Association and Predictive Value of C-Reactive Protein-Lymphocyte-Albumin (CALLY) Index with Cardiovascular Disease in Patients with CardiovascularKidneyMetabolic Syndrome Stage 3

Mei Yuan,1, Luohua Li,2, Yueyuan Hou,1, Ling Wei,1 Rou Zhang,3 Hongying Jiang1 1Department of Nephrology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650101, People’s Republic of China; 2Department of Nephrology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of China; 3Department of Sleep Medicine, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, 650101, People’s Republic of ChinaThese authors contributed equally to this workCorrespondence: Hongying Jiang, Department of Nephrology, The Second Hospital Affiliated to Kunming Medical University, No. 374, Dianmian Avenue, Kunming, Yunnan Province, 650101, People’s Republic of China, Tel +86 13033371998, Email 1627248965@qq.comBackground: Cardiovascular–kidney–metabolic (CKM) syndrome stage 3 is a high-risk condition for cardiovascular disease (CVD), characterized by intertwined metabolic dysregulation, chronic inflammation, and immune dysfunction. This study aimed to evaluate the association and predictive value of the C-reactive protein–lymphocyte–albumin (CALLY) index for CVD in this population.Methods: In a retrospective cohort of patients with CKM stage 3, the CALLY index was calculated from baseline laboratory data. Its association with incident CVD was assessed using multivariable Cox proportional hazards models. To test robustness, sensitivity and subgroup analyses were performed. Predictive performance was evaluated by time-dependent receiver operating characteristic (ROC) analysis, integrated discrimination improvement (IDI), and net reclassification improvement (NRI).Results: Among 826 patients followed for a median of 51 months, a higher CALLY index was independently associated with a lower risk of CVD (adjusted hazard ratio 0.37, 95% CI: 0.25– 0.55). The association remained robust in sensitivity and subgroup analyses. The index demonstrated superior discrimination for CVD (area under the curve 0.806, 95% CI: 0.774– 0.838). The CALLY index provided significant incremental predictive value compared to using its individual components (CRP, albumin, or lymphocyte count alone).Conclusion: A lower CALLY index is independently associated with an increased risk of CVD in patients with CKM stage 3 and exhibits robust predictive performance. This readily available composite biomarker may aid in cardiovascular risk stratification for this high-risk group.Keywords: cardiovascular disease, metabolic dysfunction, inflammation, biomarker