The Association of Atrial Fibrillation and Ischemic Stroke in Patients on Hemodialysis: A Competing Risk Analysis

Mark Findlay* (Corresponding Author), Rachael MacIsaac, Mary J. Macleod, Wendy Metcalfe, Manish Sood, Jamie P. Traynor, Jesse Dawson, Patrick Mark

*Corresponding author for this work

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    Background:
    Stroke is common in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) and associated with high mortality rate. In the general population, atrial fibrillation (AF) is a major risk factor for stroke and therapeutic anticoagulation is associated with risk reduction, whereas in ESRD the relationship is less clear.

    Objective:
    The purpose of this study is to demonstrate the influence of AF on stroke rates and probability in those on HD following competing risk analyses.

    Design:
    A national record linkage cohort study.

    Setting:
    All renal and stroke units in Scotland, UK.

    Patients:
    All patients with ESRD receiving HD within Scotland from 2005 to 2013 (follow-up to 2015).

    Measurements:
    Demographic, clinical, and laboratory data were linked between the Scottish Renal Registry, Scottish Stroke Care Audit, and hospital discharge data. Stroke was defined as a fatal or nonfatal event and mortality derived from national records.

    Methods:
    Associations for stroke were determined using competing risk models: the cause-specific hazards model and the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of all stroke, ischemic stroke, and first-ever stroke.

    Results:
    Of 5502 patients treated with HD with 12 348.6-year follow-up, 363 (6.6%) experienced stroke. The stroke incidence rate was 26.7 per 1000 patient-years. Multivariable regression on the cause-specific hazard for stroke demonstrated age, hazard ratio (HR) (95% confidence interval [CI]) = 1.04 (1.03-1.05); AF, HR (95% CI) = 1.88 (1.25-2.83); prior stroke, HR (95% CI) = 2.29 (1.48-3.54), and diabetes, HR (95% CI) = 1.92 (1.45-2.53); serum phosphate, HR (95% CI) = 2.15 (1.56-2.99); lower body weight, HR (95% CI) = 0.99 (0.98-1.00); lower hemoglobin, HR (95% CI) = 0.88 (0.77-0.99); and systolic blood pressure (BP), HR (95% CI) = 1.01 (1.00-1.02), to be associated with an increased stroke rate. In contrast, the subdistribution HRs obtained following Fine and Gray regression demonstrated that AF, weight, and hemoglobin were not associated with stroke risk. In both models, AF was significantly associated with nonstroke death.

    Limitations:
    Our analyses derive from retrospective data sets and thus can only describe association not causation. Data on anticoagulant use are not available.

    Conclusions:
    The incidence of stroke in HD patients is high. The competing risk of “prestroke” mortality affects the relationship between AF and risk of future stroke. Trial designs for interventions to reduce stroke risk in HD patients, such as anticoagulation for AF, should take account of competing risks affecting associations between risk factors and outcomes.
    Original languageEnglish
    Pages (from-to)1-13
    Number of pages13
    JournalCanadian Journal of Kidney Health and Disease
    Volume6
    Early online date27 Sep 2019
    DOIs
    Publication statusPublished - 2019

    Fingerprint

    Atrial Fibrillation
    Renal Dialysis
    Stroke
    Confidence Intervals
    Chronic Kidney Failure
    Scotland
    Proportional Hazards Models
    Mortality
    Hemoglobins
    Blood Pressure
    Kidney
    Incidence
    Risk Reduction Behavior
    Causality
    Anticoagulants

    Keywords

    • stroke
    • hemodialysis
    • atrial fibrillation
    • competing risk
    • mortality

    Cite this

    The Association of Atrial Fibrillation and Ischemic Stroke in Patients on Hemodialysis : A Competing Risk Analysis. / Findlay, Mark (Corresponding Author); MacIsaac, Rachael; Macleod, Mary J.; Metcalfe, Wendy; Sood, Manish; Traynor, Jamie P.; Dawson, Jesse; Mark, Patrick.

    In: Canadian Journal of Kidney Health and Disease, Vol. 6, 2019, p. 1-13.

