Advanced Carotid Disease Research Articles

Carotid Revascularization is Associated with Improved Mood in Patients with Advanced Carotid Disease.

To investigate the impact of carotid interventions on patients' mental condition in patients with carotid stenosis. Ongoing research highlights the impact of carotid interventions on neurocognitive function in patients with advanced carotid atherosclerosis. However, data regarding the impact of carotid revascularization on mood is scarce. A total of 157 patients undergoing carotid revascularization were prospectively recruited. The primary outcome was depression, evaluated pre-operatively, and at 1-,6- and 12-month post-intervention using the long form of the geriatric depression scale (GDS-30) questionnaire. Other tests were also used to assess cognition at the respective timepoints. Statistical analyses were performed to assess the postoperative outcomes compared to baseline. Baseline depression (GDS>9) was observed in 49(31%) subjects, whereas 108(69%) patients were not depressed (GDS≤9). The average pre-operative GDS score was 15.42 ± 4.40(14.2-16.7) and 4.28 ±2.9(3.7-4.8) in the depressed and non-depressed groups, respectively. We observed a significant improvement in GDS scores within the depressed group at 1-month (P=0.002), 6-months (P=0.027), and 1-year (P<0.001) post-intervention compared to preop, whereas the non-depressed group had similar post-op GDS scores at all time points compared to baseline. Significant improvement in measures of executive function was seen in non-depressed patients at all three timepoints whereas depressed patients showed an improvement at 1-year follow-up. Our study highlights improvement in mood among patients with advanced carotid disease who screened positive for depression at baseline. Further studies with larger sample sizes are warranted to investigate the association between depression, carotid disease, and carotid intervention.

Carotid Revascularization Improves Mood in Depressed Patients With Advanced Carotid Disease

Carotid Revascularization Improves Mood in Depressed Patients With Advanced Carotid Disease

Endarterectomy patients with elevated levels of circulating IL-16 have fewer cardiovascular events during follow-up

Background and purposeIncreased interleukin 16 (IL-16) levels in carotid plaques have been associated with reduced incidence of cardiovascular (CV) events during follow-up in patients who underwent carotid endarterectomy (CEA). In the present study we aimed to determine whether high circulating levels of IL-16 also are associated with a decreased risk of CV events after CEA. MethodsPatients, who had their carotid plaques surgically removed (n=473), were followed for a mean follow-up time of 3.1years. Plasma levels of IL-16 the day before surgery were analyzed by proximity extension assay (PEA) and associated with the occurrence of CV events during follow-up (n=98). ResultsHigh levels of circulating IL-16 were independently associated with a decreased risk of CV events when comparing the highest versus the lowest IL-16 tertile (hazard ratio [HR] 0.47; 95% CI 0.27–0.81; P=0.007), as well as with CV deaths (HR 0.25; 95% CI 0.09–0.70; P=0.008). ConclusionThese present findings indicate an association between IL-16 and less clinical complications of atherosclerosis in a population with known advanced carotid disease.

Carotid artery stenting

### Learning objectives After reading this article the reader should: In western countries, stroke is the fourth leading cause of death, after heart disease, cancer and chronic respiratory diseases.1 Carotid...

Carotid artery stenting: current role of proximal neuroprotection and technical advancements in stroke prevention

For more than 50 years, carotid endarterectomy has been considered the gold standard therapy to prevent stroke in patients with carotid artery disease. Carotid artery stenting (CAS) has emerged in the last 15 years as minimally invasive alternative to surgery, especially in patients at high surgical risk. Recent randomized trials have challenged this concept reporting a relatively high incidence rate (4–6%) of post-CAS neurological adverse events. The aim of this study is to evaluate the current role of CAS in all-comers with advanced carotid disease, managed with mandatory proximal neuroprotection in a high-volume centre. From our database, the last 393 consecutive patients, from January 2011 to August 2013, undergoing CAS under proximal neuroprotection were analysed (mean age 72 ± 8 years). Indications included symptomatic stenoses ≥60% ( n = 87; 22%) and asymptomatic stenoses ≥80% ( n = 306; 78%). In an intention-to-treat approach, CAS success rate was 100%. The in-hospital all stroke/death rate was 1% (minor stroke 1%, major stroke 0%, and death 0%), and the rate of myocardial infarction was 0.3%. The minor stroke rate was 2.3% in symptomatic patients and 0.7% in asymptomatic patients. Carotid artery stenting performed in a high experience centre with the use of proximal embolic protection device is safe and has a low incidence rate of stroke.

