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With both an aging population and greater post-stroke survival, multimorbidity is a growing healthcare challenge, affecting over 40% of stroke patients, and rising rapidly and predictably with increasing age. Commonly defined as the co-occurrence of two or more chronic conditions, multimorbidity burden is a strong adverse prognostic factor, associated with greater short- and long-term stroke mortality, worse rehabilitation outcomes, and reduced use of secondary prevention. Chronic kidney disease can be considered as the archetypal comorbidity, being age-dependent and also affecting about 40% of stroke patients. Chronic kidney disease and stroke share very similar traditional cardiovascular risk factor profiles such as hypertension and diabetes, though novel chronic kidney disease-specific risk factors such as inflammation and oxidative stress have also been proposed. Using chronic kidney disease as an exemplar condition, we explore the mechanisms of risk in multimorbidity, implications for management, impact on stroke severity, and downstream consequences such as post-stroke cognitive impairment and dementia. [ABSTRACT FROM AUTHOR]

Background: Intracranial atherosclerotic stenosis is a highly prevalent cause of stroke worldwide with important ethnic disparities. Widely considered to be a common cause of stroke in Asian and Afro-Caribbean populations, relatively less is known about the burden and significance of intracranial atherosclerotic stenosis in Caucasians. Aims: We aim to highlight recent insights and advances into the prevalence, prognosis, and treatment of symptomatic and asymptomatic atherosclerotic intracranial atherosclerotic stenosis in Caucasian patients. Summary of review: We identified 48 articles studying intracranial atherosclerotic stenosis in Caucasian patients with ischemic stroke or transient ischemic attack. Most studies were on hospital-based cohorts of consecutive patients and half were graded as "fair" quality. There was significant variation between studies in the definition of intracranial atherosclerotic stenosis and in the imaging modalities used to detect intracranial atherosclerotic stenosis. Overall, 12.1% of Caucasian patients were found to have any intracranial atherosclerotic stenosis, 6.4% symptomatic intracranial atherosclerotic stenosis and 11.1% asymptomatic intracranial atherosclerotic stenosis, with higher rates at older ages. In studies reporting prognosis, there were 61 and 10 same-territory ischemic strokes in 1000 person-years in patients with symptomatic and asymptomatic intracranial atherosclerotic stenosis, respectively. Percutaneous stenting and angioplasty have not proven superior to intensive medical management in patients with symptomatic intracranial atherosclerotic stenosis. Conclusions: Intracranial atherosclerotic stenosis has previously been neglected as a cause of stroke in Caucasians but is highly prevalent at older ages and frequently discovered with the growing use of noninvasive angiography. Intensive medical therapy is the treatment of choice, but there is a need to develop novel treatments or therapeutic approaches to lower the risk of stroke in higher risk patients. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of transient ischaemic attacks (TIAs) can be difficult. There is consensus on classic symptoms (eg, motor weakness, dysphasia, hemianopia, monocular visual loss) but no consensus on several monosymptomatic events with sudden-onset, non-progressive, focal negative symptoms (eg, isolated diplopia, dysarthria, vertigo, ataxia, sensory loss, and bilateral visual disturbance), with much variation in investigation and treatment.Methods: We prospectively ascertained and investigated all strokes and sudden onset transient neurological symptoms in a population of 92 728 people (no age restrictions) from Oxfordshire, UK, who sought medical attention at nine primary care practices or at the John Radcliffe Hospital, Oxford, UK (Oxford Vascular Study). Patients classified at baseline with minor ischaemic stroke (National Institutes of Health Stroke Score <5), classic TIA, or non-consensus TIA were treated according to secondary prevention guidelines. Risks of stroke (7-day, 90-day, and 10-year risks) and risks of all major vascular events (from the time of first event, and from the time of seeking medical attention) were established by face-to-face follow-up visits and were compared with the risk expected from age and sex-specific stroke incidence in the underlying study population.Findings: Between April 1, 2002, and March 31, 2018, 2878 patients were identified with minor ischaemic stroke (n=1287), classic TIA (n=1021), or non-consensus TIA (n=570). Follow-up was to Oct 1, 2018 (median 5·2 [IQR 2·6-9·2] years). 577 first recurrent strokes after the index event occurred during 17 009 person-years of follow-up. 90-day stroke risk from time of the index event after a non-consensus TIA was similar to that after classic TIA (10·6% [95% CI 7·8-12·9] vs 11·6% [95% CI 9·6-13·6]; hazard ratio 0·87, 95% CI 0·64-1·19; p=0·43), and higher than after amaurosis fugax (4·3% [95% CI 0·6-8·0]; p=0·042). However, patients with non-consensus TIA were less likely to seek medical attention on the day of the event than were those with classic TIA (336 of 570 [59%] vs 768 of 1021 [75%]; odds ratio [OR] 0·47, 95% CI 0·38-0·59; p<0·0001) and were more likely to have recurrent strokes before seeking attention (45 of 570 [8%] vs 47 of 1021 [5%]; OR 1·77, 95% CI 1·16-2·71; p=0·007). After excluding such recurrent strokes, 7-day stroke risk after seeking attention for non-consensus TIA (2·9% [95% CI 1·5-4·3]) was still considerably higher than the expected background risk (relative risk [RR] 203, 95% CI 113-334), particularly if the patient sought attention on the day of the index event (5·0% [2·1-7·9]; RR 300, 137-569). 10-year risk of all major vascular events was similar for non-consensus and classic TIAs (27·1% [95% CI 22·8-31·4] vs 30·9% [27·2-33·7]; p=0·12). Baseline prevalence of atrial fibrillation, patent foramen ovale, and arterial stenoses were also similar for non-consensus TIA and classic TIA, although stenoses in the posterior circulation were more frequent with non-consensus TIA (OR 2·21, 95% CI 1·59-3·08; p<0·0001).Interpretation: Patients with non-consensus TIA are at high early and long-term risk of stroke and have cardiovascular pathological findings on investigation similar to those of classic TIA. Designation of non-consensus TIAs as definite cerebrovascular events will increase overall TIA diagnoses by about 50%.Funding: Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, Wolfson Foundation, Masonic Charitable Foundation, and British Heart Foundation. [ABSTRACT FROM AUTHOR]

