Association Between the Serum Creatinine to Cystatin C Ratio and Cardiovascular Disease in Middle-Aged and Older Adults in China: A Nationwide Cohort Study

Abstract

Background: The relationship between the serum creatinine to cystatin C ratio (sarcopenia index [SI]) and the risk of incident cardiovascular disease (CVD) remains unclear. Therefore, this study aims to explore the association between SI and the risk of incident CVD in middle-aged and older Chinese adults using nationally representative data.

Methods and results: We analyzed data from participants in CHARLS (China Health and Retirement Longitudinal Study) conducted in 2015 and 2018. The exposure variable was SI, calculated as the ratio of serum creatinine to cystatin C, multiplied by 100. The outcome variable was self-reported CVD (heart disease or stroke). A cross-sectional analysis was first performed using 2015 CHARLS data, which included 11 115 eligible participants (46.1% men; mean±SD age, 60.28±9.60 years). Logistic regression was used to estimate the association between SI and CVD. Longitudinal analysis was then conducted using the 2018 follow-up data, which included 8589 participants (46.4% men; mean±SD age, 59.57±9.42 years), with a median follow-up period of 3.0 years. Cox proportional hazard models were used to assess the relationship between SI and the risk of incident CVD, and a multivariate-adjusted restricted cubic spline model was used to explore the dose-response relationship. In the cross-sectional analysis, multivariate logistic regression revealed a significant negative association between SI and CVD. The longitudinal analysis identified 854 (9.94%) new CVD cases. Cox models showed that lower SI was significantly associated with an increased risk of incipient CVD. The multivariable adjusted hazard ratios for participants in the quartile 2 to quartile4 groups compared with those in the quartile 1 group were 0.94 (95% CI, 0.79-1.12), 0.63 (95% CI, 0.51-0.78), and 0.60 (95% CI, 0.47-0.75), respectively. Restricted cubic spline curves demonstrated a significant linear relationship between SI and CVD incidence (all P-nonlinear>0.05).

Conclusions: A lower SI was significantly associated with an increased risk of new-onset CVD in middle-aged and older Chinese adults. This suggests that SI has an important potential application as a serum marker of sarcopenia in predicting CVD.

Keywords: CHARLS; cardiovascular diseases; sarcopenia index.

Figure 1. Multivariate‐adjusted odds ratio (95% CI) of serum creatinine to cystatin C ratio (quartiles 1–4) for cardiovascular diseases in model 3.

Figure 2. Restricted cubic spline curves for cardiovascular diseases according to the sarcopenia index.

Hazard ratios are indicated by solid lines and 95% CIs by shaded areas. The horizontal dotted line represents the hazard ratio of 1.0. The adjusted models adjusted age, sex, body mass index, education level, marital status, residence, smoking, drinking, hypertension, dyslipidemia, diabetes, cancer, liver disease, and high‐sensitivity C‐reactive protein.

Figure 3. Subgroup and interaction analyses between the serum creatinine to cystatin C ratio (quartiles 1–4) and cardiovascular disease across various subgroups in model 3.