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

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.