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The article focuses on a study which assessed the long-term effects of successful carotid endarterectomy (CEA) in patients with asymptomatic stenosis. The study included 3,120 asymptomatic patients from 126 centers in 30 countries, who were randomized to receive either immediate CEA or indefinite deferral of any carotid procedure. Study authors concluded that successful CEA reduced 10-year stroke risks in asymptomatic patients who are younger than 75 years.

The authors comment on two studies which examined the link between carotid stenting (CAS) or carotid endarterectomy (CEA) and periprocedural risk of stroke or death, published within the issue. The first study is a meta-analysis of patient data, which found that CAS is associated with higher periprocedural risk of stroke or death compared to CEA. The other study confirmed the superiority of immediate CEA in asymptomatic carotid stenosis.

The article discusses a study which investigated the effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke. The researchers identified randomised controlled trials (RCT) from published systematic reviews and searched Medline and Cochrane databases from 1950 to first week of July 2009. Poor reporting of interindividual variation in blood pressure in RCT of antihypertensive drugs was found. Several issues that need to be discussed are also cited, including the low rate of reporting of blood pressure.

The article details a study which investigated the link between C-reactive protein (CRP) concentration and the risk of vascular and non-vascular outcomes. The study included 160,309 people without a history of vascular disease, whose risk factors and inflammatory markers were analyzed. It found some associations between CRP concentration and coronary heart disease, ischaemic stroke and vascular mortality. Study authors concluded that the link between CRP and ischaemic vascular disease is influenced by conventional risk factors and other inflammatory markers.

The article presents an overview of the mechanisms involved with thrombogenesis in atrial fibrillation. Atrial fibrillation, the most common cardiac arrhythmia, is associated with the the risk of stroke and thromboembolism. Abnormal changes in the vessel walls including endocardial denudation and aedematous or fibroelastic infiltration of the extracellular matrix are discussed. Changes in the blood constituents including haemostatic and platelet activation and inflammation and growth factor changes comprise Virchow's triad for thrombogenesis.

This article reports on a clinical trial that sought to compare the use of idraparinux to vitamin K antagonists to prevent thromboembolism in patients with atrial fibrillation. Non-valvular atrial fibrillation is the leading cause of stroke and studies have showed that anticoagulation with vitamin K antagonists can reduce the risk of stroke by a third. Despite that, the use of the drugs in clinical practice is limited due to the risk of bleeding and the complexity of monitoring the dosage. Researchers are hoping to find an unmonitored, fixed-dose anticoagulant that will be effective. This study was not the answer. It had to be stopped after patients getting the idrapariux bled excessively.

This article reports on a meta-analysis to determine the joint relevance to total cholesterol and high blood pressure on the risk of vascular mortality. The authors looked at 61 prospective observational studies in western Europe and North American which involved 900,000 adults without previous disease. The study found that total cholesterol was positively associated with ischaemic heart disease (IHD) mortality in both middle and old age and at all blood pressure levels. There was no evidence of an association between cholesterol levels and stroke mortality. The study also suggests that statins reduce heart events and strokes in patients of many ages and blood pressures.

This article presents a review of the role and safety of statins in clinical practice. Statins are commonly used to control cholesterol levels and thus reduce the risk of heart attack or stroke. There are adverse effects in a small percentage of patients such as myopathy and rhabdomyolysis in the muscles and potential damage to the liver where they increase the levels of transaminases. Both side effects are unusual at normal doses. Side-effects can be stopped with the withdrawal of the medication and most patients recover fully. How statins work to lower cholesterol levels is explained. Drugs that might interfere with statins are listed.

This article reports on a cohort study to see if there was a link between venous thromboembolism and arterial cardiovascular events such as heart attack and stroke. Venous thromboembolism is common in Western countries and is generally considered to be different from thrombotic atherosclerotic disease because arterial thrombi consist of platelets where venous thrombi mainly consist of red blood cells and fibrin. The study examined 20 years of data in Denmark and found that patients with venous thromboembolisms have a significantly higher chance of developing arterial cardiovascular episodes.

