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Elevated CD14++CD16- monocytes predict cardiovascular events
Katarina E Berg1, Irena Ljungcrantz, Linda Andersson
1Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
Insights
Classical CD14(++)CD16(-) monocytes can predict future cardiovascular events. Higher numbers of these monocytes indicate increased cardiovascular risk, independent of other known risk factors in a general population.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Epidemiology
Background:
- Peripheral blood monocytes are heterogeneous, but links between specific subsets and cardiovascular disease (CVD) risk are understudied in large populations.
- Previous research has not sufficiently highlighted the prognostic value of distinct monocyte subsets in epidemiological studies concerning CVD.
Purpose of the Study:
- To investigate the association between monocyte subsets and the incidence of ischemic cardiovascular events.
- To determine if specific monocyte populations can serve as independent predictors of future cardiovascular risk.
Main Methods:
- Analysis of 700 randomly selected subjects from the Malmö Diet and Cancer study.
- Flow cytometry was used to enumerate monocyte subsets (CD14 and CD16 expression) from cryopreserved leukocytes.
- Ischemic cardiovascular events were tracked until December 2008.
Main Results:
- Subjects experiencing cardiovascular events had increased percentages and numbers of classical CD14(++)CD16(-) monocytes compared to event-free individuals.
- A higher number of CD14(++)CD16(-) monocytes was associated with a 1.66-fold increased hazard of cardiovascular events, even after adjusting for traditional risk factors.
- Classical CD14(++)CD16(-) monocytes did not correlate with atherosclerosis extent at baseline, but CD16 expression on monocytes showed a negative association with carotid intima-media thickness.
Conclusions:
- Classical CD14(++)CD16(-) monocytes are significant predictors of future cardiovascular risk.
- This monocyte subset provides predictive value for cardiovascular events independently of established risk factors in a general population.
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 experienced ischemic cardiovascular events during the follow-up until December 2008. Mononuclear leukocytes frozen at the baseline investigation in 1991 to 1994 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 with the event-free subjects (median, 69% [interquartile range, 62% to 76%] versus 67% [59% to 72%], P=0.017; 344 [251 to 419] cells/μL versus 297 [212 to 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 with the lowest tertile, even after adjustment for common risk factors (HR, 1.66; 95% CI: 1.02 to 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 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 intima-media thickness.
Conclusions:
This study shows that classical CD14(++)CD16(-) monocytes can predict future cardiovascular risk independently of other risk factors in a randomly selected population.
