Divergent dietary thresholds for all-cause versus cardiovascular mortality in sarcopenia and advanced cardiovascular–kidney-metabolic syndrome: a national prospective cohort study

Abstract Introduction: Sarcopenia and cardiovascular–kidney–metabolic (CKM) syndrome are common comorbidities. We evaluated their cumulative impact on all-cause and cardiovascular mortality, and the modifying effect of a Composite Dietary Antioxidant Index (CDAI). Methods: This prospective study used data from the National Health and Nutrition Examination Survey linked to the National Death Index. Sarcopenia (Foundation for the National Institutes of Health criteria) and CKM syndrome (American Heart Association stages, dichotomised into advanced/non-advanced) defined the primary exposure. Outcomes were all-cause and cardiovascular mortality. Cox models estimated hazard ratios (HRs). Maximally selected rank statistics determined optimal outcome-specific CDAI thresholds. Results: Among 8782 participants (median follow-up 131 months), advanced CKM syndrome was associated with sarcopenia (odds ratio 2.29, 95% confidence interval CI 1.48–3.53). This study demonstrated a cumulative risk of comorbid advanced CKM syndrome and sarcopenia on mortality, with this group exhibiting the highest risk for all-cause (HR 3.11, 95% CI 1.72–5.61) and cardiovascular (HR 1.80, 95% CI 1.04–3.12) mortality. Furthermore, we identified an inverse relationship between disease burden and protective CDAI thresholds for all-cause mortality, whereas cardiovascular mortality exhibited a distinctly higher threshold. Specifically, the comorbidity group required lower antioxidant intake (CDAI >−3.80) than the non-comorbidity group (CDAI >−1.19) for all-cause mortality. Conversely, cardiovascular mortality required a substantially higher threshold (CDAI >3.04). Conclusion: Coexisting advanced CKM syndrome and sarcopenia present a significant cumulative mortality risk. Exploratory analyses suggest that this risk may be mitigated by dietary antioxidants, but the protective threshold is context-dependent. Modest dietary improvement was associated with improved all-cause survival in high-risk patients, whereas higher antioxidant intake correlated with better cardiovascular outcomes. These results suggest that precision nutrition strategies may vary depending on the specific health outcome.