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Original research
Creatine kinase is associated with bleeding after myocardial infarction
  1. Lizzy Maritza Brewster1 and
  2. Jim Fernand2
  1. 1CK Science Foundation, Amsterdam, The Netherlands
  2. 2Clinic for Health and Individual Medicine, Utrecht, The Netherlands
  1. Correspondence to Dr Lizzy Maritza Brewster; mail{at}


Background The ADP-scavenging enzyme creatine kinase (CK) is reported to reduce ADP-dependent platelet activation. Therefore, we studied whether highly elevated CK after ST-elevation myocardial infarction (STEMI) is associated with bleeding.

Methods Data of the Thrombolysis in Myocardial Infarction Study Group phase II trial on the efficacy of angioplasty, following intravenous recombinant tissue-type plasminogen activator (rt-PA), are used to assess whether peak plasma CK (CKmax) is independently associated with adjudicated fatal or non-fatal bleeding (primary) and combined bleeding/all-cause mortality (secondary) in multivariable binomial logistic regression analysis, adjusting for baseline and treatment allocation covariates.

Results The included patients (n=3339, 82% men, 88% white, mean age 57 years, SE 0.2) had a history of angina pectoris (55%), hypertension (38%) and/or diabetes mellitus (13%). CKmax ranged from 16 to 55 890 IU/L (mean 2389 IU/L, SE 41), reached within 8 hours in 51% of the patients (93% within 24 hours). Adjudicated fatal/non-fatal bleeding occurred in 30% of the patients (respectively 26% in the low vs 34% in the high CK tertile), and bleeding/all-cause mortality in 35% (29% in the low vs 40% in the high CK tertile). In multivariable regression analysis, the adjusted OR for fatal/non-fatal bleeding (vs not bleeding and survival) was 2.6 (95% CI 1.8 to 3.7)/log CKmax increase, and 3.1 (2.2 to 4.4) for bleeding/all-cause mortality.

Conclusion Highly elevated plasma CK after myocardial infarction might be an independent predictor of bleeding and haemorrhagic death. This biologically plausible association warrants further prospective study of the potential role of extracellular CK in ADP-dependent platelet activation and bleeding.

  • platelets
  • coronary artery disease
  • emergency medicine

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  • Contributors LMB helped in conceptualisation, data curation, formal analysis, investigation, methodology, project administration, resources, supervision, validation, visualisation, writing original draft, review and editing. JF helped in conceptualisation, investigation, methodology, resources, validation, visualisation, review and editing.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests LMB is an inventor on patent WO/2012/138226 (filed).

  • Patient consent for publication Not required.

  • Ethics approval All patients had given written informed consent to be included in the study. The current analysis was approved by the review board of the Research Ethics Committee of the Radboud University Nijmegen Medical Centre on 30 April 2019 (registration number 2019–5356), and by the US National Heart, Lung, and Blood Institute (RMDA V02 1d20120806) on 6 May 2019.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. Data are available at the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) supported by the National Heart, Lung, and Blood Institute of the United States National Institutions of Health (NIH), USA.

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