Predicting Carotid Artery Disease and Plaque Instability from Cell-derived Microparticles

Cell-derived microparticles (MPs) are small plasma membrane-derived vesicles shed from circulating blood cells and may act as novel biomarkers of vascular disease. We investigated the potential of circulating MPs to predict (a) carotid plaque instability and (b) the presence of advanced carotid disease. This pilot study recruited carotid disease patients (aged 69.3 ± 1.2 years [mean ± SD], 69% male, 90% symptomatic) undergoing endarterectomy (n = 42) and age- and sex-matched controls (n = 73). Plaques were classified as stable (n = 25) or unstable (n = 16) post surgery using immunohistochemistry. Blood samples were analysed for MP subsets and molecular biomarkers. Odds ratios (OR) are expressed per standard deviation biomarker increase. Endothelial MP (EMP) subsets, but not any vascular, inflammatory, or proteolytic molecular biomarker, were higher (p < .05) in the unstable than the stable plaque patients. The area under the receiver operator characteristic curve for CD31(+)41(-) EMP in discriminating an unstable plaque was 0.73 (0.56-0.90, p < .05). CD31(+)41(-) EMP predicted plaque instability (OR = 2.19, 1.08-4.46, p < .05) and remained significant in a multivariable model that included transient ischaemic attack symptom status. Annexin V(+) MP, platelet MP (PMP) subsets, and C-reactive protein were higher (p < .05) in cases than controls. Annexin V(+) MP (OR = 3.15, 1.49-6.68), soluble vascular cell adhesion molecule-1 (OR = 1.64, 1.03-2.59), and previous smoking history (OR = 3.82, 1.38-10.60) independently (p < .05) predicted the presence of carotid disease in a multivariable model. EMP may have utility in predicting plaque instability in carotid patients and annexin V(+) MPs may predict the presence of advanced carotid disease in aging populations, independent of established biomarkers.

Flow cytometry and gene expression profiling of immune cells of the carotid plaque and peripheral blood

ObjectivesThe relative contribution of the local vs. peripheral inflammation to the atherothrombotic processes is unknown. We compared the inflammatory status of the immune cells of the carotid plaque with similar cells in peripheral circulation of patients with advanced carotid disease (PCDs). MethodsMononuclear cells (MNCs) were extracted from carotid endarterectomy (CEA) samples by enzymatic digestion and subsequent magnetic cell sorting. The cell surface antigenic expressions, and mRNA expression levels were compared between CEA MNCs and peripheral MNCs, using flow cytometry and RT-PCR techniques. ResultsThe percentages of resting MNCs were lower, and activated MNCs, particularly monocytes, were higher in the CEAMNCs, as compared to the peripheral MNCs. The percentages of activated T cells and B cells were higher in the peripheral MNCs of PCDs, than in healthy controls (HCs), but the percentages of activated monocytes did not differ between the two groups. The expression levels of both pro-inflammatory/pro-thrombotic (P38, JNKB-1, Egr-1 PAI-1, MCP-1, TF, MMP-9, HMGB-1, TNF-α, mTOR) and anti-inflammatory (PPAR-γ, TGF-β) mediators were significantly higher in the CEA MNCs as compared to the peripheral MNCs. Furthermore, MMP-9 and PPAR-γ expression levels were higher in the peripheral MNCs of PCDs than HCs. ConclusionThe inflammatory status is higher in the immune cells of the carotid plaque, as compared to those cells in the peripheral blood. The altered expression levels of both pro-inflammatory/pro-thrombotic and anti-inflammatory mediators in the milieu of the plaque suggest that the balance between these various mediators may play a key role in carotid disease progression.

Advanced Asymptomatic Carotid Disease and Cognitive Impairment: An Understated Link?

Advanced carotid disease is known to be associated with symptomatic cerebrovascular diseases, such as stroke or transient ischemic attack (TIA), as well as with poststroke cognitive impairment. However, cognitive decline often occurs in patients with advanced carotid stenosis without clinically evident stroke or TIA, so it is also suspected to be an independent risk factor for dementia. Neurosonological methods enable simple and noninvasive assessment of carotid stenosis in patients at risk of advanced atherosclerosis. Cognitive status in patients diagnosed with advanced carotid stenosis is routinely not taken into consideration, although if cognitive impairment is present, such patients should probably be called symptomatic. In this paper, we discuss results of some most important studies that investigated cognitive status of patients with asymptomatic advanced carotid disease and possible mechanisms involved in the causal relationship between asymptomatic advanced carotid disease and cognitive decline.