Objective: Cerebral autoregulation (CA) is critical to maintenance of cerebral perfusion but its relevance to the risk of stroke and dementia has been under-studied due to small study sizes and a lack of consensus as to the optimal method of measurement. We determined the reliability and reproducibility of multiple CA indices and the effect of intensive data-processing in a large population with transient ischaemic attack or minor stroke. Approach: Consecutive, consenting patients in the population-based Oxford Vascular Study (OXVASC) Phenotyped cohort underwent up to 10-min supine continuous blood pressure monitoring (Finometer) with bilateral middle cerebral artery (MCA) transcranial ultrasound (DWL-Dopplerbox). Un-processed waveforms (Un-A) were median-filtered, systematically reviewed, artefacts corrected and their quality blindly graded (optimal (A) to worst (E)). CA metrics were derived in time-domain (autoregulatory index (ARI), Pearson's Mx, Sx, Dx) and in very-low (VLF) and low-frequency (LF) domains (WPS-SI: wavelet phase synchronisation, transfer function analysis), stratified by recording quality. Reliability and reproducibility (Cronbach's alpha) were determined comparing MCA sides and the first vs. second 5-min of monitoring. Main results: In 453 patients, following manual data-cleaning, there was good reliability of indices when comparing MCA sides (Mx: 0.77; WPS-SI-VLF: 0.85; WPS-SI-LF 0.84), or repeated five minute epochs (Mx: 0.57; WPS-SI-VLF: 0.69; WPS-SI-LF 0.90), with persistently good reliability between sides even in lower quality Groups (Group D: Mx: 0.79; WPS-SI-VLF: 0.92; WPS-SI-LF: 0.91). Reliability was greatest for Pearson's Mx and wavelet synchronisation index, with reasonable reliability of transfer function analyses, but ARI was prone to occasional, potentially defective, extreme estimates (left vs right MCA: 0.68). Significance: Resting-state measures of CA were valid, reproducible and robust to moderate noise, but require careful data-processing. Mx and wavelet synchronisation index were the most reliable indices for determining the prognostic value of CA in large epidemiological cohorts and its potential as a treatment target. [ABSTRACT FROM AUTHOR]

Ischaemic heart disease and stroke are the leading causes of death worldwide at 119 per 100,000 and 85 per 100,000 population. For the USA, heart disease is leading cause of death at 165 per 100,000 population. In developed countries, strokes and acute myocardial infarction in the general population have fallen from smoking reduction, lifestyle modifications and therapeutic interventions including statins. In a population-based stroke study in the UK involving primary care practices, of in-hospital strokes 90% were ischaemic, and 37% occurred within 1 week of an operation. Approximately 50% of the patients were not on a statin. In the UK, there is a national screening initiative for the prevention of atherosclerotic cardiovascular disease (ASCVD) offered to people aged 40-74 yr old. The QRISK3 tool calculates the risk of developing heart disease or stroke over 10 yr, from which recommendations are made on interventions for the prevention of ASCVD up to age 84 yr, with similar screening and assessment tools in Europe and the US. If the QRISK3 score tool for calculating cardiovascular risk is considered sufficiently robust for population screening in primary care, should anaesthetists not use the same screening for secondary care? We present a case for statin use over the perioperative period, to reduce early vascular adverse events based on statins' early pleiotropic actions, using the primary care QRISK tool for screening of ASCVD risk. [ABSTRACT FROM AUTHOR]

Hypertension affects more than one in four adults. The brain is an early target of hypertension- induced organ damage, and may manifest as stroke, subclinical cerebrovascular abnormalities and dementia. Hypertension- related small vessel disease can cause vascular dementia and can potentiate Alzheimer's pathology, lowering the threshold at which signs and symptoms manifest. Many hypertensive emergencies may also have a neurological presentation, such as hypertensive encephalopathy, haemorrhagic stroke or preeclampsia. Here we highlight the importance of blood pressure in maintaining brain health and the brain's role in controlling blood pressure. [ABSTRACT FROM AUTHOR]

Background: Proteinuria has emerged as an important vascular risk factor for adverse cardiovascular events including stroke. Hypertension has been proposed as the principal confounder of this relationship but its role has not been systematically examined. Aim: We aimed to determine if proteinuria remains an independent predictor of stroke after more complete adjustment for blood pressure. Summary of review: We performed a systematic review, searching MEDLINE and EMBASE (to February 2018) for cohort studies or randomized controlled trials that reported stroke incidence in adults according to baseline proteinuria ± glomerular filtration rate. Study and participant characteristics and relative risks were extracted. Estimates were combined using a random effects model. Heterogeneity was assessed by χ 2 statistics and I2, and by subgroup strata and meta-regression, with a particular focus on the impact of more complete adjustment for blood pressure on the association. The quality of cohort studies and post hoc analyses was assessed using the Newcastle–Ottawa Scale. We identified 38 studies comprising 1,735,390 participants with 26,405 stroke events. Overall, the presence of any level of proteinuria was associated with greater stroke risk (18 studies; pooled crude relative risk 2.00, 95%CI 1.63–2.46; p < 0.001) even after adjustment for established cardiovascular risk factors (33 studies; pooled adjusted relative risk 1.72, 1.51–1.95; p < 0.001), albeit with considerable heterogeneity between studies (p < 0.001; I2 = 77.3%). Moreover, the association did not substantially attenuate with more thorough adjustment for hypertension: single baseline blood pressure measure (10 studies; pooled adjusted relative risk = 1.92, 1.39–2.66; p < 0.001); history or treated hypertension (four studies; pooled adjusted relative risk = 1.76, 1.13–2.75, p = 0.013); multiple blood pressure measurements over months to years (four studies; relative risk = 1.68, 1.33–2.14; p < 0.001). Conclusions: Even after extensive adjustment for hypertension, proteinuria is strongly and independently associated with incident stroke risk, possibly indicating a shared renal and cerebral susceptibility to vascular injury that is not fully explained by traditional vascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Risk of dementia after stroke is a major concern for patients and carers. Reliable data for risk of dementia, particularly after transient ischaemic attack or minor stroke, are scarce. We studied the risks of, and risk factors for, dementia before and after transient ischaemic attack and stroke.Methods: The Oxford Vascular Study is a prospective incidence study of all vascular events in a population of 92 728 people residing in Oxfordshire, UK. Patients with transient ischaemic attack or stroke occurring between April 1, 2002, and March 31, 2012, were ascertained with multiple methods, including assessment in a dedicated daily emergency clinic and daily review of all hospital admissions. Pre-event and post-event (incident) dementia were diagnosed at initial assessment and during 5-years' follow-up on the basis of cognitive testing supplemented by data obtained from hand searches of all hospital and primary care records. We assessed the association between post-event dementia and stroke severity (as measured with the US National Institutes of Health Stroke Scale [NIHSS] score), location (ie, dysphasia), previous events, markers of susceptibility or reserve (age, low education, pre-morbid dependency, leucoaraiosis), baseline cognition, and vascular risk factors with Cox regression models adjusted for age, sex, and education. We compared incidence and prevalence of dementia in our population with published UK population age-matched and sex-matched rates.Findings: Among 2305 patients (mean age 74·4 years [SD 13·0]), 688 (30%) had transient ischaemic attacks and 1617 (70%) had strokes. Pre-event dementia was diagnosed in 225 patients; prevalence was highest in severe stroke (ie, NIHSS >10) and lowest in transient ischaemic attack. Of 2080 patients without pre-event dementia, 1982 (95%) were followed up to the end of study or death. Post-event dementia occurred in 432 of 2080 patients during 5 years of follow-up. The incidence of post-event dementia at 1 year was 34·4% (95% CI 29·7-41·5) in patients with severe stroke (NIHSS score >10), 8·2% (6·2-10·2) in those with minor stroke (NIHSS score <3), and 5·2% (3·4-7·0) in those with transient ischaemic attack. Compared with the UK age-matched and sex-matched population, the 1-year standardised morbidity ratio for the incidence of dementia was 47·3 (95% CI 35·9-61·2), 5·8 (4·4-7·5), and 3·5 (2·5-4·8), respectively. Consequently, prevalence of dementia in 1-year survivors was brought forward by approximately 25 years in those who had severe strokes, 4 years in those who had minor strokes, and 2 years in those who had transient ischaemic attacks. 5-year risk of dementia was associated with age, event severity, previous stroke, dysphasia, baseline cognition, low education, pre-morbid dependency, leucoaraiosis, and diabetes (p<0·0001 for all comparisons, except for previous stroke [p=0·006]).Interpretation: The incidence of dementia in patients who have had a transient ischaemic attack or stroke varies substantially depending on clinical characteristics including lesion burden and susceptibility factors. Incidence of dementia is nearly 50 times higher in the year after a major stroke compared with that in the general population, but excess risk is substantially lower after transient ischaemic attack and minor stroke.Funding: Wellcome Trust, Wolfson Foundation, British Heart Foundation, National Institute for Health Research, and the National Institute for Health Research Oxford Biomedical Research Centre. [ABSTRACT FROM AUTHOR]

