Compared to carotid endarterectomy, carotid artery stenting (CAS) is reportedly associated with higher perioperative risks in elderly patients. To verify the long-term safety and efficacy of CAS with embolic protection in elderly patients, we retrospectively reviewed the medical records of patients with carotid stenosis treated between January 2003 and March 2010 at the Department of Neurology of a large university hospital in China. We included patients with symptomatic, moderate, or severe carotid stenosis of atherosclerotic etiology (other etiologies were excluded), with a disability score ≤ 3 on the modified Rankin Scale, and who received CAS instead of carotid endarterectomy. The clinical endpoints studied were stroke recurrence and all-cause death. The 84 patients included in this study (median follow-up, 8.08 years) were stratified according to age at surgery (<70 vs. ≥70 years), and no significant between-group difference was found regarding baseline characteristics. Of the 14 patients (16.67%) who experienced a defined clinical endpoint, 4 (7.14%) were aged <70 years and 10 (35.71%) were aged ≥70 years (
The gradual increase in the incidence of cerebrovascular disease reflects the aging trend in many populations. Cerebrovascular death has become one of the three major disease-related causes of death worldwide. Approximately 15% to 20% of ischemic strokes are caused by carotid artery stenosis [
In China, CAS is widely used, and the safety and efficacy of revascularization therapy in the elderly population have become the focus of various studies. A meta-analysis [
All patients described in the manuscript provided informed consent for undergoing the procedures. The requirement for informed consent was waived on account of the retrospective nature of our study and the fact that no identifiable data are presented. Upon review of the medical records (including baseline and clinical characteristics), the candidates for this study were recruited from among the patients with symptomatic, moderate, or severe carotid stenosis with atherosclerotic etiology, treated between January 2003 and March 2010 at the Department of Neurology of Southwest Hospital, which is affiliated to the Third Military Medical University. The degree of stenosis was determined according to the standard applied in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) [
The retrospective review of medical records collected data on epidemiologic variables (e.g., age and sex), classical risk factors for cerebrovascular disease (hypertension, diabetes mellitus, ischemic heart disease, alcohol consumption, and smoking), and risk factors for stroke recurrence (multiple arterial stenosis and plaque instability). Because the study aimed to verify the safety and efficacy of CAS among the elderly, the patients were stratified according to age at surgery (<70 vs. ≥70 years). The two groups were compared in terms of baseline characteristics and incidence of endpoints, and the potential risk factors for long-term mortality after CAS were evaluated.
The clinical endpoints analyzed in this study were stroke recurrence (any stroke), death, and the combined endpoint of any stroke or death later than 120 days after the surgery (until the end of follow-up). Stroke was defined as an acute deficit of focal neurological function with symptoms lasting for longer than 24 h, resulting from intracranial vascular disturbance (ischemia or hemorrhage). Visual loss that resulted from retinal ischemia and lasted for longer than 24 h was also considered a stroke endpoint. In-stent restenosis was defined as stenosis with blockage ≥ 50%.
The patients were followed up by neurologists at the outpatient clinic to monitor for recurrent stroke (ipsilateral or contralateral) and assess the functional outcomes in terms of the mRS score. For patients who died during follow-up, relevant clinical information including the time and cause of death were recorded. Carotid ultrasonography was performed by sonographers in available patients. If restenosis was suspected, computed tomography angiography or digital subtraction angiography was performed for confirmation.
All analyses were carried out using the SPSS statistical software package, version 22.0 (IBM Corp., Armonk, NY, USA). Age data had nonnormal distribution and were represented as median (interquartile difference). Frequency (%) was used to represent count data including age and stenosis severity distribution, as well as the incidence of hypertension, diabetes mellitus, alcohol consumption, ischemic heart disease, smoking, multiple stenoses, plaque instability, death, ischemic stroke, and mRS score < 2. Fisher’s exact test and the chi-square test were used to evaluate the differences in baseline characteristics and clinical endpoints between the two groups defined in terms of age at surgery (<70 vs. ≥70 years). Univariable and multivariable logistic regression analyses were used to evaluate potential risk factors for death, including age group, sex, hypertension, diabetes mellitus, alcohol consumption, ischemic heart disease, smoking, multiple stenoses, stenosis severity, and plaque instability; the results were expressed as odds ratios (OR) with 95% confidence intervals (95% CIs). In all analyses, the level of significance was set at a
Of the 98 patients that were considered candidates based on the inclusion and exclusion criteria, 84 had complete clinical and follow-up data and were thus included in the study. The median age in our study sample was 65 years (interquartile range, 20–26 years), 66 patients (78.57%) were male, and 28 were older than 70 years at the time of surgery. The distribution of carotid stenosis risk factors and associated diseases is summarized in Table
Baseline characteristics of patients undergoing carotid artery stenting.