Cognitive Performance in Asymptomatic Patients With Advanced Carotid Disease

: In the absence of stroke or transient ischemic attack, patients with advanced carotid stenosis or occlusion (ICAs/o) are considered asymptomatic, yet they are prone to mostly subtle cognitive impairment. : The Mini-Mental State Examination (MMSE) often fails to detect mild cognitive impairment. The Montreal Cognitive Assessment (MoCA) is more sensitive in recognizing such changes. : Scores on the MoCA and MMSE were compared in 70 asymptomatic patients with ICAs/o and 70 controls matched for demographic variables and vascular risk factors. : MMSE scores fell mostly within the normal range in both patients and controls. Differences were significant for total MoCA scores (P<0.001). Patients with ICAs/o performed worse on visuospatial and executive function (P=0.018), abstraction (P<0.001), and delayed recall (P<0.001). Lower MoCA scores were associated with diabetes (odds ratio=6.41; 95% confidence interval, 1.277-32.220; P=0.024) and older age (odds ratio=0.86; 95% confidence interval, 0.780-0.956; P=0.004). Patients with diabetes performed worse on delayed recall (P<0.001), and patients with hypertension were worse on the MoCA naming subtest (P=0.04). : The MoCA successfully identified reduced cognitive status in patients with ICAs/o. The MoCA subtest scores revealed a pattern of cognitive impairment similar to that documented in other studies using more extensive neuropsychological tests. MoCA could be used as part of the clinical evaluation of patients with ICAs/o.

080 Obstructive sleep apnoea and atherosclerosis, vascular dysfunction and cardiac remodelling as assessed by CMR

<h3>Objective</h3> Obstructive sleep apnoea (OSA) is associated with hypertension, coronary artery disease, heart failure and stroke. We investigated whether OSA represents an additional independent risk factor for preclinical atherosclerosis, vascular dysfunction and cardiac remodelling as assessed by CMR. We also examined the effect of OSA severity as expressed by Oxygen Desaturation Index (ODI) on MR derived cardiac and vascular markers. <h3>Methods</h3> In total, 58 patients with OSA and 39 control subjects without sleep apnoea underwent Cardiovascular Magnetic Resonance (CMR) scanning.42 OSA patients were meticulously matched for demographics, body size and cardiovascular risk factors to the 39 controls. CMR protocol: Our assessment included carotid and aortic atheroma burden quantification, central aortic distensibility assessment and left ventricular (LV) as well as right ventricular (RV) diastolic mass and volumes measurements. Multiple weighting, high resolution, imaging of the carotid vessels was used for carotid atheroma composition characterisation. Pulmonary artery (PA) acceleration time, a non invasive pulmonary artery pressure marker, was derived from velocity-encoded pulmonary artery flow imaging. <h3>Results</h3> Carotid (p&lt;0.05 (abstract 080 figure 1a)) and aortic (p&lt;0.001 (abstract 080 figure1b)) wall thickness were increased in OSA patients in comparison with controls. Through multivariate regression analysis, ODI emerged as an independent predictor of both carotid (β=0.41(0.15)(p&lt;0.01)) and aortic wall thickness (β=0.61(0.21)(p&lt;0.01)). Carotid plaques, advanced carotid disease and “high risk” of carotid atheroma were all more prevalent among individuals suffering from OSA (p&lt;0.05)(abstract 080 figure 2). Aortic distensibility was decreased in OSA (p&lt;0.05)(abstract 080 figure 3). Although ODI correlated with aortic distensibility (r=−0.35, p&lt;0.01), this association was not significant after adjustment for age and systolic blood pressure. LV mass (p&lt;0.05) and volume (p&lt;0.01) as well as RV mass (p&lt;0.05) - all indexed to body surface area - were increased in OSA (abstract 080 figure 4). On multivariate regression analysis, ODI emerged as an independent predictor of LV mass (β=0.41(0.17)(p&lt;0.05)), LV volume (β=0.34(0.16)(p&lt;0.05)) and RV mass (β=0.16(0.07)(p&lt;0.05)) in OSA. PA acceleration time was significantly shortened in OSA (p&lt;0.005)(abstract 080 figure5) and significantly correlated with ODI (r=−0.38, p&lt;0.05), RV volume (r=−0.47, p&lt;0.01) and RV mass, even after adjustment for ODI (β=−0.13(0.05)(p&lt;0.05)). <h3>Conclusions</h3> OSA is associated with increased atheroma burden and complicated atheromatic lesions. Increased central aortic stiffening, that appears to be dependent on an increase in systolic blood pressure, is detected in OSA. An independent association between OSA and eccentric LV remodelling and hypertrophy is demonstrated by CMR. CMR reveals for the first time an association between the presence and severity OSA and RV hypertrophy, which may be dependent on an concomitant increase in pulmonary arterial pressure.

