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Circulating Levels of Biomarkers of Cerebral Injury in Patients with Atrial Fibrillation

Published:September 06, 2019DOI:https://doi.org/10.1016/j.amjcard.2019.08.027
      Atrial fibrillation (AF) is a source of altered brain perfusion and ischemia, potentially leading to cerebral injury and blood brain barrier (BBB) disruption, which may result in the permeation of neurospecific molecules into the bloodstream. We retrospectively analyzed circulating levels of biomarkers of cerebral injury: Astrocyte-specific glial acidic fibrillary protein (GFAP), calcium-binding protein B (S100 b), stress response marker growth differential factor 15 (GDF15), and microtubule associated Tau protein, in patients with AF and non-AF controls. A total of 196 AF cases and 47 non-AF controls were enrolled in this study all without previous clinical stroke or cerebral injury. Plasma samples were obtained from the Intermountain INSPIRE biobank registry. AF status was determined at the time of the sample draw using clinical diagnosis. Assessment of circulating biomarkers was conducted with EIA. Multivariate linear modeling, using natural log, and square root transformation of the biomarkers, was done adjusting for (1) CHA2DS2-VASc and anticoagulation, and (2) age, gender, coronary artery disease and anticoagulation. Circulating Tau, GDF15, and GFAP were elevated in AF cases. After multivariate adjustment, GFAP and Tau remained significantly elevated in the AF, whereas the signal for GDF15 was confounded by age. In conclusion, circulating biomarkers of neuronal and glial injury Tau and GFAP are elevated in patients with AF that are consistent with subclinical cerebral injury and disruption of the BBB, which can predispose these patients to the development of cognitive dysfunction and/or dementia later in life.
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      References

        • Chinitz JS
        • Castellano JM
        • Kovacic JC
        • Fuster V
        Atrial fibrillation, stroke, and quality of life.
        Ann N Y Acad Sci. 2012; 1254: 140-150
        • Santangeli P
        • Di Biase L
        • Bai R
        • Mohanty S
        • Pump A
        • Brantes MC
        • Horton R
        • Burkhardt JD
        • Lakkireddy D
        • Reddy YM
        Atrial fibrillation and the risk of incident dementia: a meta-analysis.
        Heart Rhythm. 2012; 9: 1761-1768
        • Charidimou A
        • Inamura S
        • Nomura T
        • Kanno A
        • Kim SN
        • Imaizumi T
        Cerebral microbleeds and white matter hyperintensities in cardioembolic stroke patients due to atrial fibrillation: single-centre longitudinal study.
        J Neurol Sci. 2016; 369: 263-267
        • Charidimou A
        • Shoamanesh A
        • Wilson D
        • Gang Q
        • Fox Z
        • Jager HR
        • Benavente OR
        • Werring DJ
        Cerebral microbleeds and post-thrombolysis intracerebral hemorrhage risk: updated meta-analysis.
        Neurology. 2015; 85 (15927-924)
        • Kwok CS
        • Loke YK
        • Hale R
        • Potter JF
        • Myint PK
        Atrial fibrillation and incidence of dementia: a systematic review and meta-analysis.
        Neurology. 2011; 76: 914-2226
        • Prince M
        • Bryce R
        • Albanese E
        • Wimo A
        • Ribeiro W
        • Ferri CP
        The global prevalence of dementia: a systematic review and metaanalysis.
        Alzheimers Dement. 2013; 9: 63-75
        • Bunch TJ
        • Weiss JP
        • Crandall BG
        • May HT
        • Bair TL
        • Osborn JS
        • Anderson JL
        • Muhlestein JB
        • Horne BD
        • Lappe DL
        • Day JD
        Atrial fibrillation is independently associated with senile, vascular, and Alzheimer's dementia.
        Heart Rhythm. 2010; 7: 433-437
        • Jacobs V
        • Woller SC
        • Stevens S
        • May HT
        • Bair TL
        • Anderson JL
        • Crandall BG
        • Day JD
        • Johanning K
        • Long Y
        Time outside of therapeutic range in atrial fibrillation patients is associated with long-term risk of dementia.