    Research output: Contribution to journalArticle

    Findlay, Mark ; MacIsaac, Rachael ; Macleod, Mary J. ; Metcalfe, Wendy ; Sood, Manish ; Traynor, Jamie P. ; Dawson, Jesse ; Mark, Patrick. / The Association of Atrial Fibrillation and Ischemic Stroke in Patients on Hemodialysis : A Competing Risk Analysis. In: Canadian Journal of Kidney Health and Disease. 2019 ; Vol. 6. pp. 1-13.
    @article{31c68e7512a448f197031aa48f5705c2,
    title = "The Association of Atrial Fibrillation and Ischemic Stroke in Patients on Hemodialysis: A Competing Risk Analysis",
    abstract = "Background:Stroke is common in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) and associated with high mortality rate. In the general population, atrial fibrillation (AF) is a major risk factor for stroke and therapeutic anticoagulation is associated with risk reduction, whereas in ESRD the relationship is less clear.Objective:The purpose of this study is to demonstrate the influence of AF on stroke rates and probability in those on HD following competing risk analyses.Design:A national record linkage cohort study.Setting:All renal and stroke units in Scotland, UK.Patients:All patients with ESRD receiving HD within Scotland from 2005 to 2013 (follow-up to 2015).Measurements:Demographic, clinical, and laboratory data were linked between the Scottish Renal Registry, Scottish Stroke Care Audit, and hospital discharge data. Stroke was defined as a fatal or nonfatal event and mortality derived from national records.Methods:Associations for stroke were determined using competing risk models: the cause-specific hazards model and the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of all stroke, ischemic stroke, and first-ever stroke.Results:Of 5502 patients treated with HD with 12 348.6-year follow-up, 363 (6.6{\%}) experienced stroke. The stroke incidence rate was 26.7 per 1000 patient-years. Multivariable regression on the cause-specific hazard for stroke demonstrated age, hazard ratio (HR) (95{\%} confidence interval [CI]) = 1.04 (1.03-1.05); AF, HR (95{\%} CI) = 1.88 (1.25-2.83); prior stroke, HR (95{\%} CI) = 2.29 (1.48-3.54), and diabetes, HR (95{\%} CI) = 1.92 (1.45-2.53); serum phosphate, HR (95{\%} CI) = 2.15 (1.56-2.99); lower body weight, HR (95{\%} CI) = 0.99 (0.98-1.00); lower hemoglobin, HR (95{\%} CI) = 0.88 (0.77-0.99); and systolic blood pressure (BP), HR (95{\%} CI) = 1.01 (1.00-1.02), to be associated with an increased stroke rate. In contrast, the subdistribution HRs obtained following Fine and Gray regression demonstrated that AF, weight, and hemoglobin were not associated with stroke risk. In both models, AF was significantly associated with nonstroke death.Limitations:Our analyses derive from retrospective data sets and thus can only describe association not causation. Data on anticoagulant use are not available.Conclusions:The incidence of stroke in HD patients is high. The competing risk of “prestroke” mortality affects the relationship between AF and risk of future stroke. Trial designs for interventions to reduce stroke risk in HD patients, such as anticoagulation for AF, should take account of competing risks affecting associations between risk factors and outcomes.",
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    author = "Mark Findlay and Rachael MacIsaac and Macleod, {Mary J.} and Wendy Metcalfe and Manish Sood and Traynor, {Jamie P.} and Jesse Dawson and Patrick Mark",
    year = "2019",
    doi = "10.1177/2054358119878719",
    language = "English",
    volume = "6",
    pages = "1--13",
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    TY - JOUR

    T1 - The Association of Atrial Fibrillation and Ischemic Stroke in Patients on Hemodialysis

    T2 - A Competing Risk Analysis

    AU - Findlay, Mark

    AU - MacIsaac, Rachael

    AU - Macleod, Mary J.

    AU - Metcalfe, Wendy

    AU - Sood, Manish

    AU - Traynor, Jamie P.

