Is the prevalence of the factor V Leiden mutation in patients with pulmonary embolism and deep vein thrombosis really different?

INTRODUCTION: Previous investigations have suggested a lower prevalence of the factor V Leiden mutation in patients with pulmonary embolism, as compared to patients with deep leg vein thrombosis. METHODS: We studied unselected patients with pulmonary embolism, in whom we also assessed the presence of deep vein thrombosis by ultrasonography. We assessed the prevalence of heterozygosity for the factor V Leiden mutation and compared the outcome of patients with a normal ultrasound (primary pulmonary embolism) to those with an abnormal ultrasound (combined form of venous thromboembolism). Furthermore, we performed a literature search to identify all articles regarding the prevalence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and a combined form of venous thromboembolism. We calculated a (common) odds ratio for these 3 manifestations of venous thromboembolism, including the current findings. RESULTS: In 92 patients with proven pulmonary embolism, 25 (27%) had also an abnormal ultrasound. In these patients, the prevalence of the factor V Leiden mutation was 24% (95% CI 9%-45%), whereas the mutation was present in 5 of 67 patients with primary pulmonary embolism (7%; 95% CI 2%-16%). The literature analysis indicated the common odds ratio for the presence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and the combined form of venous thromboembolism to be 7.9 (95% CI 5-12), 3.5 (95% CI 2-6) and 6.8 (95% CI 3-14), respectively. CONCLUSION: In patients with primary pulmonary embolism the prevalence of the factor V Leiden mutation appears to be half of that reported in patients with primary deep vein thrombosis. The mechanism remains unclear.     

Outpatient treatment of pulmonary embolism with dalteparin

BACKGROUND: Pulmonary embolism is a common complication of deep vein thrombosis. It has been established that low molecular weight heparin may be used to treat deep vein thrombosis or pulmonary embolism and randomized studies have established that outpatient management of deep vein thrombosis with low molecular weight heparin is at least as effective as in-hospital management with unfractionated heparin. METHODS: This was a prospective cohort study of eligible patients with pulmonary embolism managed as outpatients using dalteparin (200 U/kg s/c daily) for a minimum of five days and warfarin for 3 months. Outpatients included those managed exclusively out of hospital and those managed initially for 1-3 days as inpatients who then completed therapy out of hospital. Reasons for admission included hemodynamic instability; hypoxia requiring oxygen therapy; admission for another medical reason; severe pain requiring parenteral analgesia or high risk of major bleeding. Patients were followed for three months for clinically apparent recurrent venous thromboembolism and bleeding. RESULTS: Between three teaching hospitals, a total of 158 patients with pulmonary embolism were identified. Fifty patients were managed as inpatients and 108 as outpatients. Of the outpatients, 27 were managed for an average of 2.5 days as inpatients and then completed dalteparin therapy as outpatients. The remaining 81 patients were managed exclusively as outpatients with dalteparin. For all outpatients the overall symptomatic recurrence rate of venous thromboembolism was 5.6% (6/108) with only 1.9% (2/108) major bleeds. There were a total of four deaths with none due to pulmonary embolism or major bleed. CONCLUSIONS: This prospective study suggests that outpatient management of pulmonary embolism is feasible and safe for the majority of patients.     

Age- and sex-specific incidence, risk, and latency period of a perioperative acute thromboembolism syndrome (PATS)

We investigated age- and sex-specific incidence, risk factors, and latency period of a perioperative acute thromboembolism syndrome (PATS) in a large cohort study. We prospectively analyzed data on 21903 consecutive surgery patients to determine the incidence of myocardial infarction, pulmonary embolism, deep venous thrombosis, stroke, and cardiovascular death within 30 postoperative days. Among 255 (1.2 percent) patients with thromboembolism, 105 (0.48 percent) suffered myocardial infarction (mean latency: 5 days), 30 (0.14 percent) suffered pulmonary embolism (6 days), 23 (0.11 percent) suffered deep venous thrombosis (10 days), 97 (0.44 percent) suffered stroke (11 days), and 13 (0.06 percent) died (12 days).The critical period was postoperative week 1 for myocardial infarction and pulmonary embolism, and postoperative week 1 and 2 for deep venous thrombosis, stroke, and death. Risk of all events increased with age (P<0.0001), particularly for over 70 years (odds ratio: 12.5; 95 percent confidence interval, 7.8 to 19.9). Males had an increased risk (P<0.0001) of myocardial infarction (odds ratio; 1.5; 95 percent confidence interval, 1.0 to 2.3). Females had an increased risk (P<0.0001) of pulmonary embolism (odds ratio: 2.7; 95 percent confidence interval, 1.3 to 5.9) and deep venous thrombosis (odds ratio: 9.8; 95 percent confidence interval, 3.3 to 29.3). Risk of thromboembolic event was higher (P<0.0001) in patients with a history of arterial thrombotic events or cancer. Trend analysis indicates that thromboembolic events will increase 3-fold over the next decade. Our findings enable identification of higher risk patients for prophylactic anti-thromboembolic treatment and awareness of the critical postoperative period.     

