Ethnic differences and optimal management strategy for DM patients with carotid stenosis
Although our study cohort consisted of only Koreans and may not be representative of other ethnic groups, the prevalence of type 2 DM has been increasing throughout Asia, and the speed of this increase is much faster than in Western countries [
16]. In Korea, the prevalence of DM increased slightly between 2007 and 2014: 7.7% to 8.0% in the general population and 30.7% to 32.4% in the stroke population [
31]. The prevalence of DM among Korean adults is expected to rise to 11.4% by 2030, accelerated by the aging of the population [
32]. A large-scale meta-analysis project, the Asia Pacific Cohort Studies Collaboration, showed that the HRs of DM for ischemic stroke and MI are similar between Asian and Western countries [
33]; moreover, glucose intolerance and DM are risk factors for stroke and MI in most Asian countries, as they are in Western countries [
34‐
37]. Similar results were reported by the recently published “Stroke Statistics in Korea” project [
31]; DM is an important risk factor for stroke. Although stroke mortality is gradually declining, it remains as high as 30 deaths per 100,000 individuals in Korea [
31]. The trends of increased DM prevalence, higher risks of DM-related significant carotid stenosis and stroke occurrence highlight the importance of carotid revascularization as a primary or secondary preventive management strategy for this fast-growing, vulnerable population in Korea.
Although carotid artery stenosis patients undergoing CEA or carotid artery stenting (CAS) had similar 30-day readmission rates [
38], Columbo et al. [
39] recently reported that patients who undergo CEA have a long-term survival advantage over those who undergo CAS in real-world practice, despite no difference in long-term survival in randomized trials. Furthermore, according to a recent multicenter study in Korea, although the risk of major adverse cardiovascular events did not differ significantly within 4 years among Korean CAS and CEA patients, there was a higher risk of stroke with CAS during the periprocedural period [
40]. However, the optimal management strategy for DM patients with significant carotid stenosis remains to be defined, because randomized clinical trials have focused on comparing the effectiveness of CEA and CAS for high-risk [
41] or standard-risk [
29,
42,
43] patients, with minimal specific focus on patients with DM [
4,
9]. Moreover, controversy exists about the long-term benefit of stroke prevention after CEA in the diabetic population, with varying conclusions across different Western studies [
6,
8,
13‐
15]. There have been few reports to document the impact of DM on early and late outcomes after CEA in Asian populations.
In our study, we compared the outcomes after CEA between diabetic and non-diabetic patients and found that DM patients are not at greater risk of 30-day MAEs after CEA compared with non-DM patients; however, the 4-year risk MAE occurrence is significantly greater among DM patients. Following the perioperative period, the rate of major stroke was less than 1.0% at 4 years in both DM and non-DM patients. However, the rate of stroke (of any severity) was 7.2% at 4 years in the DM group compared with 2.7% in the non-DM group, confirming that the efficacy of CEA for stroke prevention might be poorer in the long term in the presence of DM. Nevertheless, the inclusion of minor neurologic complications influenced significance for the combined outcome. Furthermore, patients in the DM group had a higher prevalence of atherosclerotic risk factors and DM-related comorbidities than those in the non-DM group. In addition to DM itself, these baseline differences also affected the 4-year MAE incidence differences between the two groups, and the present observations corroborate a report by Adegbala et al. [
9], which found that the presence of DM with chronic complications is an important risk factor for poorer outcomes after CEA.
Considering that there are conflicting reports on the impact of DM on the outcomes of patients who have undergone CEA, our findings are also inconsistent with some previously reported results, almost all of which were from studies on Western populations [
4,
8,
13,
44]. Although our study sample was small, the discrepancies between our findings and those of previous studies are likely attributable in part to ethnic disparities between Asian and Western populations. There are limited data available derived from studies on Asian populations, and therefore our findings could help inform clinicians about the best treatment options for Asian DM patients with significant carotid stenosis. Further studies of larger cohorts are needed to better understand the impact of DM on clinical outcomes following CEA in Asian populations.
Impact of risk factors on outcomes after CEA
The deleterious effects of obesity on patient survival in the general population are well known [
45]. Among patients with metabolic syndrome, obesity is a confirmed independent risk factor for carotid plaque destabilization, particularly among males aged < 70 years [
46]. In our analysis, increased body mass index (BMI) within the normal range was not associated with increased risk of 30-day or 4-year MAE occurrence after CEA. Although the recent Westernization of dietary habits has resulted in increasing mean BMI in most Asian countries, Asian populations remain less obese than Western populations.
As for other atherosclerosis risk factors, dyslipidemia, diagnosed before CEA, has a protective effect on 30-day MAE and stroke occurrence, whereas there is no significant impact of dyslipidemia on the 4-year risks of MAEs or the individual MAE manifestations. Two randomized trials and several cohort studies have demonstrated the effectiveness of a short preoperative statin course to improve the 30-day outcomes of postoperative cardiovascular morbidity and mortality after major vascular surgery [
44,
47‐
51]. Considering that all patients diagnosed with dyslipidemia received statins before CEA in our study population, this potentially explained our observation of a protective effect of dyslipidemia on 30-day MAE and stroke occurrence. This current finding adds support to the previous report by Visser et al. [
44], which found that statin use is significantly associated with a decreased risk of MAEs after CEA.
Other data reveal the association between medical management of DM and an increased risk of MAE occurrence among DM patients taking insulin [
52‐
54]. The need for insulin might be associated with more than a sevenfold increased risk of perioperative stroke and death after CEA. This may suggest that a more advanced stage of DM with chronic complications, or a different metabolic status requiring more aggressive glycemic control among DM patients requiring insulin, could lead to higher risk of ischemic events and death [
8]. Concerning 4-year any-cause mortality, our data, consistent with previous studies, showed that insulin use was significantly associated with a worse 4-year survival rate. The presence of DM might both increase neointimal hyperplasia and accelerate the growth of new carotid plaques at the site of arterial injury [
8], thereby implying an increased risk of restenosis after CEA [
14,
55]. However, this hypothesis has remained controversial; our study, as well as others in the literature [
5,
56], indicated that DM patients have similar restenosis rates after CEA compared with non-DM patients.
Study limitations
It is clear that our study has substantial limitations, including its retrospective design and small sample size in a single-center cohort. There was potential for selection and information biases on the part of the physicians or patients, owing to the retrospective study design; hence, the incidence of MAEs may have been underestimated, and the number of excluded patients was considerable. Furthermore, we calculated the DM duration at baseline using patient self-reported age at DM onset, which may have been inaccurate owing to the lag times between disease onset, diagnosis, and self-reporting for study purposes. Additionally, several important factors were not available from our data sources, such as biochemical assessments to evaluate glycemic or metabolic control among DM and non-DM patients. Patient adherence to prescribed DM medications was not supervised, because a substantial proportion of patients were followed up at other hospitals once stability had been established at our DM center. Owing to the lack of data on serial measurements of glycated hemoglobin levels and other DM-related factors, we could not account for differences in glycemic control in this analysis. Furthermore, the study cohort consisted entirely of Korean Asians; therefore, our results may not be generalizable to other ethnic groups. Finally, as with all observational studies, we cannot draw conclusions about causality.