Gustav Fraedrich

Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: a preplanned meta-analysis of individual patient data.

BACKGROUND Results from randomised controlled trials have shown a higher short-term risk of stroke associated with carotid stenting than with carotid endarterectomy for the treatment of symptomatic carotid stenosis. However, these trials were underpowered for investigation of whether carotid artery stenting might be a safe alternative to endarterectomy in specific patient subgroups. We therefore did a preplanned meta-analysis of individual patient data from three randomised controlled trials. METHODS Data from all 3433 patients with symptomatic carotid stenosis who were randomly assigned and analysed in the Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial, and the International Carotid Stenting Study (ICSS) were pooled and analysed with fixed-effect binomial regression models adjusted for source trial. The primary outcome event was any stroke or death. The intention-to-treat (ITT) analysis included all patients and outcome events occurring between randomisation and 120 days thereafter. The per-protocol (PP) analysis was restricted to patients receiving the allocated treatment and events occurring within 30 days after treatment. FINDINGS In the first 120 days after randomisation (ITT analysis), any stroke or death occurred significantly more often in the carotid stenting group (153 [8·9%] of 1725) than in the carotid endarterectomy group (99 [5·8%] of 1708, risk ratio [RR] 1·53, [95% CI 1·20-1·95], p=0·0006; absolute risk difference 3·2 [1·4-4·9]). Of all subgroup variables assessed, only age significantly modified the treatment effect: in patients younger than 70 years (median age), the estimated 120-day risk of stroke or death was 50 (5·8%) of 869 patients in the carotid stenting group and 48 (5·7%) of 843 in the carotid endarterectomy group (RR 1·00 [0·68-1·47]); in patients 70 years or older, the estimated risk with carotid stenting was twice that with carotid endarterectomy (103 [12·0%] of 856 vs 51 [5·9%] of 865, 2·04 [1·48-2·82], interaction p=0·0053, p=0·0014 for trend). In the PP analysis, risk estimates of stroke or death within 30 days of treatment among patients younger than 70 years were 43 (5·1%) of 851 patients in the stenting group and 37 (4·5%) of 821 in the endarterectomy group (1·11 [0·73-1·71]); in patients 70 years or older, the estimates were 87 (10·5%) of 828 patients and 36 (4·4%) of 824, respectively (2·41 [1·65-3·51]; categorical interaction p=0·0078, trend interaction p=0·0013]. INTERPRETATION Stenting for symptomatic carotid stenosis should be avoided in older patients (age ≥70 years), but might be as safe as endarterectomy in younger patients. FUNDING The Stroke Association.

Clinical and angiographic risk factors for stroke and death within 30 days after carotid endarterectomy and stent- protected angioplasty: a subanalysis of the SPACE study

BACKGROUND Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are used to prevent ischaemic stroke in patients with stenosis of the internal carotid artery. Better knowledge of risk factors could improve assignment of patients to these procedures and reduce overall risk. We aimed to assess the risk of stroke or death associated with CEA and CAS in patients with different risk factors. METHODS We analysed data from 1196 patients randomised to CAS or CEA in the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE) trial. The primary outcome event was death or ipsilateral stroke (ischaemic or haemorrhagic) with symptoms that lasted more than 24 h between randomisation and 30 days after therapy. Six predefined variables were assessed as potential risk factors for this outcome: age, sex, type of qualifying event, side of intervention, degree of stenosis, and presence of high-grade contralateral stenosis or occlusion. The SPACE trial is registered at Current Controlled Trials, with the international standard randomised controlled trial number ISRCTN57874028. FINDINGS Risk of ipsilateral stroke or death increased significantly with age in the CAS group (p=0.001) but not in the CEA group (p=0.534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2.7% (8/293) in patients who were 68 years old or younger and 10.8% (34/314) in older patients. Other variables did not differ between the CEA and CAS groups. INTERPRETATION Of the predefined covariates, only age was significantly associated with the risk of stroke and death. The lower risk after CAS versus CEA in patients up to 68 years of age was not detectable in older patients. This finding should be interpreted with caution because of the drawbacks of post-hoc analyses.

Co-expression of p53 and MDM2 in human atherosclerosis : Implications for the regulation of cellularity of atherosclerotic lesions

