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Biomedical subjects

Didier Leys

Publications and source records attributed to Didier Leys.

36 records · Page 2Linked to original sources
PubMed2004

Comparison of secondary vascular prevention in practice after cerebral ischemia and coronary heart disease.

BACKGROUND: Secondary prevention measures in patients with cerebral ischemia or coronary heart disease (CHD) consist of vascular risk factors management and antithrombotic therapy. The aim of this study was to compare how secondary prevention measures are applied in practice between patients with a history of CHD or cerebral ischemia. METHOD: We compared vascular risk factors management and antithrombotic therapy between patients with a history of CHD and patients with a history of cerebral ischemia that occurred 2 months to 6 years earlier. Whether patients were properly treated or not was determined by a comparison between their current treatments and European guidelines for stroke and CHD management. RESULTS: We included 107 consecutive patients with a history of cerebral ischemia and 85 consecutive patients with a history of CHD. We found that: (i). most patients did not receive an appropriate secondary prevention in both groups: 76 of 107 patients with previous cerebral ischemia (71 %) and 73 of 85 patients with CHD (85.9 %); (ii). identification of risk factors, such as hypercholesterolemia, diabetes mellitus and smoking, did not differ between both groups, but arterial hypertension was more frequent in CHD patients; (iii). an inappropriate management of risk factors was more frequent in patients with TIA vs. ischemic stroke, and angina pectoris vs. myocardial infarction; (iv). arterial hypertension and hypercholesterolemia were the 2 more frequent risk factors that were not properly treated; (v). more than half diabetic patients had hyperglycemia > or= 126 mg/dl in both groups; (vi). patients with previous CHD had twice more frequently stopped smoking than those with cerebral ischemia. CONCLUSION: Many patients were not properly treated in both groups, and differences between practice and guidelines were more frequent in the CHD group, where guidelines are more strict.

Aged↗
PubMed2004

Diffusion/perfusion-weighted magnetic resonance imaging after carotid angioplasty and stenting.

BACKGROUND AND PURPOSE: Carotid angioplasty and stenting, a so far non-validated procedure, may be an alternative to surgery in patients with a high surgical risk. However, it carries also a risk of cerebral embolic events. The purpose of this study was to evaluate tissue signal abnormalities in the brain before and after carotid angioplasty and stenting by means of diffusion- (DWI) and perfusion (PWI) weighted magnetic resonance imaging (MRI). METHODS: We performed cerebral MRI before and after carotid angioplasty in 22 consecutive patients, with 23 treated high-grade carotid stenoses. The lesions were located at the origin of the internal carotid artery (ICA) in 20 patients, and at the origin of the common carotid artery (CCA) in 2. MRI was performed the day before, and repeated within 24 hours after the procedure, and examined by two neuroradiologists. RESULTS: All stent implantations were successful but 4 patients developed an acute neurological deficit within 24 hours after carotid angioplasty. On PWI, Time To Peak (TTP) values ipsilateral to the carotid stenosis were increased before the procedure in 15 patients, and had remained normal in 6 and were not assessable in 1. After the procedure, TTP values were normal in 12 patients, increased in 8 and not assessable in 2. On DWI, new ipsilateral lesions were detected in 2 patients: 1 with an acute neurological deficit and 1 symptom free. CONCLUSION: Perfusion deficits may be present in severe carotid stenosis and be improved within 24 hours by carotid angioplasty and stenting. Asymptomatic infarcts may occur.

Aged↗
PubMed2004

Stroke prevention and atrial fibrillation: reasons leading to an inappropriate management. Main results of the SAFE II study.

AIMS: The aim of the Stroke and Atrial Fibrillation Ensemble (SAFE) II study was to identify the reasons underlying the under-utilization of oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: We investigated from all available sources the reasons why patients hospitalized for a stroke, who had a previously known NVAF, were not receiving OAC beforehand. We interviewed general practitioners (GPs) and cardiologists with a structured questionnaire, to identify the reasons for their therapeutic choice. RESULTS: Of 370 patients, 257 were theoretically eligible for OAC according to guidelines and the presence of contra-indications, but only 82 (22.2%) of them had actually received OAC before. We found that factors independently associated with the prescription of OAC were being followed-up by a cardiologist and having a younger GP. The leading reason evoked by GPs or cardiologists to explain why patients were not treated with OAC was the presence of a 'potential contra-indication', which was often inappropriate, followed by 'there was no indication', 'low compliance' and 'fear of bleeding'. CONCLUSIONS: An important reason for not prescribing OAC was the lack of knowledge about trials and guidelines. Medical education about OAC in NVAF should therefore be improved.

