Nutr Metab Cardiovasc Dis. 2026 May 13:104800. doi: 10.1016/j.numecd.2026.104800. Online ahead of print.
ABSTRACT
BACKGROUND AND AIM: 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.
METHODS AND RESULTS: 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.
CONCLUSION: 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.
PMID:42243018 | DOI:10.1016/j.numecd.2026.104800