title: Mechanisms of progression in native coronary artery disease: role of healed plaque disruption.
abstract: OBJECTIVE
  To determine the role of healed plaque disruption in the generation of chronic high grade coronary stenosis.
  
  
  METHODS
  Coronary arteries obtained at necropsy were perfuse fixed with formal saline for 24 hours at 100 mg Hg. The percentage lumen diameter stenosis was measured in each 3 mm segment containing a plaque, using the lumen size at the nearest histologically normal segment as the reference point. Each segment was prepared for histological examination and stained with Sirius red and immunohistochemistry for smooth muscle actin. Healed disruption was considered to be present when under polarised light there was a break in the yellow-white dense collagen of the cap filled in by more loosely arranged green collagen. Increased smooth muscle density in the green staining areas was required. Each section was read independently by two observers; any segment with discordant views was considered negative.
  
  
  METHODS
  31 men aged 51-69 dying suddenly of ischaemic heart disease. 39 coronary arteries were studied containing 256 separate plaques, after excluding coronary arteries with old total occlusions, an acute culprit thrombotic lesion, diffuse disease without normal arterial segments, and arteries related to old myocardial scars.
  
  
  RESULTS
  16 of 99 plaques causing < 20% diameter stenosis had prior disruption. In the 21-50% stenosis range 16 of 86 plaques showed healed disruption. Stenosis >/= 51% by diameter was present in 71 plaques, 52 of which showed a healed disruption pattern. The difference between stenosis < 50% and stenosis >/= 51% was significant by the chi(2) test (p < 0.001).
  
  
  CONCLUSIONS
  Subclinical episodes of plaque disruption followed by healing are a stimulus to plaque growth that occurs suddenly and is a major factor in causing chronic high grade coronary stenosis. This mechanism would explain the phasic rather than linear progression of coronary disease observed in angiograms carried out annually in patients with chronic ischaemic heart disease.
authors.affiliation: St George's Hospital Medical School, British Heart Foundation Cardiovascular Pathology Unit, Cranmer Terrace, London SW17 ORE, UK.
authors.forename: J
authors.initials: J
authors.lastname: Mann
authors.forename: M J
authors.initials: MJ
authors.lastname: Davies
mesh_terms: D000368:Aged; D003094:Collagen / Q000032:analysis; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology*; D016757:Death, Sudden, Cardiac / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D014945:Wound Healing
chemical_list: D003094:Collagen