Timing of procedural stroke and death in asymptomatic patients undergoing carotid endarterectomy: individual patient analysis from four RCTs.

BACKGROUND: The effectiveness of carotid endarterectomy (CEA) for stroke prevention depends on low procedural risks. The aim of this study was to assess the frequency and timing of procedural complications after CEA, which may clarify underlying mechanisms and help inform safe discharge policies. METHODS: Individual-patient data were obtained from four large carotid intervention trials (VACS, ACAS, ACST-1 and GALA; 1983-2007). Patients undergoing CEA for asymptomatic carotid artery stenosis directly after randomization were used for the present analysis. Timing of procedural death and stroke was divided into intraoperative day 0, postoperative day 0, days 1-3 and days 4-30. RESULTS: Some 3694 patients were included in the analysis. A total of 103 patients (2·8 per cent) had serious procedural complications (18 fatal strokes, 68 non-fatal strokes, 11 fatal myocardial infarctions and 6 deaths from other causes) [Correction added on 20 April, after first online publication: the percentage value has been corrected to 2·8]. Of the 86 strokes, 67 (78 per cent) were ipsilateral, 17 (20 per cent) were contralateral and two (2 per cent) were vertebrobasilar. Forty-five strokes (52 per cent) were ischaemic, nine (10 per cent) haemorrhagic, and stroke subtype was not determined in 32 patients (37 per cent). Half of the strokes happened on the day of CEA. Of all serious complications recorded, 44 (42·7 per cent) occurred on day 0 (20 intraoperative, 17 postoperative, 7 with unclear timing), 23 (22·3 per cent) on days 1-3 and 36 (35·0 per cent) on days 4-30. CONCLUSION: At least half of the procedural strokes in this study were ischaemic and ipsilateral to the treated artery. Half of all procedural complications occurred on the day of surgery, but one-third after day 3 when many patients had been discharged.

ANTECEDENTES: La efectividad de la endarterectomía carotídea (carotid endarterectomy, CEA) en la prevención de un accidente cerebrovascular depende de que este procedimiento tenga pocos riesgos. El objetivo de este estudio fue evaluar la frecuencia y el momento de aparición de las complicaciones tras una CEA, lo que podría clarificar los mecanismos subyacentes y ayudar a establecer una política de altas hospitalarias segura. MÉTODOS: Se utilizaron los datos de los pacientes incluidos en cuatro grandes ensayos de intervención carotídea (VACS, ACAS, ACST-1 y GALA; 1983-2007). Para el presente análisis se utilizaron los datos de pacientes sometidos a CEA por estenosis de la arteria carótida asintomática recogidos inmediatamente tras la aleatorización. Se consideraron diferentes intervalos entre el procedimiento, la muerte o el accidente cerebrovascular: intraoperatorio día 0, postoperatorio día 0, postoperatorio días 1-3 y postoperatorio días 4-30. RESULTADOS: En el análisis se incluyeron 3.694 pacientes. Se detectaron complicaciones graves relacionadas con el procedimiento en 103 (2,8%) pacientes (18 accidentes cerebrovasculares fatales, 68 accidentes cerebrovasculares no fatales, 11 infartos de miocardio fatales y 6 muertes por otras causas). De los 86 accidentes cerebrovasculares, 67 (78%) fueron ipsilaterales, 17 (20%) contralaterales y dos (2%) vertebrobasilares. Los accidentes cerebrovasculares fueron isquémicos en 45 (52%) casos, hemorrágicos en 9 (10%) y no se pudo determinar el subtipo de ictus en 32 (37%). La mitad de los accidentes cerebrovasculares ocurrieron el día de la CEA. De todas las complicaciones graves registradas, 44 (43%) ocurrieron en el día 0 (20 intraoperatorias, 17 postoperatorias y 7 en períodos poco definidos), 23 (22%) entre los días 1-3 y 36 (35%) entre los días 4-30. CONCLUSIÓN: En este estudio, al menos la mitad de los accidentes cerebrovasculares relacionados con la CEA fueron isquémicos e ipsilaterales respecto a la arteria tratada. La mitad de todas las complicaciones de la CEA ocurrieron el día de la cirugía, pero un tercio de los casos se presentaron después del día 3, cuando muchos pacientes ya habían sido dados de alta.

