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Bleeding events are associated with an increase in markers of inflammation in acute coronary syndromes: an ACUITY trial substudy

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Abstract

Bleeding events have been associated with adverse early and late outcomes in virtually all clinical settings. The mechanism behind this observation remains poorly understood. We sought to determine if the reason might be the provocation of an inflammatory response by bleeding events. In a formal substudy of the ACUITY trial, plasma samples of a range of biomarkers were collected at baseline, discharge, 30 days, and 1 year from 192 patients with acute coronary syndromes (ACS) and were analyzed in a central core laboratory. Temporal changes in biomarker levels were assessed in patients who experienced in-hospital hemorrhagic events, recurrent ischemic events, or neither. Sixteen patients were excluded from the study (7 with incomplete samples, 5 undergoing coronary artery bypass grafting (CABG) during index hospitalization; 1 had both bleeding and ischemic events). Median high sensitivity C-reactive protein (hs-CRP) levels (mg/l) increased significantly more from admission to discharge among the 9 patients who experienced an in-hospital major bleed compared to either the 9 patients who had a recurrent ischemic event (+6.0 vs. +0.70, P = 0.04) or the 151 patients who had no event (+6.0 vs. +0.60, P = 0.003). Compared to patients with no in-hospital events, median interleukin-6 (IL-6) levels (pg/ml) increased from admission to hospital discharge non-significantly in those with a bleeding event (+0.92 vs. +2.46, P = 0.55) and in those who experienced an in-hospital recurrent ischemic event (+0.92 vs. +3.60, P = 0.09). These data suggest that major bleeding is associated with development of a pro-inflammatory state. If confirmed, this mechanism may in part explain the poor prognosis of patients experiencing an acute hemorrhagic event.

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Disclosures: Relationship with industry

Charles L. Campbell—Research support, the Medicines Company; Steven R. Steinhubl—Employee and stock options, the Medicines Company; W. Craig Hooper—None; Joseph Jozic—None; Susan S. Smyth—Research support, the Medicines Company; Debra Bernstein—Employee and stock options, the Medicines Company; Christine De Staercke—None; George Syros—None; Brian H. Negus—Research support and stock holder (<$25,000), the Medicines Company; Thomas Stuckey—None; Gregg W. Stone—none; Roxana Mehran—Speakers Honoraria, the Medicines Company; George Dangas—Speakers Honoraria, the Medicines Company.

Funding

The ACUITY trial was sponsored by The Medicines Company and Nycomed.

Author information

Authors and Affiliations

  1. Gill Heart Institute, University of Kentucky, 326 Charles T. Wethington Building, 900 South Limestone, Lexington, KY, 40536-0293, USA

    Charles L. Campbell & Susan S. Smyth

  2. Lexington VA Medical Center, Lexington, KY, USA

    Charles L. Campbell & Susan S. Smyth

  3. Geisinger Medical Center, Danville, PA, USA

    Steven R. Steinhubl

  4. The Medicines Company, Parsippany, NJ, USA

    Debra Bernstein

  5. Centers for Disease Control, Atlanta, GA, USA

    William C. Hooper & Christine De Staercke

  6. Harrington-McLaughlin Heart & Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH, USA

    Joseph Jozic

  7. Columbia University Medical Center and the Cardiovascular Research Foundation, New York, NY, USA

    George Syros & Gregg W. Stone

  8. Chattanooga Heart Institute, Chattanooga, TN, USA

    Brian H. Negus

  9. LeBauer Cardiovascular Research Foundation, Greensboro, NC, USA

    Thomas Stuckey

  10. Mount Sinai Medical Center, Cardiovascular Institute, New York, NY, USA

    Roxana Mehran

  11. Cardiovascular Institute, Mount Sinai Hospital, Box 1030, One G. Levy Place, New York, NY, 10029, USA

    George Dangas

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  1. Charles L. Campbell
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Correspondence to George Dangas.

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Campbell, C.L., Steinhubl, S.R., Hooper, W.C. et al. Bleeding events are associated with an increase in markers of inflammation in acute coronary syndromes: an ACUITY trial substudy. J Thromb Thrombolysis 31, 139–145 (2011). https://doi.org/10.1007/s11239-010-0513-1

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