Abstract
AIM: Estimated glomerular filtration rate (eGFR) derived from Cystatin C (eGFR(Cystatin C)), and the difference between Cystatin C and creatinine based eGFR (eGFR(diff)) has been suggested to be associated with cardiovascular disease. However, the association between eGFR(Cystatin C),eGFR(diff) and heart failure (HF) risk has not been elucidated in a relatively healthy cohort. METHODS: We used cohort study data from the NHANES 2001-2002. Mendelian randomization (MR) study used GWAS data from 437,846 European participants. The exposures are eGFR(Cystatin C) & eGFR(diff), outcome is self reported heart failure. Weighted multivariable-adjusted logistic regression and Kaplan-Meier survival analysis was used in corhort study. Inverse variance weighted (IVW) was applied in MR study. RESULTS: The cohort study included 2155 participants. Importantly, we simplified eGFR(diff) classification into ≥0 and < 0, and found that eGFR(diff)≥0 was associated with 52 % reduction of HF risk (OR 0.48, [95 % CI, 0.29-0.80], p = 0.005). We also found that 1 ml/min/1.73 m(2) of eGFR(Cystatin C) had a significant negative association with HF after adjusting for covariates. Interestingly, we showed a non-linear association between eGFR(Cystatin C) and HF, eGFR(diff) and HF. In participants without know HF, during a median follow-up of 17.3 years, those in the low eGFR(Cystatin C) or low eGFR(diff) groups showed significantly poorer survival. Moreover, MR analysis found genetic predisposition to cystatin C was significantly associated with an increased risk of HF. CONCLUSION: Both decreased eGFR(Cystatin C) and eGFR(diff) levels were associated with heart failure and poor survival, but the latter seems more obvious.