Boston, MA - An unusual study - employing an engineering method more often used to build bridges, cars, and planes - bolsters the theory, now widely held in cardiology circles, that it is lipid-filled, not calcified lesions that represent the greatest danger to patients. Researchers writing in the February 27, 2001 issue of Circulation report that calcified plaques, by bearing some of the mechanical load of the structure, are actually less likely to rupture than plaques with a soft lipid core.1

"The big thing here is that calcium really, within a given lesion, is probably not a critical factor, whereas the amount of lipid is probably an incredibly important factor," senior author, Dr Richard T Lee (Brigham and Women's Hospital, Boston, MA), told heartwire. The presence of calcified plaques indicates more serious, diffuse disease, but identifying lipid-filled lesions is probably more relevant in determining an individual's actual risk.

Looking for calcium may be a very reasonable thing to do in terms of assessing the extent of atherosclerosis, but the lipid is more likely to be the main problem.

In the Circulation study, Dr Hayden Huang (Massachusetts Institute of Technology) and colleagues calculated the mathematical properties of 10 ruptured and 10 stable coronary lesions taken during autopsy. Using a numerical method called finite element analysis that can predict the behavior and check the strength of structures, the authors were able to estimate the maximum stress on the lesions' fibrous caps. They found that maximum stress was positively correlated with the percentage of lipid, but not with percentage of calcification. When the investigators removed calcification from the equation, "replacing" it with fibrous plaque, stress changed insignificantly. The authors hypothesize that calcification does not increase stress, and that, in fact, "removal of larger amounts of calcification may result in a less stable atheroma."

Lee explains: "What we were doing was mathematical, but it's sort of the only approach to this kind of problem. What we're suggesting is that looking for calcium may be a very reasonable thing to do in terms of assessing the extent of atherosclerosis, but that lipid is more likely to be the main problem."

Whipped cream vs steel: no contest, says Lee

Lee notes that the findings are consistent with the dramatic success of lipid-lowering therapies in reducing coronary events. They also "make sense" from an engineering standpoint. "It's equivalent to taking a wooden table and replacing one leg with steel - that's what calcium would do - or replacing it with whipped cream, which is what lipid would do. And in one case, obviously, it has very little effect, and in the other case it obviously has an enormous effect."

Huang et al's study touches briefly on the value of scanning techniques, such as the widely promoted electron beam computed tomography (EBCT). The authors observe that clinicians should consider treating "systemic manifestations of atherosclerosis" rather than relying on interventional therapies directed at calcified lesions that have been detected by EBCT.

EBCT is a good way of detecting the extent of atherosclerosis in certain ages and subgroups of people.

Lee elaborates, noting that there is ample data on calcium and how to image it, but that finding a way to image lipids might be much more specific for identifying vulnerable plaques. He concedes: "No one is going around claiming that individual calcified lesions are the problem, they're just claiming that EBCT is a good way of detecting the extent of atherosclerosis in certain ages and subgroups of people." Indeed, calcification may be particularly important if it is proven to be more common in the setting of inflammation, the authors note. At the same time, a strategy like intravascular ultrasound elastography "holds promise" because it can detect softer materials, such as lipid.

Lee emphasizes that the study carries no immediate significance for clinical practice. "I think that clinical decisions should be based on very strong clinical data and that's not what we're proposing. What we're really doing is providing a framework for understanding some of the things that are going on in terms of assessing plaque stability and future strategies."