Effect of magnesium on cognition after aneurysmal subarachnoid haemorrhage in a randomized trial.

BACKGROUND AND PURPOSE: In randomized trials magnesium supplementation did not improve clinical outcome after aneurysmal subarachnoid haemorrhage (aSAH) on handicap scales. After aSAH, many patients have cognitive problems that may not translate into handicap. The effect of magnesium on cognitive outcome after aSAH was studied. METHODS: In total, 209 patients who had been included in the Magnesium for Aneurysmal Subarachnoid Haemorrhage (MASH-2) trial in the University Medical Centre of Utrecht were studied. Patients had been randomized to 64 mmol magnesium sulfate daily or placebo during hospitalization. Three months after aSAH patients underwent a neuropsychological examination (NPE) consisting of six neuropsychological tests or a brief cognitive assessment. Poisson and linear regression analyses were used to analyse the effect of magnesium on cognition. RESULTS: In the magnesium group 53 (49.5%) of the 107 patients and in the placebo group 51 (50.0%) of the 102 patients scored lower than the median cognitive score [relative risk 0.99, 95% confidence interval (CI) 0.76-1.30]. Linear regression analyses showed no significant relationship between intervention and cognition (B = 0.05, 95% CI -0.15 to 0.33). CONCLUSIONS: Treatment with magnesium has no effect on cognitive outcome after aSAH.

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.

Safety of intra-arterial treatment in acute ischaemic stroke patients on oral anticoagulants. A cohort study and systematic review.

BACKGROUND AND PURPOSE: An elevated international normalized ratio (INR) of >1.7 is a contraindication for the use of intravenous thrombolytics in acute ischaemic stroke. Local intra-arterial therapy (IAT) is considered a safe alternative. The safety and outcome of IAT were investigated in patients with acute ischaemic stroke using oral anticoagulants (OACs). METHODS: Data were obtained from a large national Dutch database on IAT in acute stroke patients. Patients were categorized according to the INR: >1.7 and ≤1.7. Primary outcome was symptomatic intracerebral hemorrhage (sICH), defined as deterioration in the National Institutes of Health Stroke Scale score of ≥4 and ICH on brain imaging. Secondary outcomes were clinical outcome at discharge and 3 months. Occurrence of outcomes was compared with risk ratios and corresponding 95% confidence intervals. Further, a systematic review and meta-analysis on sICH risk in acute stroke patients on OACs treated with IAT was performed. RESULTS: Four hundred and fifty-six patients were included. Eighteen patients had an INR > 1.7 with a median INR of 2.4 (range 1.8-4.1). One patient (6%) in the INR > 1.7 group developed a sICH compared with 53 patients (12%) in the INR ≤ 1.7 group (risk ratio 0.49, 95% confidence interval 0.07-3.13). Clinical outcomes did not differ between the two groups. Our meta-analysis showed a first week sICH risk of 8.1% (95% confidence interval 3.9%-17.1%) in stroke patients with elevated INR treated with IAT. CONCLUSION: The use of OACs, leading to an INR > 1.7, did not seem to increase the risk of an sICH in patients with an acute stroke treated with IAT.

The ThRombolysis in UnconTrolled Hypertension (TRUTH) protocol: an observational study on treatment strategy of elevated blood pressure in stroke patients eligible for IVT.