    AU - Dawson, Jesse

    AU - Mark, Patrick

    PY - 2019

    Y1 - 2019

    N2 - Background:Stroke is common in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) and associated with high mortality rate. In the general population, atrial fibrillation (AF) is a major risk factor for stroke and therapeutic anticoagulation is associated with risk reduction, whereas in ESRD the relationship is less clear.Objective:The purpose of this study is to demonstrate the influence of AF on stroke rates and probability in those on HD following competing risk analyses.Design:A national record linkage cohort study.Setting:All renal and stroke units in Scotland, UK.Patients:All patients with ESRD receiving HD within Scotland from 2005 to 2013 (follow-up to 2015).Measurements:Demographic, clinical, and laboratory data were linked between the Scottish Renal Registry, Scottish Stroke Care Audit, and hospital discharge data. Stroke was defined as a fatal or nonfatal event and mortality derived from national records.Methods:Associations for stroke were determined using competing risk models: the cause-specific hazards model and the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of all stroke, ischemic stroke, and first-ever stroke.Results:Of 5502 patients treated with HD with 12 348.6-year follow-up, 363 (6.6%) experienced stroke. The stroke incidence rate was 26.7 per 1000 patient-years. Multivariable regression on the cause-specific hazard for stroke demonstrated age, hazard ratio (HR) (95% confidence interval [CI]) = 1.04 (1.03-1.05); AF, HR (95% CI) = 1.88 (1.25-2.83); prior stroke, HR (95% CI) = 2.29 (1.48-3.54), and diabetes, HR (95% CI) = 1.92 (1.45-2.53); serum phosphate, HR (95% CI) = 2.15 (1.56-2.99); lower body weight, HR (95% CI) = 0.99 (0.98-1.00); lower hemoglobin, HR (95% CI) = 0.88 (0.77-0.99); and systolic blood pressure (BP), HR (95% CI) = 1.01 (1.00-1.02), to be associated with an increased stroke rate. In contrast, the subdistribution HRs obtained following Fine and Gray regression demonstrated that AF, weight, and hemoglobin were not associated with stroke risk. In both models, AF was significantly associated with nonstroke death.Limitations:Our analyses derive from retrospective data sets and thus can only describe association not causation. Data on anticoagulant use are not available.Conclusions:The incidence of stroke in HD patients is high. The competing risk of “prestroke” mortality affects the relationship between AF and risk of future stroke. Trial designs for interventions to reduce stroke risk in HD patients, such as anticoagulation for AF, should take account of competing risks affecting associations between risk factors and outcomes.

    AB - Background:Stroke is common in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) and associated with high mortality rate. In the general population, atrial fibrillation (AF) is a major risk factor for stroke and therapeutic anticoagulation is associated with risk reduction, whereas in ESRD the relationship is less clear.Objective:The purpose of this study is to demonstrate the influence of AF on stroke rates and probability in those on HD following competing risk analyses.Design:A national record linkage cohort study.Setting:All renal and stroke units in Scotland, UK.Patients:All patients with ESRD receiving HD within Scotland from 2005 to 2013 (follow-up to 2015).Measurements:Demographic, clinical, and laboratory data were linked between the Scottish Renal Registry, Scottish Stroke Care Audit, and hospital discharge data. Stroke was defined as a fatal or nonfatal event and mortality derived from national records.Methods:Associations for stroke were determined using competing risk models: the cause-specific hazards model and the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of all stroke, ischemic stroke, and first-ever stroke.Results:Of 5502 patients treated with HD with 12 348.6-year follow-up, 363 (6.6%) experienced stroke. The stroke incidence rate was 26.7 per 1000 patient-years. Multivariable regression on the cause-specific hazard for stroke demonstrated age, hazard ratio (HR) (95% confidence interval [CI]) = 1.04 (1.03-1.05); AF, HR (95% CI) = 1.88 (1.25-2.83); prior stroke, HR (95% CI) = 2.29 (1.48-3.54), and diabetes, HR (95% CI) = 1.92 (1.45-2.53); serum phosphate, HR (95% CI) = 2.15 (1.56-2.99); lower body weight, HR (95% CI) = 0.99 (0.98-1.00); lower hemoglobin, HR (95% CI) = 0.88 (0.77-0.99); and systolic blood pressure (BP), HR (95% CI) = 1.01 (1.00-1.02), to be associated with an increased stroke rate. In contrast, the subdistribution HRs obtained following Fine and Gray regression demonstrated that AF, weight, and hemoglobin were not associated with stroke risk. In both models, AF was significantly associated with nonstroke death.Limitations:Our analyses derive from retrospective data sets and thus can only describe association not causation. Data on anticoagulant use are not available.Conclusions:The incidence of stroke in HD patients is high. The competing risk of “prestroke” mortality affects the relationship between AF and risk of future stroke. Trial designs for interventions to reduce stroke risk in HD patients, such as anticoagulation for AF, should take account of competing risks affecting associations between risk factors and outcomes.

    KW - stroke

    KW - hemodialysis

    KW - atrial fibrillation

    KW - competing risk

    KW - mortality

    U2 - 10.1177/2054358119878719

    DO - 10.1177/2054358119878719

    M3 - Article

    C2 - 31632680

    VL - 6

    SP - 1

    EP - 13

    JO - Canadian Journal of Kidney Health and Disease

    JF - Canadian Journal of Kidney Health and Disease

    SN - 2054-3581

    ER -