title: Elevated CD14++CD16- monocytes predict cardiovascular events.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors.forename: Katarina E
authors.initials: KE
authors.lastname: Berg
authors.forename: Irena
authors.initials: I
authors.lastname: Ljungcrantz
authors.forename: Linda
authors.initials: L
authors.lastname: Andersson
authors.forename: Carl
authors.initials: C
authors.lastname: Bryngelsson
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Gunilla N
authors.initials: GN
authors.lastname: Fredrikson
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.forename: Harry
authors.initials: H
authors.lastname: Björkbacka
mesh_terms: D000368:Aged; D000073883:CX3C Chemokine Receptor 1; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D054390:Receptors, CCR2 / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D012307:Risk Factors
chemical_list: C515334:CCR2 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D018950:Lipopolysaccharide Receptors; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D017452:Receptors, IgG