Cystatin C is a predictor for long-term All-Cause and Cardiovascular Mortality in US Adults with Metabolic Syndrome

J Clin Endocrinol Metab. 2024 Apr 10:dgae225. doi: 10.1210/clinem/dgae225. Online ahead of print.

Abstract

Objective: This study examined the relationship between Cystatin C (CysC) levels and all-cause, 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 1,980 MetS participants. To assess CysC levels and all-cause, CVD, and cancer mortality, fitted curves, Kaplan-Meier survival curves, cox regression analysis, and ROC 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<0.05). 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<0.05). Later 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<0.05). 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 CRP. CysC alone exhibited substantial predictive value for all-cause (AUC 0.773; P<0.05) and CVD mortality (AUC 0.726; P<0.05). Combining CysC with age enhanced the predictive value for all-cause mortality to 0.861 and CVD mortality to 0.771 (P<0.05).

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.

Keywords: CVD mortality; Cystatin C; all-cause mortality; cancer mortality; metabolic syndrome; prognostic marker.