Invited commentary

Abstract

How many of you consider gender when deciding whether carotid endarterectomy (CEA) might be appropriate in patients with asymptomatic carotid disease? Chances are, relatively few! Yet, the Asymptomatic Carotid Atherosclerosis Study (ACAS) showed no conclusive evidence that surgery conferred benefit in women, and once perioperative strokes were included, neither did the Asymptomatic Carotid Surgery Trial (ACST). When the data from the two trials are combined, the gender differences are difficult to ignore.1Rothwell P.M. ACST: Which subgroups will benefit most from carotid endarterectomy?.Lancet. 2004; 364: 1122-1123Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar Two observations from the trials might explain why women gained less benefit. First, women had a lower natural history of stroke risk than men. Second, women incurred higher morbidity and mortality after CEA, a phenomenon common to many cardiovascular operations. Accordingly, the overall benefit from CEA will be diminished. So should all asymptomatic women now be denied surgery? Definitely not! It is, however, becoming untenable to simply treat all asymptomatic men and women as if they derived equivalent benefit. Combined ACAS and ACST data1Rothwell P.M. ACST: Which subgroups will benefit most from carotid endarterectomy?.Lancet. 2004; 364: 1122-1123Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar indicate that CEA conferred a twofold reduction in stroke in men (odds ratio, 2.0; 95% confidence interval, 1.5 to 2.8) compared with neutral benefit in women (OR 1.04; 95% confidence interval, 0.7 to 1.6). However, because the confidence intervals straddle “1,” there is still a degree of statistical uncertainty. It is inevitable, therefore, that certain women will gain considerable benefit from surgery, but can they be identified? Hellings et al have reported one of the first studies to correlate plaque biology with symptom status and gender. They hypothesize that thromboembolic stroke may be less likely to occur in women because their plaques exhibit features that are less likely to predispose them to acute plaque disruption, including reduced fat, less macrophage activity, more smooth muscle cells, higher collagen, and reduced interleukin-8 and matrix metalloproteinase-8 expression, with “asymptomatic women demonstrating the highest prevalence of stable plaques.” These are important observations, despite the unexpected finding that surface thrombus was unrelated to gender, but do their data support the statement that “selecting patients for CEA based on plaque characteristics may hold promise for the future?” Readers of the Journal of Vascular Surgery will have heard this Holy Grail being quoted many times during the last 20 years! The fundamental problem remains that no one has successfully translated postoperative histologic/biochemical features into preoperative plasma markers or ultrasound/magnetic resonance imaging parameters that can then reliably and accurately identify the high-risk patient sitting in the outpatient clinic. This is largely because few unbiased asymptomatic cohorts are now available for testing the Helling and colleagues’ hypothesis. There is, however, a potential solution. There are plans to undertake randomized trials comparing CEA with angioplasty. One, the Transatlantic Asymptomatic Carotid Intervention Trial (TACIT), intends to include “best medical therapy” as a third limb, largely because many believe pharmacotherapy to have advanced considerably since ACAS and ACST were recruiting. Patients randomized in this trial could undergo preoperative assessment of plasma markers and ultrasound/magnetic resonance imaging so that the Helling and colleagues’ hypothesis can be tested. Surgical patients would provide samples for histologic and biochemical analysis, whilst medically treated patients would provide valuable natural history data. This could be the last chance to determine optimal patient selection on the basis of evidence rather than dogma. Gender-associated differences in plaque phenotype of patients undergoing carotid endarterectomyJournal of Vascular SurgeryVol. 45Issue 2PreviewCarotid endarterectomy to prevent a stroke is less beneficial for women compared with men. This benefit is lower in asymptomatic women compared with asymptomatic men or symptomatic patients. A possible explanation for this gender-associated difference in outcome could be found in the atherosclerotic carotid plaque phenotype. We hypothesize that women, especially asymptomatic women, have more stable plaques than men, resulting in a decreased benefit of surgical plaque removal. Full-Text PDF Open Archive