Journal Report
09/20/2004

Inflammation markers signal rapidly advancing coronary disease

DALLAS, Sept. 21 –   High levels of C-reactive protein and other inflammation markers may signal rapid progression of coronary artery disease (CAD) in patients with chest pain,  according to a study published in Circulation: Journal of the American Heart Association.

“This is the first study to assess the specific question of whether elevated levels of inflammation markers predict the rapid evolution of CAD stenosis in patients with stable angina (chest pain),” said Juan Carlos Kaski, M.D., one of the study’s lead authors.

Coronary artery stenosis is the narrowing of the coronary arteries, the vessels which supply blood to the heart muscle.

“The study is important because it confirms a role for inflammation in the rapid progression of CAD, and may open new areas of research to identify and test agents that may reduce inflammation,” said Kaski, professor of cardiovascular science at the University of London and head of the department of cardiological sciences at St. George’s Hospital Medical School.

Patients with a rapid increase in stenosis severity (‘progressors’) had higher levels of inflammatory markers and markers of macrophage (white blood cell) activation.

Researchers studied 124 patients with stable angina, defined as chest pains that never escalated to a major cardiac event over three months or more.  These patients, 84 of whom were men, underwent an initial angiogram between January and June 2000 to measure stenosis in their coronary arteries.  They were placed on waiting lists for non-urgent coronary angioplasty after the angiogram.  They had a second angiogram within three to 12 months of the first one.

Researchers assessed differences in stenosis between the first and second angiograms in 321 lesions.  They considered a stenosis of at least 50 percent diameter reduction to be significant and progressing, and a lesion less than 50 percent to be mild.

In three to 12 months, CAD progression occurred in 28 percent of patients.  Of these 35 “progressors,” 51 percent had a 10 percent or greater diameter reduction of at least one pre-existing partial blockage.  Twenty-six percent had a greater than 30 percent diameter reduction of a pre-existing blockage.  Seventeen percent of patients developed a new blockage and 6 percent experienced progression of a partial blockage to total blockage.

Four inflammatory markers, some of which are indicators of macrophage activation, predicted rapid CAD progression: C-reactive protein (CRP), neopterin, matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecules (sICAM).  Levels of these markers were higher in “progressors” vs. “non-progressors.”

Individuals with neopterin levels of greater than 7.5 nanomole/liter (the middle quartile) had a five-fold higher risk of developing rapid progression compared to those in the lowest quartile.  Patients in the middle quartile for CRP had a three-fold higher risk of progression than those in the lowest quartile.  Individuals who had sICAM levels (mean of the total sICAM concentration) greater than 271.4 nanograms per milliliter had about a four-fold higher risk than those in the lowest quartile.  Patients with MMP-9 concentration greater than 47.9 micrograms per liter (the median of total MMP-9 concentration) had a three-fold higher risk for CAD progression than those with lower levels.

“Detecting macrophage activation in the clinical setting may be a useful tool to identify the vulnerable patient and facilitate systemic therapies that may avoid both CAD progression and the development of CAD,” Kaski said.

Co-authors are Emmanouil Zouridakis, M.D.; Pablo Avanzas, M.D.; Ramón Arroyo-Espliguero, M.D.; and Salim Fredericks, Ph.D.

Statements and conclusions of study authors that are published in the American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect association policy or position.  The American Heart Association makes no representation or warranty as to their accuracy or reliability.

NR04 – 1307 (Circ/Kaski)

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