Summary Background Results of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) show significantly lower rates of coronary and stroke events in individuals allocated an amlodipine-based combination drug regimen than in those allocated an atenolol-based combination drug regimen (HR 0·86 and 0·77, respectively). Our aim was to assess to what extent these differences were due to significant differences in blood pressures and in other variables noted after randomisation. Methods We used data from ASCOT-BPLA (n=19 257) and compared differences in accumulated mean blood pressure levels at sequential times in the trial with sequential differences in coronary and stroke events. Serial mean matching for differences in systolic blood pressure was used to adjust HRs for differences in these events. We used an updated Cox-regression model to assess the effects of differences in accumulated mean levels of various measures of blood pressure, serum HDL-cholesterol, triglycerides and potassium, fasting blood glucose, heart rate, and bodyweight on differences in event rates. Findings We noted no temporal link between size of differences in blood pressure and different event rates. Serial mean matching for differences in systolic blood-pressure attenuated HRs for coronary and stroke events to a similar extent as did adjustments for systolic blood-pressure differences in Cox-regression analyses. HRs for coronary events and stroke adjusted for blood pressure rose from 0·86 (0·77-0·96) to 0·88 (0·79-0·98) and from 0·77 (0·66-0·89) to 0·83 (0·72-0·96), respectively. Multivariate adjustment gave HRs of 0·94 (0·81-1·08) for coronary events (HDL cholesterol being the largest contributor) and 0·87 (0·73-1·05) for stroke events. Interpretation Multivariate adjustment accounted for about half of the differences in coronary events and for about 40% of the differences in stroke events between the treatment regimens tested in ASCOT-BPLA, but residual differences were no longer significant. These residual differences could indicate inadequate statistical adjustment, but it remains possible that differential effects of the two treatment regimens on other variables also contributed to the different rates noted, particularly for stroke. [ABSTRACT FROM AUTHOR]

Summary Background Effective early management of patients with transient ischaemic attacks (TIA) is undermined by an inability to predict who is at highest early risk of stroke. Methods We derived a score for 7-day risk of stroke in a population-based cohort of patients (n=209) with a probable or definite TIA (Oxfordshire Community Stroke Project; OCSP), and validated the score in a similar population-based cohort (Oxford Vascular Study; OXVASC, n=190). We assessed likely clinical usefulness to front-line health services by using the score to stratify all patients with suspected TIA referred to OXVASC (n=378, outcome: 7-day risk of stroke) and to a hospital-based weekly TIA clinic (n=210; outcome: risk of stroke before appointment). Results A six-point score derived in the OCSP (age [&ges;60 years=1], blood pressure [systolic >140 mm Hg and/or diastolic &ges;90 mm Hg=1], clinical features [unilateral weakness=2, speech disturbance without weakness=1, other=0], and duration of symptoms in min [&ges;60=2, 10-59=1, <10=0]; ABCD) was highly predictive of 7-day risk of stroke in OXVASC patients with probable or definite TIA (p<0·0001), in the OXVASC population-based cohort of all referrals with suspected TIA (p<0·0001), and in the hospital-based weekly TIA clinic-referred cohort (p=0·006). In the OXVASC suspected TIA cohort, 19 of 20 (95%) strokes occurred in 101 (27%) patients with a score of 5 or greater: 7-day risk was 0·4% (95% CI 0-1·1) in 274 (73%) patients with a score less than 5, 12·1% (4·2-20·0) in 66 (18%) with a score of 5, and 31·4% (16·0-46·8) in 35 (9%) with a score of 6. In the hospital-referred clinic cohort, 14 (7·5%) patients had a stroke before their scheduled appointment, all with a score of 4 or greater. Conclusions Risk of stroke during the 7 days after TIA seems to be highly predictable. Although further validations and refinements are needed, the ABCD score can be used in routine clinical practice to identify high-risk individuals who need emergency investigation and treatment. [ABSTRACT FROM AUTHOR]