Premature carotid artery disease in pediatric cancer survivors treated with neck irradiation

While carotid artery disease and strokes have been documented in adult cancer patients treated with neck irradiation, little information is available on pediatric patients. The purpose of this study is to determine if carotid disease is more prevalent among pediatric cancer survivors treated with neck irradiation than among healthy controls. Thirty pediatric cancer survivors who received neck irradiation (2,000-6,660 cGy) and 30 healthy subjects underwent bilateral carotid ultrasounds. Study outcome measures were common carotid intima-media thickness (IMT) and plaque (present or absent). Multivariate methods were used to compare cases and controls and to identify risk factors related to carotid disease in childhood cancer survivors. IMT was greater for cancer survivors than controls (0.46 mm (SD 0.12) vs. 0.41 mm (SD 0.06), P < 0.001). Plaque was present in 18% of irradiated vessels and 2% of non-irradiated vessels (P < 0.01). Among cancer survivors, IMT was positively associated with female gender (P < 0.05), non-white ethnicity (P < 0.01), positive family history of stroke/heart attack (P < 0.05), BMI (P < 0.001), total cholesterol (P < 0.01), cancer relapse (P < 0.001), and years off treatment (P < 0.0001). Plaque was positively associated with relapse (P < 0.05) and C-reactive protein (P < 0.01). There was no significant relationship between radiation dose at levels >or=2,000 cGy and IMT or plaque. Carotid artery disease was more prevalent among cancer survivors treated with neck irradiation than among controls. Due to the high risk of stroke associated with advanced carotid disease, larger prospective studies are needed to better define disease risk in these long-term survivors.

Hochauflösende Bildgebung atherosklerotischer Gefäßwandläsionen der Karotiden durch die Magnetresonanztomografie

Stroke is the third most common cause of mortality in the United States with an incidence rate of approximately 700 000 deaths per year. As a means to prevent cerebrovascular events, current concepts advocate endarterectomy or carotid stenting in patients with advanced carotid disease. Arterial stenosis alone has been shown to be a poor predictor of cardiovascular events and therefore both arterial stenosis and patient symptom status are taken as indications for interventional therapy. Several studies have shown that symptomatic subjects benefit more from a carotid endarterectomy than asymptomatic subjects: 3-6 carotid endarterectomies are needed to prevent one stroke per year in symptomatic subjects with > 70 % stenosis compared to 14 - 17 carotid endarterectomies in asymptomatic patients with > 50 % stenosis. It is commonly accepted today that factors other than the degree of luminal stenosis can determine a patient's symptom status, such as the composition or the superficial structure of atherosclerotic plaque. High-resolution magnetic resonance imaging has overcome the limitations of current angiographic techniques and has emerged as a leading non-invasive imaging modality for atherosclerotic disease, especially within carotid arteries and other large vessels. In this review, the state of the art in MRI of atherosclerosis is presented in terms of hardware and image acquisition protocols. Also, the results of validation studies for measuring lesion size, composition and inflammation will be summarized. Finally, the status of several clinical trials involving MRI of atherosclerosis will be reviewed.