In this article the author talks about the risk of major stroke in the week after a transient ischemic attack (TIA) or minor stroke can be as high. It mentions that the antiplatelet drug has been shown to be clearly superior to aspirin in the acute phase after TIA or minor stroke, and dipyridamole and cilostazol appear to be less effective than aspirin.

Background: A one-dose-fits-all approach to use of aspirin has yielded only modest benefits in long-term prevention of cardiovascular events, possibly due to underdosing in patients of large body size and excess dosing in patients of small body size, which might also affect other outcomes.Methods: Using individual patient data, we analysed the modifying effects of bodyweight (10 kg bands) and height (10 cm bands) on the effects of low doses (≤100 mg) and higher doses (300-325 mg or ≥500 mg) of aspirin in randomised trials of aspirin in primary prevention of cardiovascular events. We stratified the findings by age, sex, and vascular risk factors, and validated them in trials of aspirin in secondary prevention of stroke. Additionally, we assessed whether any weight or height dependence was evident for the effect of aspirin on 20-year risk of colorectal cancer or any in-trial cancer.Results: Among ten eligible trials of aspirin in primary prevention (including 117 279 participants), bodyweight varied four-fold and trial median weight ranged from 60·0 kg to 81·2 kg (p<0·0001). The ability of 75-100 mg aspirin to reduce cardiovascular events decreased with increasing weight (pinteraction=0·0072), with benefit seen in people weighing 50-69 kg (hazard ratio [HR] 0·75 [95% CI 0·65-0·85]) but not in those weighing 70 kg or more (0·95 [0·86-1·04]; 1·09 [0·93-1·29] for vascular death). Furthermore, the case fatality of a first cardiovascular event was increased by low-dose aspirin in people weighing 70 kg or more (odds ratio 1·33 [95% CI 1·08-1·64], p=0·0082). Higher doses of aspirin (≥325 mg) had the opposite interaction with bodyweight (difference pinteraction=0·0013), reducing cardiovascular events only at higher weight (pinteraction=0·017). Findings were similar in men and women, in people with diabetes, in trials of aspirin in secondary prevention, and in relation to height (pinteraction=0·0025 for cardiovascular events). Aspirin-mediated reductions in long-term risk of colorectal cancer were also weight dependent (pinteraction=0·038). Stratification by body size also revealed harms due to excess dosing: risk of sudden death was increased by aspirin in people at low weight for dose (pinteraction=0·0018) and risk of all-cause death was increased in people weighing less than 50 kg who were receiving 75-100 mg aspirin (HR 1·52 [95% CI 1·04-2·21], p=0·031). In participants aged 70 years or older, the 3-year risk of cancer was also increased by aspirin (1·20 [1·03-1·47], p=0·02), particularly in those weighing less than 70 kg (1·31 [1·07-1·61], p=0·009) and consequently in women (1·44 [1·11-1·87], p=0·0069).Interpretation: Low doses of aspirin (75-100 mg) were only effective in preventing vascular events in patients weighing less than 70 kg, and had no benefit in the 80% of men and nearly 50% of all women weighing 70 kg or more. By contrast, higher doses of aspirin were only effective in patients weighing 70 kg or more. Given that aspirin's effects on other outcomes, including cancer, also showed interactions with body size, a one-dose-fits-all approach to aspirin is unlikely to be optimal, and a more tailored strategy is required.Funding: Wellcome Trust and National Institute for Health Research Oxford Biomedical Research Centre. [ABSTRACT FROM AUTHOR]