Atherosclerosis is a fibroproliferative disease of the arterial intima. It was recently found that wild‐type p53 (wt p53) accumulates in human atherosclerotic tissue. Wt p53 is a cell cycle regulator involved in DNA repair, DNA synthesis, cell differentiation, and apoptosis and might therefore make an important contribution to the cellularity of atherosclerotic plaques. The product of the MDM2 gene is a nuclear protein which forms a complex with p53, thereby inhibiting the negative regulatory effects of wt p53 on cell cycle progression. In order to address a potential role of the interaction of p53 with MDM2 for the regulation of cellularity in atherosclerotic tissue, 22 carotid atheromatous plaques from patients undergoing endarterectomy were studied to determine the presence of p53 immunoreactivity (IR), MDM2 IR, cell proliferation as evidenced by MIB1/Ki‐67 IR and DNA fragmentation by in situterminal transferase‐mediated dUTP 3′ end labelling (TUNEL), as a marker for apoptosis. p53 IR localized to areas with evidence of chronic inflammation (22/22) and was observed in virtually all cell types in 68·79±7·51 per cent of the nuclei. p53 staining in the control tissue from human internal mammary arteries was present in 0·2±0·29 per cent of the cells (P≤0·002). MDM2 IR was present in all cases (22/22) in macrophages and smooth muscle cells (SMCs) in 60·53±8·32 per cent of the nuclei (controls: 0·8±0·65 per cent, P≤0·002) and co‐localized with p53 IR as shown by examination of adjacent sections and by double immunofluorescence labelling. Importantly, co‐immunoprecipitation and western blot analysis revealed that p53 and MDM2 were physically associated, indicating that MDM2–p53 complex formation takes place in vivoin human atherosclerotic tissue. Positive TUNEL staining and MIB1/Ki‐67 IR present in 3·01±1·27 per cent of the nuclei (controls: 0 per cent, P≤0·002) localized to the same plaque compartments as p53 IR and MDM2 IR. Thus, the fate of cells with p53 accumulation may depend on the interaction and the stoichiometry of the p53 and MDM2 proteins. Cells were indeed found with strong p53 accumulation and nuclear morphology typical for apoptosis and there were a few MIB1/Ki‐67‐positive cells with co‐expression of MDM2, indicating a possible role for MDM2 in reversing the negative regulatory effects of p53 for cell cycle progression. The nuclear co‐localization of p53 IR with MDM2 IR and the co‐immunoprecipitation assay indicate the presence of p53–MDM2 complex formation in vivo in human atherosclerotic tissue. The destiny of individual p53 and MDM2‐co‐expressing cells either to undergo p53‐dependent apoptosis or to re‐enter the cycle of cell proliferation may depend on the relative ratios of the two proteins. p53 and MDM2 may therefore play an important role in regulating cellularity and inflammatory activity in human atherosclerotic plaques.

Hyperperfusion Syndrome of the Deltoid Muscle after Subclavian Artery Angioplasty and Stenting

Purpose: To report a case of hyperperfusion syndrome of the deltoid muscle after percutaneous transluminal angioplasty of a symptomatic high-grade subclavian artery stenosis. Case Report: Immediately after balloon dilation of a left-sided subclavian artery stenosis, a 53-year-old man developed severe ipsilateral shoulder pain and swelling. Computed tomographic angiography revealed no extravasation or hematoma. Sonography showed massive edema and increased anteroposterior diameter of the left deltoid muscle (3.5 cm compared to 2.0 cm on the right). Hyperperfusion syndrome was suspected, and decompression by anterolateral fasciotomy was performed. Subsequently, both pain and swelling decreased. At day 3, the skin incision, which was temporarily covered with a synthetic skin substitute, was sutured; the wound healed uneventfully. Two weeks after surgery, both muscle strength and shoulder movements showed no restrictions. Conclusions: Hyperperfusion syndrome after endovascular treatment of subclavian artery stenosis should be considered in the differential diagnosis of atypical muscle pain in the upper extremity. It may present as a compartment syndrome requiring surgical decompression.

Ongoing Randomized Controlled Trials Comparing Interventional Methods and Optimal Medical Treatment in the Treatment of Asymptomatic Carotid Stenosis

To the Editor: A recent Stroke publication, “Contemporary Results of Carotid Endarterectomy for Asymptomatic Carotid Stenosis,” underlines the importance of realizing new randomized clinical trials comparing best medical treatment with interventional therapies (carotid endarterectomy [CEA] and carotid artery stenting [CAS]) for the treatment of asymptomatic carotid artery stenosis.1 We entirely agree with this statement regarding the fact that the following questions need to be re-evaluated. Current recommendations concerning treatment of asymptomatic carotid stenosis are essentially still based on data of 2 large trials having compared CEA with conservatively treated control groups: Asymptomatic Carotid Atherosclerosis Study (ACAS) and …

Microcirculatory assessment of vascular acrosyndrome in anorexia nervosa and analysis of manifestation factors

OBJECTIVE Acrocyanosis (AC) is a common manifestation of starving syndrome in anorexia nervosa. We characterized microvascular changes associated with AC and determined discriminating factors between acrally symptomatic and nonsymptomatic patients. METHODS We examined 34 patients with anorexia nervosa (15 restrictive-anorectic type, 19 binge-eating/purging type, duration 1-25 years). Nineteen were symptomatic (SP) and 15 were nonsymptomatic (NSP). All underwent photo-pletysmography, sonography of the brachial artery, capillary microscopy and laboratory analysis. RESULTS Disease characteristics and body mass index did not differ between SP and NSP. In SP more dilated efferent capillary loops and venoles were present (P<.001) and capillary flow velocities were reduced (0.21+/-0.12 ml/min vs. 0.34+/-0.15 ml/min; P=.015). Flow-mediated and nitroglycerin-induced dilatation showed no differences. Symptomatic patients had lower leukocyte counts (P=.008), lower eosinophils (P=.003) and lower LDL (P=.045) concentrations. A logistic regression model identified only leukocytes (P=.017) and eosinophils (P=.023) to be associated with AC. CONCLUSIONS In acrally symptomatic patients the typical microvascular features of AC are present. AC is associated with lower leukocyte counts and lower eosinophils.

Why the US Center for Medicare and Medicaid Services should not extend reimbursement indications for carotid artery angioplasty/stenting.

Why the US Center for Medicare and Medicaid Services Should Not Extend Reimbursement Indications for Carotid Artery Angioplasty/Stenting