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

Ga Young Heo; Hee Byung Koh; Chan-Young Jung; Jung Tak Park; Seung Hyeok Han; Tae-Hyun Yoo; Shin-Wook Kang; Hyung Woo Kim

doi:10.1053/j.ajkd.2023.11.004

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

Am J Kidney Dis. 2024 Jan 1:S0272-6386(23)01004-1. doi: 10.1053/j.ajkd.2023.11.004. Online ahead of print.

Authors

Ga Young Heo¹, Hee Byung Koh², Chan-Young Jung³, Jung Tak Park¹, Seung Hyeok Han¹, Tae-Hyun Yoo¹, Shin-Wook Kang¹, Hyung Woo Kim⁴

Affiliations

¹ Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, South Korea.
² Division of Nephrology, International Saint Mary's Hospital, Catholic Kwandong University, Gangneung, South Korea.
³ Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, South Korea.
⁴ Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, South Korea; Institute for Innovation in Digital Healthcare, Yonsei University, Seoul, South Korea. Electronic address: drhwint@yuhs.ac.

PMID: 38171411
DOI: 10.1053/j.ajkd.2023.11.004

Abstract

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 (<-15mL/min/1.73m²), midrange (-15 to 15mL/min/1.73m²), or positive (≥15mL/min/1.73m²).

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 10mL/min/1.73m² 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.

Plain-language summary: The difference between cystatin C-based estimated glomerular filtration rate (eGFR) and creatinine-based eGFR has recently gained attention as a potential indicator of cardiovascular outcomes influenced by factors other than kidney function. This study investigated the association between the differences in 2 eGFRs (cystatin C-based eGFR minus creatinine-based eGFR) and incident atrial fibrillation (AF) among>340,000 participants from the UK Biobank Study. Compared with those with a near zero eGFR difference, participants with a negative eGFR difference had a higher risk of AF, while those with a positive eGFR difference had a lower risk. These findings suggest that measuring eGFR differences may help identify individuals at a higher risk of developing AF.

Keywords: Atrial fibrillation; cystatin C; estimated glomerular filtration rate; serum creatinine.