BACKGROUND: Intravenous thrombolysis (IVT) with (recombinant) tissue plasminogen activator is an effective treatment in acute ischemic stroke. However, IVT is contraindicated when blood pressure is above 185/110 mmHg, because of an increased risk on symptomatic intracranial hemorrhage. In current Dutch clinical practice, two distinct strategies are used in this situation. The active strategy comprises lowering blood pressure with antihypertensive agents below these thresholds to allow start of IVT. In the conservative strategy, IVT is administered only when blood pressure drops spontaneously below protocolled thresholds. A retrospective analysis in two recent stroke trials showed a non-significant signal towards better functional outcome in the active group; robust evidence for either strategy, however, is lacking. We hypothesize that (I) the active strategy leads to a better functional outcome three months after acute ischemic stroke. Secondary hypotheses are that this effect occurs despite (II) increasing the number of symptomatic intracranial hemorrhages, and could be attributable to (III) a higher rate of IVT treatments and (IV) a shorter door-to-needle time. METHODS AND DESIGN: The TRUTH is a prospective, observational, cluster-based, parallel group follow-up study; in which participating centers continue their current local treatment guidelines. Outcomes of patients admitted to centers with an active will be compared to those admitted to centers with a conservative strategy. The primary outcome is functional outcome on the modified Rankin Scale at three months. Secondary outcomes are symptomatic intracranial hemorrhage, IVT treatment and door-to-needle time. We based our sample size estimate on an ordinal analysis of the mRS with the "proportional odds" model. With the aforementioned signal observed in a recent retrospective study in these patients as an estimate of the effect size and with alpha 0 · 05, this analysis would have an 80 % power with a total number of 600 patients. Corrections for expected imbalance in group size and clustering effects resulted in a sample size of 1235 patients. DISCUSSION: The TRUTH is the first large prospective study specifically studying IVT-candidates with elevated blood pressure, and has the potential to change clinical practice and optimize acute stroke care in these patients.

The value of CT angiography in patients with acute severe headache.

Patients with acute severe headache may have a secondary form of headache. Standard head computer tomography (CT) and cerebrospinal fluid (CSF) examination are often performed in the absence of neurological deficits to exclude subarachnoid hemorrhage (SAH). Increasingly, patients undergo subsequent CT angiography (CTA) to exclude cerebral venous thrombosis (CVT), dissection or reversible cerebral vasoconstriction syndrome (RCVS). It is unknown whether this additional imaging increases diagnostic yield. We aimed to evaluate the yield of CTA in patients with acute severe headache with normal neurological examination and no abnormalities at standard CT and CSF analysis. We included consecutive patients presenting to the emergency room between January 2008 and May 2011 with acute severe headache and without abnormalities at neurological examination, CT and CSF research, who received a CTA in the diagnostic process in our teaching hospital. All scans were rereviewed by an experienced neuroradiologist. We included 70 patients, 71% were women and average age was 45 years. We found a vascular abnormality in 13 (19%) of our patients. Four had either a prior aneurysm or CVT. Eight patients had an unruptured intracranial aneurysm (UIA) on CTA (11%), two had CVT (3%), two had RCVS (3%) and one had cerebral ischemia (1%). We found a high percentage of vascular abnormalities. A third of these patients had a prior episode of either an aneurysm or CVT. In patients with a history of UIA or CVT performing CTA despite normal CT and LP therefore seems warranted. A prospective study to delineate indications for CTA is needed.

Carotid stenting: is there an operator effect? A pooled analysis from the carotid stenting trialists' collaboration.

BACKGROUND AND PURPOSE: Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists' Collaboration database. METHODS: The Carotid Stenting Trialists' Collaboration is a pooled individual patient database including all patients recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol. RESULTS: Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience (P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was significantly higher in patients treated by operators with low (mean ≤3.2 procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36-3.87]) and intermediate annual in-trial volumes (3.2-5.6 procedures/y; 8.4%; adjusted risk ratio=1.93 [1.14-3.27]) compared with patients treated by high annual in-trial volume operators (>5.6 procedures/y; 5.1%). CONCLUSIONS: Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year.

Risk factors in patients with perimesencephalic hemorrhage.

