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Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function.

Abstract

BACKGROUND

Early evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function.

METHODS AND RESULTS

Retrospective cohort study using administrative healthcare databases in Ontario, Canada (2002-2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin-to-creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow-up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow-up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF (P<0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, P<0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0-5.1] and 2.6 [95% CI, 2.4-2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses.

CONCLUSIONS

Proteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF.

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  • Authors+Show Affiliations

    ,

    Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

    ,

    Institute for Clinical Evaluative Sciences, London, Ontario, Canada.

    ,

    Institute for Clinical Evaluative Sciences, London, Ontario, Canada.

    ,

    Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada. Epidemiology, Western University, London, Ontario, Canada. Institute for Clinical Evaluative Sciences, London, Ontario, Canada.

    ,

    Nephrology, St. Michael's Hospital, University of Toronto, Ontario, Canada.

    ,

    Institute for Clinical Evaluative Sciences, London, Ontario, Canada.

    ,

    Nephrology, St. Michael's Hospital, University of Toronto, Ontario, Canada.

    ,

    Nephrology, St. Michael's Hospital, University of Toronto, Ontario, Canada.

    ,

    Division of Nephrology, Department of Medicine, University of Ottawa, Ontario, Canada.

    Institute for Clinical Evaluative Sciences, London, Ontario, Canada msood@toh.on.ca. Division of Nephrology, Department of Medicine, University of Ottawa, Ontario, Canada. Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

    Source

    MeSH

    Adult
    Aged
    Albuminuria
    Atrial Fibrillation
    Biomarkers
    Chi-Square Distribution
    Creatinine
    Disease Progression
    Female
    Glomerular Filtration Rate
    Humans
    Incidence
    Kidney
    Kidney Diseases
    Male
    Middle Aged
    Multivariate Analysis
    Ontario
    Prognosis
    Proportional Hazards Models
    Retrospective Studies
    Risk Assessment
    Risk Factors
    Time Factors

    Pub Type(s)

    Comparative Study
    Journal Article

    Language

    eng

    PubMed ID

    28684642

    Citation

    Molnar, Amber O., et al. "Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function." Journal of the American Heart Association, vol. 6, no. 7, 2017.
    Molnar AO, Eddeen AB, Ducharme R, et al. Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function. J Am Heart Assoc. 2017;6(7).
    Molnar, A. O., Eddeen, A. B., Ducharme, R., Garg, A. X., Harel, Z., McCallum, M. K., ... Sood, M. M. (2017). Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function. Journal of the American Heart Association, 6(7), doi:10.1161/JAHA.117.005685.
    Molnar AO, et al. Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function. J Am Heart Assoc. 2017 Jul 6;6(7) PubMed PMID: 28684642.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function. AU - Molnar,Amber O, AU - Eddeen,Anan Bader, AU - Ducharme,Robin, AU - Garg,Amit X, AU - Harel,Ziv, AU - McCallum,Megan K, AU - Perl,Jeffrey, AU - Wald,Ron, AU - Zimmerman,Deborah, AU - Sood,Manish M, Y1 - 2017/07/06/ PY - 2017/7/8/entrez PY - 2017/7/8/pubmed PY - 2018/5/17/medline KW - atrial fibrillation KW - chronic kidney disease KW - risk factor JF - Journal of the American Heart Association JO - J Am Heart Assoc VL - 6 IS - 7 N2 - BACKGROUND: Early evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function. METHODS AND RESULTS: Retrospective cohort study using administrative healthcare databases in Ontario, Canada (2002-2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin-to-creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow-up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow-up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF (P<0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, P<0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0-5.1] and 2.6 [95% CI, 2.4-2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses. CONCLUSIONS: Proteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF. SN - 2047-9980 UR - https://www.unboundmedicine.com/medline/citation/28684642/Association_of_Proteinuria_and_Incident_Atrial_Fibrillation_in_Patients_With_Intact_and_Reduced_Kidney_Function_ L2 - http://www.ahajournals.org/doi/full/10.1161/JAHA.117.005685?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -