Search PubMed⌕ Search

Biomedical subjects

Peter M Rothwell

Publications and source records attributed to Peter M Rothwell.

At least 37 records · Page 2Linked to original sources
PubMed2005

Family history of stroke does not predict risk of stroke after transient ischemic attack.

BACKGROUND AND PURPOSE: Animal models suggest a genetic contribution to cerebral susceptibility to ischemia. Family history of stroke (FHxstroke) is a risk factor for ischemic stroke, but there is significant confounding by heritability of hypertension and other intermediate phenotypes, and it is uncertain whether genetic factors have a direct independent influence on cerebral susceptibility to ischemia in man. METHODS: We related detailed FHxstroke to baseline characteristics and subsequent risk of stroke in 2 population-based incidence studies and a consecutive hospital-referred series of patients with recent transient ischemic attack (TIA). RESULTS: In none of the cohorts or the pooled data (757 patients; 5515 patient years follow-up; 200 ischemic strokes; 126 myocardial infarctions [MIs]) did FHxstroke predict ischemic stroke (odds ratio [OR], 0.87; 95% CI, 0.57 to 1.32). No associations were revealed by analyses stratified by age or hypertension in the proband, FHx(stroke) in parents versus siblings, number of affected relatives, or their age at stroke. FHxstroke was unrelated to presence of ischemic lesions on baseline computed tomography (OR, 0.96; 0.52 to 1.76) or risk of MI during follow-up. There was no bias attributable to any relationship between FHxstroke and risk factor control or medication. CONCLUSIONS: Family history of stroke does not predict risk of ischemic stroke after TIA.

Aged↗
PubMed2005

Potential consequences for recruitment, power, and external validity of requirements for additional risk factors for eligibility in randomized controlled trials in secondary prevention of stroke.

BACKGROUND AND PURPOSE: Eligibility criteria determine the external validity (generalizability) of the results of randomized controlled trials. To increase the number of outcome events, and hence statistical power, some recent stroke prevention trials have required additional vascular risk factors for eligibility. METHODS: To assess the merits of additional eligibility criteria in stroke prevention trials, we analyzed data from 3 trials and 1 hospital-referred series of patients with a transient ischemic attack or minor ischemic stroke. Patients were stratified according to 2 sets of additional risk factors similar to those used in recent trials (MATCH, SPORTIF and PRoFESS); risk of stroke, myocardial infarction, or vascular death was calculated in relation to the number of risk factors. RESULTS: Although the observed risk during follow-up did increase with the number of risk factors present (P<0.01 for both sets), the risks in patients with > or =1 risk factors were not substantially greater than those in all patients. Consequently, although the proportions of patients with no risk factors in the 4 cohorts differed substantially between the 2 sets of eligibility criteria (21% to 28% versus 56% to 73%), in neither case could their exclusion be justified on statistical grounds. CONCLUSIONS: The degree of patient selection introduced by use of additional vascular risk factors as eligibility criteria for trials can differ substantially between apparently similar sets of risk factors. Given that the potential for additional eligibility criteria to undermine generalizability and prolong recruitment outweighs any benefits in terms of statistical power, the exclusion of patients with no risk factors is difficult to justify.

Aged↗
PubMed2005

Prevention of stroke in patients with diabetes mellitus and the metabolic syndrome.

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.

Diabetes Mellitus, Type 2↗
PubMed2005

Risk of myocardial infarction and vascular death after transient ischemic attack and ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Whether stroke patients should be investigated for asymptomatic coronary artery disease remains matter of debate. Absolute risks of myocardial infarction (MI) and vascular death after a stroke have not been accurately assessed. We performed a systematic review and a meta-analysis to determine the risk of MI and nonstroke vascular death after transient ischemic attack (TIA) and ischemic stroke. Cohort studies of TIA or ischemic stroke patients were included if they were published between 1980 and March 2005, reported risk of MI and nonstroke vascular death, enrolled >100 patients, and had at least 1 year of follow-up. We included 39 studies in a total of 65,996 patients with mean follow-up of 3.5 years. Two reviewers independently carried out data extraction using a standardized form. Absolute annual risks were estimated through weighted meta-regressions with a random effect. To test the predictions of expected event rates derived from our analysis, we used individual patient data. SUMMARY OF REVIEW: The annual risks were 2.1% (CI 95%: 1.9 to 2.4) for nonstroke vascular death, 2.2% (1.7 to 2.7) for total MI, 0.9% (0.7 to 1.2) for nonfatal MI and 1.1% (0.8 to 1.5) for fatal MI. The time course of risk was linear. Estimated risks fitted well with observed risks at the individual level. There was no heterogeneity in the absolute risks according to baseline study characteristics. CONCLUSIONS: Patients with TIA or stroke have a relatively high risk of MI and nonstroke vascular death. Additional research is needed to identify the determinants of coronary artery disease in stroke patients.

Aged↗
PubMed2005

A systematic comparison of the quality and volume of published data available on novel risk factors for stroke versus coronary heart disease.

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.

Apolipoproteins↗
PubMed2005

Screening for aspirin responsiveness after transient ischemic attack and stroke: comparison of 2 point-of-care platelet function tests with optical aggregometry.

BACKGROUND AND PURPOSE: Recent studies suggest that patients who do not respond to aspirin (ASA) therapy may be at increased risk of ischemic vascular events. The availability of simple to use point-of-care (POC) platelet function tests now potentially allows aspirin nonresponsiveness to be identified in routine clinical practice. However, there are very few data on whether the different tests produce consistent results. We therefore compared 2 POC tests (PFA-100 device and the Ultegra-RPFA [RPFA]) with conventional light transmission aggregometry (LTA). METHODS: Platelet function was assessed by all 3 tests in 100 patients receiving low-dose ASA therapy after transient ischemic attack (TIA) or ischemic stroke. RESULTS: The incidence of ASA nonresponsiveness was 17% by the RPFA and 22% by the PFA-100, compared with only 5% by LTA (ie, as defined with both arachidonic acid and ADP). Agreement between the RPFA and the PFA-100 and arachidonic acid induced LTA was poor (kappa=0.16, 95% CI, -0.08 to 0.39, P=0.11; and kappa=0.09 -0.12 to 0.30, P=0.32, respectively). Agreement between the 2 POC tests was also poor (kappa=0.14, -0.08 to 0.36, P=0.15). Only 2% of patients were aspirin nonresponders by all 3 tests. CONCLUSIONS: The prevalence of apparent ASA nonresponsiveness was higher with both the POC tests than with LTA. However, agreement between the tests was poor and very few patients were ASA nonresponsive by all 3 tests. Aspirin nonresponsiveness is therefore highly test-specific and large prospective studies will be required to determine the prognostic value of each of the separate tests.

Adult↗
PubMed2005

Timing of TIAs preceding stroke: time window for prevention is very short.

BACKGROUND: Patients with TIA are at increased risk of ischemic stroke and require preventive treatment. However, clinical guidelines differ on how urgently patients should be assessed. OBJECTIVE: To determine the potential consequences of delays in investigation and treatment, the authors studied the timing of TIAs preceding ischemic stroke. METHODS: The authors studied patients who presented with a recent ischemic stroke and had a preceding TIA in two population-based studies (Oxford Vascular Study [OXVASC]; Oxfordshire Community Stroke Project [OCSP]) and two randomized trials (UK TIA Aspirin Trial [UK-TIA]; European Carotid Surgery Trial [ECST]). RESULTS: Of 2,416 patients who had presented with an ischemic stroke, 549 (23%) gave a history of a preceding TIA (18% in OXVASC, 15% in OCSP, 23% in UK-TIA, 26% in ECST). Where a preceding TIA had occurred, the timing was highly consistent across the studies, with 17% occurring on the day of the stroke, 9% on the previous day, and 43% at some point during the 7 days prior to the stroke. No clinical characteristics or vascular risk factors identified patients in whom there was a close temporal association between TIA and stroke. CONCLUSION: In patients presenting with ischemic stroke, TIAs occur most often during the hours and days immediately preceding the stroke.

Causality↗
PubMed2005

Family history of stroke in patients with transient ischemic attack in relation to hypertension and other intermediate phenotypes.

