These paradoxical observations come from a researcher who has devoted the past decade to studying the physiology and pathophysiology of coronary arteries, Attilio Maseri, MD, of Rome.

Dr. Maseri, who delivered the First American College of Cardiology International Lecture at ACC'02 on March 19, stressed that the mechanism and importance of inflammation and inflammatory markers in coronary artery disease is a very complexissue. At this point, researchers and clinicians should be wary of making clinical decisions based on these factors, he advised.

“Although there is evidence of widespread inflammation in the coronary vasculature of patients with unstable angina, the inflammation may have multiple causes, and only the understanding of the process of coronary inflammation may open the way to novel therapeutic strategies,” said Dr. Maseri.

International Outreach

On his last day as president of the College, Douglas P. Zipes, MD, introduced Dr. Maseri, noting that this lecture, which will become an annual tradition, is part of the College’s efforts to reach out to researchers and clinicians in other countries around the world.

Dr. Maseri was unanimously selected by an ACC committee to be its first International Lecturer, noted Dr. Zipes.

Dr. Maseri’s principal message was that coronary artery inflammation in unstable angina has multiple causes and that markers of inflammation do not always predict severity of disease.

“If we take shortcuts and start manipulating treatment in terms of anti-inflammatory treatments, that may lead to great acceleration,” but it may also lead to false conclusions, he said. “One must proceed with great caution, patience, and humility because the problem is very complex, and it is different from one patient to another.”

Dr. Maseri said he became interested in inflammatory pathways when he and colleagues noted that some patients with von Willebrand’s disease had elevated CRP levels but no evidence of atherosclerosis. His research has progressed, reaching into the mechanics of inflammation in acute coronary syndromes, he said, rather than into its predictive value.

“We have not been looking for a common denominator—-infection—-but for the reason there are differences among patients,” he said.

For example, he said, there are puzzling cases of patients with severe atheroma who do not have unstable plaque and have no signs of infection. There are also patients with no history of angina who have a fatal myocardial infarction “out of the blue,” all suggesting multiple pathologic mechanisms.

Keep Looking

Coronary artery inflammation is characterized by immunologically modified lymphocytes, Dr. Maseri said, as well as by intense IL-6 production by monocytes in response to a wide variety of stimuli, some of which are undoubtedly still unknown.

Inflammation might be component of atherosclerosis in a patient with unstable angina, he said, or it could be an acute consequence of ischemia.

Furthermore, inflammatory markers such as CRP appear to be independent of atherosclerosis and ischemia, Dr. Maseri said, while CRP as a prognostic marker appears to be independent of troponin.

“Keep looking,” Dr. Maseri advised researchers delving into the origins and meaning of coronary inflammation, “and you will find more.”