Sex, Diabetes, and Stroke After Carotid Endarterectomy

While diabetes is associated with increased risk of perioperative stroke among subjects who undergo carotid endarterectomy (1–3), women and minorities have been generally underrepresented in such trials (4). The North American Symptomatic Carotid Endarterectomy Trial (NASCET) was a randomized study of 2,885 eligible patients with carotid stenosis <70% who received either medical (n = 1,449) or surgical therapy (n = 1,436 patients) (3). The median study age was 66 years, and 93% of study subjects were white. Approximately 30% of NASCET subjects were female, and ∼22% had a history of diabetes, which was almost always type 2 diabetes (3). The study showed that endarterectomy safely and efficaciously reduced the risk of stroke in symptomatic patients with higher-grade carotid arterial stenosis when compared with medical therapy (3). Multivariate analysis indicated an increased risk of perioperative stroke in subjects with a history of diabetes (relative risk [RR] 2.0, 95% CI 1.2–3.1) (3). Because NASCET had a relatively high proportion of both female and diabetic subjects, we addressed the hypothesis that there would be differences between diabetic men and women with respect to the risk of peri- and postoperative complications. Subjects were subdivided by surgical or medical therapy and then subdivided again by sex and diabetes history. End point data regarding strokes and deaths were collected.

Diabetic men had a significantly increased risk of stroke or death 30 days postendarterectomy compared with nondiabetic men (RR 2.3, 95% CI 1.4–3.7), with no difference between diabetic and nondiabetic women (1.1, 0.5–2.4). Furthermore, diabetic men had a significantly increased risk of stroke 3 years postendarterectomy compared with nondiabetic men (RR 1.9, 95% CI 1.3–2.8), again with no difference between diabetic and nondiabetic women (1.0, 95% CI 0.6–1.9). However, at 3 years postrandomization, diabetic men who received medical treatment had no increased risk of stroke compared with nondiabetic men (RR 0.7, 0.5–1.1). In contrast, at 3 years postrandomization, diabetic women who received medical treatment had a significantly increased risk of stroke compared with nondiabetic women (1.7, 1.1–2.8).

The results support the emerging impression of sex-related differences among diabetic subjects with respect to vascular disease (5,6). Perioperative neurological morbidity of carotid endarterectomy is mainly due to embolization at the time of clamping or clamp release, ischemia during clamping of extracranial arteries, and intracerebral hemorrhage (7). There has been a steady decrease in postoperative morbidity among patients who undergo carotid endarterectomy as a result of both improved surgical technique and patient selection (7). Baseline clinical attributes are also helpful predictors of postoperative mortality and morbidity from stroke (3). Our analysis suggests that among diabetic subjects who undergo carotid endarterectomy, there may be sex-related differences in postoperative neurological morbidity. As with any post hoc subgroup analysis, the results should be interpreted cautiously and must be replicated in other studies. However, if these findings are confirmed, it might be appropriate to consider sex and diabetes status in strategies to optimize the management of patients with carotid disease (8).