Background: Aspirin is recommended for secondary prevention after transient ischaemic attack (TIA) or ischaemic stroke on the basis of trials showing a 13% reduction in long-term risk of recurrent stroke. However, the risk of major stroke is very high for only the first few days after TIA and minor ischaemic stroke, and observational studies show substantially greater benefits of early medical treatment in the acute phase than do longer-term trials. We hypothesised that the short-term benefits of early aspirin have been underestimated.Methods: Pooling the individual patient data from all randomised trials of aspirin versus control in secondary prevention after TIA or ischaemic stroke, we studied the effects of aspirin on the risk and severity of recurrent stroke, stratified by the following time periods: less than 6 weeks, 6-12 weeks, and more than 12 weeks after randomisation. We compared the severity of early recurrent strokes between treatment groups with shift analysis of modified Rankin Scale (mRS) score. To understand possible mechanisms of action, we also studied the time course of the interaction between effects of aspirin and dipyridamole in secondary prevention of stroke. In a further analysis we pooled data from trials of aspirin versus control in which patients were randomised less than 48 h after major acute stroke, stratified by severity of baseline neurological deficit, to establish the very early time course of the effect of aspirin on risk of recurrent ischaemic stroke and how this differs by severity at baseline.Findings: We pooled data for 15,778 participants from 12 trials of aspirin versus control in secondary prevention. Aspirin reduced the 6 week risk of recurrent ischaemic stroke by about 60% (84 of 8452 participants in the aspirin group had an ischaemic stroke vs 175 of 7326; hazard ratio [HR] 0·42, 95% CI 0·32-0·55, p<0·0001) and disabling or fatal ischaemic stroke by about 70% (36 of 8452 vs 110 of 7326; 0·29, 0·20-0·42, p<0·0001), with greatest benefit noted in patients presenting with TIA or minor stroke (at 0-2 weeks, two of 6691 participants in the aspirin group with TIA or minor stroke had a disabling or fatal ischaemic stroke vs 23 of 5726 in the control group, HR 0·07, 95% CI 0·02-0·31, p=0·0004; at 0-6 weeks, 14 vs 60 participants, 0·19, 0·11-0·34, p<0·0001). The effect of aspirin on early recurrent ischaemic stroke was due partly to a substantial reduction in severity (mRS shift analysis odds ratio [OR] 0·42, 0·26-0·70, p=0·0007). These effects were independent of dose, patient characteristics, or aetiology of TIA or stroke. Some further reduction in risk of ischaemic stroke accrued for aspirin only versus control from 6-12 weeks, but there was no benefit after 12 weeks (stroke risk OR 0·97, 0·84-1·12, p=0·67; severity mRS shift OR 1·00, 0·77-1·29, p=0·97). By contrast, dipyridamole plus aspirin versus aspirin alone had no effect on risk or severity of recurrent ischaemic stroke within 12 weeks (OR 0·90, 95% CI 0·65-1·25, p=0·53; mRS shift OR 0·90, 0·37-1·72, p=0·99), but dipyridamole did reduce risk thereafter (0·76, 0·63-0·92, p=0·005), particularly of disabling or fatal ischaemic stroke (0·64, 0·49-0·84, p=0·0010). We pooled data for 40,531 participants from three trials of aspirin versus control in major acute stroke. The reduction in risk of recurrent ischaemic stroke at 14 days was most evident in patients with less severe baseline deficits, and was substantial by the second day after starting treatment (2-3 day HR 0·37, 95% CI 0·25-0·57, p<0·0001).Interpretation: Our findings confirm that medical treatment substantially reduces the risk of early recurrent stroke after TIA and minor stroke and identify aspirin as the key intervention. The considerable early benefit from aspirin warrants public education about self-administration after possible TIA. The previously unrecognised effect of aspirin on severity of early recurrent stroke, the diminishing benefit with longer-term use, and the contrasting time course of effects of dipyridamole have implications for understanding mechanisms of action.Funding: Wellcome Trust, the National Institute of Health Research (NIHR) Biomedical Research Centre, Oxford. [ABSTRACT FROM AUTHOR]

The article discusses a study that assessed if it is safe to lower blood pressure with a daily glyceryl nitrate patch for a week after acute stroke and whether to continue or withdraw antihypertensive drugs. Topics discussed include the potential causes of the transient increase in blood pressure, association of high blood pressure after acute stroke with poor outcomes and the absence of adverse effects with glyceryl trinitrate.

Antihypertensive drugs reduce headache but it is unclear whether there are differences between drug classes. Calcium channel blockers (CCBs) decrease variability in systolic blood pressure (SBPV) and stroke risk more than other classes, possibly due to decreased vascular tone. If so, there might be a correlation between drug-class effects on variability in SBP and on headache. We determined antihypertensive class effects on SBPV and headache during follow-up in a systematic review of randomized controlled trials. We determined pooled estimates of treatment effect on group variability in BP (variance ratio, VR) and on the odds ratio for headache (OR) by random-effects meta-analysis. Antihypertensive drugs reduced the incidence of headache compared to placebo (OR = 0.75, 95% CI 0.69-0.82, p < 0.0001, 198 comparisons, 43,672 patients), but there was significant heterogeneity between drug classes ( p = 0.0007) with a greater effect of beta-blockers compared to placebo (VR = 0.49, 0.33-0.68, p < 0.0001, 16 trials) or all other drug classes (OR = 0.73, 0.62-0.85, p = 0.0002, 49 trials) and a lack of effectiveness of CCBs (vs. placebo-OR = 0.95, 0.79-1.15, 65 trials; vs. other drugs-OR = 1.19, 1.05-1.35, p = 0.009, 101 trials). Drug-class effects on headache were opposite to effects on variability in SBP (vs. other drugs: CCB-VR = 0.81, 0.71-0.85, p < 0.0001; beta-blocker VR = 1.17, 1.07-1.28, p < 0.0001), but were unrelated to differences in mean SBP. Antihypertensive drugs reduce headache but the effect differs between classes, corresponding to their effects on SBPV and the risk of stroke. This may partly be explained by consistent antihypertensive class effects on vascular tone in the peripheral (variability) and cerebrovascular circulations (headache). [ABSTRACT FROM AUTHOR]

