Association of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality among individuals in cardiovascular-kidney-metabolic syndrome stages 0–3: a cohort study from the NHANES 2001–2018

Abstract Background The association between vitamin D status and mortality risk among adults with cardiovascular-kidney-metabolic (CKM) syndrome stages 0–3 requires further elucidation. We investigated the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and all-cause and cause-specific mortality among United States adults diagnosed with CKM syndrome stages 0–3. Methods Data from 37,551 adults presenting with CKM syndrome stages 0–3 were examined using National Health and Nutrition Examination Survey records (2001–2018). Death outcomes were determined via National Death Index linkage through December 31, 2019. Cox proportional hazards modeling and two-piecewise Cox regression approaches were utilized to assess nonlinear relationships between serum 25(OH)D levels and mortality risk, incorporating stratified analyses for high-risk population identification. Results Throughout 337,921 person-years of observation, we documented 4,039 deaths from all causes, encompassing 1,078 cardiovascular disease (CVD)-related deaths. Following multivariable adjustment, reduced serum 25(OH)D levels demonstrated significant associations with elevated all-cause and CVD mortality risk through nonlinear patterns. L-shaped dose-response curves emerged, revealing mortality risk plateaus at 52.20 nmol/L for all-cause mortality and 53.90 nmol/L for CVD mortality. Individuals maintaining 25(OH)D levels above these threshold values exhibited 2% reduced all-cause mortality risk (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.97–0.99) and 2% decreased CVD mortality risk (HR 0.98, 95% CI 0.97–0.99) relative to participants below these cutoff points. Conclusions Nonlinear relationships between serum 25(OH)D levels and both all-cause and CVD mortality were demonstrated among United States adults with CKM syndrome stages 0–3. These findings warrant confirmation through randomized controlled trials.