Perforating artery flow velocity and pulsatility in patients with carotid occlusive disease. A 7 tesla MRI study.

Patients with carotid occlusive disease express altered hemodynamics in the post-occlusive vasculature and lesions commonly attributed to cerebral small vessel disease (SVD). We addressed the question if cerebral perforating artery flow measures, using a novel 7T MRI technique, are altered and related to SVD lesion burden in patients with carotid occlusive disease. 21 patients were included with a uni- (18) or bilateral (3) carotid occlusion (64±7 years) and 19 controls (65±10 years). Mean flow velocity and pulsatility in the perforating arteries in the semi-oval center (CSO) and basal ganglia (BG), measured with a 2D phase contrast 7T MRI sequence, were compared between patients and controls, and between hemispheres in patients with unilateral carotid occlusive disease. In patients, relations were assessed between perforating artery flow measures and SVD burden score and white matter hyperintensity (WMH) volume. CSO perforating artery flow velocity was lower in patients than controls, albeit non-significant (mean difference [95% confidence interval] 0.08 cm/s [0.00-0.16]; p = 0.053), but pulsatility was similar (0.07  [-0.04-0.18]; p = 0.23). BG flow velocity and pulsatility did not differ between patients and controls (velocity = 0.28 cm/s [-0.32-0.88]; p = 0.34; pulsatility = 0.00 [-0.10-0.11]; p = 0.97). Patients with unilateral carotid occlusive disease showed no significant interhemispheric flow differences. Though non-significant, within patients lower CSO (p = 0.06) and BG (p = 0.11) flow velocity related to larger WMH volume. Our findings suggest that carotid occlusive disease may be associated with abnormal cerebral perforating artery flow and that this relates to SVD lesion burden in these patients, although our observations need corroboration in larger study populations.

Detection of Early Ischemic Changes with Virtual Noncontrast Dual-Energy CT in Acute Ischemic Stroke: A Noninferiority Analysis.

BACKGROUND AND PURPOSE: Dual-energy virtual NCCT has the potential to replace conventional NCCT to detect early ischemic changes in acute ischemic stroke. In this study, we evaluated whether virtual NCCT is noninferior compared with standard linearly blended NCCT, a surrogate of conventional NCCT, regarding the detection of early ischemic changes with ASPECTS. MATERIALS AND METHODS: Adult patients who presented with suspected acute ischemic stroke and who underwent dual-energy NCCT and CTA and brain MR imaging within 48 hours were included. Standard linearly blended images were reconstructed to match a conventional NCCT. Virtual NCCT images were reconstructed from CTA. ASPECTS was evaluated on conventional NCCT, virtual NCCT, and DWI, which served as the reference standard. Agreement between CT assessments and the reference standard was evaluated with the Lin concordance correlation coefficient. Noninferiority was assessed with bootstrapped estimates of the differences in ASPECTS between conventional and virtual NCCT with 95% CIs. RESULTS: Of the 193 included patients, 100 patients (52%) had ischemia on DWI. Compared with the reference standard, the ASPECTS concordance correlation coefficient for conventional and virtual NCCT was 0.23 (95% CI, 0.15-0.32) and 0.44 (95% CI, 0.33-0.53), respectively. The difference in the concordance correlation coefficient between virtual and conventional NCCT was 0.20 (95% CI, 0.01-0.39) and did not cross the prespecified noninferiority margin of -0.10. CONCLUSIONS: Dual-energy virtual NCCT is noninferior compared with conventional NCCT for the detection of early ischemic changes with ASPECTS.

Residual cardiovascular risk reduction guided by lifetime benefit estimation in patients with symptomatic atherosclerotic disease: effectiveness and cost-effectiveness.

