Difference Between Estimated GFR Based on Cystatin C Versus Creatinine and Incident Atrial Fibrillation: A Cohort Study of the UK Biobank

Rationale & Objective: The difference between cystatin C-based and creatinine-based estimated glomerular filtration rate (eGFR(diff)) has been suggested to reflect factors distinct from kidney function that are associated with cardiovascular risk. However, the association between eGFR(diff) and atrial fibrillation (AF) risk has not been extensively evaluated. Study Design: Prospective cohort study. Setting & Participants: Using data from the UK Biobank, this study included 363,494 participants with measured serum creatinine and cystatin C levels and without a prior diagnosis of AF or a history of related procedures. Exposure: Estimated GFR(diff), calculated as cystatin C-based eGFR minus creatinine-based eGFR. Estimated GFR(diff) was also categorized as negative (<-15 mL/min/1.73 m(2)), midrange (-15 to 15 mL/min/1.73 m(2)), or positive (>= 15 mL/min/1.73 m(2)). Outcome: Incident AF. Analytical Approach: Subdistribution hazard models were fit, treating death that occurred before development of AF as a competing event. Results: During the median follow-up period of 11.7 years, incident AF occurred in 18,994 (5.2%) participants. In the multivariable-adjusted model, participants with a negative eGFR(diff) had a higher risk of incident AF (subdistribution HR [SHR], 1.25 [95% CI, 1.20-1.30]), whereas participants with a positive eGFR(diff) had a lower risk of AF (SHR, 0.81 [95% CI, 0.77-0.87]) compared with those with a midrange eGFR(diff). When eGFR(diff) was treated as a continuous variable in the adjusted model, every 10 mL/min/1.73 m(2) higher eGFR(diff) was associated with a 0.90-fold decrease in the risk of incident AF. Limitations: A single measurement of baseline serum creatinine and cystatin C levels. Conclusions: The difference between cystatin C- and creatinine-based eGFRs was associated with the risk of AF development. A higher eGFR(diff) was associated with a lower risk of AF. These findings may have implications for the management of patients at risk of incident AF.