Comparison of outcomes after hospitalization for deep venous thrombosis or pulmonary embolism

Venous thrombosis and pulmonary embolism are commonly viewed as different manifestations of a single disease process, venous thromboembolism. Recent evidence suggests that there may be important differences between patients who manifest these two conditions. Using linked hospital discharge records we analyzed 71,250 patients hospitalized with a principal diagnosis of venous thrombosis alone or pulmonary embolism and analyzed predictors of rehospitalization within 6 months for venous thrombosis or pulmonary embolism. There were 51233 patients diagnosed with venous thrombosis alone and 21,625 diagnosed with pulmonary embolism. Comparing patients initially diagnosed with venous thrombosis alone to patients with pulmonary embolism, the relative risk of being rehospitalized with venous thrombosis within 6 months for venous thrombosis was 2.7. Conversely, when patients with pulmonary embolism were compared to patients with venous thrombosis alone, the relative risk of rehospitalization within 6 months with a diagnosis of pulmonary embolism was 4.2. In multivariate models the strongest predictor of recurrent thromboembolism manifest as pulmonary embolism was an initial diagnosis of pulmonary embolism and the strongest predictor of recurrence as venous thrombosis was an initial diagnosis of venous thrombosis. We conclude that the initial clinical manifestation of thromboembolism strongly predicts the manifestation of a recurrence. Venous thrombosis and pulmonary embolism appear to be distinct, albeit overlapping, clinical entities with different natural histories.     

Deep vein thrombosis in patients with stroke

A frequent condition affecting patients with stroke is venous thromboembolism (VTE), which consists of two components: deep vein thrombosis, and pulmonary embolism as its complication The main risk factors of VTE are: age over 65 years, motor deficit with immobilisation, heart failure, infection, obesity and coagulopathy Typical symptoms of deep vein thrombosis (pain, tenderness, swelling of calf and increased skin temperature) can be masked by sensory and autonomic deficits following brain ischaemia Diagnosis of VTE is based on clinical symptoms confirmed by biochemical and radiological findings The treatment of VTE consists of anticoagulation; prevention of VTE in stroke patients is based on use of low-molecular heparins and non-pharmacological methods.     

高血压性脑出血患者并发下肢静脉血栓的危险因素及对策

目的探讨高血压性脑出血后下肢静脉血栓形成的危险因素和防治措施。方法回顾分析9例高血压性脑出血患者发生下肢静脉血栓的临床资料。确诊后均给予抬高患肢、抗血小板、溶栓及抗凝治疗。结果 9例患者中痊愈6例,好转2例,死亡1例。患者肢体瘫痪、高凝状态、下肢血液回流缓慢、静脉壁损伤及血管内异物为下肢静脉血栓形成的高危因素。结论一旦发生下肢深静脉血栓,积极给予抗血小板、溶栓及抗凝等治疗措施,并采取抬高患肢、减少活动是防止血栓脱落发生致死性肺动脉栓塞的关键。     

Atrial fibrillation as a risk factor for deep venous thrombosis and pulmonary emboli in stroke patients

In 539 consecutive stroke patients admitted to a rehabilitation department, we studied the possible role of atrial fibrillation as a risk factor for deep venous thrombosis and pulmonary embolism by analyzing a series of relevant clinical data in patients with and without atrial fibrillation and in patients with and without venous thromboembolic complications. Deep venous thrombosis as well as advanced age and cardiac disease were significantly (p less than 0.001) more frequent in patients with atrial fibrillation. However, in a model of simultaneous logistic regression carried out on the presence of absence of venous thromboembolic complications, atrial fibrillation was the only significant risk factor. In view of the morbidity and mortality linked to deep venous thrombosis, our findings argue for preventive anticoagulation therapy in stroke patients suffering from atrial fibrillation and merit further study.     

