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Comparative Study
. 2025 Jan 24;24(1):41.
doi: 10.1186/s12933-025-02590-2.

Proteinuria and the risk of Incident atrial fibrillation according to glycemic stages: a nationwide population-based cohort study

Muhan Yeo #  1 , So-Ryoung Lee #  1   2 , Eue-Keun Choi  3   4 , JungMin Choi  2 , Kyung-Yeon Lee  2 , Soonil Kwon  5 , Hyo-Jeong Ahn  2 , Bong-Seong Kim  6 , Kyung-Do Han  7 , Seil Oh  1   2 , Gregory Y H Lip  1   8   9
Affiliations
Comparative Study

Proteinuria and the risk of Incident atrial fibrillation according to glycemic stages: a nationwide population-based cohort study

Muhan Yeo et al. Cardiovasc Diabetol. .

Abstract

Background: Diabetes mellitus (DM) and proteinuria each independently raise the risk of atrial fibrillation (AF). We aimed to investigate the relationship between proteinuria and the risk of incident AF across glycemic stages.

Methods: A cohort of 4,044,524 individuals without prior AF and type 1 DM was selected from the 2009 Korean National Health Insurance Service health checkup data. The individuals were categorized into five glycemic stages: normal, prediabetes, new-onset DM, early DM (< 5 years), and late DM (≥ 5 years). Proteinuria was graded using a urine dipstick test. The development of incident AF was tracked until 2023.

Results: Overall, the cohort (mean age 47 ± 14 years, 44.8% female) showed increasing annual AF incidence rates from 2.05 to 7.22 per 1000 person-years from normal to late DM (p < 0.001). Incidence rates increased from 2.46 to 8.18 per 1000 person-years with increasing proteinuria (p < 0.001). Adjusted Cox regression models revealed a heightened AF risk with higher proteinuria across all glycemic stages (adjusted hazard ratios for urine dipstick 3+/4+: 1.58, 1.64, 2.39, 2.12, and 2.53 for normal, prediabetes, new-onset DM, early DM, and late DM, respectively). The proteinuria-AF association was more pronounced in individuals with DM than in those without DM but was similar among the new-onset and established DM groups.

Conclusions: Proteinuria is an independent and significant risk factor for incident AF at all glycemic stages. The risk of incident AF in patients with DM can be stratified by measuring the level of proteinuria rather than comparing the duration of DM. Tailoring clinical strategies to proteinuria level could potentially mitigate this risk, improving patient outcomes.

Keywords: Atrial fibrillation; Diabetes Mellitus; Proteinuria.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study received an exemption from the IRB of Seoul National University Hospital (IRB no. 2408-098-1562). Informed consent was not obtained because the database was anonymized. The utilization of the NHID for 2009–2023 will be approved in 2024. Consent for publication: Not applicable. Competing interests: EKC: Research grants or speaking fees from Abbott, Bayer, BMS/Pfizer, Biosense Webster, Chong Kun Dang, Daewoong Pharmaceutical Co., Daiichi-Sankyo, DeepQure, Dreamtech Co., Ltd., Jeil Pharmaceutical Co. Ltd, Medtronic, Samjinpharm, Samsung Electronics Co., Ltd., Seers Technology, and Skylabs. GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. He is a National Institute for Health and Care Research (NIHR) Senior Investigator.

Figures

Fig. 1
Fig. 1
Study population and design. T1DM: type 1 diabetes mellitus; AF: atrial fibrillation; DM: diabetes mellitus
Fig. 2
Fig. 2
Kaplan-Meier curves for AF incidence corresponding to glycemic stages and proteinuria level. DM: diabetes mellitus; Prediabetes: impaired fasting glucose (fasting glucose level from 100 to 126 mg/dL); New-onset DM: DM first diagnosed at the time of screening; Early DM: DM duration after diagnosis < 5 years; Late DM: DM duration after diagnosis ≥ 5 years
Fig. 3
Fig. 3
AF incidence rates and hazard ratios in Cox Proportional-Hazards Regression Model 4. DM: diabetes mellitus; Prediabetes: impaired fasting glucose (fasting glucose level from 100 to 126 mg/dL); New-onset DM: DM first diagnosed at the time of screening; Early DM: DM duration after diagnosis < 5 years; Late DM: DM duration after diagnosis ≥ 5 years
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