Subgroups of monocytes predict cardiovascular events in patients with coronary heart disease. The PHAMOS trial (Prospective Halle Monocytes Study)

Hellenic J Cardiol. Sep-Oct 2019;60(5):311-321. doi: 10.1016/j.hjc.2019.04.012. Epub 2019 May 2.

Abstract

Background: Monocytes can be differentiated by the presence of CD14 and CD16 (CD14++CD16-, classical; CD14++CD16+, intermediate and CD14 + CD16++, non-classical monocytes). Recent studies have reported conflicting results regarding an association between subtypes of monocytes as defined by the expression of these two surface markers in atherosclerosis.

Methods: We investigated subtypes of monocytes in n = 994 patients with angiographically documented coronary artery disease (CAD). We compared total numbers of monocyte subgroups stratified by tertiles with the occurrence of the pre-defined combined endpoint (non-fatal myocardial infarction, cardiovascular death and non-haemorrhagic cerebral insult). Patients were followed up for a minimum of 52 weeks. Classical risk factors of coronary heart disease were included in multivariate analysis.

Results: The primary endpoint occurred 134 times at a median time of 34.5 weeks (IR 10.6/59.6). Intermediate (p = 0.813), non-classical (p = 0.725) and the number of total monocytes (p = 0.626) stratified by tertiles showed no significant association with the combined endpoint. However, a higher absolute number of classical monocytes divided in tertiles was associated with incidence of the combined endpoint {T1 = 8.9% vs T2 = 14.2% vs T3 = 16.0% (p = 0.021)}. When comparing the third with the first tertile of Mo1 population, multivariate analysis showed a hazard ratio of 1.646 (CI: 1.005-2.699, p = 0.048).

Conclusions: The absolute counts of classical monocytes divided in tertiles are predictive of major adverse cardiac events in patients with CAD. A tremendous shift from classical to intermediate monocytes was also confirmed in patients with CAD. These data highlight the importance of CD14++ monocytes in cardiovascular diseases.

Keywords: Atherosclerosis; CD14; CD16; Cardiovascular disease; Monocytes.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Atherosclerosis / metabolism*
  • Atherosclerosis / physiopathology
  • Biomarkers / metabolism
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / immunology*
  • Case-Control Studies
  • Comorbidity
  • Coronary Angiography / methods
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / immunology*
  • Female
  • GPI-Linked Proteins / immunology
  • Humans
  • Lipopolysaccharide Receptors / immunology
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Predictive Value of Tests
  • Prospective Studies
  • Receptors, IgG / immunology
  • Risk Factors

Substances

  • Biomarkers
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Lipopolysaccharide Receptors
  • Receptors, IgG