Antipsychotic and antidepressant drug use in the elderly and the risk of venous thromboembolism

BACKGROUND: Preliminary evidence suggests that use of antipsychotic drugs is associated with an increased risk of venous thromboembolism. OBJECTIVE: To evaluate the relationship between antipsychotic or antidepressant drug use and venous thromboembolism among adults aged 65 years and older. DESIGN: Retrospective cohort study using linked health care administrative databases over a nine year period. SETTING: The entire province of Ontario, Canada. PARTICIPANTS: Individuals aged 65 years and over exclusively prescribed either antipsychotic drugs (n = 22,514), antidepressant drugs (n = 75,649) or thyroid replacement hormones (33,033), the referent control group. We excluded those with an antecedent history of cardiovascular disease, venous thromboembolism or cancer, as well as those dispensed warfarin before study entry. MEASUREMENTS: Diagnosis of deep vein thrombosis or pulmonary embolism. RESULTS: Relative to those prescribed thyroid hormones, neither antidepressant (adjusted hazard ratio 1.02, 95% CI 0.91-1.14) nor antipsychotic (adjusted hazard ratio 1.13, 95% CI 0.96-1.32) drug use was associated with an increased risk for deep vein thrombosis. Similar risk estimates were found for deep vein thrombosis or pulmonary embolism. In a sub-group analysis, only butyrophenone use was found to be associated with a slightly increased risk of deep vein thrombosis (adjusted HR 1.51, 95% CI 1.23-1.86) as well as deep vein thrombosis or pulmonary embolism (adjusted HR 1.43, 95% CI 1.18-1.74). CONCLUSIONS: In a large cohort of adults aged 65 years and older, neither antipsychotic or antidepressant drug use was associated with an increased risk of venous thromboembolism, with the exception of a slightly increased risk among those prescribed butyrophenones. Further data are required before use of these psychoactive drugs can be considered a risk factor for venous thromboembolism.     

Antithrombotic therapy in acute ischaemic stroke: an overview of the completed randomised trials.

A formal statistical overview of all truly randomised trials was undertaken to determine whether antithrombotic therapy is effective and safe in the early treatment of patients with acute stroke. There were 15 completed randomised controlled trials of the value of early antithrombotic treatment in patients with acute stroke. The regimes tested in acute presumed or confirmed ischaemic stroke were: heparin, 10 trials with 1047 patients: oral anticoagulants, one trial with 51 patients: antiplatelet therapy, three trials with 103 patients. Heparin was tested in one trial with 46 patients with acute haemorrhagic stroke. Outcome measures were deep venous thrombosis (confirmed by I125 scanning or venography), pulmonary embolism, death from all causes, haemorrhagic transformation of cerebral infarction, level of disability in survivors. In patients with acute ischaemic stroke, allocation to heparin was associated with a highly significant 81% (SD 8, 2p < 0.00001) reduction in deep venous thrombosis detected by I125 fibrinogen scanning or venogram. Only three trials systematically identified pulmonary emboli, which occurred in 6/106 (5.7%) allocated control vs 3/132 (2.3%) allocated heparin, a non-significant 58% reduction (SD 45.7, 2p > 0.1). There were relatively few deaths in the trials in patients with presumed ischaemic stroke: 94/485 (19.4%) among patients allocated to the control group vs 79/497 (15.9%) among patients who were allocated heparin. The observed 18% (SD 16) reduction in the odds of death was not statistically significant. The least biased estimated of the effect of treatment on haemorrhagic transformation of the cerebral infarct (HTI) comes from trials where all patients were scanned at the end of treatment, irrespective of clinical deterioration; using this analysis, haemorrhagic transformation occurred in 7/102 (6.9%) control vs 8/106 (7.5%) treated, a non-significant 12% increase (SD 56, 2p > 0.1). These data cannot exclude the possibility that heparin substantially increases the risks of HTI. No data on disability in survivors could be obtained. Early heparin treatment might be associated with substantial reductions in deep venous thrombosis (and probably also pulmonary embolism) and possibly a one fifth reduction in mortality (equivalent to the avoidance of 20-40 early deaths per thousand patients treated.) However, the data were wholly inadequate on safety, particularly on the risk of haemorrhagic transformation of the infarct and on the hazards of heparin therapy in patients with known intracerebral haemorrhage. The trials of oral anticoagulants (15 deaths among 57 patients) and antiplatelet therapy (two deaths among 103 patients) were too small to be informative. Much larger randomized trials-comparing aspirin, heparin and the combination of both drugs against control-in patients with acute ischaemic stroke are justified (and several are now planned or underway).     

