Fig. 18.1
Deaths by cause in men and women, Europe (European Cardiovascular Disease Statistics, 2012)
Annually in the United States, there are more than 700,000 new cases of stroke. Of these, it is estimated that 15–20 % depends on the carotid occlusive disease, and about 70–80 % of these events occurs as the first manifestation of the disease, but there have been earlier clinical symptoms related to transient cerebral ischemia. In Italy a stroke affects about 6.5 % of the population over 65, and a percentage between 20 and 40 % of ischemic stroke is correlated with the presence of carotid artery stenosis in extracranial district. Therefore, carotid stenosis, symptomatic and asymptomatic, remains a significant cause of stroke and the subsequent morbidity and mortality related to it. It is estimated that the incidence of asymptomatic carotid disease in the general population is not negligible, averaging between 2 and 8 %. Advanced age is a strong risk of increased incidence of disease. In fact, if in patients aged <65 years the incidence is about 0.5–1 %, this increases to 2.7 % in patients aged > 65 years and reaches 10 % in patients aged > 80 years. There is also the strong correlation of asymptomatic carotid disease in the presence of classic risk factors for cardiovascular disease (dyslipidemia, diabetes, cigarette smoking, high blood pressure) [4].
Carotid stenosis is considered the most common cause of acute ischemic cerebrovascular events. The treatment of extracranial carotid stenosis is therefore of great importance in the prevention of cerebrovascular disease [5].
18.1.2 Carotid Artery Revascularization
Since the carotid endarterectomy (CEA) was described in 1954 as a treatment for stroke prevention, this procedure was subjected, to determine its effectiveness and duration, in various large-scale randomized clinical trials like the European Carotid Surgery Trial (ECST) [6] and the North American Symtomatic Carotid Endarterectomy Trial (NASCET) [7] which showed that the surgical removal of plaque by endarterectomy is superior to medical therapy in preventing stroke in patients with symptomatic carotid stenosis disease criticism. For asymptomatic carotid disease, it is useful to refer to the data derived by ACAS (Asymptomatic Carotid Atherosclerosis Study) [8], the first large randomized trial that compared medical treatment to surgical treatment. This study demonstrated a risk of ipsilateral stroke at 5 years, respectively, of 5.1 % in the surgical arm and 11 % in the medical therapy arm (p = 0.004). The study, therefore, showed a relative risk reduction of 53 % with a greater benefit in men (66 %) compared to females (17 %). The ACST (Asymptomatic Carotid Surgery Trial) [9] has finally confirmed the role of the superiority of surgery compared to medical therapy alone in the treatment of asymptomatic carotid disease. In this randomized study, the risk of stroke at 5 years was 6.4 % in the treatment arm CEA against 11.8 % in the group treated with medical therapy alone (p <0.0001). This has led to consider the CEA treatment of reference (gold standard) in symptomatic or asymptomatic carotid disease. It should be noted, however, that some of the patients with carotid stenosis was excluded from these trials because it was considered “high-risk surgery.” Moreover all these reference works are dated and were conducted without the modern medical therapy.
18.1.2.1 Carotid Artery Stenting
In recent decades the endovascular treatment of carotid stenosis has developed considerably, guided by the success achieved in the coronary district, since the latter has some advantages such as less invasiveness, the absence of risk of injury of cranial nerves, no need for general anesthesia, and reduced hospitalization time. After the first carotid angioplasty performed by Mathias in 1977 [10], the endovascular techniques have rapidly developed, especially after the introduction of the self-expandable stent. In 1996, Dietrich et al. reported the first large series of patients, suffering from symptomatic and asymptomatic carotid stenosis, treated with angioplasty and carotid stenting [11]. In 1997, Yadav et al. reported the results of the first study carried out on the basis of a defined protocol and having an independent neurological assessment [12]. In that series, in which most of the 126 patients included could not be treated by TEA, on the basis of the exclusion criteria of NASCET, it has been reported a technical success of 100 % and a rate of stroke and death equal to 2.4 %. These results have led to a rapid spread of such a procedure, so that Wholey and colleagues reported in 2000 over 5000 procedures of carotid stenting in the world [13].
18.1.2.2 CEA Versus CAS
In 2001 the results of the first trial that compared CAS to CEA was published. The CAVATAS (Carotid and Vertebral Artery Transluminal Angioplasty Study) evaluated patients with high-grade carotid stenosis, treated by carotid angioplasty, with or without stenting and without any cerebral protection or by CEA. The incidence of stroke or death at 30 days and in the follow-up was almost the same. CAS, compared with CEA, however, demonstrated a lower incidence of cranial nerve injury. An increased incidence of severe restenosis at follow-up 1 year, however, was observed after CAS (14 % vs. 4 %) [14].
