title: Different stages of intraplaque hemorrhage are associated with different plaque phenotypes: a large histopathological study in 794 carotid and 276 femoral endarterectomy specimens.
abstract: OBJECTIVE
  Intraplaque hemorrhage (IPH) is an important determinant of progression and destabilization of atherosclerotic plaque. We recently demonstrated that IPH is an independent predictor of cardiovascular events. IPH has become more clinically relevant since magnetic resonance imaging (MRI) technique is able to visualize IPH in vivo. Different stages of IPH have been described. However, etiology of the different stages is not known and it is unclear if these detected different stages are all associated with the vulnerable plaque phenotype.
  
  
  RESULTS
  1070 patients who underwent a carotid (n=794) or femoral (n=276) endarterectomy were included. Histopathological presence of IPH was determined and divided into 3 types: recent, organized and amorphous IPH. Carotid IPH was observed in 644/794 (81%) plaques, divided into 14 (2%) recent, 70 (11%) organized and 560 (87%) amorphous. Femoral IPH was observed in 175/276 (63%) plaques, divided into 2 (1%) recent, 89 (51%) organized and 84 amorphous (48%). Overall presence of carotid IPH was associated with a large lipid core, no or minor staining of smooth muscle cells, no or minor calcification and high microvessel density. Overall presence of femoral IPH was associated with moderate to heavy staining of macrophages. Plaques with organized IPHs revealed more macrophages, a larger lipid core, less smooth muscle cells, less calcification and higher microvessel density than plaques with amorphous IPHs.
  
  
  CONCLUSIONS
  IPH is a significant characteristic of carotid and femoral atherosclerotic plaque and can be classified into different types. Organized IPH is associated with unstable and amorphous IPH with stable plaque characteristics.
authors.affiliation: Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Wouter J M
authors.initials: WJ
authors.lastname: Derksen
authors.forename: Wouter
authors.initials: W
authors.lastname: Peeters
authors.forename: Guus W
authors.initials: GW
authors.lastname: van Lammeren
authors.forename: Claudia
authors.initials: C
authors.lastname: Tersteeg
authors.forename: Jean-Paul P M
authors.initials: JP
authors.lastname: de Vries
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
mesh_terms: D000368:Aged; D002339:Carotid Arteries / Q000473:pathology*; D003094:Collagen / Q000737:chemistry; D003430:Cross-Sectional Studies; D004691:Endarterectomy / Q000379:methods*; D016894:Endarterectomy, Carotid / Q000379:methods; D005260:Female; D005263:Femoral Artery / Q000473:pathology*; D006470:Hemorrhage / Q000473:pathology*; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000145:classification / Q000473:pathology*
chemical_list: D003094:Collagen