Aged↗
PubMed2003

Peroxisome proliferator-activated receptor-alpha activation as a mechanism of preventive neuroprotection induced by chronic fenofibrate treatment.

The treatment of ischemic strokes is limited to the prevention of cerebrovascular risk factors and to the modulation of the coagulation cascade during the acute phase. A new therapeutic strategy could be to preventively protect the brain against noxious biological reactions induced by cerebral ischemia such as oxidative stress and inflammation to minimize their neurological consequences. Here, we show that a peroxisome proliferator-activated receptor (PPAR-alpha) activator, fenofibrate, protects against cerebral injury by anti-oxidant and anti-inflammatory mechanisms. A 14 d preventive treatment with fenofibrate reduces susceptibility to stroke in apolipoprotein E-deficient mice as well as decreases cerebral infarct volume in C57BL/6 wild-type mice. The neuroprotective effect of fenofibrate is completely absent in PPAR-alpha-deficient mice, suggesting that PPAR-alpha activation is involved as a mechanism of the protection against cerebral injury. Furthermore, this neuroprotective effect appears independently of any improvement in plasma lipids or glycemia and is associated with (1) an improvement in middle cerebral artery sensitivity to endothelium-dependent relaxation unrelated to an increase in nitric oxide synthase (NOS) type III expression, (2) a decrease in cerebral oxidative stress depending on the increase in numerous antioxidant enzyme activities, and (3) the prevention of ischemia-induced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in cerebral vessels without any change in NOS II expression. These data demonstrate that PPAR-alpha could be a new pharmacological target to preventively reduce the deleterious neurological consequences of stroke in mice and suggest that PPAR-alpha activators could preventively decrease the severity of stroke in humans.

Animals↗
PubMed2003

Poststroke dementia: influence of hippocampal atrophy.

BACKGROUND: The prevalence of dementia is increased after stroke. Medial temporal lobe atrophy (MTLA) is associated with Alzheimer disease, and with prestroke dementia in patients who have had a stroke. OBJECTIVE: To determine the influence of MTLA on the long-term risk of dementia after stroke, after excluding the patients who had prestroke dementia. METHODS: The study was conducted in 144 consecutive patients who had a stroke, who were aged 40 years or older (66 women and 78 men; median age, 72 years), and who had an Informant Questionnaire on Cognitive Decline in the Elderly score lower than 104. On admission to the hospital all patients underwent a noncontrast computed tomographic scan including temporal lobe-positioned slices. A cut-off of 11.5 mm was used to differentiate patients with MTLA from those without MTLA. Patients were followed up with clinical and cognitive assessments over a 3-year period. RESULTS: Three years after stroke, 34 patients (23.6%) had developed new-onset dementia. The cumulative proportion of survivors without dementia was 57.6% in patients with MTLA and 80.8% in patients without MTLA (P =.02). The unadjusted relative risk of poststroke dementia associated with MTLA was 2.3 (95% confidence interval, 1.1-4.7). However, using the Cox proportional hazards model, MTLA did not seem to be an independent predictor of poststroke dementia. Independent predictors of poststroke dementia were increasing age, diabetes mellitus, severity of the clinical deficit at admission, and severity of leukoaraiosis on computed tomography. CONCLUSIONS: Patients who had a stroke and MTLA more frequently develop dementia than patients without MTLA, but our study does not suggest that MTLA independently contributes to dementia. A longer follow-up may be necessary to reevaluate the influence of MTLA.

Adult↗
PubMed2003

Influence of prestroke dementia on early and delayed mortality in stroke patients.

