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Stroke. 2003;34:1124-1125
Published online before print April 17, 2003, doi: 10.1161/01.STR.0000071141.69453.F7
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(Stroke. 2003;34:1124.)
© 2003 American Heart Association, Inc.

Original Contributions

Editorial Comment—Female Sex: A Questionable Risk Factor for Carotid Endarterectomy

Enzo Ballotta, MD, Guest Editor

Section of Vascular Surgery, Department of Medical and Surgical Sciences, University of Padua School of Medicine, Padua, Italy

The misconception that clinical manifestations of cardiovascular disease are a much more significant problem among male patients is hard to eliminate, supported by the higher incidence of cardiac, cerebrovascular, and peripheral arterial diseases in men than in women.1

Our understanding of cerebrovascular disease in women is hampered by a paucity of studies including an adequate number of female patients. Most studies are heavily biased toward the male sex. The efficacy of aspirin in primary and secondary stroke prevention trials has been demonstrated almost exclusively in men.2 Men were also the majority of the population recruited in the major clinical trials on symptomatic (North American Symptomatic Carotid Endarterectomy Trial [NASCET] and European Carotid Surgery Trial [ECST])3,4 and asymptomatic (Asymptomatic Carotid Atherosclerosis Study [ACAS]) carotid stenoses,5 and no women were enrolled in the Veteran Administration trials.6,7 Unfortunately, neither the original report from the NASCET nor the one from ECST analyzed data specifically by sex. Although the superiority of carotid endarterectomy (CEA) over the best medical management in protecting against stroke for selected symptomatic and asymptomatic patients with carotid lesions was well demonstrated,3–7 post-hoc analyses,8,9 along with several reviews and large single-center studies, have prompted a reevaluation of the role of CEA in women.10–14

The NASCET results did not distinguish, however, between men and women with regard to perioperative risk in patients with severe stenosis,3 and they showed no apparent benefit from CEA in women with moderate stenosis.8 Furthermore ACAS investigators found a slightly higher, albeit statistically insignificant, perioperative stroke and/or death rate in women (3.6% versus 1.7%), that probably meant an estimated 5-year relative risk reduction for ipsilateral stroke of just 17% in women compared with 66% in men.5 On the other hand, several other studies specifically focusing on sex-related differences in perioperative stroke and death rates failed to find any such differences in the perioperative risks of CEA, suggesting that CEA is equally safe in men and women.15–21

In the accompanying article, Kapral et al analyze the findings on sex-related differences in perioperative outcome emerging from an impressive population-based series of 6038 consecutive patients undergoing CEA in a real-world setting over a 4-year period, ie, more than 4 and 3 times the number of patients enrolled in the surgical arm of NASCET and ECST, respectively, and nearly 4 times the entire population of the ACAS.3–5 Women accounted for more than one third of the whole surgically treated population of the NASCET.3 The baseline characteristics of men and women were similar, except that the women were less likely to have a history of coronary artery or peripheral vascular disease and more likely to have a history of hypertension; there were no significant sex differences in the preoperative symptom status, degree of carotid stenosis, need for shunting, or type of anesthesia. Sex did not affect the risk of perioperative stroke or death in symptomatic and asymptomatic patients. In addition, women were more likely to have a stroke and less likely to die within 2 years of CEA.

This study is interesting for several reasons. First, given that the role of CEA in the management of women with symptomatic, and especially asymptomatic, carotid stenoses remains debatable, any additional information on this issue is welcome. This is particularly relevant at a time when some are advocating carotid angioplasty and stenting as a less invasive and potentially less risky treatment of carotid disease in symptomatic and asymptomatic patients.

Second, women had a slightly higher incidence, albeit statistically insignificant, of adverse events (6.2% versus 5.9%), confirming a trend observed in large randomized trials and real-world clinical experience, possibly due to the sample of women being smaller than that of the men (2096, 35% versus 3942, 65%). The reported overall crude perioperative complication rates (7.3% and 4.7% for symptomatic and asymptomatic patients, respectively) also exceeded the recommended upper limits for perioperative risk and mortality rates supporting the beneficial effects of CEA in symptomatic and asymptomatic patients.22 This potential drawback of the study could be explained by the fact that 9% of the CEAs were performed at low-volume (albeit teaching) institutions and 18% by low-volume surgeons, leading to higher-than-expected complication rates and revealing the challenge in translating the efficacy demonstrated in clinical trials (CEA performed in an ideal scenario of selected patients and selected surgeons) into typical clinical setting effectiveness. However, it would be interesting to know the incidence of perioperative stroke and death relating to urgent CEA procedures and the frequency of perioperative thrombosis of the endarterectomized vessel, all matters relating to the surgeon’s expertise rather than to the patient’s baseline characteristics.

Third, patch closure of the internal carotid artery was statistically more frequent among women. This is important, especially if we consider that in the ACAS only a few women were patched selectively, and results such as those reported in the ACAS have clearly affected medical practice. However, because the data were reviewed retrospectively and the decision to use a patch was subjective, and because the study was not designed specifically to address the association between the type of arteriotomy closure and perioperative neurologic morbidity, we can only speculate as to the reasons behind this and the implications in the comparison of outcome between the two sexes.

Finally, the intriguing finding of a higher incidence of late stroke in women is unexplained. Because no information is available in the study regarding the characteristics of late stroke (ie, ischemic or hemorrhagic, fatal or nonfatal, cardioembolic or lacunar, ipsilateral or contralateral to the operated side) and given the higher incidence of lacunar strokes in the female population in general23 and the higher incidence of hypertension in the women in the study, one might expect to find a higher incidence of lacunar cerebral infarctions in this group. Lacunae are caused by an intrinsic disease of the single perforating branch artery that supplies the infarct (either lipohyalinosis or atheromatous branch disease), however, so they are unrelated to the surgical procedure. Moreover, lacunar strokes have a relatively good prognosis, and this could account for the lower late mortality rate in women than in men.

The results from this study strongly support the hypothesis that female sex is not a risk factor for perioperative stroke and death after CEA. I am also convinced that the outcome of CEA is affected exclusively by the surgeon and his technique, which demands a meticulous performance, expert intraoperative judgment, optimal anesthesiologic management, and appropriate patient selection.


*    References
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 *References
 

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