The levels of inflammatory markers in the treatment of stroke study (limits): Inflammatory biomarkers as risk predictors after lacunar stroke

M. S V Elkind, J. M. Luna, C. S. Coffey, L. A. McClure, K. M. Liu, S. Spitalnik, M. C. Paik, A. Roldan, C. White, R. Hart, O. Benavente

    Research output: Contribution to journalArticle

    20 Citations (Scopus)

    Abstract

    Background: Inflammation is increasingly recognised as playing a central role in atherosclerosis, and peripheral blood markers of inflammation have been associated with incident and recurrent cardiac events. The relationship of these potentially modifiable risk markers to prognosis after ischaemic stroke is less clear. The Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) study will address hypotheses related to the role of inflammatory markers in secondary stroke prevention in an efficient manner using the well-established framework of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (NCT00059306). Methods: SPS3 is an ongoing Phase III multicentre secondary prevention trial focused on preventing recurrent stroke in patients with small vessel ischaemic stroke, or lacunes. In SPS3, patients are assigned in a factorial design to aspirin vs. aspirin plus clopidogrel, and to usual vs. aggressive blood pressure targets. The purpose of LIMITS is to determine whether serum levels of inflammatory markers - including high-sensitivity C-reactive protein, serum amyloid A, CD40 ligand, and monocyte chemoattractant protein-1 - predict recurrent stroke and other vascular events among lacunar stroke patients. The project will also determine whether these markers predict which people will respond best to dual antiplatelet therapy with clopidogrel and aspirin, as well the relationship to cognitive function. Analysis plan: Multivariable Cox proportional hazard regression modeling will be used to estimate hazard ratios for the effect of marker levels on risk of recurrent stroke and other outcomes after adjusting for additional potential risk factors, including age, gender, ethnicity, treatment arm, and traditional stroke risk factors. Interactions between marker levels and treatment assignment for both arms of the SPS3 study will be assessed. Observations will be censored at the time of last follow-up visit.Conclusions:LIMITS represents an efficient approach to the identification of novel inflammatory biomarkers for use in risk prediction and treatment selection in patients with small vessel disease.

    Original languageEnglish (US)
    Pages (from-to)117-125
    Number of pages9
    JournalInternational Journal of Stroke
    Volume5
    Issue number2
    DOIs
    StatePublished - Apr 2010

    Fingerprint

    Lacunar Stroke
    Biomarkers
    Stroke
    clopidogrel
    Secondary Prevention
    Therapeutics
    Aspirin
    Inflammation
    Serum Amyloid A Protein
    CD40 Ligand
    Chemokine CCL2
    C-Reactive Protein
    Cognition
    Patient Selection
    Blood Vessels
    Atherosclerosis

    Keywords

    • Antiplatelet therapy
    • Aspirin
    • Cerebral infarction
    • Epidemiology
    • Ischaemic stroke
    • Prevention
    • Protocols
    • Risk factors

    ASJC Scopus subject areas

    • Neurology

    Cite this

    The levels of inflammatory markers in the treatment of stroke study (limits) : Inflammatory biomarkers as risk predictors after lacunar stroke. / Elkind, M. S V; Luna, J. M.; Coffey, C. S.; McClure, L. A.; Liu, K. M.; Spitalnik, S.; Paik, M. C.; Roldan, A.; White, C.; Hart, R.; Benavente, O.

    In: International Journal of Stroke, Vol. 5, No. 2, 04.2010, p. 117-125.