BACKGROUND AND PURPOSE: Smoking and hypertension are risk factors for aneurysmal subarachnoid hemorrhage (aSAH), whilst excessive alcohol consumption is less consistently linked with aSAH. Perimesencephalic hemorrhage (PMH) is a benign subset of non-aneurysmal subarachnoid hemorrhage. The exact cause of PMH is unknown, and its risk factor profile may help to elucidate the pathogenesis. The influence of smoking, hypertension and excessive alcohol consumption on the occurrence of PMH was studied. METHODS: Seventy-nine patients admitted with a PMH to the University Medical Center Utrecht were studied. As controls 574 persons were selected from five different general practices in the referral region of the University Medical Center Utrecht. All participants filled in a questionnaire about smoking habits, the presence of hypertension and alcohol consumption before their hemorrhage. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to assess the association of risk factors and PMH, and multivariable logistic regression was used to adjust for possible confounding by age and sex. RESULTS: Adjusted ORs for the occurrence of PMH were 1.7 (95% CI 1.0-2.8) for smoking cigarettes, cigars, pipes or any combination of these, 1.1 (95% CI 0.6-2.0) for hypertension and 1.1 (95% CI 0.5-2.1) for excessive alcohol consumption. CONCLUSIONS: Similar to aSAH, smoking is a risk factor for PMH and excessive alcohol consumption is not. In contrast to aSAH, hypertension is not a risk factor for PMH. This implies that the pathophysiological mechanisms causing PMH might be slightly different from those causing aSAH.

Risk of vascular events after nondisabling small and large vessel cerebral ischemia.

BACKGROUND: Small- and large-vessel disease (SVD and LVD, respectively) might have a different pathogenesis and prognosis but the long-term risk of death and recurrent stroke appears to be similar in previous studies. In this study, we investigated the long-term vascular prognosis of patients with LVD and SVD in a large cohort of well-documented patients. METHODS: We included 971 patients with transient ischemic attack (TIA) or nondisabling ischemic stroke of atherosclerotic origin referred to a university hospital in the Netherlands between 1994 and 2005 and followed them for the occurrence of vascular events or death. The primary outcome was a composite of stroke, myocardial infarction and vascular death, whichever happened first. Classification of SVD/LVD was primarily based on brain imaging. We used regression analyses to generate hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses were performed in subsets of the population, i.e. patients with subtype classification based on imaging, excluding TIA patients, first-ever stroke patients and LVD patients without a symptomatic carotid stenosis. RESULTS: During a mean follow-up of 6.3 years, new vascular events occurred in 56 of 312 SVD patients (3.3%/year) and in 128 of 659 LVD patients (2.9%/year). These were ischemic strokes in 33 of the 56 events in SVD patients (2.0%/year) and 54 of the 128 events in LVD patients (1.2%/year). The corresponding age- and sex-adjusted HR for all new vascular events for LVD versus SVD was 0.76 (95% CI 0.56-1.05) for the total follow-up period. When this risk was split into early risk (<1 year) and late risk (>1 year), it was not significantly different for the 1-year risk of vascular events (HR 1.04, 95% CI 0.57-1.91); however, after 1 year of follow-up, LVD patients had fewer outcome events compared with SVD patients (HR 0.66, 95% CI 0.46-0.96). For ischemic strokes, the overall HR was 0.60 (95% CI 0.39-0.94). As with the primary outcome, here also the 1-year risk was not significantly different from >1-year risk (HR 1.31, 95% CI 0.62-2.81, and HR 0.36, 95% CI 0.21-0.63, respectively). The sensitivity analyses showed virtually the same results. CONCLUSION: In patients with nondisabling cerebrovascular disease, we found, despite no differences at baseline in terms of vascular risk factors, a better long-term prognosis for patients with LVD for all vascular events, especially for recurrent strokes. Our observations support a different pathogenesis in SVD and LVD patients, and optimal prevention is indicated for patients with what was formerly regarded as 'benign' SVD stroke.

Is isolated aphasia a typical presentation of presumed cardioembolic transient ischemic attack or stroke?