AIMS: To determine the (cost)-effectiveness of blood pressure lowering, lipid-lowering, and antithrombotic therapy guided by predicted lifetime benefit compared to risk factor levels in patients with symptomatic atherosclerotic disease. METHODS AND RESULTS: For all patients with symptomatic atherosclerotic disease in the UCC-SMART cohort (1996-2018; n = 7697) two treatment strategies were compared. The lifetime benefit-guided strategy was based on individual estimation of gain in cardiovascular disease (CVD)-free life with the SMART-REACH model. In the risk factor-based strategy, all patients were treated the following: low-density lipoprotein cholesterol (LDL-c) < 1.8 mmol/L, systolic blood pressure <140 mmHg, and antithrombotic medication. Outcomes were evaluated for the total cohort using a microsimulation model. Effectiveness was evaluated as total gain in CVD-free life and events avoided, cost-effectiveness as incremental cost-effectivity ratio (ICER). In comparison to baseline treatment, treatment according to lifetime benefit would lead to an increase of 24 243 CVD-free life years [95% confidence interval (CI) 19 980-29 909] and would avoid 940 (95% CI 742-1140) events in the next 10 years. For risk-factor based treatment, this would be an increase of 18 564 CVD-free life years (95% CI 14 225-20 456) and decrease of 857 (95% CI 661-1057) events. The ICER of lifetime benefit-based treatment with a treatment threshold of ≥1 year additional CVD-free life per therapy was €15 092/QALY gained and of risk factor-based treatment €9933/QALY gained. In a direct comparison, lifetime benefit-based treatment compared to risk factor-based treatment results in 1871 additional QALYs for the price of €36 538/QALY gained. CONCLUSION: Residual risk reduction guided by lifetime benefit estimation results in more CVD-free life years and more CVD events avoided compared to the conventional risk factor-based strategy. Lifetime benefit-based treatment is an effective and potentially cost-effective strategy for reducing residual CVD risk in patients with clinical manifest vascular disease.

Variation in perioperative cerebral and hemodynamic monitoring during carotid endarterectomy.

BACKGROUND: Hemodynamic disturbances cause half of the perioperative strokes following carotid endarterectomy (CEA). Guidelines strongly recommend strict pre- and postoperative blood pressure (BP) monitoring in CEA patients, but do not provide firm practical recommendations. Although in the Netherlands 50 centres perform CEA, no national protocol on perioperative hemodynamic, and cerebral monitoring exists. To assess current monitoring policies of all Dutch CEA-centres, a national survey was conducted. METHODS: Between May and July 2017 all 50 Dutch CEA-centres were invited to complete a 42-question survey addressing perioperative hemodynamic and cerebral monitoring during CEA. Nonresponders received a reminder after 1 and 2 months. By November 2017 the survey was completed by all centres. RESULTS: Preoperative baseline BP was based on a single bilateral BP-measurement at the outpatient-clinic in the majority of centres (n = 28). In 43 centres (86%) pre-operative monitoring (transcranial Doppler (TCD, n = 6), electroencephalography (EEG, n = 11), or TCD + EEG (n = 26)) was performed as a baseline reference. Intraoperatively, large diversity for type of anaesthesia (general: 45 vs. local [LA]:5) and target systolic BP (>100 mm hg - 160 mm hg [n = 12], based on preoperative outpatient-clinic or admission BP [n = 18], other [n = 20]) was reported. Intraoperative cerebral monitoring included EEG + TCD (n = 28), EEG alone (n = 13), clinical neurological examination with LA (n = 5), near-infrared spectroscopy with stump pressure (n = 1), and none due to standard shunting (n = 3). Postoperatively, significant variation was reported in standard duration of admission at a recovery or high-care unit (range 3-48 hr, mean:12 hr), maximum accepted systolic BP (range >100 mm hg - 180 mm Hg [n = 32]), postoperative cerebral monitoring (standard TCD [n = 16], TCD on indication [n = 5] or none [n = 24]) and in timing of postoperative cerebral monitoring (range directly postoperative - 24 hr postoperative; median 3 hr). CONCLUSIONS: In Dutch centres performing CEA the perioperative hemodynamic and cerebral monitoring policies are widely diverse. Diverse policies may theoretically lead to over- or under treatment. The results of this national audit may serve as the baseline dataset for development of a standardized and detailed (inter)national protocol on perioperative hemodynamic and cerebral monitoring during CEA.

The diagnostic value of skin biopsies in Sneddon syndrome.

