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Original research article
Serum PCSK9 is modified by interleukin-6 receptor antagonism in patients with hypercholesterolaemia following non-ST-elevation myocardial infarction
  1. Thor Ueland1,2,3,
  2. Ola Kleveland4,5,
  3. Annika E Michelsen1,2,
  4. Rune Wiseth4,5,
  5. Jan Kristian Damås6,
  6. Pål Aukrust1,2,7,
  7. Lars Gullestad2,8,9,
  8. Bente Halvorsen1,2 and
  9. Arne Yndestad1,2,9
  1. 1 Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
  2. 2 Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  3. 3 KG Jebsen TREC, University of Tromsø, Tromsø, Norway
  4. 4 Department of Clinic of Cardiology, St Olavs Hospital, Trondheim, Norway
  5. 5 Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
  6. 6 Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
  7. 7 Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
  8. 8 Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
  9. 9 Center for Heart Failure Research, University of Oslo, Oslo, Norway
  1. Correspondence to Dr Thor Ueland; thor.ueland{at}medisin.uio.no

Abstract

Objective It is unclear if activation of inflammatory pathways regulates proprotein convertase subtilisin-kexin type 9 (PCSK9) levels.

Approach We evaluated (1) the temporal course of serum PCSK9 during hospitalisation following acute coronary syndrome and associations with markers of inflammation (leucocyte counts, interleukin (IL)-6, C-reactive protein) and lipid levels and (2) the effect of inhibition of IL-6 signalling with the IL-6 receptor antibody tocilizumab on PCSK9 levels in a randomised, double-blind, placebo-controlled trial release in patients with non-ST-elevation myocardial infarction.

Results Serum PCSK9 increased during the acute phase and this response was modestly associated with neutrophil counts (r=0.24, p=0.009) and presence of hypercholesterolaemia (r=0.019, p=0.045), but was not modified by tocilizumab. However, a modifying effect of tocilizumab on PCSK9 levels was observed in patients with hypercholesterolaemia (p=0.024, repeated measures analysis of variance) and this effect was strongly correlated with the decrease in neutrophils (r=0.66, p=0.004).

Conclusions Our study suggests that patients with a more atherogenic profile may benefit from anti-IL-6 therapy with regard to PCSK9.

Trial registration number NCT01491074.

  • PCSK9
  • acute coronary syndrome
  • anti-IL6 therapy
  • inflammation

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors TU and AEM performed the ELISA analyses. TU performed the statistical analysis and presentation of data. OK, RW, JKD, PA, LG and TU designed the study. TU, AY and BH initiated the current substudy. TU, AY and PA drafted the manuscript. All authors made critical revision and accepted the article in its current form.

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

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Regional Committee for Medical and Health Research Ethics of South-Eastern Norway and the Norwegian Medicines Agency.

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

  • Data sharing statement There are no additional data available for this paper.

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