BACKGROUND: Previous studies have suggested that patients with a transient ischemic attack (TIA) or minor ischemic stroke and isolated aphasia should be carefully screened for a potential cardiac source of embolism. Most of these publications, however, were case reports or small-series. The purpose of this study was to assess the relationship between isolated aphasia and atrial fibrillation (AF) as the cause of presumed cardioembolic TIA or stroke within the setting of 2 large multicenter trials. METHODS: The frequency of isolated aphasia was compared between patients with a TIA or minor ischemic stroke either with AF [European Atrial Fibrillation Trial (EAFT), n = 1,001] or without AF [Dutch TIA Trial (DTT), n = 3,150]. We analyzed data with univariable and multivariable logistic regression. Isolated aphasia was defined as aphasia without dysarthria, visual-field defects or motor or sensory deficits of the arm, leg or face. Because dysarthria can be difficult to detect in aphasic patients, a second analysis was done without excluding dysarthric patients. In a third analysis, we excluded patients with a symptomatic lacunar infarct from the DTT, as these patients were overrepresented due to the exclusion of patients with AF. Subgroup analysis was performed for patients presenting with TIA and minor stroke. RESULTS: Of 4,151 patients, 210 (5.1%) had isolated aphasia, 109 from the EAFT and 101 from the DTT, crude odds ratio (OR) 3.69, 95% confidence interval (CI) 2.79-4.89. Patients with isolated aphasia were older (mean age 70.3 vs. 66.8 years, p < 0.01), more often female (OR 1.87, 95% CI 1.41-2.46), and more often had diabetes (OR 1.73, 95% CI 1.16-2.59) and hypercholesterolemia (OR 1.83, 95% CI 1.11-3.03) than those without aphasia. After simultaneous adjustment for age, sex, diabetes and hypercholesterolemia, patients with isolated aphasia still had AF more often than patients without isolated aphasia (adjusted OR 2.94, 95% CI 2.16-4.01). Both after inclusion of patients with dysarthria in the group of patients with isolated aphasia and after exclusion of patients with a symptomatic lacunar infarct, essentially the results remained the same. Patients presenting with isolated aphasia due to a TIA tended to have AF more often than patients with a minor ischemic stroke. CONCLUSIONS: Isolated aphasia is an independent sign of AF in patients with a TIA or minor ischemic stroke. Careful cardiac screening seems warranted in patients with isolated aphasia, as secondary prevention is different in patients with a cardiac source of embolism.

Interprocedural comparison of changes in natural flow velocity patterns in the internal carotid artery following CAS or CEA.

BACKGROUND AND PURPOSE: Different flow velocities have been reported after carotid angioplasty with stenting (CAS) than after carotid endarterectomy (CEA). We compared blood flow velocities following CAS and CEA in the International Carotid Stenting Study (ICSS; ISRCTN25337470). MATERIALS AND METHODS: In total, 254 patients (70% male; 129 CAS and 125 CEA) were included. Mean peak systolic velocities (PSVICA) were assessed at baseline, 30 days, 1 and 2 years. Following both treatments, restenosis ≥ 50% was defined as PSVmean >125 cm s(-1). RESULTS: CAS and CEA resulted in a similar reduction in PSVICA 1 month after treatment. Post-intervention analysis for each treatment separately revealed that PSVICA following CAS increased significantly during follow-up (30 days to 2 years; 22.4 cm s(-1); 95% confidence interval (CI), 14.3 to 30.5). On the contrary, PSVICA following CEA remained relatively stable during follow-up (4.7 cm s(-1); 95% CI, -6.5 to 15.9). When we analysed the increase in PSVICA between both treatments after 2 years of follow-up, no significant interprocedural difference was observed. The internal carotid artery/common carotid artery (ICA/CCA) PSV ratio increased after CAS but not after CEA: 1.2 vs. 1.1 (0.04, 95% CI; -0.16 to 0.25) at 30 days; 1.5 vs. 1.1 (0.39, 95% CI; 0.13 to 0.65) at 1 year; and 1.5 vs. 1.1 (0.36; 95% CI, 0.08 to 0.63) at 2 years. The rate of apparent ipsilateral ICA restenosis >50% was higher following CAS (hazard ratio 2.35; 95% CI, 1.35 to 4.09). CONCLUSION: Two years after carotid revascularisation, no significant interprocedural difference was observed in the increase of PSVICA between CAS and CEA. However, the ICA/CCA ratio increased more following CAS resulting in an apparent higher rate of restenosis following CAS.

Flow velocities in the external carotid artery following carotid revascularization.