Treatment and prophylaxis of venous thromboembolism during pregnancy

The treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) in pregnant patients is challenging for several reasons. Coumarins can cause embryopathy and other adverse effects in the fetus. Although unfractionated heparin and low-molecular-weight heparins, the cornerstones of initial therapy, are safe for the fetus, they can have significant maternal side effects, including osteoporosis and thrombocytopenia. Because they must be given parenterally, long-term administration is inconvenient. Further, although low-molecular-weight heparins probably cause less maternal osteoporosis and thrombocytopenia than unfractionated heparin, the appropriate dosing regimens for prevention and treatment of thrombosis during pregnancy have not been established. In addition, there is a paucity of reliable information on the incidence of venous thromboembolism and the risk of recurrent thrombosis during pregnancy. This paper briefly reviews the areas of controversy and provides recommendations for the treatment and prophylaxis of acute deep vein thrombosis and pulmonary embolism in pregnant patients.     

细胞黏附分子血浆E-选择素水平与下肢深静脉血栓形成

背景：研究表明，深静脉内白细胞参与的炎症反应在深静脉血栓形成中起了很重要的作用，而E-选择素的主要作用是介导炎症过程中白细胞与血管内皮细胞黏附的起始过程。 目的：拟观察细胞黏附分子E-选择素水平与下肢深静脉血栓形成的关系。 设计、时间及地点：配对设计，直线相关分析，于2007-09/12在重庆医科大学附属第一医院血管外科及重庆医科大学临床检验诊断学实验室完成。 对象：选择发病在3 d 内或病情加重的27例下肢深静脉血栓形成患者，男16例，女11例，平均年龄(57±15)岁。 方法：入院时采集第1次血液标本，经过溶栓，抗凝治疗72 h 后采集第2次血液标本。用ELISA法测定血浆中E-选择素的质量浓度，同时测定第1次采血样本的血小板计数及其凝血功能，包括部分激活凝血活酶时间、凝血酶原时间、血浆纤维蛋白原。 主要观察指标：治疗前后患者E-选择素的水平，治疗前凝血功能、血小板计数及与E-选择素相关性分析。 结果：27例下肢深静脉血栓形成患者在治疗期间均未发生急性肺栓塞，1例行Forgart导管取栓术，其余26例患者72 h 后，15例患者临床症状明显好转，11例临床症状未见好转。①下肢深静脉血栓形成患者经过溶栓、抗凝治疗临床缓解者血浆E-选择素水平明显下降(P=0.001)，而临床未缓解者血浆E-选择素水平则呈上升表现(P=0.003)。②下肢深静脉血栓形成患者治疗前E-选择素水平与血小板计数无相关性(r=-0.113，P=0.576)，与纤维蛋白原含量无相关性(r=-0.050，P=0.802)，与部分激活凝血活酶时间无相关性(r=-0.046，P=0.822)，与凝血酶原时间亦无相关性(r=-0.080，P=0.690)。 结论：血浆E-选择素水平与深静脉血栓形成症状严重程度呈正相关性。     

Effects of low-dose subcutaneous heparin on the occurrence of deep vein thrombosis in patients with ischemic stroke

The effectiveness of low-dose subcutaneous heparin in the prophylaxis of deep vein thrombosis in patients with ischemic stroke was investigated in an unblinded controlled study. The frequency of deep vein thrombosis and pulmonary embolism in the control group was 23% versus 2% in the patients receiving heparin. There were no bleeding complications in the test group and there were no differences in the occurrence of hemorrhage changes in the cerebral ischemic infarction in both groups.     

