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. 2025 May 7;25(1):1685.
doi: 10.1186/s12889-025-22924-9.

Association of chronic kidney disease and cardiovascular disease risk with all-cause mortality: an interaction, joint and mediation analysis in Chinese adults

Yang Li #  1   2   3 , Yiqin Shi #  1   2   3 , Bowen Zhu  1   2   3 , Yafei Chen  1   2   3 , Bo Shen  1   2   3 , Shuan Zhao  1   2   3 , Nana Song  1   2   3 , Yi Fang  4   5   6 , Xiaoqiang Ding  7   8   9
Affiliations

Association of chronic kidney disease and cardiovascular disease risk with all-cause mortality: an interaction, joint and mediation analysis in Chinese adults

Yang Li et al. BMC Public Health. .

Abstract

Background: Chronic kidney disease (CKD) is a global public health problem. This study aimed to evaluate the complex relationship of CKD and cardiovascular disease (CVD) risk with mortality in different age groups and the mediation effect of CVD risk among Chinese adults.

Methods: A total of 7533 participants from the 2009 wave of China Health and Nutrition Survey (CHNS) cohort were included in this study and followed up to 2015. CKD was defined as the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. Framingham risk score (FRS) was used to assess CVD risk. The interaction, joint association of CVD risk and CKD on mortality, and subsequent mediation effect were evaluated using multivariable Cox regression.

Results: CHNS cohort recorded 266 deaths over a mean follow-up time of 5.04 years. The all-mortality rates among adults with CKD and high CVD risk were significantly higher than healthy controls (22.48 and 21.30 per 1000 person-years). After adjusting for covariates of age, gender, BMI, hypertension, diabetes, hyperuricemia, smoking status, and alcohol consumption, the adjusted hazard ratios (aHR) of CKD and high CVD risk were 1.70 (95% CI 1.27-2.28) and 1.62 (95%CI 1.26-2.09), respectively. Joint effect analysis revealed that mortality hazard was highest in CKD patients with high CVD risk (aHR = 3.15, 95% CI 1.92-5.16). Mediation analysis showed that significant partial mediation by SBP and fasting glucose, accounting for 19.2% (p < 0.001) and 3.52% (p = 0.012) of the total effect of CKD on mortality.

Conclusions: Comprehensive strategies including lifestyle modifications, diet restrictions, and cardio-nephrology multidisciplinary treatment for mitigating CVD risk in CKD patients should focus on middle-aged people and early disease detection.

Keywords: Cardiovascular disease; China health and nutrition survey; Chronic kidney disease; Mediation analysis; Mortality.

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Conflict of interest statement

Declarations. Ethical approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all participants. CHNS was approved by the Institutional Review Board (IRB) at the University of North Carolina at Chapel Hill and local IRB. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Survival analysis of CKD and CVD risk for all-cause mortality. (A. K-M curves, B. Cox regression models overall and across age groups)
Fig. 2
Fig. 2
Cox regression models examining the effects of CKD and CVD risk on all-cause mortality overall and across age groups (A. stratified by CVD risk grade, B. stratified by CKD)
Fig. 3
Fig. 3
Joint effect of CKD and CVD risks for all-cause mortality (overall and across age groups)
Fig. 4
Fig. 4
Mediation analysis for all-cause mortality (A. total cholesterol (TC), B. high-density lipoprotein cholesterol (HDL-C), C. systolic blood pressure (SBP), D. fasting glucose.unadjusted, B-D. moderated by age, the solid and dashed lines represent CKD group and non-CKD group)
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