CA Calcification Seen as Marker of Plaque Stability

BY BRUCE K. DIXON

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CHICAGO -- New data, indicating that carotid atherosclerotic plaque calcification is a structural marker of plaque stability, should help vascular surgeons stratify patients with asymptomatic stenosis, according to Dr. Carl-Magnus Wahlgren at the annual meeting of the Midwestern Vascular Surgical Society.

In vivo assessment of carotid plaque calcification with imaging techniques such as spiral CT may help identify patients with asymptomatic carotid plaques who are at risk of cerebrovascular and ocular ischemic events and would therefore benefit from intervention, said Dr. Wahlgren, who was a clinical fellow at the University of Chicago's section of vascular surgery under the direction of Dr. Hisham Bassiouny, chief of vascular surgery.

This research effort centered on 15 type Va (noncalcified) carotid artery plaques and 15 type Vb (calcified) plaques, as defined by the American Heart Association 1995 consensus. Using laser capture microdissection, the fibrous caps and shoulder regions were excised from carotid plaques removed at endarterectomy, said Dr. Wahlgren, now at Karolinska University Hospital, Stockholm.

After total RNA extraction and reverse transcription, the gene expression of pro- (interleukin-1, interleukin-8, and monocyte chemotactic protein-1 [MCP-1], which plays a role in the recruitment of monocytes to sites of injury and infection) and anti-inflammatory (interleukin-10) factors and bone formation mediators were quantified by real-time PCR. Protein levels also were determined, he said.

"Although there was no significant difference between patient age and atherosclerotic risk factors in the two groups, there were significantly more symptomatic patients in the noncalcified group," said Dr. Wahlgren, adding that two-fifths of noncalcified plaques and one-fifth of calcified plaques were symptomatic. There was no difference in the mean percentage of stenosis between groups, although the calcification area was significantly larger in the more calcified plaques.

The mean percentage of carotid stenosis and calcification were 79% and 5% respectively in the Va group, and 77% and 42% in the Vb group.

There were more macrophages in the noncalcified plaque sections (280 versus 150; P less than .01), and mRNA expression of MCP-1 and interleukin-8, as well as protein levels of IL-8, also were greater in Va plaques, compared with Vb plaques (seven-, four-, and twofold greater respectively). Protein levels and mRNA expression of osteocalcin were two- and sevenfold greater in Vb plaques.

"Carotid plaque fibrous-cap macrophage infiltration is a salient feature of noncalcified plaques, and we've shown that the mRNA expression of MCP-1, interleukin-8, and protein levels of interleukin-8 were greater in noncalcified, [compared with] calcified plaques; the protein levels of mRNA expression of osteocalcin were significantly greater in calcified plaque; and the lack of plaque calcification is more prevalent in symptomatic disease." He added that fibrous-cap inflammation is more likely to occur in noncalcified plaques.

"These findings indicate that the carotid atherosclerotic plaque calcification is a structural marker of carotid plaque stability; conversely, noncalcified, high-grade stenoses are more vulnerable to disruption," he explained. "A patient with less calcification and an asymptomatic, rapidly progressing plaque is more likely to have an active, vulnerable plaque, which may disrupt and cause cerebral or retinal embolization, or strokes,."

"The current wide use of spiral [CT angiography] can readily evaluate the presence and degree of carotid plaque calcification and will hopefully add another objective measure for subselecting asymptomatic patients who are at risk for retinal or cerebral ischemia," said Dr. Bassiouny.

When asked to comment on this story, Dr. Kwame S. Amankwah, assistant professor of vascular surgery, SUNY Upstate Medical University, Syracuse, stated: "Prior work utilizing ultrasound to look at the carotid plaque characteristics had established an increased risk of neurological events among patients who had dense or soft plaque compared to those with calcified plaque. Furthermore, looking at the plaque characteristics and the degree of stenosis, it was determined that 75% or greater stenosis was associated with an increase risk of cerebral events.

"The current use of spiral CTA and high-resolution B mode ultrasound has continued to significantly assist the vascular surgeon in stratifying patients who may benefit from intervention. The work strengthens our knowledge of plaque calcification as a structural marker of plaque stability."

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