Chemokine ligand 18 predicts all-cause mortality in patients hospitalized with chest pain of suspected coronary origin

Dennis W T Nilsen; Reidun Aarsetoey; Volker Poenitz; Thor Ueland; Pål Aukrust; Annika E Michelsen; Trygve Brugger-Andersen; Harry Staines; Heidi Grundt

doi:10.1016/j.ijcrp.2024.200264

Chemokine ligand 18 predicts all-cause mortality in patients hospitalized with chest pain of suspected coronary origin

Int J Cardiol Cardiovasc Risk Prev. 2024 Mar 27:21:200264. doi: 10.1016/j.ijcrp.2024.200264. eCollection 2024 Jun.

Authors

Dennis W T Nilsen^{1

2}, Reidun Aarsetoey¹, Volker Poenitz¹, Thor Ueland^{3

4}, Pål Aukrust^{4

5

6}, Annika E Michelsen^{4

5}, Trygve Brugger-Andersen⁷, Harry Staines⁸, Heidi Grundt^{1

9}

Affiliations

¹ Stavanger University Hospital, Department of Cardiology, Stavanger, Norway.
² University of Bergen, Department of Clinical Science, Bergen, Norway.
³ Department of Clinical Medicine, Thrombosis Research Center, UiT - The Arctic University of Norway, Tromsø, Norway.
⁴ University of Oslo, Faculty of Medicine, Oslo, Norway.
⁵ Oslo University Hospital, Rikshospitalet, Research Institute of Internal Medicine, Oslo, Norway.
⁶ Oslo University Hospital, Rikshospitalet, Section of Clinical Immunology and Infectious Diseases, Oslo, Norway.
⁷ Stavanger Heart Center, Stavanger, Norway.
⁸ Sigma Statistical Services, Balmullo, Northern Ireland, United Kingdom.
⁹ Stavanger University Hospital, Department of Respiratory Medicine, Stavanger, Norway.

Abstract

Introduction: Chemokines mediate recruitment and activation of leucocytes. Chemokine ligand 18 (CCL18) is mainly expressed by monocytes/macrophages and dendritic cells. It is highly expressed in chronic inflammatory diseases, and locally in atherosclerotic plaques, particularly at sites of reduced stability, and systemically in acute coronary syndrome patients. Reports on its prognostic utility in the latter condition, including myocardial infarction (MI), are scarce.

Aim: To assess the utility of CCL18 as a prognostic marker of recurrent cardiovascular events in patients hospitalized with chest pain of suspected coronary origin.

Methods: The population consisted of 871 consecutive chest-pain patients, of whom 386 were diagnosed with acute myocardial infarction (AMI) based on Troponin-T (TnT) levels >50 ng/L. Stepwise Cox regression models, applying normalized continuous log_e/SD values, were fitted for the biomarkers with cardiac mortality within 2 years and total mortality within 2 and 7 years as the dependent variables.

Results: Plasma samples from 849 patients were available. By 2 years follow-up, 138 (15.8%) patients had died, of which 86 were cardiac deaths. Univariate analysis showed a positive, significant association between CCL18 and total death [HR 1.55 (95% 1.30-1.83), p < 0.001], and for cardiac death [HR 1.32 (95% 1.06-1.64), p = 0.013]. Associations after adjustment were non-significant. By 7 years follow-up, 332 (38.1%) patients had died. CLL18 was independently associated with all-cause mortality [HR 1.14 (95% CI, 1.01-1.29), p = 0.030], but not with MI (n = 203) or stroke (n = 55).

Conclusion: CCL18 independently predicts long-term all-cause mortality but had no independent prognostic bearing on short-term cardiac death and CVD events.

Keywords: Acute coronary syndrome (ACS); Biomarkers; Cardiovascular disease (CVD) events; Chemokine ligand 18/pulmonary activation regulated chemokine (CCL18/PARC); Mortality.