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

Rationale & ObjectiveThe difference between cystatin C-based and creatinine-based estimated glomerular filtration rate (eGFRdiff) has been suggested to reflect factors distinct from kidney function that are associated with cardiovascular risk. However, the association between eGFRdiff and atrial fibrillation (AF) risk has not been extensively evaluated.Study DesignProspective cohort study.Setting & ParticipantsUsing data from 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.ExposureseGFRdiff, calculated as cystatin C-based eGFR minus creatinine-based eGFR. eGFRdiff was also categorized as negative (<-15 mL/min/1.73m2), midrange (-15 to 15 mL/min/1.73.m2), or positive (≥15 mL/min/1.73.m2).Main OutcomeIncident AF.Analytical ApproachSub-distribution hazard models were fit, treating death that occurred before development of AF as a competing event.ResultsDuring the median follow-up of 11.7 years, incident AF occurred in 18,994 (5.2%) participants. In the multivariable-adjusted model, participants with a negative eGFRdiff had a higher risk of incident AF (sub-distribution hazard ratios [sHRs], 1.25; 95% confidence interval [CI], 1.20–1.30), whereas participants with a positive eGFRdiff had a lower risk of AF (sHRs, 0.81; 95% CI, 0.77–0.87), compared to those with a midrange eGFRdiff. When eGFRdiff was treated as a continuous variable in the adjusted model, every 10 mL/min/1.73 m2 higher eGFRdiff was associated with a 0.90-fold decrease in the risk of incident AF.LimitationA single measurement of baseline serum creatinine and cystatin C levels.ConclusionsThe difference between cystatin C- and creatinine-based eGFRs was associated with the risk of AF development. A higher eGFRdiff was associated with a lower risk of AF. These findings may have implications for the management of patients at risk of incident AF.