Causes of early and delayed death after stroke differ. It has been suggested that delayed mortality rate was increased in patients with post-stroke dementia. Prestroke dementia is frequent: its influence on survival in stroke patients has never been evaluated. The aim of this study was to evaluate the influence of prestroke dementia on early and delayed mortality rate after stroke. In a cohort of 202 consecutive stroke patients aged >or= 40 years admitted between November 1995 and May 1996 in a primary care center, the prevalence of prestroke dementia was determined using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) with a cut-off of 104. Patients were followed-up for 3 years. Statistics were performed using life-table methods. Of 202 patients, 33 had prestroke dementia. Of 142 survivors at month-6, 44 were demented, of them 15 having prestroke and 29 new-onset post-stroke dementia. No patient was lost to follow-up. The risk of death at month-6 was higher in patients with prestroke dementia (RR 2.7; 95 % CI: 1.6-4.8). However, independent predictors of early death were age, severity of the deficit at admission, type and etiology of stroke. The risk of delayed death was higher in patients with prestroke dementia (RR 4.97; 95 % CI: 1.76-13.98) as in patients with new-onset post-stroke dementia (RR 6.24; 95 % CI: 2.67-14.57), compared with non-demented patients. The mortality rate did not differ between patients with prestroke and new-onset post-stroke dementia. Dementia at month-6 was an independent predictor of delayed death (RR 5.7; 95 % CI: 2.4-13.4), with age and stroke recurrence. Causes of death did not differ between demented and non-demented patients. Dementia adversely influences vital outcome in stroke patients, perhaps partly because the therapeutic approach differs between demented and non-demented patients.

Adult↗
PubMed2003

Cerebral magnetic resonance imaging within 6 hours of stroke onset: inter- and intra-observer reproducibility.

BACKGROUND: Magnetic resonance imaging (MRI) provides valuable pathophysiological information during the very first hours of cerebral ischemia. However, the reliability of prime-time MRI in the setting of emergency care remains unknown. AIM: To evaluate the reproducibility between and within observers of the assessment of MRI scans in stroke patients. METHOD: We performed a MRI scan within 6 h of stroke onset, with time-of-flight (TOF), T2* gradient echo, FLAIR, diffusion- (DWI) and perfusion- (PWI) weighted images, in 17 consecutive patients. Four observers, blinded to the clinical history, separately performed a visual assessment of all scans, and repeated the assessment 2-8 days later. Two neuroradiologists made volumetric measures of diffusion and perfusion abnormalities using a semi-automatic technique 2 weeks after the 2nd visual assessment. We evaluated: (i) in the whole set of MRI scans, the quality of scans and their ability to identify primary hemorrhages on T2* gradient echo sequences; (ii) in patients with acute cerebral ischemia only, the inter- and intra-observer agreement for the presence of arterial occlusion and cerebral abnormalities on TOF sequences, and (iii) on DWI and PWI sequences, the relationship between visual and automatic assessments for the presence of a mismatch (defined as the difference between the perfusion and diffusion abnormalities) of >20%. Statistics used the kappa (kappa) method. RESULTS: The median delay between clinical onset and MRI was 285 min. Two patients had primary cerebral hemorrhages, 1 a post-ictal deficit, and 14 cerebral ischemia. The quality of the scans was judged as appropriate for all scans in all sequences except for FLAIR. All observers identified the 2 patients with hemorrhages. The inter- and intra-observer reliability was substantial to excellent (kappa values ranging from 0.63 to 1.00) for all sequences. The agreement between visual and automatic assessments for the presence of a mismatch of >20% was excellent in all observers. CONCLUSION: The visual assessment of T2* gradient echo, TOF, diffusion and perfusion sequences at the acute stage of stroke is reproducible between and within observers. The visual assessment is as good as the volumetric assessment to detect a mismatch of >20%.

Adult↗
PubMed2003

Neurological protection provided by candesartan: reviewing the latest study results.

Arterial hypertension is closely correlated with the occurrence of stroke and also with the loss of cognitive function and dementia. The results of several trials, including Syst-Eur, PROGRESS, and the preliminary findings from SCOPE open the way to the possible prevention of dementia by antihypertensive treatment. In this respect, candesartan seems to be a promising drug as it has been shown to have neuroprotective effects in animal models of cerebral ischaemia and can prevent non-fatal strokes in elderly subjects with arterial hypertension.

Aged↗
PubMed2002

Stroke prevention: management of modifiable vascular risk factors.

