Relationship between serum cystatin C and long-term mortality in patients with self-reported COPD: evidence from two large population-based surveys

INTRODUCTION: Serum cystatin C (Cys-C) is an indicator of ageing, and its connection with the long-term prognosis in patients with chronic obstructive pulmonary disease (COPD) is poorly understood. We aimed to examine the association between Cys-C levels and long-term mortality in patients with COPD. METHODS: This cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS) and the National Health and Nutrition Examination Survey (NHANES). We included patients with COPD with Cys-C data from 2011 in CHARLS and 1999-2004 in NHANES. We analysed the association between Cys-C and long-term mortality in COPD using multivariate logistic regression and Cox regression. Multiple models were adjusted to reduce potential bias. Fitted curves were used to analyse the dose-response relationship between Cys-C and long-term mortality. Receiver operating characteristic (ROC) curve and subgroup analyses were also performed. RESULTS: 1030 patients with COPD from two cohorts were included in our study. When grouped by Cys-C quartiles, the high Cys-C Q4 group was older and had higher proportions of males and a higher mortality rate. Regression analysis showed a positive association between Cys-C and long-term mortality in COPD after adjusting for covariates (CHARLS: OR=3.34, 95% CI 1.51 to 7.38, p=0.003; NHANES: HR=1.35, 95% CI 1.02 to 1.75, p=0.033). Analysing the data in a categorical fashion using quartiles, the Q4 group (CHARLS: OR=2.80, 95% CI 1.07 to 7.33, p=0.036; NHANES: HR=2.12, 95% CI 1.08 to 4.19, p=0.030) had a higher mortality rate compared with the Q1 group. The area under the curve for ROC was 73.7% (CHARLS) and 73.3% (NHANES). The results of subgroup analyses showed an interaction of sex in Cys-C and COPD mortality (p for interaction=0.035 in CHARLS and 0.042 in NHANES), with a more pronounced effect on females. CONCLUSIONS: Our study found that high Cys-C was related to increased long-term mortality in patients with COPD. This association appears more pronounced in females.