Background Individuals homozygous for the T allele of the MTHFR C677T polymorphism have higher plasma homocysteine concentrations (the phenotype) than those with the CC genotype, which, if pathogenetic, should put them at increased risk of stroke. Since this polymorphism is distributed randomly during gamete formation, its association with stroke should not be biased or confounded. We investigated consistency between the expected odds ratio for stroke among TT homozygotes, extrapolated from genotype-phenotype and phenotype-disease studies, and the observed odds ratio from a meta-analysis of genotype-disease association studies. [ABSTRACT FROM AUTHOR]

Background Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce ulcer complications compared with nonselective non-steroidal anti-inflammatory drugs, but evidence is limited, and the possibility that these inhibitors increase cardiovascular events has been raised. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) aimed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs, naproxen and ibuprofen. Methods 18 325 patients age 50 years or older with osteoarthritis were randomised to lumiracoxib 400 mg once daily n=9156), naproxen 500 mg twice daily (4754), or ibuprofen 800 mg three times daily (4415) for 52 weeks, in two substudies of identical design (lumiracoxib vs ibuprofen or naproxen). Randomisation was stratified for low-dose aspirin use and age. The primary endpoint was the difference in time-to-event distribution of upper gastrointestinal ulcer complications (bleeding, perforation, or obstruction); analysis was by modified intention to treat. The principle measure of adverse cardiovascular events was the Antiplatelet Trialists' Collaboration endpoint (myocardial infarction, stroke, or cardiovascular death); this analysis was intention to treat. Findings 81 (0.44%) patients did not start treatment and 7120 (39%) did not complete the study. In patients not taking aspirin, the cumulative 1-year incidence of ulcer complications was 1.09% (95% CI 0.82-1.36) with nonsteroidal anti-inflammatory drugs (64 events) versus 0.25% (95% CI 0.12-0.39) with lumiracoxib (14 events; hazard ratio 0.21 [95% CI 0.12-0.37], p<0.0001). Reductions in ulcer complications were also significant in the overall population (0.34 [0.22-0.52], p<0.0001) but not in those taking aspirin (0.79 [0.40-1.55], p=0.4876). [ABSTRACT FROM AUTHOR]

Background Carotid endarterectomy reduces the risk of stroke in patients with recently symptomatic stenosis. Benefit depends on the degree of stenosis, and we aimed to see whether it might also depend on other clinical and angiographic characteristics, and on the timing of surgery. Methods We analysed pooled data from the European Carotid Surgery Trial and North American Symptomatic Carotid Endarterectomy Trial. The risk of ipsilateral ischaemic stroke for patients on medical treatment, the perioperative risk of stroke and death, and the overall benefit from surgery were determined in relation to seven predefined and seven post hoc subgroups. Results 5893 patients with 33 000 patient-years of follow-up were analysed. Sex (p=0.003), age (p=0.03), and time from the last symptomatic event to randomisation (p=0.009) modified the effectiveness of surgery. Benefit from surgery was greatest in men, patients aged 75 years or older, and those randomised within 2 weeks after their last ischaemic event, and fell rapidly with increasing delay. For patients with 50% or higher stenosis, the number of patients needed to undergo surgery (ie, number needed to treat) to prevent one ipsilateral stroke in 5 years was nine for men versus 36 for women, five for age 75 years or older versus 18 for younger than 65 years, and five for those randomised within 2 weeks after their last ischaemic event, versus 125 for patients randomised after more than 12 weeks. These results were consistent across the individual trials. Interpretation: Benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other clinical characteristics such as delay to surgery after the presenting event. Ideally, the procedure should be done within 2 weeks of the patient's last symptoms. [ABSTRACT FROM AUTHOR]

Interpretation: Low total serum cholesterol is not an independent risk factor for either intracerebral or subarachnoid haemorrhagic stroke in Korean men. [ABSTRACT FROM AUTHOR]

Assesses the contributions of blood pressure and blood cholesterol concentrations to stroke risk in populations from eastern Asia. Methods; Findings; Interpretation that blood pressure is an important determinant of stroke risk.