Stroke prevention is a crucial issue because (i) stroke is a frequent and severe disorder, and (ii) acute stroke therapies that are effective at the individual level have only a little impact in term of public health. Stroke prevention consists of the combination of 3 strategies: an optimal management of vascular risk factors, associated when appropriate with antithrombotic therapies, carotid surgery, or both. Primary prevention trials have shown that reducing blood pressure in hypertensive subjects reduces their vascular risk, including stroke. The association of perindopril plus indapamide reduces the vascular risk in patients who have had a stroke or TIA during the last 5 years, irrespective of their baseline blood pressure. Lowering serum cholesterol with statins or gemfibrozil in patients with hypercholesterolemia or coronary heart disease (CHD), reduces the risk of stroke. However, no trial of cholesterol-lowering therapy has been completed in stroke patients. A strict control of high cholesterol levels should be encouraged, because of benefits in terms of CHD. Statins should be prescribed for stroke patients with CHD, or increased cholesterol levels. Cigarette smoking is associated with an increased risk of stroke and should be avoided. Careful control of all risk factors, especially arterial hypertension in type 1 and type 2 diabetics is recommended, together with a strict glycemic control to reduce systemic microvascular complications. Estrogens prescribed in hormone replacement or oral contraceptive therapies are not recommended after an ischemic stroke. It is also recommended to reduce alcohol consumption and obesity, and to increase physical activity in patients at risk for first-ever or recurrent stroke. An optimal management of risk factors for stroke is crucial to reduce the risks of first-ever stroke, recurrent stroke, any vascular event after stroke and vascular death. One of the major public health issues for the coming years will be to focus more on risk factor recognition and management.

Alcoholism↗
PubMedDate not supplied

Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial.

BACKGROUND: Clopidogrel was superior to aspirin in patients with previous manifestations of atherothrombotic disease in the CAPRIE study and its benefit was amplified in some high-risk subgroups of patients. We aimed to assess whether addition of aspirin to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk. METHODS: We did a randomised, double-blind, placebo-controlled trial to compare aspirin (75 mg/day) with placebo in 7599 high-risk patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor who were already receiving clopidogrel 75 mg/day. Duration of treatment and follow-up was 18 months. The primary endpoint was a composite of ischaemic stroke, myocardial infarction, vascular death, or rehospitalisation for acute ischaemia (including rehospitalisation for transient ischaemic attack, angina pectoris, or worsening of peripheral arterial disease). Analysis was by intention to treat, using logrank test and a Cox's proportional-hazards model. FINDINGS: 596 (15.7%) patients reached the primary endpoint in the group receiving aspirin and clopidogrel compared with 636 (16.7%) in the clopidogrel alone group (relative risk reduction 6.4%, [95% CI -4.6 to 16.3]; absolute risk reduction 1% [-0.6 to 2.7]). Life-threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone (96 [2.6%] vs 49 [1.3%]; absolute risk increase 1.3% [95% CI 0.6 to 1.9]). Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality. INTERPRETATION: Adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemic attack is associated with a non-significant difference in reducing major vascular events. However, the risk of life-threatening or major bleeding is increased by the addition of aspirin.

Aged↗
PubMedDate not supplied

Atrial fibrillation and stroke: from scientific evidence to practice.

Nonvalvular atrial fibrillation (NVAF) is the most frequent cause of cardioembolic stroke. Due to the aging of the population, NVAF is becoming an important public health issue. Despite the impressive results of trials with oral anticoagulation (OAC) in primary and secondary prevention of stroke in NVAF patients, OAC remains underused or misused in practice. Beyond the risk of bleeding, there also are several arguments for a lack of knowledge about trials and guidelines. Medical education could then be one of the most effective way to improve stroke prevention in NVAF patients in practice.

Anticoagulants↗
PubMedDate not supplied

Thrombolysis beyond the three-hour time window.