Summary: Background: Long-term follow-up of randomised trials of aspirin in prevention of vascular events showed that daily aspirin reduced the incidence of colorectal cancer and several other cancers and reduced metastasis. However, statistical power was inadequate to establish effects on less common cancers and on cancers in women. Observational studies could provide this information if results can be shown to be reliable. We therefore compared effects of aspirin on risk and outcome of cancer in observational studies versus randomised trials. Methods: For this systematic review, we searched for case–control and cohort studies published from 1950 to 2011 that reported associations between aspirin use and risk or outcome of cancer. Associations were pooled across studies by meta-analysis and stratified by duration, dose, and frequency of aspirin use and by stage of cancer. We compared associations from observational studies with the effect of aspirin on 20-year risk of cancer death and on metastasis in the recent reports of randomised trials. Findings: In case–control studies, regular use of aspirin was associated with reduced risk of colorectal cancer (pooled odds ratio [OR] 0·62, 95% CI 0·58–0·67, psig<0·0001, 17 studies), with little heterogeneity (phet=0·13) in effect between studies, and good agreement with the effect of daily aspirin use on 20-year risk of death due to colorectal cancer from the randomised trials (OR 0·58, 95% CI 0·44–0·78, psig=0·0002, phet=0·45). Similarly consistent reductions were seen in risks of oesophageal, gastric, biliary, and breast cancer. Overall, estimates of effect of aspirin on individual cancers in case–control studies were highly correlated with those in randomised trials (r 2=0·71, p=0·0006), with largest effects on risk of gastrointestinal cancers (case–control studies, OR 0·62, 95% CI 0·55–0·70, p<0·0001, 41 studies; randomised trials, OR 0·54, 95% CI 0·42–0·70, p<0·0001). Estimates of effects in cohort studies were similar when analyses were stratified by frequency and duration of aspirin use, were based on updated assessments of use during follow-up, and were appropriately adjusted for baseline characteristics. Although fewer observational studies stratified analyses by the stage of cancer at diagnosis, regular use of aspirin was associated with a reduced proportion of cancers with distant metastasis (OR 0·69, 95% CI 0·57–0·83, psig<0·0001, phet=0·89, five studies), but not with any reduction in regional spread (OR 0·98, 95% CI 0·88–1·09, psig=0·71, phet=0·88, seven studies), consistent again with the findings in randomised trials. Interpretation: Observational studies show that regular use of aspirin reduces the long-term risk of several cancers and the risk of distant metastasis. Results of methodologically rigorous studies are consistent with those obtained from randomised controlled trials, but sensitivity is particularly dependent on appropriately detailed recording and analysis of aspirin use. Funding: None. [Copyright &y& Elsevier]

The article presents randomised controlled trials of risks and benefits of daily low-dose aspirin on cancer incidence, mortality and non-vascular death. It explores cancer deaths in trials of daily aspirin versus control, as well as the time course of effects of aspirin on cancer and outcomes in primary prevention. Results show short-term reductions in cancer incidence and mortality and risk of extracranial bleeds through extended use.

The article presents a study on the effect of daily aspirin on the risk of having metastasis among cancer patients. It states that five randomised trials of aspirin were conducted. Results show that 978 out of 17, 285 participants were diagnosed of new cancer during mean in-trial follow-up of 6.5 years and that the effects were independent of sex and age.

The article discusses a targeted and multifaceted approach to secondary prevention, described as one of the important themes contributing to the improvement of stroke outcomes in developed countries. It explores the association between a fatal or disabling stroke and a transient ischaemic attack (TIA) or minor stroke. It then suggests urgent initiation of secondary prevention with antiplatelet agents, anti-hypertensives, statins and anticoagulation, and carotid endarterectomy after TIA.

The article discusses a study on the effect of daily aspirin on long-term risk of death due to colorectal cancer and other cancers in Great Britain. The study used individual patient data from all randomised trials of daily aspirin versus no aspirin with mean duration of scheduled trial treatment of 4 years or longer. It was shown that allocation to aspirin reduced death due to cancer in eight eligible trials conducted. It was also concluded that benefit increased with duration of treatment and was consistent across the different study populations.

The article presents information on a study which examined the effects of aspirin on incidence and mortality due to colorectal cancer in association to dose, duration of treatment and site of tumor. A follow up of four randomized trials of aspirin versus control in primary (Thrombosis Prevention Trial, British Doctors Aspirin Trial) and secondary (Swedish Aspirin Low Dose Trial, UK-TIA Aspirin Trial) prevention of vascular incidence was conducted. A discussion on the research findings is detailed.

Summary: Background: Analyses of some randomised trials show that calcium-channel blockers reduce the risk of stroke more than expected on the basis of mean blood pressure alone and that β blockers are less effective than expected. We aimed to investigate whether the effects of these drugs on variability in blood pressure might explain these disparities in effect on stroke risk. Methods: The Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA) compared amlodipine-based regimens with atenolol-based regimens in 19 257 patients with hypertension and other vascular risk factors and the Medical Research Council (MRC) trial compared atenolol-based and diuretic-based regimens versus placebo in 4396 hypertensive patients aged 65–74 years. We expressed visit-to-visit variability of blood pressure during follow-up in the two trials as standard deviation (SD) and as transformations uncorrelated with mean blood pressure. For ASCOT-BPLA, we also studied within-visit variability and variability on 24 h ambulatory blood-pressure monitoring (ABPM). Results: In ASCOT-BPLA, group systolic blood pressure (SBP) SD was lower in the amlodipine group than in the atenolol group at all follow-up visits (p<0·0001), mainly because of lower within-individual visit-to-visit variability. Within-visit and ABPM variability in SBP were also lower in the amlodipine group than in the atenolol group (all p<0·0001). Analysis of changes from baseline showed that variability decreased over time in the amlodipine group and increased in the atenolol group. The lower risk of stroke in the amlodipine group (hazard ratio 0·78, 95% CI 0·67–0·90) was partly attenuated by adjusting for mean SBP during follow-up (0·84, 0·72–0·98), but was abolished by also adjusting for within-individual SD of clinic SBP (0·99, 0·85–1·16). Findings were similar for coronary events. In the ABPM substudy, reduced variability in daytime SBP in the amlodipine group (p<0·0001) partly accounted for the reduced risk of vascular events, but reduced visit-to-visit variability in clinic SBP had a greater effect. In the MRC trial, group SD SBP and all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo group and the diuretic group during initial follow-up (all p<0·0001). Subsequent temporal trends in variability in blood pressure during follow-up in the atenolol group correlated with trends in stroke risk. Interpretation: The opposite effects of calcium-channel blockers and β blockers on variability of blood pressure account for the disparity in observed effects on risk of stroke and expected effects based on mean blood pressure. To prevent stroke most effectively, blood-pressure-lowering drugs should reduce mean blood pressure without increasing variability; ideally they should reduce both. Funding: None. [Copyright &y& Elsevier]

The article presents a clinical review of the shortcomings of the usual blood-pressure hypothesis in accounting for all blood-pressure-related risk of vascular events. It is noted that there is a little understanding on how hypertension causes end-organ damage and vascular events. A background to reports on the importance of blood-pressure variability in prediction of risk of vascular events is presented. The article also discusses the implications of the review for guidelines, practice and research on hypertension.

The article discusses a study which intended to establish the prognostic significance of visit-to-visit variability in blood pressure, maximum blood pressure reached, untreated episodic hypertension, and residual variability in treated patients. The study involved patients with previous transient ischaemic attack and those with treated hypertension. It was concluded that there was no causal link between variability in blood pressure and stroke, but there had been strong and consistent relations in several cohorts.