Studies the risk of cerebrovascular disease in the distribution of an asymptomatic carotid artery. Advocation for screening and endarterectomy procedures; Efficacy of carotid endarterectomy in patients who had symptomatic carotid stenosis; Characteristics of studied patients; Burden of disability resulting from stroke in the asymptomatic carotid stenosis distribution.

Investigates the relation between anticardiolipin antibodies (ACAs) and susceptibility to stroke/cerebrovascular disease. Prevalence of high titres of ACAs; Implications on therapeutic intervention and the practice of routine ACA screening in stroke.

Assesses whether high concentrations of tissue plasminogen activator (tPA) among apparently healthy men are associated with the occurrence of stroke. Incidence of stroke; Risk factors for stroke; Hypothesis that the activation of the endogenous fibrinolytic system precedes arterial vascular occlusion.

Considers how mechanisms involved in progression of stoke are little understood. Results of study which looked for an association between concentrations of glutamate and glycine in plasma and cerebrospinal fluid and early progression in a prospective study of 128 patients with acute ischaemic stroke; Methods; Findings; Interpretation.

Discusses a study to assess if the risk of stroke in adult life is linked to impaired fetal growth. Methods of the study; Findings of the study; Interpretation of the findings.

The author examines the clinical implications of data from three studies which discovered an excess risk of stroke and death posed by angioplasty and stenting. He presents an overview of the studies, which included the International Carotid Stenting Study and the Carotid Revascularization Endarterectomy Versus Stent Trial. He cites several reasons for the difficulty of justifying routine stenting in symptomatic patients. The author also describes the advantages of endarterectomy over stenting.

This article comments on a study in this issue which reported a significant association between venous thromboembolism and myocardial infarction or stroke. The study showed the risk of heart attack or stroke was the highest in the first years after diagnosis of venous thromboembolism which is odd because the standard treatment of anticoagulant drugs should lower the risk. The author says more studies are needed on shed light on this.

This editorial examines a prediction chart made by the World Health Organization (WHO) in collaboration with the International Society of Hypertension (ISH) to make available cost-effective strategies for potential heart attack and stroke victims in middle to low-income countries. It is estimated that by 2015, 20 million people will die from one of these occurrences. The risk prediction chart allows treatment to be targeted to those most at risk which saves valuable resources.

The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was designed to test whether, for the same achieved blood pressures, regimens based on valsartan or amlodipine would have differing effects on cardiovascular endpoints in high risk hypertension. But inequalities in blood pressure, favouring amlodipine, throughout the multiyear trial precluded comparison of outcomes. A technique of serial median matching, applied at 6 months when treatment adjustments intended to achieve control of blood pressure were complete, created 5006 valsartan-amlodipine patient pairs matched exactly for systolic blood pressure, age, sex, and the presence or absence of previous coronary disease, stroke, or diabetes. Subsequent combined cardiac events, myocardial infarction, stroke, and mortality were almost identical in the two cohorts, but admission to hospital for heart failure was significantly lower with valsartan. Reaching blood pressure control (systolic <140 mm Hg) by 6 months, independent of drug type, was associated with significant benefits for subsequent major outcomes; the blood pressure response after just 1 month of treatment predicted events and survival. [ABSTRACT FROM AUTHOR]

