Editorial Slides VP Watch –July 10, 2002 - Volume 2, Issue 27

Coronary Pan-Artritis; How Specific Is Inflammation to Culprit Lesions?

Atherogenic diet in animals induces monocytes adhesion to vascular endothelium and accumulation in lesion-prone arterial sites. 1

Davis et al. showed that coronary plaques with positive remodeling have a higher lipid content and macrophage count which explain why plaque rupture is often apparent at sites with only modest luminal stenoses. 5

Macrophage-rich areas are more frequently found in patients with unstable angina and non-Q-wave MI.

Moreno, Falk, and others suggested that macrophages are a marker of vulnerable plaques and play a significant role in pathophysiology of acute coronary syndromes.3

Libby et al. have shown that inflammation links atherosclerosis to thrombosis. 12

Inflammation of atherosclerotic plaque seems to be a feature in a cascade of events that eventually lead to plaque rupture. 7,8

• In 1997 Boyle studied the extent of inflammation in 351 coronary ruptured and unruptured plaques. He found a prevalence of inflammation of 5% to 10% in superficial plaque of control group. 9

• Boyle described that inflammation was common ( 40%) in deeper layers of the atherosclerotic plaque and was associated with lipid but not with rupture. 9

Pasterkamp and coworkers found that inflammation of cap and shoulder of the plaque is a common feature, locally observed, in atherosclerotic femoral and coronary arteries. 6

They suggest that high prevalence of local inflammatory responses should be considered if they are used as a diagnostic target to detect vulnerable, rupture-prone lesions. 6

• Casscells, Willerson, and coworkers found a temperature rise in 37% of 50 samples of carotid artery specimens. 10

• Temperature differences were correlated significantly with cell density in the plaques. 10

• They showed that temperature differences could be observed very close to one another (<1 mm). 10

As reported in VP Watch of this week, Buffon, Maseri, and colleagues by measuring neutrophil myeloperoxidase found that patients with unstable angina had evidence of inflammation in left coronary artery even if it was free of substantial atherosclerosis and culprit stenosis was in the right coronary artery.

They found that neutrophil myeloperoxidase content of aortic blood was lower in unstable angina compared to stable angina.

Maseri et al. found no significant increase in neutrophil activation in the great cardiac vein in controls, in patients with stable angina and documented left anterior descending coronary stenosis, or in patients with active variant angina and recurrent ischemia in the territory of the left anterior descending coronary artery.

They also did not detect any elevation in neutrophil activation through femoral circulation in any of their groups studied (unstable angina, stable angina, coronary stenosis, variant angina, and healthy controls).

Conclusion

Subjects with an increased risk of acute coronary events are likely to have many vulnerable plaques throughout the coronary tree.

Patients who are prone to unstable angina will have widespread coronary inflammation.

Questions:

• How specific is inflammation to vulnerable plaque? In other words, if a site of inflammation is found in coronary artery, what is the likelihood of becoming a culprit plaque?

• Are stable (non-vulnerable) plaques equally inflamed like vulnerable plaques?

• Given widespread coronary inflammation (pan-artritis) how can coated stent stand as the treatment of choice?

Questions:

• Ross R. Atherosclerosis -- an inflammatory disease. N Engl J Med 1999;340:115-126.

• van der Wal AC, Becker AE, van der Loos CM, Das PK. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994;89:36-44.

• Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT. Macrophage infiltration in acute coronary syndromes: implications for plaque rupture. Circulation 1994;90:775-778.

• Shah PK, Falk E, Badimon JJ, et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques: potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation 1995;92:1565-1569.

• Varnava AM, Mills PG, Davies MJ. Relationship between coronary artery remodeling and plaque vulnerability. Circulation. 2002 Feb 26;105(8):939-43.

• Gerard Pasterkamp; Arjan H. Schoneveld; Allard C. van der Wal; Dirk-Jan Hijnen; Willem J. A. van Wolveren; Simon Plomp; Hans L. J. M. Teepen; Cornelius Borst Inflammation of the atherosclerotic cap and shoulder of the plaque is a common and locally observed feature in unruptured plaques of femoral and coronary arteries. Arterioscler Thromb Vasc Biol. 1999 Jan;19(1):54-8

• Davies MJ, Thomas AC. Plaque fissuring: the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J. 1985;53:363–373

• Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995;92:657–671

• Boyle JJ. Association of coronary plaque rupture and atherosclerotic inflammation. J Pathol. 1997;181:93–99

• Casscells W, Hathorn B, David M, Krabach T, Vaughn WK, McAllister HA, Bearman G, Willerson JT. Thermal detection of cellular infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis. Lancet. 1996;347:1447–144

• Davies MJ, Bland JM, Hangartner JRW, Angelini A, Thomas AC. Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischemic death. Eur Heart J. 1989;10:203–208

• Peter Libby; Vasc Med 1998;3(3):225-9 The interface of atherosclerosis and thrombosis: basic mechanisms.

References