Diagnostic issues of VTE in pregnancy

Venous thromboembolism is a major cause of maternal morbidity and mortality, and accurate diagnostic workup upon suspicion of deep vein thrombosis or pulmonary embolism in a pregnant woman is of utmost importance. The diagnostic repertoire for venous thromboembolism is, however, less well studied in pregnant women. The clinical assessment is influenced by common symptoms of pregnancy such as leg swelling or shortness of breath. The role of D-Dimer is limited, since — even during uncomplicated pregnancy — D-Dimer levels increase with gestational age. Preliminary data indicate that a normal D-Dimer in a healthy pregnant woman with a low clinical probability may exclude deep vein thrombosis. Compression ultrasonography and ventilation perfusion scanning or helical computed tomography are the imaging techniques of choice in a pregnant woman with suspected deep vein thrombosis or pulmonary embolism, respectively. The role of magnetic resonance imaging for the diagnosis of venous thromboembolism during pregnancy is uncertain and contraindications particularly to contrast media have to be considered.     

Recurrent restenosis after percutaneous transluminal coronary angioplasty in a patient with congenital protein C deficiency and high activated factor VII level

Congenital protein C deficiency is known to be associated with increased risk of venous thrombosis and pulmonary embolism (1). However, it is controversial whether the protein C deficiency increases the risk of arterial diseases. Clinically, more than 75% of all thrombotic episodes in congenital protein C deficiency patients are deep venous thrombosis and pulmonary embolism, and arterial diseases such as myocardial infarction or stroke are very rare (2%, and 1%, respectively) (2). There have been only a few cases reported about this deficiency in patients with myocardial infarction (3, 4) or brain infarction (5). We describe a patient with protein C deficiency and a high level of activated factor VII who presented with myocardial infarction and restenosis that recurred 6 times after percutaneous transluminal coronary angioplasty (PTCA).     

神经外科术后静脉栓塞症发病率及早期诊断

目的对神经外科术后患者静脉栓塞症（深静脉血栓和肺栓塞）发病率及早期诊断进行前瞻性研究。方法37例神经外科术后患者均按照静脉血栓预防指南进行了弹力袜和（或）四肢间隙气动压迫的预防性治疗。在术后平均12d进行血管彩色超声检查,并通过增强CT扫描明确诊断。结果本组研究中下肢深静脉血栓发生率为13．5％,在发生深静脉血栓患者中肺栓塞发生率为60％,所有静脉血栓患者在临床上均没有症状。结论在神经外科术后患者中静脉血栓症的发病率很高,在采用了预防措施后部分患者依然不能避免,早期预防和早期发现对于减少神经外科术后静脉栓塞症非常重要。     

Low-molecular-weight heparins and heparinoids in acute ischemic stroke : a meta-analysis of randomized controlled trials

BACKGROUND AND PURPOSE: Low-molecular-weight heparins and heparinoids (LMWHs) are superior to unfractionated heparin in the prevention and treatment of venous thromboembolism and acute coronary syndromes. We performed a systematic review of randomized controlled trials (RCTs) to examine the safety and efficacy of LMWH in acute ischemic stroke. METHODS: Randomized, controlled, and nonconfounded trials of LMWH in acute ischemic stroke were identified from the Cochrane Library (version 2, 1999), previous systematic reviews, and a review of publication quality relating to acute stroke trials. The authors each independently extracted data by treatment group and assessed trial quality using Cochrane Collaboration criteria. RESULTS: Eleven completed RCTs involving 3048 patients were identified; data were available from 10 of these. Four trials explicitly excluded patients with presumed cardioembolic stroke. Treatment with LMWH was associated with significant reductions in prospectively identified deep vein thrombosis (OR 0.27, 95% CI 0.08 to 0.96) and symptomatic pulmonary embolism (OR 0.34, 95% CI 0.17 to 0.69) and with increased major extracranial hemorrhage (OR 2.17, 95% 1.10 to 4.28). Nonsignificant increases in end-of-treatment (OR 1.20, 95% CI 0.86 to 1.69) and end-of-trial (OR 1.05, 95% CI 0.83 to 1.32) case fatality and symptomatic intracranial hemorrhage (OR 1.77, 95% CI 0. 95 to 3.31) were observed. End-of-trial death and disability was nonsignificantly reduced (OR 0.87, 95% CI 0.72 to 1.06). CONCLUSIONS: ++LMWHs reduce venous thromboembolic events in patients with acute ischemic stroke and increase the risk of extracranial bleeding. A nonsignificant reduction in combined death and disability and nonsignificant increases in case fatality and symptomatic intracranial hemorrhage were also observed. On the basis of the current evidence, LMWH should not be used in the routine management of patients with ischemic stroke.     