Mounting evidence suggests that there is frequently considerable variation in the risk of the outcome of interest in clinical trial populations. These differences in risk will often cause clinically important heterogeneity in treatment effects (HTE) across the trial population, such that the balance between treatment risks and benefits may differ substantially between large identifiable patient subgroups; the "average" benefit observed in the summary result may even be non-representative of the treatment effect for a typical patient in the trial. Conventional subgroup analyses, which examine whether specific patient characteristics modify the effects of treatment, are usually unable to detect even large variations in treatment benefit (and harm) across risk groups because they do not account for the fact that patients have multiple characteristics simultaneously that affect the likelihood of treatment benefit. Based upon recent evidence on optimal statistical approaches to assessing HTE, we propose a framework that prioritizes the analysis and reporting of multivariate risk-based HTE and suggests that other subgroup analyses should be explicitly labeled either as primary subgroup analyses (well-motivated by prior evidence and intended to produce clinically actionable results) or secondary (exploratory) subgroup analyses (performed to inform future research). A standardized and transparent approach to HTE assessment and reporting could substantially improve clinical trial utility and interpretability. [ABSTRACT FROM AUTHOR]

Summary: Background: Reliable data on the prevalence and predictors of post-stroke dementia are needed to inform patients and carers, plan services and clinical trials, ascertain the overall burden of stroke, and understand its causes. However, published data on the prevalence and risk factors for pre-stroke and post-stroke dementia are conflicting. We undertook this systematic review to assess the heterogeneity in the reported rates and to identify risk factors for pre-stroke and post-stroke dementia. Methods: Studies published between 1950 and May 1, 2009, were identified from bibliographic databases, reference lists, and journal contents pages. Studies were included if they were on patients with symptomatic stroke, were published in English, reported on a series of consecutive eligible patients or volunteers in prospective cohort studies, included all stroke or all ischaemic stroke, measured dementia by standard criteria, and followed up patients for at least 3 months after stroke. Pooled rates of dementia were stratified by study setting, inclusion or exclusion of pre-stroke dementia, and by first, any, or recurrent stroke. Pooled odds ratios were calculated for factors associated with pre-stroke and post-stroke dementia. Findings: We identified 22 hospital-based and eight population-based eligible cohorts (7511 patients) described in 73 papers. The pooled prevalence of pre-stroke dementia was higher (14·4%, 95% CI 12·0–16·8) in hospital-based studies than in population-based studies (9·1%, 6·9–11·3). Although post-stroke (≤1 year) dementia rates were heterogeneous overall, 93% of the variance was explained by study methods and case mix; the rates ranged from 7·4% (4·8–10·0) in population-based studies of first-ever stroke in which pre-stroke dementia was excluded to 41·3% (29·6–53·1) in hospital-based studies of recurrent stroke in which pre-stroke dementia was included. The cumulative incidence of dementia after the first year was little greater (3·0%, 1·3–4·7) per year in hospital-based studies than expected on the basis of recurrent stroke alone. Medial temporal lobe atrophy, female sex, and a family history of dementia were strongly associated with pre-stroke dementia, whereas the characteristics and complications of the stroke and the presence of multiple lesions in time and place were more strongly associated with post-stroke dementia. Interpretation: After study methods and case mix are taken into account, reported estimates of the prevalence of dementia are consistent: 10% of patients had dementia before first stroke, 10% developed new dementia soon after first stroke, and more than a third had dementia after recurrent stroke. The strong association of post-stroke dementia with multiple strokes and the prognostic value of other stroke characteristics highlight the central causal role of stroke itself as opposed to the underlying vascular risk factors and, thus, the likely effect of optimum acute stroke care and secondary prevention in reducing the burden of dementia. Funding: None. [Copyright &y& Elsevier]

The early risk of recurrence after transient ischaemic attack (TIA) or minor stroke is high, ranging from 11% at 7 days in population-based studies, where patients are seen non-urgently, to 3% at 7 days in studies where patients are seen urgently in specialist services. In long-term (up to 10 years) studies of vascular risks after TIA and stroke, the risk of stroke is highest early after the event, and then falls, whereas the risk of coronary events is constant over the follow-up period at around 2% per year. In contrast to the early risk after TIA and stroke, the long-term risks are more dependent on the underlying vascular risk factors than the characteristics of the event itself. Stroke is also associated with an increased risk of dementia. Prevalence of post-stroke dementia varies between studies but is around 28% at 3 months in hospital-based studies where pre-stroke dementia was not excluded and 18% in hospital-based studies excluding pre-stroke dementia. Risk factors for post-stroke dementia include low education, prior or recurrent stroke, and older age. In conclusion, available data suggest that the risk of recurrent vascular events is considerable after TIA and stroke, even in the longer term, and that there is also a high risk of dementia after stroke. However, more studies are required to determine medium- and long-term outcomes in the current era of aggressive secondary preventive therapy. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents a method of predicting the risk of stroke after a transient ischemic attack (TIA). According to the article, TIA is recognized as a precedent to a major stroke and is a common condition with higher incidence in people over the age of 70. It states that the age, blood pressure, clinical features and duration (ABCD) of symptoms provide for a clinical score that can be used to predict early risks of stroke in patients that have experienced TIA.

The article discusses the importance of prognosis for effective clinical practice, particularly in neurology. It identifies ways on developing a useful and effective prognostic models such as it must be shown to reliably predict outcome and must have clinical credibility. It states that one of the most important requirement is that the derivation of a group of patients is representative of the sorts of patients in whom the model would be used in clinical practice.

Summary: Background: Stroke is often preceded by transient ischaemic attack (TIA), but studies of stroke risk after TIA are logistically difficult and have yielded conflicting results. However, reliable estimation of this risk is necessary for planning effective service provision, clinical trials, and public education. We therefore did a systematic review of all studies of stroke risk early after TIA. Methods: All studies of stroke risk within 7 days of TIA were identified by use of electronic databases and by hand searches of reference lists, relevant journals, and conference abstracts. Stroke risks at 2 days and 7 days after TIA were calculated overall and analyses for heterogeneity were done, if possible, after categorisation by study method, setting, population, and treatment. Findings: 18 independent cohorts were included, which reported stroke risk in 10 126 TIA patients. The pooled stroke risk was 5·2% (95% CI 3·9–6·5) at 7 days, but there was substantial heterogeneity between studies (p<0·0001), with risks ranging from 0% to 12·8%. However, the risks reported in individual studies over different durations of follow-up were highly correlated (0–7 days vs 8–90 days, r=0·89, p<0·0001), and the heterogeneity between studies was almost fully explained by study method, setting, and treatment. The lowest risks were seen in studies of emergency treatment in specialist stroke services (0·9% [95% CI 0·0–1·9], four studies) and the highest risks in population-based studies without urgent treatment (11·0% [8·6–13·5], three studies). Results were similar for stroke risk at 2 days. Interpretation: The reported early risks of stroke after TIA were highly heterogeneous, but this could be largely accounted for by differences in study method, setting, and treatment, with lowest risks in studies of emergency treatment in specialist stroke services. [Copyright &y& Elsevier]

