Key result
Negative cystatin C-to-creatinine eGFR difference is linked to ~50% higher MACE risk.
Why the study?
Differences between cystatin C-based and creatinine-based eGFR estimations have been associated with adverse outcomes, but their prevalence and impact in patients with atrial fibrillation were unclear.
Does a discrepancy between cystatin C-based and creatinine-based eGFR estimates predict major adverse cardiovascular events and heart failure hospitalization in patients with atrial fibrillation?
Cohort (n=3,804)
Yes
Does a discrepancy between cystatin C-based and creatinine-based eGFR estimates predict major adverse cardiovascular events and heart failure hospitalization in patients with atrial fibrillation?
A negative intraindividual difference between cystatin C- and creatinine-based eGFR identifies a high-risk phenotype in patients with atrial fibrillation, marked by increased incidence of cardiovascular events and heart failure hospitalization.
Aims Differences between cystatin C-based and creatinine-based glomerular filtration rate estimations (eGFRdiff) have been associated with adverse outcomes. We aimed to investigate the prevalence of eGFRdiff and its association with clinical outcomes and brain lesions in patients with atrial fibrillation (AF). Methods and results We analysed 3804 patients with AF enrolled in two prospective, multicentre cohort studies. The eGFRdiff was calculated by ‘cystatin C-based eGFR—creatinine-based eGFR’. Patients were stratified into three groups: eGFRdiff >10, −10 to 10, and <−10 mL/min/1.73 m². Associations with high-sensitivity troponin T (hs-TnT), NT-proBNP, major adverse cardiovascular (CV) events (stroke/systemic embolism, myocardial infarction and CV death), first heart failure (HF) hospitalization, and magnetic resonance imaging (MRI)-detected brain lesions were assessed. The mean age was 71 years, 28% were female, and 49% had paroxysmal AF. An eGFRdiff of >10, −10 to 10, and <−10 mL/min/1.73 m2 was present in 17.7%, 71.7%, and 10.6% of the patients, respectively. Incidence rates per 100 patient-years increased across these groups for major CV events (MACEs: 1.7, 3.9, 6.8) and HF hospitalization (1.2, 3.5, 6.1). Similarly, the prevalence of MRI-detected brain infarcts (28%, 39%, 42%) and moderate-to-severe white matter hyperintensities (38%, 55%, 63%) increased with greater eGFRdiff. The levels of hs-TnT and NT-proBNP were inversely correlated with eGFRdiff. In multivariable-adjusted linear models, lower eGFRdiff was associated with MACE (P = 0.006) and HF hospitalization (P = 0.015). Conclusion A substantial proportion of patients with AF exhibit clinically relevant eGFRdiff. More negative eGFR difference was associated with elevated cardiac biomarkers, greater burden of ischaemic brain lesions, and increased risk of CV events and HF hospitalization. ClinicalTrials.gov Identifier NCT02105844
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Krisai et al. (2026) conducted a cohort in Atrial fibrillation (n=3,804). Negative difference between cystatin C-based and creatinine-based eGFR (<-10 mL/min/1.73 m²) vs. Concordant eGFR estimates (difference of -10 to 10 mL/min/1.73 m²) was evaluated on Major adverse cardiovascular events (composite of stroke, systemic embolism, myocardial infarction, and cardiovascular death) (HR 1.50, 95% CI 1.26-1.79, p=<0.001). A negative eGFR difference (<-10 mL/min/1.73 m²) between cystatin C-based and creatinine-based estimates was associated with a higher risk of major cardiovascular events (HR 1.50) compared to concordant estimates.
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