        Heart Rhythm. 2014; 11: 2206-2213
        • Graves KG
        • May HT
        • Jacobs V
        • Bair TL
        • Stevens SM
        • Woller SC
        • Crandall BG
        • Cutler MJ
        • Day JD
        • Mallender C
        • Osborn JS
        • Peter Weiss J
        • Jared Bunch T
        Atrial fibrillation incrementally increases dementia risk across all CHADS2 and CHA2DS2VASc strata in patients receiving long-term warfarin.
        Am Heart J. 2017; 188: 93-98
        • Jacobs V
        • Cutler MJ
        • Day JD
        • Bunch TJ
        Atrial fibrillation and dementia.
        Trends Cardiovasc Med. 2015; 25: 44-51
        • Kalantarian S
        • Ay H
        • Gollub RL
        • Lee H
        • Retzepi K
        • Mansour M
        • Ruskin JN
        Association between atrial fibrillation and silent cerebral infarctions: a systematic review and meta-analysis.
        Ann Intern Med. 2014; 161: 650-658
        • Kalantarian S
        • Stern TA
        • Mansour M
        • Ruskin JN
        Cognitive impairment associated with atrial fibrillation: a meta-analysis.
        Ann Intern Med. 2013; 158: 338-346
        • Trojanowski JQ
        • Schuck T
        • Schmidt ML
        • Lee VM
        Distribution of tau proteins in the normal human central and peripheral nervous system.
        J Histochem Cytochem. 1989; 37: 209-215
        • Shahim P
        • Tegner Y
        • Wilson DH
        • Randall J
        • Skillback T
        • Pazooki D
        • Kallberg B
        • Blennow K
        • Zetterberg H
        Blood biomarkers for brain injury in concussed professional ice hockey players.
        JAMA Neurol. 2014; 71: 684-692
        • Yang Z
        • Wang KK
        Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker.
        Trends Neurosci. 2015; 38: 364-374
        • Olsson B
        • Zetterberg H
        • Hampel H
        • Blennow K
        Biomarker-based dissection of neurodegenerative diseases.
        Prog Neurobiol. 2011; 95: 520-534
        • Marchi N
        • Rasmussen P
        • Kapural M
        • Fazio V
        • Kight K
        • Mayberg MR
        • Kanner A
        • Ayumar B
        • Albensi B
        • Cavaglia M
        • Janigro D
        Peripheral markers of brain damage and blood-brain barrier dysfunction.
        Restor Neurol Neurosci. 2003; 21: 109-121
        • Hijazi Z
        • Oldgren J
        • Andersson U
        • Connolly SJ
        • Eikelboom JW
        • Ezekowitz MD
        • Reilly PA
        • Yusuf S
        • Siegbahn A
        • Wallentin L
        Growth-differentiation factor 15 and risk of major bleeding in atrial fibrillation: insights from the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial.
        Am Heart J. 2017; 190: 94-103
        • Schober A
        • Bottner M
        • Strelau J
        • Kinscherf R
        • Bonaterra GA
        • Barth M
        • Schilling L
        • Fairlie WD
        • Breit SN
        • Unsicker K
        Expression of growth differentiation factor-15/ macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in the perinatal, adult, and injured rat brain.
        J Comp Neurol. 2001; 439: 32-45
        • Fuchs T
        • Trollor JN
        • Crawford J
        • Brown DA
        • Baune BT
        • Samaras K
        • Campbell L
        • Breit SN
        • Brodaty H
        • Sachdev P
        • Smith E
        Macrophage inhibitory cytokine-1 is associated with cognitive impairment and predicts cognitive decline - the Sydney Memory and Aging Study.
        Aging cell. 2013; 12: 882-889
        • Chai YL
        • Hilal S
        • Chong JP
        • Ng YX
        • Liew OW
        • Xu X
        • Ikram MK
        • Venketasubramanian N
        • Richards AM
        • Lai MK
        • Chen CP
        Growth differentiation factor-15 and white matter hyperintensities in cognitive impairment and dementia.
        Medicine. 2016; 95: e4566
        • Blum S
        • Kuehne M
        • Rodondi N
        • Mueller A
        • Ammann P
        • Moschovitis G
        • Kobza R
        • Schlaepfer J
        • Meyre P
        • Bonati L
        1358 prevalence of silent vascular brain lesions among patients with atrial fibrillation and no known history of stroke.
        Eur Heart J. 2018; 39 (ehy565. 1358)