Background Cerebrovascular disease is thought to be a major cause of epilepsy in late life. We investigated the hypothesis that the onset of seizures after the age of 60 years in people with no history of overt stroke might be associated with an increased risk of subsequent stroke. Methods Data were obtained from the UK General Practice Research Database on 4709 individuals who had seizures beginning at or after the age of 60 years, and on 4709 randomly selected controls with no history of seizures, matched for age, sex, and general practice. Individuals with a history of cerebrovascular disease, other acquired brain injury, brain tumour, drug or alcohol misuse, or dementia were not eligible for inclusion. Computerised patients' records were searched for subsequent diagnoses of stroke. Findings Log-rank testing, adjusted for matching, showed a highly significant difference in stroke-free survival between the two groups (p<0.0001). With a Cox's model, we estimated that the relative hazard of stroke at any point for people with seizures compared with the control group was 2.89 (95% CI 2.45--3.41). Interpretation Our findings show that the onset of seizures in late life is associated with a striking increase in the risk of stroke. Further research is warranted to assess the benefit of specific interventions to prevent stroke in patients with seizures. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response the article "Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis," by Alastair Webb and colleagues, published in the March 13, 2010 issue, along with a response of the research authors.

The article presents a reprint of the article "Reducing the global burden of stroke: INTERSTROKE," by Jack V. Tu, which was published online on June 18, 2010. In this article the author discusses results of INTERSTROKE investigations on stroke risk-factors. The author emphasizes that understanding risk factors in low or medium income families is needed to reduce stroke mortality in developing countries. He also mentions several risks factors revealed by INTERSTROKE such as smoking and diet.

This article comments on a study in this issue which looked at the risk of stroke in older patients on warfarin or aspirin for atrial fibrillation. The study found warfarin was superior to aspirin in the prevention of stroke and was no more harmful to the patients in terms of major haemorrhage. The author maintains that the subjects of the study had a lower prevalence of risk factors for stroke overall and that the challenge will be to see if the results are the same on higher risk patients.

Looks at the chance for recurrent vascular events following transient ischemic attack (TIA). Reference to a study by Iris van Wijk and colleagues in the June 18, 2005 issue of "The Lancet," in which the prognosis for TIA was studied; Risk factors for stroke and other vascular events following TIA; Progression of atherosclerosis in patients who have had TIA; Importance of monitoring TIA patients for risk of cardiovascular and cerebrovascular events; Importance of taking a thorough history in the prevention and treatment of disease.

Presents a commentary on patients who suffer both stroke and epilepsy and the report in this issue which suggests a three fold risk of stroke in older people presenting with new-onset idiopathic epileptic seizures; Why this is a good study; What the limitations of the study are; Implication which is that unexplained epilepsy in older people may be due to occult cerebrovascular disease; Rarity of late on set epilepsy in clinical practice; Belief it won't harm patients to be assessed for the risk of stroke and to be considered for stroke preventing medications.

Factors which increase the risk of stroke in patients with the A3243G (mitochondrial encephalomyopathy, lactic acidosis, and stroke [MELAS]) mutation in human mitochondrial DNA are unclear. Previous work on lung-cancer cells with an A3243G mutation showed that a mutation in the mitochondrial transfer gene for leucine tRNA(Leu(CUN)) was able to ameliorate the A3243G-induced biochemical phenotype. We analysed the tRNA(Leu(CUN)) gene in 48 unrelated A3243G cases. We showed that a polymorphism, A12308G, in tRNA(Leu(CUN)) increases the risk of developing stroke in patients with the A3243G mutation (relative risk=2.17). This may have implications for genetic counselling. [ABSTRACT FROM AUTHOR]

Presents a study which investigates the link between plasma cholesterol concentrations and the risk of cerebrovascular disease (CVD) by studying the atherogenic lipid profile of elderly patients with ischaemic CVD. Background; Methods; Finding; Interpretation.

The multicentre WHO collaborative case-control study had limited power to differentiate stroke risks by progestagen component in low dose combined oral contraceptives. Given this caveat, odds ratios for ischaemic, haemorrhagic, and all strokes combined associated with use of oral contraceptives containing desogestrel or gestodene ("third generation") were found to be similar to those containing levonorgestrel in this study. [ABSTRACT FROM AUTHOR]

Evaluates the risk of idiopathic cerebral hemorrhage in users of third-generation oral contraceptives compared with that of second-generation product users. Data from the General Practice Research Database; Finding of no increased risk.

