Healed plaque ruptures and sudden coronary death : Evidence that subclinical rupture has a role in plaque progression

• Published in: Circulation (New York, N.Y.) Vol. 103; no. 7; pp. 934 - 940
• Main Authors: BURKE, Allen P, KOLODGIE, Frank D, FARB, Andrew, WEBER, Deena K, MALCOM, Gray T, SMIALEK, John, VIRMANI, Renu
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 20.02.2001; American Heart Association, Inc
• Subjects: Biological and medical sciences; Cardiology. Vascular system; Cell Differentiation; Cell Division; Coronary Artery Disease - complications; Coronary Artery Disease - epidemiology; Coronary Artery Disease - pathology; Coronary heart disease; Coronary Vessels - pathology; Death, Sudden, Cardiac - epidemiology; Death, Sudden, Cardiac - etiology; Death, Sudden, Cardiac - pathology; Demography; Heart; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Muscle, Smooth, Vascular - pathology; Organ Size; Risk Factors; Rupture, Spontaneous; Wound Healing; Human; Immunohistochemistry; Prognosis; Pathogenesis; Sudden death; Mortality; Cardiovascular disease; Coronary heart disease; Vascular disease; Pathology; Atherosclerotic plaque; Atherosclerosis; Tissue rupture
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.103.7.934

Subclinical episodes of plaque disruption followed by healing are considered a mechanism of increased plaque burden. Detailed pathological studies of healed ruptures, however, are lacking. We identified acute and healed ruptures from 142 men who died of sudden coronary death and performed morphometric measurements of plaque burden, luminal stenosis, and smooth muscle cell phenotype. Healed ruptures were found in 61% of hearts and were associated with healed myocardial infarction, increased heart weight, dyslipidemia, and diabetes. Multiple healed rupture sites with layering were frequently found in segments with acute and healed rupture; the percent area luminal narrowing increased with increased numbers of healed sites of previous rupture. The underlying percent luminal narrowing for acute ruptures (mean 79+/-15%) exceeded that for healed ruptures (mean 66+/-14%, P:=0.0001), and the area within the internal elastic lamina was significantly less in healed ruptures than in acute ruptures, when segments were grouped by distance from the ostium. Healed ruptures favored the accumulation of immature smooth muscle cells at repair sites, with a cellular proliferation index of 0.40+/-0.09%, significantly higher than the index at the sites of rupture (P:=0.008). These data provide evidence that silent plaque rupture is a form of wound healing that results in increased percent stenosis. Healed ruptures occur in arteries with less cross-sectional area luminal narrowing than acute ruptures and are a frequent finding in men who die suddenly with severe coronary atherosclerosis.