OBJECTIVE: To study the changes in peak systolic velocities of the ipsilateral external carotid artery (ECA) following carotid revascularization. METHODS: All patients randomized to carotid artery stenting (CAS) or carotid endarterectomy (CEA) in the International Carotid Stenting Study (ICSS; ISRCTN25337470) in our center were included. Peak systolic velocities (PSV) were assessed with duplex ultrasound (DUS) at baseline, at 30 days, and at 12 and 24 months after treatment. Our primary outcome measure was the change in blood flow velocities in the ECA (ΔPSVECA). Secondary outcome measure was the prevalence of post interventional ECA occlusion. RESULTS: Of 270 patients enrolled in ICSS at our center, 224 patients (mean age, 68.8 years; 154 males) were included in the present study (116 CAS, 108 CEA). Baseline PSV in the ipsilateral ECA was similar between the groups. Following CAS, PSV gradually increased during follow-up, whereas PSV remained relatively stable after CEA; mean difference of PSV between CAS and CEA: 23 cm/s (95% CI, -5 to 52), 58 cm/s (95% CI, 27-89), and 69 cm/s (95% CI, 31-107) at 30 days, 12 months, and 24 months. One new ECA occlusion occurred after CAS and two after CEA. CONCLUSION: Blood flow velocities in the ipsilateral ECA increase significantly after CAS but not after CEA. However, this does not lead to a higher rate of ECA occlusion in the first 2 years after revascularization. We conclude that CAS is not inferior to CEA in preserving the ECA as a possible potential collateral pathway for cerebral blood supply within 2 years following revascularization.

Self-rated health status as a risk factor for future vascular events and mortality in patients with symptomatic and asymptomatic atherosclerotic disease: the SMART study.

OBJECTIVES: Lower self-rated health status has been associated with worse prognosis in patients with coronary artery disease (CAD). We investigated the influence of self-rated physical and mental health status on the risk of future vascular events and mortality for various locations of symptomatic atherosclerotic disease and asymptomatic disease. DESIGN: Patients with CAD (n = 2547), cerebrovascular disease (n = 1061), peripheral arterial disease (PAD; n = 648), abdominal aortic aneurysm (AAA; n = 272) and asymptomatic atherosclerotic disease (n = 1933) were followed for a median of 4 years for the occurrence of a new vascular event or death. Self-rated health status was assessed with the Short Form-36 physical and mental component summary scales. Cox regression models were used to estimate associations between health status and vascular events and death, adjusted for age, sex, vascular risk factors and intima-media thickness. RESULTS: In the total population, lower self-rated physical health status (per 10-point decrease) increased the risk of vascular events [hazard ratio (HR) = 1.37, 95% confidence interval (CI) 1.24-1.52], and all-cause (HR = 1.45, 95% CI 1.29-1.63) and vascular mortality (HR = 1.40, 95% CI 1.20-1.64). A 10-point decrease in mental health status was associated with a modest increase in the risk of vascular events (HR = 1.19, 95% CI 1.08-1.32), and all-cause (HR = 1.19, 95% CI 1.05-1.34) and vascular mortality (HR = 1.28, 95% CI 1.09-1.49). Risk estimates of physical and mental health status were highest in patients with asymptomatic atherosclerotic disease and lowest in those with PAD. CONCLUSIONS: Poorer self-rated physical and mental health status increases the risk of vascular events and mortality in a broad population of patients with symptomatic and asymptomatic atherosclerotic disease.

How to deal with measures of association: a short guide for the clinician.

When reading medical literature as a clinician, many different measures of association are presented. To judge whether results of studies can be applied to clinical practice, it is essential to understand and to be able to interpret the measure of association reported in the article. In this paper, we will present how to deal with the most commonly used measures of association including the risk and rate difference, number needed to treat, risk and rate ratio, hazard ratio and odds ratio. By means of examples, we will discuss the different measures of association for the three main study designs used in clinical research: randomized controlled trial, observational cohort study and case-control study.

Intrinsic coagulation activation and the risk of arterial thrombosis in young women: results from the Risk of Arterial Thrombosis in relation to Oral contraceptives (RATIO) case-control study.