Proposes a hypothesis concerning the fact that children with sickle-cell anemia are predisposed to thrombotic strokes. The effects of erythropoietin, a primary regulator of red-cell production; Testing of the hypothesis.

Comments on a study of mtDNA genotypes in patients who had an occipital stroke and a history of migraine. The inclusion of patients with A3243G, a point mutation of a nucleotide; Analysis of informative polymorphisms to determine mtDNA genotypes in blood DNA; Polymorphic sites defining mtDNA haplogroups found in different populations by continent; Suggestion that mtDNA haplogroup U constitutes a risk genome that may harbor mutations in the pathogenesis of migraine-associated stroke.

Opinion. Discusses advanced atherosclerosis in the aortic arch as a possible source of cerebral emboli and an independent risk factor for ischemic stroke. Non-invasive methods of studying the aorta; Independent risk factors for cardiovascular and cerebrovascular disease associated with stiff aortas.

A letter to the editor is presented on the article "Fruit and vegetable consumption and stroke: a meta-analysis of cohort studies," by F. J. He, C. A. Nowson, and G. A. MacGregor, in the January 28, 2006 issue.

Reports on a study which suggests that young adults are ignoring the warning that a myocardial infarction or stroke in a close family member puts a person at increased risk and signals the need for risk-reducing behaviors. Comments of Kevin Kip and Larry Goldstein; Outlook for encouraging health behavior change.

Offers medical news for February 23, 2002. Indication that there is no link between climate change and the resurgence of malaria in areas of East Africa; Lack of awareness among diabetics that they have an increased risk of cardiovascular disease and stroke, according to a poll by the American Diabetes Association.

Reports that coronary calcification as detected by electron-beam computed tomography, is thought to be a predictor of coronary events such as myocardial infarction. Details of a study by Jacqueline Witteman et al in Netherlands that suggests how coronary calcification might predict stroke risk; Mention of research in Sweden on the subject.

Reports on research in Israel that indicates high blood triglyceride concentration is an independent predictor of stroke in people with coronary heart disease. Details of the study by David Tanne et al; Comment of Ralph Sacco, a New York researcher, on the relationship of lipids and stroke.

Reports on a study which assessed the relation between stress-induced blood pressure reactivity and risk of stroke in middle-aged white men. Evidence that men who were poorly educated and had high blood pressure reactivity were more likely to have a stroke than better educated men with less reactive blood pressures; Suggestion that the physiologic tendency to react strongly to stress are compounded by the difficult life circumstances associated with low levels of education.

Discusses a study which found that hormone replacement therapy with conjugated equine oestrogen and progestin neither increases nor decreases the risk of stroke in post-menopausal women. Relation to the Heart and Estrogen-progestin Replacement Study (HERS); Limitation of the findings.

Focuses on postmenopausal hormone therapy. Statement that some estrogen doses carry an increased risk of stroke; Results of a study to measure the effect of estrogen on cardiovascular health; Benefits of hormone therapy.

Reports on the deterioration seen in the rates of detecting and controlling hypertension in the United States during the 1990s. Details of a study conducted; How hypertension can lead to coronary heart disease and stroke; Improvements seen in Great Britain in terms of hypertension detection and treatment.

Discusses research on risk factors for strokes that occur during or after heart surgery. Brief statistics from a study by researchers at Washington University School of Medicine and Barnes-Jewish Hospital in Missouri; The female sex as an independent risk factor.

Reports patients who stop taking their antihypertensive drugs are at an increased risk of stroke. Amanda Thrift and coworkers in Australia finding intracerebral hemorrhage associated with hypertension was higher in patients who stopped medication; The question of why patients stop taking medications for treatment of high blood pressure.

Reports that reduction of blood pressure by as little as 5-10 mm Hg could substantially lower the risk of stroke. Details of the study which resulted in this conclusion.