Cystatin C Is a Predictor for Long-Term, All-Cause, and Cardiovascular Mortality in US Adults With Metabolic Syndrome

OBJECTIVE: This study examined the relationship between cystatin C (CysC) levels and all-cause, cardiovascular disease (CVD), and cancer mortality in US metabolic syndrome (MetS) patients. METHODS: The 1999-2002 National Health and Nutrition Examination Survey (NHANES) prospective cohort research included 1980 MetS participants. To assess CysC levels and all-cause, CVD, and cancer mortality, fitted curves, Kaplan-Meier survival curves, Cox regression analysis, and receiver operating characteristic curves were performed. RESULTS: During a mean follow-up of 15.3 ± 5.4 years, a total of 819 deaths occurred. The fitted and Kaplan-Meier survival curves revealed that greater CysC levels were linked to higher all-cause, CVD, and cancer mortality rates (P < .05). After adjusting for variables, CysC level was associated with all-cause, CVD, and cancer mortality at 1.63 (1.42-1.88), 1.53 (1.19-1.95), and 1.53 (1 ∼ 2.32), respectively (P < .05). Tertile models showed consistent results: high CysC Tertile participants showed higher risk of all-cause mortality (HR 1.87; 1.43-2.45), CVD mortality (HR 1.97, 1.15 ∼ 3.38), and cancer mortality (HR 1.72, 1.01 ∼ 2.91) compared to those in the lowest tertile (P < .05). Subgroup studies by sex and other characteristics confirmed the findings. CysC demonstrated the higher predictive efficacy across mortality outcomes, followed by eGFR, outperforming urea nitrogen, creatinine, uric acid, and C-reactive protein. CysC alone exhibited substantial predictive value for all-cause (AUC 0.773; P < .05) and CVD mortality (AUC 0.726; P < .05). Combining CysC with age enhanced predictive value for all-cause mortality to 0.861 and CVD mortality to 0.771 (P < .05). CONCLUSION: MetS patients with elevated CysC levels have a higher risk of all-cause, CVD, and cancer death. CysC may predict MetS all-cause and CVD mortality.