Objectives to measure the number of all transient ischaemic attack (TIAs) and minor strokes managed as outpatients, and hence, the need for 'TIA clinics' in comparison to current estimates of 20,000 TIAs annually in England, based on previous rates of incident-definite events. Subjects all individuals with confirmed or suspected TIA or stroke between 2002 and 2005 in a population-based study of 91,105 individuals in Oxfordshire, UK. Outcome Measures numbers, rates, and risks of recurrent stroke for incident-definite TIA, any probable or definite TIA, stroke, and all referrals of suspected TIA and stroke, stratified according to inpatient versus outpatient management. Results of 1,174 confirmed or suspected events ascertained, 729 (62.1%) were managed as outpatients and 445 (37.9%) as inpatients. Among 757 probable or definite events, 432 (57%) were managed as outpatients. Incident-definite TIAs accounted for only 18% of all referrals to outpatient services. Annual rates per 1,000 population were 2.98 (2.77-3.2) for all referrals to outpatient services and 1.88 (1.71-2.06) for inpatient admissions. Of 73 recurrent strokes within 90 days of initial TIA or stroke, 48 (65.8%) occurred in the outpatient population. Applying these rates to the population of England yields approximately 150,000 new referrals annually to TIA clinics with about 10,000 early recurrent strokes. Conclusion more patients with TIA or stroke are managed as outpatients than inpatients in the UK, and this group has the majority of possibly preventable early recurrent strokes. Current projections of need for TIA clinics in England substantially underestimate the overall requirement for outpatient services. [ABSTRACT FROM AUTHOR]

There is still considerable uncertainty about the place of carotid stenting in patients with recently symptomatic carotid bifurcation stenosis. Most reviews of carotid endarterectomy versus carotid stenting concentrate on technical aspects and advances in stenting, but the techniques involved in both carotid endarterectomy and stenting are evolving. In addition to reviewing the results of the various randomised controlled trials of carotid endarterectomy versus stenting for symptomatic carotid stenosis, this review considers recent advances and current best practice for endarterectomy. Ongoing randomized trials will determine whether or not the procedural risk of stroke and death is definitely lower with endarterectomy than with stenting, but the key issue that remains to be determined reliably is how the procedural risks of stenting vary with patient characteristics – perhaps the most important question being not whether endarterectomy is better than stenting or vice versa, but for whom is one technique likely to be better than the other. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This article presents a clinical trial on the effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke, called the EXPRESS study. Patients who have suffered a transient ischaemic attack (TIA) or minor stroke are 10 percent more likely to suffer an another episode in the week after the TIA. Models suggest that this could prevented 80-90 percent of the time but there are no studies to back up the claim. This study sought to see if rapid intervention after the first incident could prevent another immediate stroke in non-hospitalized patients. The study showed an 80 percent reduction for recurrence of stroke over the period of the study and says longer studies need to be done.

Background: It has been suggested that scores for risk stratification of TIA patients might not identify patients with carotid stenosis or atrial fibrillation (AF) and that this might undermine the usefulness of such scores. Methods: In patients with TIA in the Oxford Vascular Study, we studied the associations between ABCD and ABCD2 scores, the presence of ≥50% ipsilateral carotid stenosis or AF, and the risk of stroke at 7 days. Results: Among 285 TIA patients (from 559 referrals of possible TIA), 69 (24.2%) had either ≥50% carotid stenosis (n = 29) or AF (n = 42), or both (n = 2). Although the ABCD and ABCD2 scores were highly predictive of stroke at 7 days (p < 0.0001), there was no clear relationship between either score and the prevalence of ≥50% carotid stenosis or AF. However, the scores did predict the 7-day stroke risk in patients with these pathologies: ABCD score (trend – p = 0.05); ABCD2 (trend – p = 0.03). Five of the 6 patients with AF or symptomatic stenosis who had a stroke within 7 days of their TIA had an ABCD score of ≥5 and all 6 had an ABCD2 score of ≥4. Conclusions: The ABCD and ABCD2 risk scores appear to identify patients with ≥50% carotid stenosis or AF who are at high risk of stroke. However, these findings should be interpreted with caution due to the small number of outcomes among these subgroups, and further validations are necessary. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents the results of studies investigating the effect of aspirin use on the risk of colorectal cancer. Two randomized trials in which patients with adenomas suggesting a high future risk of cancer were given varying doses of aspirin are presented. The trials followed the subjects over a 20 year period, a needed improvement on studies that have only looked at short-term effects of the therapy. The results of the studies suggest that a 300mg plus daily dose of aspirin for a period of 5 years is an effective protection against colorectal cancer, offering a latency of 10 years.

Summary: Background: Ischaemic stroke is partly heritable. However, although the genetic and non-genetic factors responsible could be sex-specific, interactions between the sex of the parent affected and the sex of the proband or affected siblings are unknown. We sought to assess the relation between the sex and phenotype of affected probands and the sex of affected first-degree relatives. Methods: We determined the prevalence of history of stroke in the mother, father, and other first-degree relatives in female and male probands with ischaemic stroke or transient ischaemic attack in the population-based Oxford Vascular Study (OXVASC). We validated our findings using unpublished individual patient data from two independent Oxford studies. Findings: In OXVASC, detailed family history was available in 806 (93%) probands. Female probands were more likely than males to have at least one affected first-degree relative (146/423 vs 104/383; OR 1·4, 95% CI 1·1–2·0, p=0·02) due entirely to an excess of affected female relatives in female probands (female relative vs male relative OR=1·7, 1·3–2·4, p=0·0004; female only vs male only OR=2·1, 1·4–3·1, p=0·0001). Maternal stroke was more common than paternal stroke in female probands (OR=1·8, 1·2–2·7, p=0·001) but not in males (OR=1·1, 0·7–1·7, p=0·38), and female probands were more likely than males to have an affected sister (OR=3·1, 1·5–6·7, p=0·004) but not an affected brother (OR=1·1, 0·6–2·1, p=0·80). Ages at first stroke were also correlated within families among affected females (r=0·36, p=0·004) but not among affected males, such that the excess of affected female relatives of female probands was greatest when the difference in age at first stroke was less than 5 years (OR=3·7, 1·6–8·6, p=0·0007) and fell as the age difference increased (p for trend=0·004). These findings were independent of traditional risk factors and stroke subtype. Data from the other Oxford studies confirmed the excess maternal history of stroke in female probands (OR=2·3, 1·5–3·8, p<0·00001) and the lack in males (OR=1·0, 0·7–1·4, p=0·58). Interpretation: Heritability of ischaemic stroke is greater in women than in men, with an excess of affected mothers and affected sisters in female probands independent of traditional vascular risk factors, which could be explained by sex-specific genetic, epigenetic, or non-genetic mechanisms. [Copyright &y& Elsevier]