Characteristic | Total | Age < 70 years ( |
Age ≥ 70 years ( |
|||
---|---|---|---|---|---|---|
Sex | Male | 66 (78.57%) | 44 (78.57%) | 22 (78.57%) | <0.001 | >0.999 |
Hypertension | 55 (65.48%) | 36 (64.29%) | 19 (67.86%) | 0.105 | 0.746 | |
Diabetes mellitus | 15 (17.86%) | 10 (17.86%) | 5 (17.86%) | <0.001 | >0.999 | |
Alcohol consumption | 24 (28.57%) | 15 (26.79%) | 9 (32.14%) | 0.263 | 0.608 | |
Ischemic heart disease | 8 (9.52%) | 4 (7.14%) | 4 (14.29%) | / | 0.431 | |
Smoking | 40 (47.62%) | 30 (53.57%) | 10 (35.71%) | 2.386 | 0.122 | |
Multiple stenoses | 19 (22.62%) | 12 (21.43%) | 7 (25.00%) | 0.136 | 0.712 | |
Stenosis degree | Moderate | 46 (54.76%) | 33 (58.93%) | 13 (46.43%) | 1.177 | 0.278 |
Severe | 38 (45.24%) | 23 (41.07%) | 15 (53.57%) | |||
Plaque | Unstable | 62 (73.81%) | 42 (80.77%) | 20 (74.07%) | 0.472 | 0.492 |
Patients were stratified according to age at surgery (<70 vs. ≥70 years). The two groups did not differ regarding baseline characteristics (
Over a median follow-up period of 8.08 years (interquartile range, 6.83–10.45 years; maximum, 14.1 years), there were no significant between-group differences regarding prevalence of mRS score < 2, stroke recurrence, or restenosis rate. However, death and the combined clinical endpoint of stroke or all-cause death had a higher incidence in the group of older patients (≥70 years). A total of 14 patients (16.67%) experienced the combined clinical endpoint (any stroke or all-cause death). Specifically, 4 of 56 patients (7.14%) aged <70 years and 10 of 28 patients (35.71%) aged ≥70 years had stroke recurrence or died during the defined period (
Clinical endpoints of carotid artery stenting.
Endpoint | Total | Age < 70 years ( |
Age ≥ 70 years ( |
||
---|---|---|---|---|---|
Stroke or death | 14 (16.67%) | 4 (7.14%) | 10 (35.71%) | / | 0.002∗ |
Death | 12 (14.29%) | 3 (5.36%) | 9 (32.14%) | / | 0.002∗ |
Stroke | 3 (3.57%) | 1 (1.79%) | 2 (7.14%) | / | 0.256∗ |
mRS score < 2 | 26 (30.95%) | 16 (28.57%) | 10 (35.71%) | 0.446 | 0.504 |
Restenosis# | 2 (2.78%) | 1 (1.89%) | 1 (5.26%) | / | 0.460∗ |
Patients were stratified according to age at surgery (<70 vs. ≥70 years). Data are given as number of events (frequency). mRS: modified Rankin Scale; #: 12 cases were excluded from this subgroup analysis because death occurred prior to other endpoints (<70 years,
Univariable logistic regression analysis indicated that, compared to patients aged <70 years, those aged ≥70 years were at higher risk of death (OR = 8.3684, 95% CI = 2.048–34.202,
Results of the univariate and multivariate logistic regression analyses to identify independent risk factors for death after carotid artery stenting.