Intravenous (i.v.) thrombolysis with tissue plasminogen activator (rt-PA, i.v. 0.9 mg/kg body weight) has been approved by European health authorities in 2002, with a 3-hr time window. The meta-analysis of i.v. rt-PA trials suggests efficacy of rt-PA up to 4.5 to 6 hr. However, treatment efficacy declines rapidly over time: the numbers of patients needed to treat to prevent 1 death or dependency are respectively 7, 12, and > 30 in the 0-3 hr, 0-6 hr, and 3-6 hr time windows. Magnetic resonance imaging may be the best way to select candidates for thrombolysis beyond 3 hr, on the basis of the presence of arterial occlusion and mismatch between diffusion and perfusion images. New trials are testing the possibility of extending the time window. Trials with new thrombolytic agents, ultrasound thrombolysis, and mechanical thrombolysis also are running or planned in the 3- to 6-hr time window. The 3-hr limit is just a matter of safety. Patients should be treated as soon as possible, and the earliest is the best.

Drug Administration Schedule↗
PubMedDate not supplied

Hypolipemic agents for stroke prevention.

An important issue for stroke prevention is identification and treatment of risk factors such as hypercholesterolemia. The four reasons to test hypolipidemic agents in stroke prevention are: (i) a statistical link between elevated low-density lipoprotein cholesterol (LDL-c) or decreased high-density lipoprotein cholesterol (HDL-c) and ischemic stroke; (ii) a reduction in vascular risk in randomized trials in patients with coronary heart disease; (iii) evidence of a decreased plaque progression under statins, (iv) pooled analyses of primary and secondary prevention trials showing that reduction of total serum cholesterol reduces the incidence of stroke, especially with the highest rate of cholesterol reduction, and in patients with the highest risk of stroke (i.e., with statins in secondary prevention trials), and (v) prophylactic neuroprotection induced by hypolipidemic agents in animal models of cerebral ischemia. Data provided by trials conducted in subjects with coronary heart disease and in asymptomatic individuals should now be confirmed in stroke patient.

Animals↗
PubMedDate not supplied

Statins and stroke.

An important issue for stroke prevention is the identification and treatment of risk factors such as hypercholesterolaemia. The 4 reasons to test if the statins have a role in stroke prevention are: (i) a statistical link between elevated low density lipoprotein-cholesterol or decreased high density lipoprotein-cholesterol and ischaemic stroke; (ii) a reduction in vascular risk with statins in randomised trials in patients with coronary heart disease; (iii) evidence of a decreased plaque progression under statins; and (iv) pooled analyses of primary and secondary prevention trials showing that reduction of total serum cholesterol reduces the incidence of stroke, especially with the highest rate of cholesterol reduction, and in patients with the highest risk of stroke (i.e. with statins in secondary prevention trials). The question of whether statins also have a neuroprotective effect in humans and reduce the risk of post-stroke dementia remains unsettled.

Animals↗
PubMedDate not supplied

Antiplatelet agents in the perioperative period: expert recommendations of the French Society of Anesthesiology and Intensive Care (SFAR) 2001--summary statement.

PURPOSE: Antiplatelet agents are administered to an increasing number of patients. Preoperative treatment with these agents represents a major problem for the anesthesiologist. The results of a French expert meeting on their perioperative management are reported. METHODS: Responses to questions formulated by the Organizing Committee were drafted by a group of experts and reviewed by a multidisciplinary. Reading Committee. Recommendations were classified (grade) according to the evidence level of the studies supporting them. PRINCIPAL FINDINGS: First, antiplatelet agents have a variable effect on hemostasis as far as bleeding risk is concerned. Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) increase intra- and postoperative bleeding moderately, but not transfusion requirements. Very few data are available on clopidogrel and ticlopidin. Anti-glycoprotein (GP) IIb/IIIa agents may increase bleeding when surgery is required in proximity with their administration. Second, the common practice of withdrawing antiplatelet agents is now challenged because an increased incidence of myocardial infarction has been reported in patients in whom treatment was interrupted. Third, aspirin should not be withdrawn for most vascular procedures and in several additional settings. When a definite increase in intraoperative bleeding is feared, or when surgical hemostasis is difficult, aspirin, clopidogrel or ticlopidine can be replaced by short-acting NSAIDS, given for a ten-day period and interrupted the day before surgery. Platelet transfusion should only be given when overt bleeding is observed. Postoperatively, antiplatelet treatment should be resumed immediately after surgery (first six hours). CONCLUSION: Anesthesiologists should be aware of the indications, potential complications and means of substitution of these agents.

Anesthesia↗