The trial SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) evaluated patients at high surgical risk, with asymptomatic stenosis > 80 % or symptomatic > 50 %, who underwent CAS with cerebral protection system (Fig. 18.2) or endarterectomy. In this study, the protected CAS was even superior compared to surgery. Indeed, while the results were similar in regard to mortality and stroke (3.1 % vs. 3.3 %), CAS was superior considering the incidence of myocardial infarction (1.9 % vs. 6.6 %) and overall incidence of stroke, MI and death 4.4 % in patients undergoing CAS versus an incidence of 9.9 % in patients undergoing CEA [15, 16].
Fig. 18.2
Types of cerebral protection devices: (a) Filter positioned distal to the lesion of ICA. (b) Protection Balloon inflated distally to the lesion of ICA. (c) One Balloon inflated in the external Carotid artery and one inflated in the common Carotid artery in order to interrupt the anterograde flow in the ICA
Three other randomized trials have instead reported results favorable to CEA: study SPACE (Stent-protected Percutaneous Angioplasty of the Carotid vs. Endarterectomy), which evaluated CAS (with cerebral protection) versus CEA in 1214 patients with symptomatic carotid stenosis > 70 % [17]; trial EVA-3S (Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis), which has randomized 527 patients with symptomatic carotid stenosis > 60 %, undergoing protected CAS or CEA [18]; and finally the study CAVATAS 2-ICSS (International Carotid Stenting Study), which has evaluated 1713 patients at high surgical risk with symptomatic carotid stenosis > 70 % underwent to protected CAS or CEA [19]. On the basis of these trials, and of various independent works conducted by vascular surgeons, for many years the gold standard for the treatment of carotid artery disease remains CEA, and CAS has been indicated only for patients not eligible to surgery.
In 2010, however, were published the final data of the CREST (Carotid Revascularization Endarterectomy versus Stent Trial), a multicenter randomized trial which compared TEA and protected CAS in symptomatic and asymptomatic patients at high risk (carotid stenosis >50 % for the symptomatic and >70 % for asymptomatic). In this study, conducted on 2502 patients, the primary end point (stroke, MI, death from any cause in the perioperative period and ipsilateral stroke within 4 years of follow-up) showed no significant differences between the two procedure (7,2 % versus 6,8 %, p = 0.51) [20].
The impact of technology on the results of CAS was then confirmed by more recent studies in which endovascular procedures, all performed with the routine use of stents dedicated and cerebral protection system, have shown a lower incidence of stroke and death, comparable with the best results reported for the surgical treatment (43). Although CAS has proven safe and effective method in asymptomatic and symptomatic patients at high surgical risk, still it remains unsolved and debated the correct strategy for asymptomatic patients at low risk, particularly in the population of octogenarians and women.
18.1.2.3 “Tailored CAS”
The “tailored approach” to CAS consists of the planning of a specific endovascular strategy for a specific patient. This approach depends on an in-depth knowledge of all characteristics of the endovascular equipment (guiding catheters, guiding sheaths, guide wires, embolic protection devices, balloons, and stents) to precisely match the most suitable device to a specific vascular anatomy, carotid lesion, or cerebral circulation pattern as well as to the patient clinical presentation. Our group in 2009 published the results of the “tailored-CASE registry” which analyzed the use of the “tailored approach” in 1.523 procedures. A procedural success rate of 99.6 % was achieved. The 30-day all-stroke and death rates were 1.2 % and 2.7 % for the asymptomatic and symptomatic patient groups, respectively. The highest-risk population, the symptomatic patients aged more than 80 years, had a 30-day all-stroke and death rate of 4.5 %. Based on those findings, the use of the “tailored approach” by experienced operators seems to be a valuable tool to increase the overall CAS safety [21].
18.1.3 Gender Differences in Cardiovascular Diseases
The awareness of the different realities of the female begins when Bernadine Healy, in 1991, wrote a famous editorial in the prestigious New England Journal of Medicine entitled “The Yentl syndrome,” commenting on two studies that reported how women with coronary artery disease were generally cared less and receive less aggressive interventions than men [22]. The article was clearly defiant by the first woman to head the US National Institute of Health and had huge coverage in scientific world as well as the media.
In the last two decades, several studies have investigated the gender differences in clinical manifestations and prognosis of cardiovascular disease. The results of these studies showed some important differences related to gender. In fact, while the effects of gender, age, and culture on the health of man and woman have been extensively studied, what is still missing is a similar focus on the impact that gender differences have on the pathophysiology and, therefore, on the treatment of the most common social diseases, including cardiovascular disease.