Risk factor | Total | Survival |
Death |
Univariate logistic regression | Multivariate logistic regression | |||||
---|---|---|---|---|---|---|---|---|---|---|
OR (95% CI) | Wald |
OR (95% CI) | Wald |
|||||||
Age, years | <70 | 56 | 53 (94.64) | 3 (5.36) | Reference | Reference | ||||
≥70 | 28 | 19 (67.86) | 9 (32.14) | 8.368 (2.048–34.202) | 8.748 | 0.003 | 20.054 (3.094–129.987) | 9.887 | 0.002 | |
Sex | Male | 66 | 57 (86.36) | 9 (13.64) | Reference | Reference | ||||
Female | 18 | 15 (83.33) | 3 (16.67) | 1.267 (0.305–5.267) | 0.106 | 0.745 | 0.398 (0.032–4.998) | 0.510 | 0.475 | |
Hypertension | 55 | 48 (87.27) | 7 (12.73) | 0.700 (0.201–2.438) | 0.314 | 0.575 | 1.263 (0.219–7.285) | 0.068 | 0.794 | |
Diabetes mellitus | 15 | 13 (86.67) | 2 (13.33) | 0.908 (0.177–4.645) | 0.014 | 0.907 | 2.573 (0.203–32.634) | 0.532 | 0.466 | |
Alcohol consumption | 24 | 22 (91.67) | 2 (8.33) | 0.455 (0.092–2.249) | 0.934 | 0.334 | 0.732 (0.072–7.448) | 0.069 | 0.792 | |
Ischemic heart disease | 8 | 7 (87.50) | 1 (12.50) | 0.844 (0.094–7.547) | 0.023 | 0.880 | 0.477 (0.027–8.282) | 0.258 | 0.611 | |
Smoking | 40 | 37 (92.50) | 3 (7.50) | 0.315 (0.079–1.261) | 2.664 | 0.103 | 0.524 (0.065–4.241) | 0.366 | 0.545 | |
Multiple stenosis | 19 | 17 (89.47) | 2 (10.53) | 0.647 (0.129–3.246) | 0.28 | 0.597 | 0.472 (0.059–3.773) | 0.501 | 0.479 | |
Stenosis degree | 50~69% | 46 | 40 (86.96) | 6 (13.04) | Reference | Reference | ||||
70~99% | 38 | 32 (84.21) | 6 (15.79) | 1.250 (0.368–4.248) | 0.128 | 0.721 | 0.859 (0.131–5.647) | 0.025 | 0.874 | |
Plaque# | Unstable | 62 | 53 (85.48) | 9 (14.52) | 1.274 (0.248–6.538) | 0.084 | 0.772 | 1.950 (0.17–22.334) | 0.288 | 0.591 |
Patients were stratified according to age at surgery (<70 vs. ≥70 years). Elderly patients (aged ≥70 years) had a higher risk of mortality (OR = 8.3684, 95% CI = 2.048–34.202,
Twelve deaths occurred during the study period. Of the 9 elderly patients (aged ≥70 years) who died, one had survived for less than 1 year after CAS, while 6 patients had survived for more than 3 years and 1 had survived for more than 10 years. Among patients aged ≥70 years at the time of surgery, heart disease was the cause of death in 5 cases, cancer was the cause of death in 3 cases, and only 1 death had a different cause (neither heart disease nor cancer) (Figure
Analysis of survival and cause of death among elderly patients (≥70 years) who underwent carotid stenting. Deaths that occurred later than 120 days after surgery were stratified according to survival duration (<1 year, 1–3 years, 3–5 years, 5–10 years, and >10 years. Different columns represent different causes of death, with “other” indicating death not related to heart disease or cancer.
Carotid stenosis is one of the most important causes of ischemic stroke and represents an independent risk factor for ischemic cerebrovascular events [
Recent studies evaluating the long-term outcomes of CAS (median follow-up, 1.2–7.4 years) found some differences between CAS and CEA regarding the incidence of certain endpoints, but these differences were not significant. In the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) [
A meta-analysis of 5 randomized controlled trials including 2716 patients and covering a median follow-up of 62 months concluded that there may be a relationship between in-stent restenosis and stroke recurrence after CAS, and the incidence of restenosis with blockage > 70% was 10% [
Some data have indicated that elderly patients should be treated with CEA, which, compared to CAS, is associated with fewer risks in this patient population. A meta-analysis [
Upon analyzing the data regarding cause of death (Figure
The poor outcomes previously reported for transfemoral CAS in elderly patients may be due to the specific changes induced by atheromatosis in the aortic trunk and supra-aortic vessels. Transcervical CAS with flow reversal for cerebral protection avoids such unfavorable effects, and this strategy might provide higher long-term safety and effectiveness in elderly patients aged ≥70 years [
The present study has some limitations. First, the studied population was recruited from a single institution. Second, the sample was small. Third, our study was restricted to CAS recipients. In addition, some patients admitted to our department during the study period (2003–2006) were not included in the study because they were lost to follow-up or had missing data regarding the follow-up evaluations.
Among elderly patients in Southwest China, CAS for moderate-to-severe carotid stenosis can effectively prevent stroke recurrence without increasing the risk of stroke-related death but is associated with increased all-cause mortality. Age is an independent risk factor for mortality after CAS. Among elderly patients, the main causes of death after CAS for carotid stenosis are heart disease and cancer. The treatment for patients with symptomatic carotid artery stenosis should be selected according to the individual circumstances of each case.
The authors declare that there is no conflict of interests regarding the publication of this article.
Lan Wen and Suxia Wang contributed equally to this work and should be considered co-first authors.
This work was supported by the National Science Foundation of China [grant number 81471194] and by the Southwest Hospital through the program for Novel Clinical Technologies in Military Medicine and Injury Treatment [grant numbers SWH2016JSZD-02, SWH2016JHJC-03, and SWH2016JSTSYB-23].