Vitamin D deficiency, multimorbidity, and mortality in stage 2 cardiovascular-kidney-metabolic (CKM) Syndrome: evidence from the NHANES 2001–2018 cohort

This study aimed to compare mortality risks among patients with stage 2 cardiovascular-kidney-metabolic syndrome (CKM) across different multimorbidity states. Furthermore, it investigated whether sufficient serum vitamin D (≥75 nmol/L) modulates the association between multimorbidity and mortality. Using data from the 2001–2018 National Health and Nutrition Examination Survey (NHANES), we conducted a retrospective cohort study of 12,406 eligible patients. Among these patients, 913 died from all causes, and 223 died due to CVD. Survey-weighted Cox proportional hazards regression analyses revealed that compared to group 1 multimorbidity, groups 2 (all-cause mortality HR = 1.79; CVD mortality HR = 2.10), 3 (all-cause HR = 1.89; CVD HR = 1.76), and 4 (all-cause HR = 2.55; CVD HR = 3.97) had significantly increased mortality risks. Notably, sufficient serum 25-hydroxyvitamin D [25(OH)D] levels demonstrated a potential antagonistic effect on multimorbidity-related mortality, particularly for CVD. These findings indicate that maintaining adequate VD in stage 2 CKM patients may mitigate mortality risks associated with multimorbidity progression, offering insights for improving cardiovascular outcomes. People who have combinations of heart, kidney, and metabolic diseases, collectively referred to as cardiovascular-kidney-metabolic (CKM) syndrome, are at higher risk of dying earlier, especially when they have several chronic conditions at the same time (multimorbidity). Vitamin D, which the body produces through sunlight exposure and obtains from food, may influence how these diseases interact. In this study, we analyzed data from more than 12,000 adults in the U.S. National Health and Nutrition Examination Survey (NHANES) collected between 2001 and 2018. All participants were at stage 2 of CKM syndrome, meaning they had metabolic risk factors or moderate chronic kidney disease but no known cardiovascular disease. We found that individuals with a greater number of coexisting diseases had higher risks of death from any cause and from cardiovascular disease. However, participants with adequate vitamin D levels (at least 75 nmol/L) showed lower mortality risks, suggesting that maintaining sufficient vitamin D may help reduce some of the harmful effects of multimorbidity. These findings indicate that assessing and managing vitamin D levels could become an important part of early care for people with CKM syndrome. Further studies are needed to determine whether vitamin D supplementation can directly improve survival outcomes.