE: Periodic limb movements (PLM) during sleep are common in sleep-disordered breathing (SDB), but their independent association with cardiometabolic markers remains unclear. Restless legs syndrome (RLS), which frequently co-occurs with PLM, may modify this relationship. We investigated whether PLM are independently associated with cardiometabolic risk in SDB, and whether RLS modifies these associations. METHODS: Cross-sectional analysis of 643 adults (mean age 45.9 years, 59.4% male) from the NSRR APOE dataset with in-laboratory polysomnography, PLM index, RLS assessment, and fasting cardiometabolic profiling. Multivariable regression adjusted for age, sex, BMI, and oxygen desaturation index tested associations between log-transformed PLM and each outcome. We then tested whether the association of PLM with lipid levels differed by RLS status by adding interaction terms to the models. Benjamini-Hochberg false discovery rate (FDR) correction was applied. RESULTS: PLM alone were not significantly associated with any cardiometabolic outcome after FDR correction (all FDR p ≥ 0.17). However, RLS status substantially modified the PLM-lipid relationship: this was significant for HDL (β = 4.33, FDR p < 0.001), LDL (β = 8.17, FDR p = 0.008), and total cholesterol (β = 12.29, FDR p < 0.001). In participants with RLS, higher PLM was linked to higher lipids. In those without RLS, higher PLM was linked to lower lipids. This direction reversal indicates that the metabolic significance of PLM depends on concomitant RLS status. CONCLUSIONS: PLM alone do not predict cardiometabolic risk in SDB. However, RLS profoundly modifies the PLM-lipid relationship. The combination of PLM and RLS identifies a distinct cardiometabolic phenotype that may warrant targeted lipid monitoring.