Sleep disorders reshape the cardiovascular risk prediction value of systemic inflammation: a NHANES cohort study...

Sleep disorders (SD) are a known cardiovascular risk factor, with systemic inflammation implicated as a potential pathway. However, whether inflammation mediates or modifies the association between SD and cardiovascular disease (CVD) remains unclear. We investigated the role of systemic inflammation in the long-term CVD mortality risk associated with SD.

We analyzed 26,477 adults from the National Health and Nutrition Examination Survey (NHANES, 2005-2018) with a median follow-up of 9.5 years. Physician-diagnosed SD was assessed via questionnaires. Inflammation was quantified using log-transformed C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and a composite inflammation score. Survey-weighted Cox models, interaction, and mediation analyses were conducted, adjusting for demographic, metabolic, and lifestyle covariates. During follow-up, 2757 all-cause deaths and 1930 CVD deaths occurred. In fully adjusted models, SD was associated with higher all-cause mortality (hazard ratio [HR] = 1.29, 95% CI: 1.09-1.54) and CVD mortality (HR = 1.23, 95% CI: 1.05-1.51). Compared with participants without SD or baseline CVD, those with SD alone showed modest, non-significant risk elevation, while participants with both SD and baseline CVD had the highest risk (all-cause HR 1.63-2.15; CVD HR 1.15-2.39). Participants with only CVD also had increased mortality. No significant SD × inflammation interactions were observed. In the baseline CVD-free subcohort, elevated CRP, NLR, and composite inflammation scores predicted fatal CVD events only in participants without SD. Mediation analysis indicated negligible indirect effects.

Sleep disorders independently predict cardiovascular mortality and reshape the prognostic value of systemic inflammation-inflammatory markers are only predictive in individuals without sleep disorders. Integrating sleep health is essential for inflammation-based CVD risk assessment.