BACKGROUND: Sneddon syndrome (SS) is defined by widespread livedo reticularis (LR) and stroke. There is no single diagnostic test for SS and diagnosis can be solely based on clinical features. This cross-sectional case-control study aimed to determine the diagnostic value of skin biopsies in SS patients. MATERIALS AND METHODS: We studied skin biopsies from patients with a clinical diagnosis of SS or isolated LR. We also studied controls with vitiligo or normal skin. Biopsies were considered standardized if 3 biopsies were taken from the white centre of the livedo and reached until the dermis-subcutis border. Biopsies were scored for features of an occlusive microangiopathy without knowledge of the clinical features. Sensitivity and specificity of the biopsy findings were calculated with the clinical criteria as the reference standard. RESULTS: We included 34 SS patients, 14 isolated LR patients and 41 control patients. Biopsies of 17 patients with SS (50%), 4 with isolated LR (31%) and 10 control patients (24%) showed at least one artery in the deep dermis with a thickened vessel wall combined with recanalization or neovascularization (sensitivity 50% and specificity 69% with LR as reference). Standardized biopsies increased the sensitivity to 70%. In a post hoc analysis the combination of an occlusive microangiopathy and the presence of a livedo pattern in the superficial dermis increased the specificity to 92%. CONCLUSIONS: Standardized skin biopsies can support the clinical diagnosis of SS. An occlusive microangiopathy as the only positive criterion for the diagnosis of SS had insufficient specificity for a definite diagnosis.

Sneddon syndrome: a comprehensive clinical review of 53 patients.

BACKGROUND: The presence of livedo reticularis in patients with ischaemic stroke is associated with Sneddon syndrome (SS). Our objective was to present the clinical features of SS patients and to assess the role of antiphospholipid antibodies (APL). METHODS: Consecutive patients, diagnosed with SS between 1996 and 2017, were retrospectively reviewed for their demographic, neurological, dermatological, cardiac and extracerebral vascular features. Diagnosis of SS was made only if other causes of stroke were excluded. Patients with and without APL were included and compared for their clinical features. RESULTS: Fifty-three patients (79% female) were included, of whom 14 patients were APL-positive. Median age at diagnosis was 40 years. Approximately 60% of the patients had ≥ 3 cardiovascular risk factors. There were 129 previous vascular events (66 ischaemic strokes, 62 TIAs and 1 amaurosis fugax) during a median period of 2 years between the first event and diagnosis of SS. Skin biopsy was positive for SS in 29 patients (67%), mostly showing a thickened vessel wall with neovascularization in the deep dermis. After a median follow-up of 28 months, 4 patients, either on antiplatelet or oral anticoagulation therapy, had a recurrent stroke. There were few statistically significant differences between APL-negative and APL-positive patients, including the number of vascular events before diagnosis. CONCLUSIONS: SS predominantly affects young women with a relatively large number of cardiovascular risk factors. Clinical features of SS are comparable across different studies. We found no differences in the main clinical features between APL-positive and APL-negative patients.

Sex differences in intracranial and extracranial atherosclerosis in patients with acute ischemic stroke.

BACKGROUND AND AIM: To investigate sex differences with respect to presence and location of atherosclerosis in acute ischemic stroke patients. METHODS: Participants with acute ischemic stroke were included from the Dutch acute stroke trial, a large prospective multicenter cohort study performed between May 2009 and August 2013. All patients received computed tomography/computed tomography-angiography within 9 h of stroke onset. We assessed presence of atherosclerosis in the intra- and extracranial internal carotid and vertebrobasilar arteries. In addition, we determined the burden of intracranial atherosclerosis by quantifying internal carotid and vertebrobasilar artery calcifications, resulting in calcium volumes. Prevalence ratios between women and men were calculated with Poisson regression analysis and adjusted prevalence ratio for potential confounders (age, hypertension, hyperlipidemia, diabetes, smoking, and alcohol use). RESULTS: We included 1397 patients with a mean age of 67 years, of whom 600 (43%) were women. Presence of atherosclerosis in intracranial vessel segments was found as frequently in women as in men (71% versus 72%, adjusted prevalence ratio 0.95; 95% CI 0.89-1.01). In addition, intracranial calcification volume did not differ between women and men in both intracranial internal carotid (large burden 35% versus 33%, adjusted prevalence ratio 0.93; 95% CI 0.73-1.19) and vertebrobasilar arteries (large burden 26% versus 40%, adjusted prevalence ratio 0.69; 95% CI 0.41-1.12). Extracranial atherosclerosis was less common in women than in men (74% versus 81%, adjusted prevalence ratio 0.86; 95% CI 0.81-0.92). CONCLUSIONS: In patients with acute ischemic stroke the prevalence of intracranial atherosclerosis does not differ between women and men, while extracranial atherosclerosis is less often present in women compared with men.

Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation: a multidisciplinary expert advisory board.

The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5 mg, 5 mg, 15 mg and 20 mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise.

The relation between healthy lifestyle changes and decrease in systemic inflammation in patients with stable cardiovascular disease.

BACKGROUND AND AIMS: Pharmacological lowering of inflammation has proven effective in reducing recurrent cardiovascular event rates. Aim of the current study is to evaluate lifestyle changes (smoking cessation, weight loss, physical activity level increase, alcohol moderation, and a summary lifestyle improvement score) in relation to change in plasma C-reactive protein (CRP) concentration in patients with established cardiovascular disease. METHODS: In total, 1794 patients from the UCC-SMART cohort with stable cardiovascular disease and CRP levels ≤10 mg/L, who returned for a follow-up study visit after median 9.9 years (IQR 5.4-10.8), were included. The relation between changes in smoking status, weight, physical activity, alcohol consumption, a summary lifestyle improvement score and change in plasma CRP concentration was evaluated with linear regression analyses. RESULTS: Smoking cessation was related to a 0.40 mg/L decline in CRP concentration (ß-coefficient -0.40; 95%CI -0.73,-0.07). Weight loss (per 1SD = 6.4 kg) and increase in physical activity (per 1 SD = 48 MET hours per week) were related to a decrease in CRP concentration (ß-coefficients -0.25; 95%CI -0.33,-0.16 and -0.09; 95%CI -0.17,-0.01 per SD). Change in alcohol consumption was not related to CRP difference. Every point higher in the summary lifestyle improvement score was related to a decrease in CRP concentration of 0.17 mg/L (ß-coefficient -0.17; 95%CI -0.26,-0.07). CONCLUSIONS: Smoking cessation, increase in physical activity, and weight loss are related to a decrease in CRP concentration in patients with stable cardiovascular disease. Patients with the highest summary lifestyle improvement score have the most decrease in CRP concentration. These results may indicate that healthy lifestyle changes contribute to lowering systemic inflammation, potentially leading to a lower cardiovascular risk in patients with established cardiovascular disease.

MRI Vessel Wall Imaging after Intra-Arterial Treatment for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Vessel wall imaging is increasingly performed in the diagnostic work-up of patients with ischemic stroke. The aim of this study was to compare vessel wall enhancement after intra-arterial thrombosuction with that in patients not treated with thrombosuction. MATERIALS AND METHODS: From 2009 to 2017, forty-nine patients with an ischemic stroke underwent 7T MR imaging within 3 months after symptom onset as part of a prospective intracranial vessel wall imaging study. Fourteen of these patients underwent intra-arterial treatment using thrombosuction (intra-arterial treatment group). In the intra-arterial treatment group, vessel walls were evaluated for major vessel wall changes. All patients underwent pre- and postcontrast vessel wall imaging to assess enhancing foci of the vessel wall using coregistered subtraction images. A Wilcoxon signed rank test was performed to test for differences. RESULTS: In the intra-arterial treatment group, 11 of 14 patients (79%) showed vessel wall enhancement compared with 17 of 35 patients without intra-arterial treatment (49%). In the intra-arterial treatment group, more enhancing foci were detected on the ipsilateral side (n = 18.5) compared with the contralateral side (n = 3, P = .005). Enhancement was more often concentric on the ipsilateral side (n = 8) compared with contralateral side (n = 0, P = .01). No differences were found in the group without intra-arterial treatment between the number and configuration of ipsilateral and contralateral enhancing foci. CONCLUSIONS: Patients with intra-arterial treatment by means of thrombosuction showed more (concentric) enhancing foci of the vessel wall ipsilateral compared with contralateral to the treated artery than the patients without intra-arterial treatment, suggesting reactive changes of the vessel wall. This finding should be taken into account when assessing vessel wall MR images in patients with stroke.

Validity of an enhanced EQ-5D-5L measure with an added cognitive dimension in patients with stroke.

