Vulnerable Plaque May Explain Outcomes in Older Carotid Stenting Patients

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Less stable, more calcified plaque characterized by large lipid cores and low smooth muscle cell content may be a key reason for the increased risk of stroke from carotid artery stenting (CAS) in elderly patients, according to findings published online July 7, 2011, ahead of print in Stroke.

Researchers led by Gert Jan de Borst, MD, PhD, of University Medical Center Utrecht (Utrecht, The Netherlands), looked at carotid atherosclerotic plaque samples from 1,385 consecutive patients undergoing carotid endarterectomy (CEA) between 2002 and 2010. The researchers were attempting to understand the underlying pathophysiological reasons for the increased age-related risk for periprocedural events during CAS as described by recent randomized trials such as ICSS, SPACE, and EVA-3S.

After histological examination of all the samples, patients were divided into 4 age groups by 10-year increments: Less than 60 years; 60 to 69 years; 70 to 79 years; and 80-plus years.

Overall, 14.7% of the patients were asymptomatic, while 60.9% of patients had a TIA and 24.4% had a stroke prior to undergoing CEA. On histological analysis, there was a significant decrease by age group in the amount of smooth muscle cells per plaque area, while lipid cores covering more than 40% of the plaque surface and heavy plaque calcification increased with age (table 1).

Table 1. Frequency of Plaque Characteristics by Age Group

Every 10-year increase in age was associated with an adjusted regression coefficient for smooth muscle cells of -0.146 and with increases of 27% (95% CI 1.07-1.50) and 36% (95% CI 1.16-1.58) for large lipid cores and moderate-to-heavy plaque calcification, respectively. There were no significant differences found among age groups for intraplaque hemorrhage, macrophage content, collagen, and microvessels. When age was analyzed as a continuous variable, as opposed to being divided into 4 incremental groups, similar results were found, with decreasing levels of log smooth muscle cells (adjusted coefficient -0.011; adjusted P < 0.001) and increasing presence of large lipid cores (adjusted OR 1.025; 95% CI 1.008-1.042; adjusted P = 0.004) and moderate/heavy calcification (adjusted OR 1.028; 95% CI 1.012-1.043); adjusted P < 0.001).

“The findings of the current study show that carotid plaque composition changes with age, independent of symptomatic presentation, cardiovascular risk factors, and medication use,” the authors write, adding that this appears to be a gradual change, rather than a drastic shift in plaque composition that occurs at a specific cutoff point, such as age 80. “Nevertheless, when plaque composition is considered, octogenarians are at the unstable end of the spectrum, whereas patients < 60 years have markedly stable plaque. The current study provides possible pathophysiological insights into underlying contributing factors for the increased periprocedural stroke risk during CAS for older patients.”

Results Translate to CAS Population

In an e-mail communication with TCTMD, Dr. de Borst noted that although all the study subjects underwent CEA, the results still translate to the CAS population. “It’s probably the same, because these samples were taken during a period in which either CAS was not offered, or when CAS was offered only within randomized trials,” he said. “Therefore, no bias will have occurred with selecting these patients.”

Despite the current findings regarding vulnerable plaque in elderly patients, Dr. de Borst said, “other factors still play an eminent role [in increasing the risk of periprocedural events for older patients receiving CAS]. Tortuosity, aortic arch thrombus, flow reversal cerebral protection devices, also timing between event and revascularization remain important factors.”

However, the findings do not provide a simple age cut-off to guide clinical decisions. “Unfortunately, it is not an on-off phenomenon,” Dr. de Borst said. “Therefore, plaque imaging probably has to rule out the vulnerability of the plaque, followed by the decision to revascularize or not, and if the answer is yes, by which strategy.”

Increased Risk with Stenting Disputed

In a telephone interview with TCTMD, William A. Gray, MD, of Columbia University Medical Center (New York), agreed that Dr. de Borst and colleagues found real plaque differences with age. However, he disagreed with the primary assertion of the study, that elderly CAS patients encounter more complications than their surgical counterparts.

“It would be hard to argue with some of the literature that’s come out showing that there are trends toward increased complications in the elderly with CAS,” he said. “However, it’s also true there are increased complications with endarterectomy in the same age group. For instance, in CREST, the rates of complications (stroke, death, MI) over the age of 80 were exactly the same in each group. If you look at the actual rates, there was no difference in octogenarians.”

As such, “the analysis is spot on,” Dr. Gray said. “But the conclusion is a bit far reaching. It should say this may explain why stenting and surgery both carry a higher risk above the age of 80.”

Dr. de Borst, though, maintained that the link between unstable plaque and increased risk in elderly CAS patients is “strong,” although other factors must be taken into account including presenting symptoms, time delays to therapy, and use of dual antiplatelet therapy.

Plaque Might Not Be So Vulnerable

Dr. Gray also noted that although certain plaque characteristics were found to be increased in the elderly, these are not convincingly “vulnerable.”

“While I don’t have any problem with the measures and some of the statements, there are some things that are kind of missing,” he said. “They didn’t measure cap thickness, I would have liked to see more about plaque cap characteristics, which is really about plaque rupture.”

In addition, he pointed out that calcification in the coronaries is actually a stabilizing factor, while “the lack of difference among the age groups in intraplaque hemorrhage and neovascularization also suggests that these are not unstable or active plaques.”

Implications for Practice Not Clear

Regardless, the short-term clinical implications are not readily apparent. “At this stage, the findings are explanatory, but when we [can] reliably image vulnerable plaque in a non-invasive manner, this background information will affect clinical practice,” Dr. de Borst said. “[At present], an individual directed work-up and treatment strategy for the patient with relevant carotid pathology is demanded.”

Dr. Gray noted that “there are noninvasive tests that can characterize plaques pretty well, up to and including Doppler and intravascular ultrasound, but also nuclear medicine studies. The problem is the rates of complication with stenting and surgery are so low they make it difficult to know for the individual patient what to do with the plaque characterization data.”

In the meantime, the association between plaque characteristics, the elderly, and revascularization strategies is still an open question, according to Dr. Gray. “It’s difficult to know what the answer is,” he said. “We have 2 things going on. We have age-related increases in complications for both CEA and CAS, and we have age-related changes in the plaque. Are the 2 related? I don’t know. Everything else is supposition at this point.”

 

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Source:
van Lammeren GW, Reichmann BL, Moll FL, et al. Atherosclerotic plaque vulnerability as an explanation for the increased risk of stroke in elderly undergoing carotid artery stenting. Stroke. 2011;Epub ahead of print.

 

 

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