The authors focused on attempting to validate two existing prognostic scores in large independently assembled groups from different populations for stroke risk after transient ischemic attack (TIA). They found that these prognostic scores, the California and ABCD scores validate well on multiple independent cohorts. However, by combining results from the original groups used to obtain the California and ABCD prognostic scores, they generated a new score that would improve prediction of risk of stroke in the two days after TIA. High-risk patients need immediate evaluation for optimal stroke prevention.

Carotid bifurcation stenosis is an important cause of ischaemic stroke, particularly in patients with recent transient ischaemic attack or minor stroke. Large randomized trials of endarterectomy have shown that surgery reduces the risk of stroke in patients with ≥50% recently symptomatic carotid stenosis, and more recent research has gone some way to wards identifying which patients benefit the most. Individual risk modelling has been shown to be useful in selecting patients with the most to gain from endarterectomy for symptomatic stenosis, although timely surgery and optimal medical treatment are of equal importance. [ABSTRACT FROM AUTHOR]

The article considers the proposed Single Fund to be set up by the United Kingdom Medical Research Council and the National Health Service Research & Development program to administer government-funded medical research. The article calls for the fund to not neglect the practice-oriented clinical research in favor of the more glamorous laboratory-based research. Laboratory developments that are lauded as break-throughs often have little practical application, while clinical research has the benefit or originating in a practical setting.

The risk of recurrent stroke during the first few days after a transient ischaemic attack (TIA) or minor stroke is very much higher than previously estimated. However, there is considerable international variation in how patients with suspected TIA or minor stroke are managed in the acute phase, some healthcare systems providing immediate emergency inpatient care and others providing non-emergency outpatient clinic assessment. This review considers what is known about the early prognosis after TIA and minor ischaemic stroke, what factors identify individuals at particularly high early risk of stroke, and what evidence there is that urgent preventive treatment is likely to be effective in reducing the early risk of stroke. [ABSTRACT FROM AUTHOR]

This article discusses the determinants of the external validity of a randomized controlled trial (RCT). The external validity of an RCT depends on detailed understanding of the setting in which a trial is performed, selection of patients according to trial eligibility criteria and if possible a report that details the pathways to recruitment of patients and the clinical relevance of the outcomes.

Summary: The risk of recurrent stroke during the first few days after a transient ischaemic attack or minor stroke is much higher than previously estimated. However, there is substantial variation worldwide in how patients with suspected transient ischaemic attack or minor stroke are investigated and treated in the acute phase: some health-care systems provide immediate emergency inpatient care and others provide non-emergency outpatient clinical assessment. This review considers what is known about the early prognosis after transient ischaemic attack and minor ischaemic stroke, what factors identify individuals at particularly high early risk of stroke, and what evidence there is that urgent preventive treatment is likely to be effective in reducing the early risk of stroke. [Copyright &y& Elsevier]

The basic principles of stroke prevention are the same in patients with diabetes and/or the metabolic syndrome as in those without. Blood-pressure lowering is highly effective in both primary and secondary prevention of stroke in diabetics, and there is no evidence to suggest that the benefits of lipid-lowering therapy are any less. Antiplatelet agents are effective in secondary prevention and may be indicated in asymptomatic diabetic patients, who have a substantially increased risk of acute vascular events. Uncertainty over optimal management of patients with diabetes, and possibly of those with metabolic syndrome, relates more to the thresholds for initiation of treatment. The decision to initiate treatment should depend on the balance between the absolute risk of potentially preventable events and the risks of any complications of treatment. The absolute risks of ischaemic stroke and acute coronary events are significantly increased in diabetics in population-based cohort studies and the recommended thresholds for instigating blood pressure lowering and lipid lowering are therefore lower than in the general population. Optimization of strategies to prevent vascular complications must be a priority, given the rapid rises in the incidence and prevalence of type 2 diabetes and the metabolic syndrome in most populations across the globe. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: To identify new treatments to prevent stroke, it is important that we have reliable data on potential novel risk factors. Methods: We studied seven novel vascular risk factors [apo-lipoprotein (b), C-reactive protein, Chlamydia pneumoniae, fibrin-D dimer, fibrinogen, Helicobacter pylori and lipoprotein (a)] and compared the amount of published data on their relations with ischaemic stroke versus acute coronary events by systematic review of all studies published up to 2003. Results: From a total of 22,875 abstracts reviewed, 266 eligible studies were identified (167 case-control studies and 99 cohort studies). Two hundred and eleven (79%) studies included coronary events as an outcome for the purpose of a risk factor analysis. In 186 (70%) studies, coronary events were the only outcome that was analysed. Only 73 (27%) studies included stroke or TIA as an outcome event, and only 45 studies (17%) reported risk factor analyses for ischaemic stroke separately. These results were qualitatively consistent across the risk factors studied and the relative lack of data on risk factors for stroke was even greater in prospective cohort studies. Conclusion: Data on novel risk factors for stroke are lacking compared with the equivalent data for acute coronary events, and there are very few data on specific subtypes of ischaemic stroke. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Comments on the risks associated with carotid endarterectomy after a transient ischaemic attack or cerebral infarction. Operative risks in neurologically stable patients undergoing endarterectomy after stroke; Findings of randomised controlled trials concerning the potential of endarterectomy in reducing the risk of stroke; Need for patients with stenosis to undergo surgery to prevent ipsilateral stroke.

This article focuses on the treatment of symptomatic carotid stenosis. Most of the strokes that occur within the first few years after a TIA or minor ischaemic stroke in patients with carotid stenosis are ischaemic and in the territory of the symptomatic artery. All patients with recently symptomatic carotid stenosis require treatment to reduce their risk of stroke, and vascular events in other arterial territories. Some treatments are required in all patients, others should be targeted at certain specific groups and individuals. The need for targeting is discussed below for each of the main medical treatments, and for carotid surgery.