OBJECTIVE: The 5-level EuroQoL (EQ-5D-5L) is a patient-reported outcome measure frequently used in stroke research. However, it does not assess the cognitive problems many patients with stroke experience. The aim of this article is to compare the content validity, internal consistency and discriminative ability of the EQ-5D-5L with and without an additional cognitive domain (EQ-5D-5L+C), administered three months post-stroke. DESIGN: Cross-sectional study. SETTING: Six general hospitals in the Netherlands. SUBJECTS: In all, 360 individuals with stroke three months after the event. INTERVENTIONS: Not applicable. MAIN MEASURES: The modified Rankin Scale and EQ-5D-5L+C were administered in telephone interviews three months post-stroke. RESULTS: A total of 360 patients with stroke were included. Mean age was 68.8 years (standard deviation (SD) = 11.7), 143 (40%) were female, 334 (93%) had had an ischemic stroke, 165 (46%) had a National Institutes of Health Stroke Scale (NIHSS) score ⩽ 4 at presentation and the Barthel Index was 17.2 (SD = 4) four days post-stroke. Cognitive problems were reported by 199 (55%) patients three months post-stroke. Internal consistencies of the EQ-5D-5L and EQ-5D-5L+C were 0.75 and 0.77, respectively. Adding a cognitive domain resulted in a decrease of the ceiling effect from 22% to 14%. Both EQ-5D-5L and EQ-5D-5L+C showed good discriminative ability, but differences between patients with different modified Rankin Scale scores and with/without reported decrease in health and daily activities were slightly larger with the EQ-5D-5L+C compared to the EQ-5D-5L. CONCLUSIONS: The EQ-5D-5L+C, which includes a cognitive domain that is highly significant for stroke patients, showed increased content validity and good discriminative ability, without losing internal consistency.

Thyroid-stimulating hormone levels in the normal range and incident type 2 diabetes mellitus.

AIM: To evaluate the relationship between thyroid-stimulating hormone (TSH) levels within the normal range and the risk of type 2 diabetes mellitus (T2DM) in a cohort of patients at high cardiovascular risk, and to perform a systematic review and meta-analysis of previous studies. METHODS: We included 5542 patients without T2DM from the prospective Secondary Manifestations of ARTerial disease study with TSH levels between 0.35 and 5.0 mIU/L without anti-thyroid medication or thyroid-hormone replacement therapy. Cox regression was used to investigate the relationship between baseline plasma TSH levels and incident T2DM. MEDLINE, EMBASE, and Cochrane were searched for prospective cohorts assessing TSH and incident T2DM. Hazard ratios (HR) from included prospective cohort studies were pooled using a random-effects model. RESULTS: In patients at high cardiovascular risk, higher plasma TSH levels in the normal range were not associated [HR 1.07 per mIU/L increase in TSH (95% confidence interval (95% CI) 0.95-1.22)] with an increased risk of T2DM, adjusted for age, sex, smoking, total and HDL cholesterol, and triglycerides. In the meta-analysis involving three prospective cohort studies, including the present study, including 29,791 participants with 1930 incident events, there was no relation between plasma TSH levels in the normal range and incident T2DM [pooled HR 1.06 (95% CI 0.99-1.14)]. CONCLUSION: There is no apparent relation between plasma TSH levels in the normal range and incident T2DM in patients at high cardiovascular risk.

Cognitive functioning in patients with carotid artery occlusion; a systematic review.

INTRODUCTION: Patients with complete occlusion of the internal carotid artery (CAO) are vulnerable to cerebral hypoperfusion. Since cerebral hypoperfusion is associated with accelerated cognitive decline, patients with CAO may have an increased risk of cognitive impairment. We aimed to assess the prevalence and profile of cognitive impairment in patients with CAO and to explore the relation between hemodynamic impairment and cognitive functioning. METHODS: We systematically searched Medline and EMBASE for studies including patients with symptomatic or asymptomatic CAO subjected to cognitive testing that were published between 1980 and 2017. We did not include patients with carotid stenosis. We obtained data on type of study, patient characteristics, cerebral imaging and neuropsychological testing. In addition, we extracted data on potential causes of systemic hemodynamic impairment and the presence and stage of cerebral hemodynamic impairment. We assessed methodological quality of included studies with the Newcastle-Ottawa Scale. RESULTS: We found eight studies comprising 244 patients (mean age 61 years, 76% male, 93% symptomatic CAO). The proportion of patients with cognitive impairment ranged from 54 to 71% in four studies; in the other four studies patients with CAO performed worse on cognitive testing than controls, but results were not quantified. Impairment was reported in all cognitive domains. We found no data on the association between systemic hemodynamic impairment and cognitive functioning. Studies that assessed whether cerebral hemodynamic impairment was associated with cognitive functioning showed conflicting results. CONCLUSION: In patients with CAO, cognitive impairment is present in about half to two-thirds of patients and is not restricted to specific cognitive domains. The effect of systemic and cerebral hemodynamic impairment on cognitive functioning in patients with CAO deserves further study.