Prion protein is over‐expressed in intimal neovessels of complicated carotid plaques

Normal cellular prion protein (PrPc) is expressed by a variety of cells of the immune system and is present in endothelial cells (EC). Our aim was to study local and systemic PrPc expression in advanced human carotid lesions and identify its relationship to unstable angiogenic vascular regions. PrPc expression was examined by Enzyme Immunometric Assay in plasma samples from patients with advanced carotid disease (n=22) and controls (n=21). Carotid specimens obtained during endarterectomy (n=22) and control (n=10) arteries from post-mortem were studied for PrPc and CD105 expression by Western blotting and immunohistochemistry. TaqMan arrays were used to study PrPc and CD105 gene expression. In vitro studies examined expression of PrPc in coronary EC. Patients with carotid disease had significantly higher levels of plasma PrPc than the control group (4,35ng/ml vs. 1,95ng/ml, p<0,001). CD105-positive unstable plaques had higher PrPc protein expression, associated with EC and inflammatory infiltrates. There was a strong correlation between PrPc and CD105 mRNA (p <0,001; r =0,7). Increased gene and protein expression of PrPc was seen in coronary EC exposed to staurosporin and growth factor stimulation. We show that PrPc is expressed in advanced carotid specimens and may be associated with the pro-angiogenic switch and therefore a higher risk of hemorrhagic transformation. Supportorted by HEFCE.

Accelerated carotid artery disease after high-dose head and neck radiotherapy: Is there a role for routine carotid duplex surveillance?

Purpose: High-dose external radiotherapy used in the treatment of head and neck carcinoma has been implicated as a risk factor for accelerated atherosclerotic disease of the carotid arteries. However, how radiotherapy affects atherosclerotic disease is controversial, and little data exist to demonstrate a strong relationship between radiotherapy and progressive carotid disease. Methods: We performed a retrospective chart review of 69 patients (all men) who underwent duplex ultrasound scanning examinations for carotid disease between 1993 and 1998. Twenty-three patients had received high-dose radiotherapy for the treatment of head and neck carcinoma within the past 12 years (group 1; mean age, 67.8 years), and 46 patients were randomly selected as age-matched control subjects (group 2; mean age, 68.3 years). The mean radiation dose was 6060 ± 182 rads, and the average interval between radiotherapy and ultrasound scanning was 6.5 ± 1.8 years. There was no significant difference between the two groups in the presence of these comorbidities: diabetes mellitus, coronary artery disease, hypertension, tobacco use, hypercholesterolemia, peripheral vascular disease, or stroke. Similarly, there was no difference in the indications for the duplex scanning studies. Results: Five of the 23 patients in group 1 (21.7%) were found to have advanced carotid disease (70% to 99% stenosis); four patients were symptomatic, three patients went on to endarterectomy, and one patient was awaiting surgery. Two of the 46 patients in the control group (4%) had advanced carotid disease. One patient was symptomatic, and both patients underwent endarterectomy. A significant difference in the prevalence of advanced disease between the two groups was noted ( P = .037). Sixteen patients who survived irradiation underwent a second duplex scanning study and had evidence of progressive disease with significant increases in peak systolic velocities. Conclusion: High-dose radiotherapy to the head and neck region may be a significant risk factor for accelerated carotid atherosclerotic disease. Routine carotid duplex surveillance may be warranted in this high-risk patient population. (J Vasc Surg 1999;30:1045-51.)

Advanced carotid disease in patients requiring aortic reconstruction

Perioperative stroke is a devastating complication of abdominal aortic operations. Patients requiring aortic reconstruction with advanced carotid occlusive disease pose a particularly challenging management problem regarding timing of operations. All patients (n = 121) undergoing both carotid artery endarterectomy (CEA) and abdominal aortic reconstruction (AAR) within 1 year of each other between 1979 and 1989 were reviewed. The sequence of operation was analyzed to determine its effect on early and late outcome. CEA was the first operation in 99 patients (group I); AAR was performed first in 22 patients (group II). Age, gender, number, types of risk factors, and associated medical problems were similar in both groups. Indications for CEA were: transient ischemic attacks (TIAs), recent ipsilateral stroke, or high-grade asymptomatic carotid artery stenosis exceeding 80%. Indications for aortic operation included: abdominal aortic aneurysm, aortoiliac occlusive disease, and combined aortic and renovascular disease. There were five perioperative strokes, two in group I (2%) and three in group II (14%) (p < 0.04). All strokes occurred after AAR. There were five perioperative deaths (4%), four in group I (4%) and one in group II (5%). Overall survival was significantly greater in group I compared to group II (p < 0.04); 5-year survival was 77% and 51%, respectively. Multivariate analysis demonstrated age, hypertension, and diabetes to adversely affect survival; CEA as the first procedure, however, had a protective effect. Importantly, eight strokes occurred in group I in late follow-up, but only one was ipsilateral to the CEA. We conclude that CEA in selected patients who require AAR is safe, and, when performed prior to abdominal aortic repair, reduces perioperative stroke and may improve long-term survival.