eGFRCystatin C, difference between eGFRCystatin C and eGFRCre and heart failure: Insight from the NHANES 2001–2002 and Mendelian randomization analysis

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 m² 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.