This difference is particularly marked in cerebrovascular diseases where women show a higher mortality and morbidity than men (Fig. 18.3). Of the estimated 795,000 new or recurrent stroke each year in the USA, 53.3 % appears in women and 61 % of the disease-related mortality is the prerogative of the female sex.
Stroke in women kills twice than breast cancer and it is estimated that one in five women will have a stroke in their lifetime. Even the risk factors are more common in women or are specific to women. Hypertension, diabetes, atrial fibrillation, migraine with visual aura, and depression are more common in women. In addition, pregnancy, preeclampsia, use of contraceptives, postmenopausal hormone replacement therapy, and gestational diabetes are specific risk factors for cerebrovascular events in female sex. The damage produced by a cigarette in a woman is equivalent to that produced by five cigarettes in man, and diabetes increases the risk of vascular disease from three to five times in woman.
In a study published in 2009, Petrea RE et al. explored gender differences in the incidence and severity of stroke in the Framingham Heart Study, based on the data from a follow-up of 56 years. In the population of participants in the Framingham original (5119 of which 2829 women) and in the offspring cohort (4957 of which 2565 women), the authors observed 1136 strokes (638 in women) during follow-up. Women were statistically older at the time of stroke and had an increased rate of stroke over the age of 85, but minor in the other ages. Furthermore, from 3 to 6 months after the stroke, women were significantly more disabled [24].
18.1.3.1 Gender Differences in Carotid Artery Revascularization
The influence of sex on the rise in the risk of stroke and perioperative death during carotid revascularization has been well described for CEA. The Asymptomatic Carotid Atherosclerosis Study (ACAS) was the first study that showed a nonsignificant trend toward an increased risk of stroke and death in women underwent to CEA [25]. The European Carotid Surgery Trial (ECST) found a significantly increased periprocedural risk for women with symptomatic stenosis compared to men (11.1 % vs. 6.4 %, p = 0.002) [26]. Schulz and Rothwell have speculated that this effect may be caused by the anatomy of the internal carotid arteries that in women may have a diameter of up to 40 % smaller than those of men, making the surgical procedure technically most challenging [27]. These data could have led to “undertreat” women in clinical practice, particularly if asymptomatic.
In 2009, Howard et al. submitted an analysis of the lead-in phase of CREST comparing the results of 1564 patients (in which only 26.5 % were symptomatic) underwent CAS distinct by gender. There was no significant difference in the rate of periprocedural stroke and death between women and men (4.2 % vs. 4.5 %). Taking into account the symptomatic status, the difference between symptomatic and asymptomatic women (5.6 % vs. 4.1 %) was smaller than it was for men (5.9 % vs. 3.5 %). After adjustment for demographic factors (age and race), vascular characteristics (reference diameter, lesion length, percent stenosis), and cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes, and smoking), gender differences were not statistically significant [28].
In 2011, Howard et al. presented the results of CREST comparing CAS and CEA according to gender. The composite primary end point of MI, stroke, or death during the periprocedural period or ipsilateral stroke within 4 years did not differ significantly by sex. The primary end point occurred in 6.2 % of men treated with CAS compared to 6.8 % treated with CEA. The rates for women were 8.9 % in the stenting group versus 6.7 % in the surgical group. Regarding periprocedural events only, the rate of complications was 4.3 % in the male CAS group compared with 4.9 % in the male surgical group. Among women, the rate in the CAS group was 6.8 % compared with 3.8 % in the CEA group [29]. The result of CREST has definitely changed the knowledge about the superior of CEA over CAS and about a more conservative treatment of carotid stenosis in women, even if the debate is still open.
18.2 Women and Carotid Artery Disease: The “Maria Cecilia Hospital” Experience
Maria Cecilia Hospital has gained a renowned experience in percutaneous treatment of carotid artery disease. As a single high-volume center performing CAS, we performed a large number of procedures using a “tailored” approach according to patient’s and lesion’s characteristics.
18.2.1 CAS Procedures: Our Common Practice
We retrospectively collected all CAS procedures performed in the Department of Diagnostics and Interventional Cardio-Angiology at Maria Cecilia Hospital (Group GVM Care & Research) of Cotignola between March 2012 and January 2015.
A total number of 516 procedures of CAS in 461 patients with symptomatic or asymptomatic carotid stenosis ≥ 70 % were identified, and demographic data, risk factors, cardiovascular and neurological history, as well as clinical status at presentation were collected. In addition, for each patient a systematic review of the angiography of supra-aortic vessels performed before the procedure considering anatomical features like aortic arch type (Fig. 18.4), arch bovine type, and vascular tortuosity (Fig. 18.5) was defined according to the criteria of Weibel and Fields.