BACKGROUND: Classically, intrinsic coagulation proteins are thought to have a minor role in hemostasis. Recently, these proteins, especially FXII, were implicated as possible key players in the pathogenesis of arterial thrombosis. This study aims to determine the risks of arterial thrombosis conferred by increased activation of intrinsic coagulation proteins in young women and the effect of oral contraceptive use on this association. METHODS AND RESULTS: The Risk of Arterial Thrombosis In relation to Oral contraceptives (RATIO) study is a population-based case-control study including young women (age 18 to 50 years) with myocardial infarction (n=205) and ischemic stroke (n=175) and 638 healthy controls. Intrinsic coagulation protein activation was determined by measuring activated protein-inhibitor complexes. This complex is with C1 esterase inhibitor (FXIIa-C1-INH, FXIa-C1-INH, Kallikrein-C1-INH) or antitrypsin inhibitor (FXIa-AT-INH). Odds ratios (ORs) and corresponding confidence intervals (95% CIs) were calculated with logistic regression. High levels of protein activation (>90th percentile of controls) showed an increased risk of ischemic stroke: FXIIa-C1-INH (OR, 2.1; 95% CI, 1.3 to 3.5), FXIa-C1-INH (OR, 2.8; 95% CI, 1.6 to 4.7), FXIa-AT-INH (OR, 2.3; 95% CI, 1.4 to 4.0), and Kallikrein-C1 (OR, 4.3; 95% CI, 2.6 to 7.2). If anything, myocardial infarction risk was only increased by Kallikrein-C1-INH (OR, 1.5; 95% CI, 0.9 to 2.5). Oral contraceptive use further increased the risks. CONCLUSIONS: High levels of activated proteins of the intrinsic coagulation system are associated with arterial thrombosis, whereas the strength of these associations differs for myocardial infarction and ischemic stroke. This contradicts similar analyses among men in the Northwick Park Heart Study. Together with the finding that oral contraceptive use further increases the risks, the question of whether the role of intrinsic coagulation proteins in the pathogenesis of arterial thrombosis is sex-specific is raised.

Medical treatment after peripheral bypass surgery over the past decade.

OBJECTIVE: The Dutch Bypass and Oral anticoagulants or Aspirin (BOA) Study demonstrated that in patients with peripheral arterial disease after bypass surgery oral anticoagulants were more effective in preventing venous graft occlusions than aspirin, while aspirin was more effective in non-venous grafts. We evaluated if this finding was implemented in the clinical practice of former BOA participants by reconstructing a 10-year overview of their applied various drug treatments including anti-hypertensive and lipid-lowering drugs. METHODS: In 482 patients from six centers that contributed most patients anti-thrombotic, anti-hypertensive, and lipid-lowering drug use was recorded at baseline (n = 478), retrospectively up to two years after BOA (n = 388), and prospectively for patients still alive between 2005 and 2009 (n = 209). RESULTS: At baseline, 54% of patients received anti-thrombotics which increased to 96% at follow-up. At baseline 15% of patients were treated with lipid-lowering drugs and 49% with anti-hypertensives. This increased over time to 65% and 76%, respectively. CONCLUSION: After the BOA Study its recommendations were applied marginally. Despite improvements over time, current lipid-lowering and anti-hypertensive drug use remained suboptimal. Our trend analyses, however, should be interpreted with caution, because drug use and compliance in survivors might be better than average.

Comparison of patient and proxy responses on risk factors for stroke.

BACKGROUND: For studies on chronic risk factors and trigger (i.e. acute risk) factors, stroke researchers often have to rely on proxies. The reliability of proxy responses regarding trigger factors for stroke is unknown. METHODS: Thirty patients with stroke and their proxies were interviewed about chronic risk factors and trigger factors. We assessed the completeness of proxy-derived data by calculating the level of non-response and the level of agreement using Cohen kappa statistics. RESULTS: For most chronic risk factors and trigger factors, the response rate to whether or not exposure had taken place in the past year was 87% or higher. If couples agreed on exposure, patient and proxy could also provide a comparable estimate of the average frequency of exposure. Although the non-response on last time of exposure was higher, proxies who could answer provide a reasonably good estimate for most trigger factors. CONCLUSIONS: Proxies provide reliable information on exposure to chronic risk factors and trigger factors for stroke. For exposure and average frequency of exposure, non-response is low and the level of agreement is high for most chronic risk factors; for last time of exposure non-response is higher, but proxies who could respond provided reliable estimates of last time of exposure to most trigger factors.