Correction to: Carotid endarterectomy in patients with recurrent symptoms associated with an ipsilateral carotid artery near occlusion with full collapse.

The original version of this article unfortunately contained a mistake.

[When is carotid endarterectomy actually indicated for stenosis?] / Wie moet er eigenlijk nog aan vernauwing in de A. carotis geopereerd worden?

Criteria for carotid endarterectomy are based on the results of clinical trials that were conducted more than two decades ago. In the meantime medical treatment has improved, and surgery can be performed more safely. As such, it is currently unknown which patients should be recommended to undergo carotid surgery. The aim of the currently running European Carotid Surgery Trial 2 is to find better answers to this dilemma.

Carotid endarterectomy in patients with recurrent symptoms associated with an ipsilateral carotid artery near occlusion with full collapse.

OBJECTIVE: Near occlusion (NO) of the internal carotid artery (ICA) with full collapse (NOFC) is a rare condition, with a prevalence of around 1%. Guidelines on carotid stenosis recommend a conservative treatment in patients with a single-event ipsilateral to a NOFC, but the optimal treatment for patients with recurrent symptoms associated with NOFC remains uncertain. We describe a consecutive series of patients with recurrent symptoms associated with NOFC (RSNOFC) who underwent carotid endarterectomy (CEA). METHODS: From 2008 to 2017, 17 consecutive patients with RSNOFC were treated according to our standardized multidisciplinary work-up and protocol and included for this single-center cohort study. NO was defined according to the angiographic North American Symptomatic Carotid Endarterectomy Trial criteria. Only patients with NOFC were included in this study. RESULTS: Standard longitudinal CEA was performed in 15 patients, whereas in 2 patients the ICA was ligated with concomitant endarterectomy of the ECA. Within 30 postoperative days, one patient died from a hemorrhagic infarction. During follow-up (median 23 months) one patient died of unknown cause 90 days after CEA. No TIA, stroke, myocardial infarction or re-stenosis occurred in the remaining patients. CONCLUSION: In patients with RSNOFC, CEA may be considered a potential treatment option. Although procedural risks in this small subgroup may be higher as compared to patients with low-to-moderate risk anatomy, this risk may outbalance the natural course.

Experience of a single center in the conservative approach of 20 consecutive cases of asymptomatic extracranial carotid artery aneurysms.

BACKGROUND AND PURPOSE: The clinical course and optimal treatment strategy for asymptomatic extracranial carotid artery aneurysms (ECAAs) are unknown. We report our single-center experience with conservative management of patients with an asymptomatic ECAA. METHODS: A search in our hospital records from 1998 to 2013 revealed 20 patients [mean age 52 (SD 12.5) years] with 23 ECAAs, defined as a 150% or more fusiform dilation or any saccular dilatation compared with the healthy internal carotid artery. None of the aneurysms were treated and we had no pre-defined follow-up schedule for these patients. The primary study end-point was the yearly rate for ipsilateral ischemic stroke. Secondary end-points were ipsilateral transient ischemic attack, any stroke-related death, other symptoms related to the aneurysm or growth defined as any diameter increase. RESULTS: The ECAA was either fusiform (n = 6; mean diameter 10.2 mm) or saccular (n = 17; mean diameter 10.9 mm). Eleven (55%) patients with 13 ECAAs received antithrombotic medication. During follow-up [median 46.5 (range 1-121) months], one patient died due to ipsilateral stroke and the ipsilateral cerebral stroke rate was 1.1 per 100 patient-years (95% confidence interval, 0.01-6.3). Three patients had ECAA growth, two of whom were asymptomatic and one was the patient who suffered a stroke. CONCLUSIONS: In this retrospective case series of patients with an asymptomatic ECAA, the risk of cerebral infarction is small but not negligible. Conservative management seems justified, in particular in patients without growth. Large prospective registry data are necessary to assess follow-up imaging strategies and the role of antiplatelet therapy.