Fig. 18.4
Fig. 18.5
All carotid stenting procedures were performed by an interventional cardiologist with extensive experience in carotid revascularization using the concept of “tailored CAS.”
The different types of stents used included Xact Carotid Stent System (Abbott Vascular), Monorail Carotid Wallstent Endoprothesis (Boston Scientific), Cristallo Ideale (Platform Invatec, Medtronic), RoadSaver (Terumo), ViVEXX (VIVA), and noncarotid stents (off-label use).
In 98.4 % of cases, access was transfemoral, while in seven cases it was transradial. A guide catheter of appropriate shape and a hydrophilic standard guidewire 0.035 inch (Terumo Corporation) were used. A distal filter (EPI FilterWire, Boston Scientific, Nanterre, France, Spider, ev3, Irvine, USA) or a proximal cerebral protection system (Mo.Ma system, Invatec, Roncadelle, Italy) was used for cerebral protection.
In every case, a self-expanding stent was released at the level of the carotid bifurcation, without predilatation if possible, and then was performed a postdilatation with an appropriate balloon (Fig. 18.6).
Fig. 18.6
A self expanding stent is released (a–c) and then a postdilatation with a baloon inflaten within the stent is performed (d)
Hemostasis was achieved by positioning device closure system Angio-Seal (St. Jude Medical) in 79.5 % of cases, Perclose ProGlide (Abbott Vascular) in 4.1 % of cases, or by manual compression in the remaining 16.3 % of cases.
18.2.2 CAS Procedures: Our Data About Gender Differences
A total of 435 procedures were included in the study, 165 (37.9 %) of these were performed on female individuals. The baseline characteristics of the study population are shown in Table 18.1. The two populations were homogeneous for age, BMI, and cardiovascular risk factors, with the exception of smoking where it is interesting to note that although men with a history of smoking status are prevalent (49.4 % vs. 31.8 %, p = 0.0003), in the subgroup of current smokers, women do prevail (19.1 % vs. 14.2 %, p = 0.19). Women had more frequently at least moderate renal dysfunction (45.9 % vs. 34.4 %, p = 0.03), while in men a history of ischemic heart disease (48.2 % vs. 31, 2 %, p = 0.00099) as well as evidence of peripheral vascular disease (19.2 % vs. 12.1 %, p = 0.07) was significantly more prevalent. No difference instead was recorded between the two groups on the clinical status at presentation, although TIA was more frequent in the group of men (9.5 % vs. 1.9 %, p = 0.005).
Table 18.1
Baseline characteristics of population studied
Females | Males | p value | |
|---|---|---|---|
Population (%) | 165 (39.7) | 270 (62.1) | |
Baseline characteristics | |||
Age (years) | 72.6 ± 7.9 | 73.4 ± 8.1 | 0.31 |
BMI | 26.5 ± 4.3 | 26.7 ± 3.7 | 0.54 |
Creatinine clearance (mL/min) | 66.7 ± 24.3 | 70.9 ± 24.6 | 0.09 |
Risk factors (%) | |||
Hypertension | 136 (86.6) | 205 (81.0) | 0.18 |
Dyslipidemia | 120 (76.4) | 189 (74.7) | 0.78 |
Diabetes | 45 (28.7) | 76 (30.0) | 0.85 |
Current smoking | 30 (19.1) | 36 (14.2) | 0.19 |
Previous smoker (>1 anno) | 20 (12.7) | 89 (35.2) | <0.001 |
Family history of IHD | 24 (15.3) | 44 (17.4) | 0.67 |
Kidney disease (ClCr <60 mL/min) | 72 (45.9) | 87 (34.4) | 0.03 |
Obesity | 31 (19.8) | 42 (16.6) | 0.50 |
Clinical history (%) | |||
IHD | 49 (31.2) | 122 (48.2) | <0.001 |
PAD | 19 (12.1) | 49 (19.4) | 0.07 |
AVS | 9 (5.7) | 25 (9.9) | 0.19 |
Previous CEA/CAS | 40 (24.4) | 66 (24.4) | 1.00 |
Clinical presentation (%) | |||
Symptoms | 33 (21.0) | 69 (27.3) | 0.19 |
Stroke | 16 (10.2) | 18 (7.1) | 0.36 |
TIA | 3 (1.9) | 24 (9.5) | 0.005 |
Other | 14 (8.9) | 27 (10.3) | 0.24 |
CEA restenosis | 14 (8.5) | 10 (3.7) | 0.06
 Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
Get Clinical Tree app for offline access
|