    Research output: Contribution to journalArticle

    Elkind, MSV, Luna, JM, Coffey, CS, McClure, LA, Liu, KM, Spitalnik, S, Paik, MC, Roldan, A, White, C, Hart, R & Benavente, O 2010, 'The levels of inflammatory markers in the treatment of stroke study (limits): Inflammatory biomarkers as risk predictors after lacunar stroke', International Journal of Stroke, vol. 5, no. 2, pp. 117-125. https://doi.org/10.1111/j.1747-4949.2010.00420.x
    Elkind, M. S V ; Luna, J. M. ; Coffey, C. S. ; McClure, L. A. ; Liu, K. M. ; Spitalnik, S. ; Paik, M. C. ; Roldan, A. ; White, C. ; Hart, R. ; Benavente, O. / The levels of inflammatory markers in the treatment of stroke study (limits) : Inflammatory biomarkers as risk predictors after lacunar stroke. In: International Journal of Stroke. 2010 ; Vol. 5, No. 2. pp. 117-125.
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    abstract = "Background: Inflammation is increasingly recognised as playing a central role in atherosclerosis, and peripheral blood markers of inflammation have been associated with incident and recurrent cardiac events. The relationship of these potentially modifiable risk markers to prognosis after ischaemic stroke is less clear. The Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) study will address hypotheses related to the role of inflammatory markers in secondary stroke prevention in an efficient manner using the well-established framework of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (NCT00059306). Methods: SPS3 is an ongoing Phase III multicentre secondary prevention trial focused on preventing recurrent stroke in patients with small vessel ischaemic stroke, or lacunes. In SPS3, patients are assigned in a factorial design to aspirin vs. aspirin plus clopidogrel, and to usual vs. aggressive blood pressure targets. The purpose of LIMITS is to determine whether serum levels of inflammatory markers - including high-sensitivity C-reactive protein, serum amyloid A, CD40 ligand, and monocyte chemoattractant protein-1 - predict recurrent stroke and other vascular events among lacunar stroke patients. The project will also determine whether these markers predict which people will respond best to dual antiplatelet therapy with clopidogrel and aspirin, as well the relationship to cognitive function. Analysis plan: Multivariable Cox proportional hazard regression modeling will be used to estimate hazard ratios for the effect of marker levels on risk of recurrent stroke and other outcomes after adjusting for additional potential risk factors, including age, gender, ethnicity, treatment arm, and traditional stroke risk factors. Interactions between marker levels and treatment assignment for both arms of the SPS3 study will be assessed. Observations will be censored at the time of last follow-up visit.Conclusions:LIMITS represents an efficient approach to the identification of novel inflammatory biomarkers for use in risk prediction and treatment selection in patients with small vessel disease.",
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    AU - Elkind, M. S V

    AU - Luna, J. M.

    AU - Coffey, C. S.

    AU - McClure, L. A.

    AU - Liu, K. M.

    AU - Spitalnik, S.

    AU - Paik, M. C.

    AU - Roldan, A.

    AU - White, C.

    AU - Hart, R.

    AU - Benavente, O.

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    N2 - Background: Inflammation is increasingly recognised as playing a central role in atherosclerosis, and peripheral blood markers of inflammation have been associated with incident and recurrent cardiac events. The relationship of these potentially modifiable risk markers to prognosis after ischaemic stroke is less clear. The Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) study will address hypotheses related to the role of inflammatory markers in secondary stroke prevention in an efficient manner using the well-established framework of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (NCT00059306). Methods: SPS3 is an ongoing Phase III multicentre secondary prevention trial focused on preventing recurrent stroke in patients with small vessel ischaemic stroke, or lacunes. In SPS3, patients are assigned in a factorial design to aspirin vs. aspirin plus clopidogrel, and to usual vs. aggressive blood pressure targets. The purpose of LIMITS is to determine whether serum levels of inflammatory markers - including high-sensitivity C-reactive protein, serum amyloid A, CD40 ligand, and monocyte chemoattractant protein-1 - predict recurrent stroke and other vascular events among lacunar stroke patients. The project will also determine whether these markers predict which people will respond best to dual antiplatelet therapy with clopidogrel and aspirin, as well the relationship to cognitive function. Analysis plan: Multivariable Cox proportional hazard regression modeling will be used to estimate hazard ratios for the effect of marker levels on risk of recurrent stroke and other outcomes after adjusting for additional potential risk factors, including age, gender, ethnicity, treatment arm, and traditional stroke risk factors. Interactions between marker levels and treatment assignment for both arms of the SPS3 study will be assessed. Observations will be censored at the time of last follow-up visit.Conclusions:LIMITS represents an efficient approach to the identification of novel inflammatory biomarkers for use in risk prediction and treatment selection in patients with small vessel disease.

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    KW - Prevention

    KW - Protocols

    KW - Risk factors

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