Chronic kidney disease and bleeding risk in patients at high cardiovascular risk: a cohort study.

Essentials The association between chronic kidney disease and bleeding is unknown. We followed 10 347 subjects at high cardiovascular risk for bleeding events. Chronic kidney disease was associated with a 1.5-fold increased bleeding risk. Especially albuminuria rather than decreased kidney function was associated with bleeding events. SUMMARY: Background There are indications that patients with chronic kidney disease have an increased bleeding risk. Objectives To investigate the association between chronic kidney disease and bleeding in patients at high cardiovascular risk. Methods We included 10 347 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2015 for an outpatient visit with classic risk factors for arterial disease or with symptomatic arterial disease (Second Manifestation of Arterial disease [SMART] cohort). Patients were staged according to the KDIGO guidelines, on the basis of estimated glomerular filtration rate (eGFR) and albuminuria, and were followed for the occurrence of major hemorrhagic events until March 2015. Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding were calculated with Cox proportional hazards analyses. Results The incidence rate for bleeding in subjects with chronic kidney disease was 8.0 per 1000 person-years and that for subjects without chronic kidney disease was 3.5 per 1000 person-years. Patients with chronic kidney disease (n = 2443) had a 1.5-fold (95% CI 1.2-1.9) increased risk of bleeding as compared with subjects without chronic kidney disease (n = 7904) after adjustment. Subjects with an eGFR of < 45 mL min-1  1.73 m-2 with albuminuria had a 3.5-fold (95% CI 2.3-5.3) increased bleeding risk, whereas an eGFR of < 45 mL min-1  1.73 m-2 without albuminuria was not associated with an increased bleeding risk (HR 1.3, 95% CI 0.7-2.5). Conclusion Chronic kidney disease is a risk factor for bleeding in patients with classic risk factors for arterial disease or with symptomatic arterial disease, especially in the presence of albuminuria.

Relation between adiposity and vascular events, malignancy and mortality in patients with stable cerebrovascular disease.

BACKGROUND: Abdominal adiposity is associated with various risk factors including hypertension, and is therefore particularly relevant in patients with stable cerebrovascular disease (CeVD). A U-shaped relation between body mass index (BMI, kg m-2) and cardiovascular events is often described. Whether this U-shape persists for abdominal adiposity, and consequently which reference values should guide clinical practice, is unclear. We described the relation between multiple adiposity measurements and risk of vascular events, vascular mortality, malignancy and all-cause mortality in patients with clinically stable CeVD. METHODS: During a median follow-up time of 6.8 years, 1767 patients were prospectively followed. Relations were assessed using multivariable adjusted Cox proportional hazards models. Adiposity was assessed with BMI, waist circumference (stratified by gender) and the contribution of visceral fat to total abdominal fat (VAT%) measured using ultrasound. Relations were nonlinear if the χ2-statistic of the nonlinear term was significant (P-value<0.05). Nadirs were reported for nonlinear and hazard ratios (HRs) for linear relations. RESULTS: The relations between BMI and outcomes were nonlinear with nadirs ranging between 27.1 (95% confidence interval (CI) 21.9-29.3) kg m2 for vascular mortality and 28.1 (95% CI, 19.0-38.2)) kg m-2 for malignancy. The relation between waist circumference and all-cause mortality was nonlinear with a nadir of 84.0 (95% CI, 18.7-134.8) cm for females and 94.8 (95% CI, 80.3-100.1) cm for males. No nonlinearity was detected for VAT%. A 1-s.d. (9.8%) increase in VAT% was related to both vascular (HR, 1.23, 95% CI 1.00-1.51) and all-cause mortality (HR, 1.22, 95% CI 1.05-1.42). CONCLUSIONS: In patients with CeVD, a BMI around 27-28 kg m-2 relates to the lowest risk of vascular events, vascular mortality, malignancy and all-cause mortality. However, increasing abdominal adiposity confers a higher risk of all-cause mortality. Thus, whereas traditional BMI cutoffs may be re-evaluated in this population, striving for low abdominal obesity should remain a goal.