Cleveland, OH - The findings from a new analysis of two intravascular ultrasound (IVUS) studies could help clinicians identify patients most likely to derive benefit from the implementation of aggressive risk-factor modification strategies [1]. In this new analysis, researchers showed that various components of atheroma responded differently to treatment, with calcified atheroma the most resistant to change with medical therapy.

"We found that patients who had more calcium had more plaque at baseline, and this is certainly consistent with the findings from other investigators," lead investigator Dr Stephen Nicholls (Cleveland Clinic, OH) told heartwire. "But the really novel finding is that the patients who had more calcium were less likely to undergo any substantial change in their atheroma volume. In other words, not only were they less likely to progress, they were also less likely to regress. It is more likely that the plaque volume of these patients stayed essentially the same."

The results of the study are published online January 10, 2007 in the Journal of the American College of Cardiology.

In an interview with heartwire, Nicholls noted that the assessment of coronary calcium is one of the most topical issues in cardiovascular medicine, with much debate regarding how clinicians should effectively be using calcium-imaging modalities for predicting risk and stratifying patients to different medical therapies.

Using serial IVUS assessments from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) and Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT) trials, two studies that assessed the impact of intensive lipid lowering and antihypertensive therapy on the rate of coronary atherosclerotic plaque progression, Nicholls and colleagues sought to investigate the effect of calcified plaque on the rates of progression of atherosclerosis and how it might have an impact on the efficacy of those different therapies.

Overall, atheroma volume was measured in serial IVUS pullbacks in matched arterial segments of 776 patients with angiographic coronary artery disease. Patients with a calcium index above the median were older, typically male, and more likely to have a history of hypertension. In addition, patients with a calcium score above the median had a greater percentage of atheroma volume and total atheroma volume and more images that contained plaque.

In examining the relationship between baseline coronary artery calcification and the rate of change of plaque and remodeling, investigators found that patients with evidence of substantial changes in percentage of atheroma volume, with >5% relative change in either direction, had lower baseline calcium indices. A greater proportion of patients with a baseline calcium index below the median were likely to undergo significant changes in atheroma volume, defined as a greater than 5% change in percentage atheroma volume.

There really is a dichotomy in what we're seeing in terms of calcium and what we might be seeing in the plaque overall. Purely assessing changes in calcification might not be giving a clear indication of what is going on in the plaque.

"One of the rationales we considered was that if a plaque contains more calcium, it would intuitively appear to contain less lipid and less inflammatory material," said Nicholls. "We know that calcified plaque, from pathology studies, is less likely to rupture, and this would be related to that lack of inflammation and lack of lipid material. The findings of this study that patients are less likely to progress or less likely to regress if they have more calcium is probably consistent with that concept, that there is less material to flux in and out of the plaque."

In an editorial accompanying the published findings, Dr Lloyd Klein (Rush Medical College, Chicago, IL) writes that the findings are "extraordinarily relevant" to understanding the vascular response to statin and antihypertensive therapy [2]. In addition, given these findings, he writes that the use of serial assessments of coronary calcification to determine response to medical therapy is now questionable.

"[The] imaging techniques that assess clinical response to therapy on the basis of changes in the degree of calcification may be theoretically flawed," suggests Klein.

Nicholls told heartwire that these findings would likely have implications on the use of imaging modalities to measure coronary calcification, especially in terms of directing a patient to more aggressive medical therapy.

"We have seen a large body of evidence that shows that more coronary calcification predicts the presence of extensive disease and predicts the risk of having a clinical event," he said. "But what we don't really know is the utility of that approach. . . . There really is a dichotomy in what we're seeing in terms of calcium and what we might be seeing in the plaque overall. Purely assessing changes in calcification might not be giving a clear indication of what is going on in the plaque."

According to Klein, if potentially vulnerable plaque is the form of atherosclerosis most amenable to regression, improved imaging techniques that reliably identify it are required. "A better comprehension of where soft and vulnerable plaques are located within a field of atherosclerosis is necessary to develop imaging techniques most apt to reliably find them," he writes. "Then, the natural history of these plaques must be definitively established for therapeutic judgments to be made once they are found."