Elevated CD14++CD16- Monocytes Predict Cardiovascular Events.

Summary, in English

BACKGROUND: -Although monocytes in peripheral blood are no longer considered to be a homogeneous population, associations between distinct monocyte subsets and cardiovascular disease have not been highlighted in large epidemiological studies. METHODS AND RESULTS: -The study included 700 randomly selected subjects from the cardiovascular arm of the Malmö Diet and Cancer study. Among these, 123 subjects suffered ischemic cardiovascular events during the follow-up until December 2008. Mononuclear leukocytes frozen at the baseline investigation in 1991-94 were thawed and analyzed with flow cytometry to enumerate monocyte subsets based on CD14 and CD16 expression. The percentage and number of classical CD14(++)CD16(-) monocytes were increased in the cardiovascular-event group compared to the event-free subjects (median 69% (inter-quartile range 62-76)% vs. 67 (59-72)%, p=0.017; 344 (251-419) cells/μL vs. 297 (212-384) cells/μL, p=0.003). The hazard ratio was 1.66 for suffering a cardiovascular event in the highest tertile of the number of CD14(++)CD16(-) monocytes compared to the lowest tertile even after adjustment for common risk factors (HR 1.66, 95%CI: 1.02-2.72). CD14(++)CD16(-) monocytes did not, however, associate with the extent of atherosclerosis at baseline. In contrast, the percentage of monocytes expressing CD16 was negatively associated to the extent of carotid atherosclerosis measured as intima-media thickness (IMT) at baseline. The chemokine receptors CCR2, CX3CR1 and CCR5 were not differentially expressed between cases and controls on any of the monocyte subsets, but CCR5 expression on CD14(+)CD16(++) monocytes was negatively associated to carotid IMT. CONCLUSIONS: -This study shows that classical CD14(++)CD16(-) monocytes can predict future cardiovascular risk independently of other risk factors in a randomly selected population.