[Discussing the resuscitation policy at a geriatric ward: the experience of patients or their representatives]. / Bespreken van het reanimatiebeleid op een afdeling geriatrie: de ervaring van patiënt en familie.

AIM: To identify geriatric patients' and their surrogate decision makers' experience with regard to discussing cardio pulmonary resuscitation (CPR) policy. METHODS: This is a prospective, observational, explorative survey. During 10 weeks, all patients admitted to a geriatric ward of a general Dutch hospital or their representatives were asked for their experience regarding discussion of the resuscitation policy with the physician in attendance. Discussing this policy is a standard procedure at the first day of admission. We also asked on several factors which could influence their experience and on factors to improve discussing resuscitation policies. The primary outcome was the participant's satisfaction expressed on a scale of 1 to l0 regarding satisfaction with the CPR discussion. RESULTS: Seventy-six participants were included, of which 29 patients and 47 surrogate decision makers. Discussing the resuscitation policy took an average of 4,5 minutes (SD 3.2) to complete. In 70% (n=53) of cases a do-not-resuscitate decision was made. Discussing the resuscitation policy was experienced positive, with an average rate of 7,8 (SD 1.5). A total of 121 positive comments were made, as opposed to 70 negative comments. When they talked about their resuscitation policy, most patients expressed positive emotional responses. As most important improvements were mentioned: a better introduction to discussing this subject (17%), a better explanation of resuscitation and chances of survival (17%) and providing information prior to admission to the ward, so that patient and surrogate decision maker have been informed that the resuscitation policy will be discussed (12%). CONCLUSION: Most patients and relatives in this study wished to discuss their resuscitation policy with physicians. Still, there is room for improvement in several respects. Patients and surrogate decision makers are in favour of discussing the standard resuscitation policy with the doctor, and evaluate this conversation with a 7.8 / 10. In order to improve both discussing the CPR policy preparing the patient and his representatives and communicating more extensively during the interview are recommended.

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.

Effectiveness of a hospital-based vascular screening programme (SMART) for risk factor management in patients with established vascular disease or type 2 diabetes: a parallel-group comparative study.

AIMS: Modification of vascular risk factors is effective in reducing mortality and morbidity in patients with symptomatic atherosclerosis; however, it is difficult to achieve and maintain. The aim of the Risk management in Utrecht and Leiden Evaluation (RULE) study was to assess risk factor status after referral in patients with established vascular disease or type 2 diabetes who took part in the multidisciplinary hospital-based vascular screening programme, Second Manifestations of ARTerial disease, compared with a group who did not participate in such a programme. METHODS AND RESULTS: Patients with type 2 diabetes, coronary artery disease, cerebrovascular disease or peripheral arterial disease referred by general practitioners to the medical specialist at the University Medical Center (UMC) Utrecht (a setting with a vascular screening programme of systematic screening of risk factors followed by treatment advice) and the Leiden UMC (a setting without such a screening programme), were enrolled in the study. Blood pressure, levels of lipids, glucose and creatinine, weight, waist circumference and smoking status were measured in patients 12-18 months after referral to the two hospitals. A total of 604 patients were treated in the setting with a vascular screening programme and 566 in the setting without such a programme; 70% of all patients were male, with a mean age of 61 +/- 10 years. Amongst screened patients, systolic blood pressure [2.5 mmHg, 95% confidence interval (CI) 0.3-4.6] and the level of LDL cholesterol (0.3 mmol L(-1), 95% CI 0.2-0.4) were lower compared with the group that received usual care, after a median of 16 months from referral. CONCLUSION: Systematic screening of risk factors, followed by evidence-based, tailored treatment advice contributed to slightly better risk factor reduction in patients with established vascular disease or type 2 diabetes. However, a large proportion of patients did not reach the treatment goals according to (inter)national guidelines. Systematic screening of vascular risk factors alone is not enough for adequate risk factor management in high-risk patients.