Serum zinc deficiency and progression of cardiovascular- kidney-metabolic syndrome.

INTRODUCTION: Cardiovascular-kidney-metabolic (CKM) syndrome represents an interconnected disease continuum linking metabolic dysfunction, chronic kidney disease (CKD), and cardiovascular disease. Serum zinc deficiency (SZD) has been associated with adverse cardiovascular and renal outcomes; however, its association with CKM progression remains unclear. METHODS: This retrospective cohort study was conducted using the TriNetX. Adults with CKM stage 1 or 2 were enrolled in the study. SZD was defined as a serum zinc concentration < 70 μg/dL, while individuals with zinc concentrations between 70 and 120 μg/dL served as controls. After 1:1 matching, 74,245 patients were included in each group. The primary outcome was operational progression from CKM stage 1-2 to stage 3-4. Secondary outcomes included major adverse cardiovascular events, coronary artery disease, peripheral artery disease, atrial fibrillation, ischemic stroke, heart failure, advanced CKD, and all-cause mortality. RESULTS: Among 148,490 matching individuals, SZD was associated with a significantly increased risk of operational progression to CKM stage 3-4 compared with normal zinc status (HR, 1.36; 95% CI, 1.30-1.41; P < 0.001). SZD was also associated with increased risks of other secondary outcomes (all P < 0.0056 after Bonferroni correction). CONCLUSION: Among patients with CKM stage 1-2, SZD was associated with a significantly increased risk of operational progression to CKM stage 3-4 and a broad spectrum of adverse cardiovascular, renal, and mortality outcomes. These findings suggest that SZD may represent an important marker of adverse CKM health and may help identify individuals at increased risk for CKM progression.