Hemolytic anemia presenting as idiopathic intracranial hypertension

The authors report three cases of ischemic stroke in young adults that occurred during or after an airplane flight. Workup was negative for any cause of stroke other than the presence of a patent foramen ovale (PFO). There is an increasing awareness of deep vein thrombosis and pulmonary embolism occurring in relation to long flights. Individuals with a PFO under these circumstances may be vulnerable to stroke from paradoxic embolism. "Economy class" stroke syndrome may be underdiagnosed and is an eminently preventable cause of stroke.     

Familial hyperhomocysteinemia-related cerebral venous sinus thrombosis and pulmonary embolism: a case report

Elevated plasma homocysteine levels are associated with an increased risk of deep vein thrombosis. Herein we report a case of familial hyperhomocysteinemia-related cerebral venous sinus thrombosis and pulmonary embolism in a 21-year-old man who presented with severe headache over bilateral frontal areas. Neurological examination revealed no evidence of focal neurological deficit. Chest CT showed pulmonary thromboembolism in bilateral basal lung fields and brain MRI disclosed right transverse and sigmoid venous sinus thrombosis. Routine immunological tests, coagulation factors and occult tumor screening were normal, as were vitamin B12 and folate levels. The DIC profile was negative, The only risk factor we were able to identify was an elevated serum homocysteine level, namely 46.23 microM/L. Hyperhomocysteinemia was also noted in the patient's asymptomatic elder brother (68.0 microM/L) and, to a lesser extent, in his parents (father 12.5 microM/L; mother 11.7 microM/L). In conclusion, the cause of cerebral venous thrombosis and pulmonary embolism in this young patient was most likely related to familial hyperhomocysteinemia, with the thromboembolic events precipitated by a preceding systemic infection. After anticoagulation therapy; the patient recovered completely without any residual neurological deficit.     

Isolated internal auditory artery aneurysm

Anticoagulant therapy is effective and prevents death in more than 95% of patients with pulmonary embolism following deep vein thrombosis. We report a patient who developed deep vein thrombosis following rupture of a dissecting aneurysm of the internal auditory artery. The parent artery was occluded before anticoagulant therapy as a prophylactic measure to prevent intracranial haemorrhage. We discuss some of the clinical features, therapeutic difficulties, and pitfalls in the management of internal auditory artery aneurysm complicated by deep vein thrombosis.     

Trends in hospital admission for stroke in Calgary

BACKGROUND: Stroke incidence has fallen since 1950. Recent trends suggest that stroke incidence may be stabilizing or increasing. We investigated time trends in stroke occurrence and in-hospital morbidity and mortality in the Calgary Health Region. MEthods: All patients admitted to hospitals in the Calgary Health Region between 1994 and 2002 with a primary discharge diagnosis code (ICD-9 or ICD-10) of stroke were included. In-hospital strokes were also included. Stroke type, date of admission, age, gender, discharge disposition (died, discharged) and in-hospital complications (pneumonia, pulmonary embolism, deep venous thrombosis) were recorded. Poisson and simple linear regression was used to model time trends of occurrence by stroke type and age-group and to extrapolate future time trends. RESULTS: From 1994 to 2002, 11642 stroke events were observed. Of these, 9879 patients (84.8%) were discharged from hospital, 1763 (15.1%) died in hospital, and 591 (5.1%) developed in-hospital complications from pneumonia, pulmonary embolism or deep venous thrombosis. Both in-hospital mortality and complication rates were highest for hemorrhages. Over the period of study, the rate of stroke admission has remained stable. However, total numbers of stroke admission to hospital have faced a significant increase (p=0.012) due to the combination of increases in intracerebral hemorrhage (p=0.021) and ischemic stroke admissions (p=0.011). Sub-arachnoid hemorrhage rates have declined. In-hospital stroke mortality has experienced an overall decline due to a decrease in deaths from ischemic stroke, intracerebral hemorrhage and sub-arachnoid hemorrhage. CONCLUSIONS: Although age-adjusted stroke occurrence rates were stable from 1994 to 2002, this is associated with both a sharp increase in the absolute number of stroke admissions and decline in proportional in-hospital mortality. Further research is needed into changes in stroke severity over time to understand the causes of declining in-hospital stroke mortality rates.