Difference between cystatin C- and creatinine-based estimated glomerular filtration rate and incident hypertension and the mediating role of Triglyceride Glucose Index

Estimated glomerular filtration rate (eGFR) is usually calculated based on serum creatinine (eGFR_Scr) or cystatin C (eGFR_CysC). This study aimed to investigate the association between cystatin C-creatinine eGFR discordance (ΔeGFR_CysC-Scr) and new-onset hypertension and to assess the mediating role of triglyceride glucose (TyG) index based on the China Health and Retirement Longitudinal Study. The ΔeGFR_CysC-Scr was calculated by eGFR_CysC - eGFR_Scr. A Cox proportional risk model was used to assess the association between ΔeGFR_CysC-Scr and risk of new-onset hypertension. The mediating role of TyG was assessed using mediation analysis, and thresholds were obtained <i>via</i> Receiver Operating Characteristic curve. A total of 4,644 participants (median age 59 years, 55.5% female) were finally included. During a mean follow-up period of 5.0 years, 613 new cases of hypertension occurred. Multivariable analysis showed that, individuals in negative-ΔeGFR_CysC-Scr group (< -15) had a 24% increase risk of hypertension (Hazard ratio [HR] = 1.24; 95% confidence interval [95% CI]: 0.99, 1.56), while positive-ΔeGFR_CysC-Scr group (≥15) had a 20% decrease risk of hypertension (HR = 0.80; 95% CI: 0.63, 1.02), compared with those in the reference group (-15 ≤ ΔeGFR_CysC-Scr < 15 mL/min/1.73 m²). In addition, each 15 mL/min/1.73m² increase in ΔeGFR_CysC-Scr was associated with a 13.4% reduction in the risk of new-onset hypertension (HR= 0.87; 95% CI: 0.79, 0.95). TyG acted as a partial mediator, explaining 9.3% of the total effect. The present study demonstrates an association between ΔeGFR_CysC-Scr and the risk of new-onset hypertension and reveals the important mediating role of TyG in this association.