BACKGROUND AND PURPOSE: Family history of stroke (FHx(stroke)) is a risk factor for ischemic stroke, but there are insufficient data on the relationship with stroke subtypes and intermediate phenotypes (IPs), such as hypertension. Specifically, there are no reliable data on the associations of FHx(stroke) in patients with transient ischemic attack (TIA) in whom relationships with IPs are likely to be determined most reliably. METHODS: We studied FHx(stroke) and FHx of myocardial infarction (FHx(MI)) in TIA patients from 2 population-based incidence studies and 2 prospective consecutive hospital-referred series. We related the presence of FHx to baseline characteristics, clinical subtype, and IPs. RESULTS: Results were similar in the 4 cohorts, and so data on all 783 patients were pooled. FHx(stroke) was less common than FHx(MI) (189 versus 254; P=0.0003). FHx(stroke) and FHx(MI) were strongly related to history of hypertension in the proband (odds ratio [OR], 1.78; 95% CI, 1.28 to 2.48; P=0.0008; and OR, 2.10, 95% CI, 1.55 to 2.85; P<0.0001, respectively). Highest recorded premorbid systolic and diastolic blood pressures (mm Hg) were significantly higher in cases with FHx(stroke) than those without and increased with the number of affected first-degree relatives (0 181/100; 1 185/104; > or =2 198/109; P=0.03). There was no association between FHx(stroke) and age, diabetes, smoking, plasma glucose, cholesterol, or territory of TIA, but FHx(stroke) was less common in patients with ocular TIA than in cases with cerebral TIA (OR, 0.53; 95% CI, 0.34 to 0.82; P=0.004), although the association was no longer significant after adjustment for hypertension. CONCLUSIONS: The strong association between hypertension and FHx(stroke) suggests that familial susceptibility to cerebral ischemia is attributable, at least partly, to familial predisposition to hypertension. This should be taken into account in studies of the genetics of ischemic stroke.

Blood Pressure↗
PubMed2005

Cost-effectiveness of diagnostic strategies prior to carotid endarterectomy.

The main objective of this study was to assess the long-term cost-effectiveness of five alternative diagnostic strategies for identification of severe carotid stenosis in recently symptomatic patients. A decision-analytical model with Markov transition states was constructed. Data sources included a prospective study involving 167 patients who had screening Doppler ultrasound (DUS), confirmatory contrast-enhanced magnetic resonance angiography (CEMRA) and confirmatory digital subtraction angiography (DSA), individual patient data from the European Carotid Surgery Trial and other published clinical and cost data. A "selective" strategy, whereby all patients receive DUS and CEMRA (only proceeding to DSA if the CEMRA is positive and the DUS is negative), was most cost-effective. This was both the cheapest imaging and treatment strategy (35,205 dollars per patient) and yielded 6.1590 quality-adjusted life years (QALYs), higher than three alternative imaging strategies. Probabilistic sensitivity analysis demonstrated that there was less than a 10% probability that imaging with either DUS or DSA alone are cost-effective at the conventional 50,000 dollars/QALY threshold. In conclusion, DSA is not cost-effective in the routine diagnostic workup of most patients. DUS, with additional imaging in the form of CEMRA, is recommended, with a strategy of "CEMRA and selective DUS review" being shown to be the optimal imaging strategy.

Aged↗
PubMed2005

Risk modeling to identify patients with symptomatic carotid stenosis most at risk of stroke.

We have reliable data on the degree of stenosis above which endarterectomy for symptomatic carotid stenosis is beneficial, but benefit is also influenced by other factors, particularly age, sex, the timing of surgery, plaque surface morphology and the nature of the presenting symptomatic event(s). This review will consider the selection of patients for carotid surgery based on the factors that influence the likely risk of stroke on medical treatment. In order to take into account all of the relevant factors, a risk prediction model is considered.

Adult↗
PubMed2005

The need for emergency treatment of transient ischemic attack and minor stroke.

The risk of recurrent stroke following transient ischemic attack or minor stroke has recently been shown to be 5-10% at 1 week and 10-20% at 3 months, depending on study population and methods. This is considerably higher than previously estimated and current clinical guidelines reflect the need for rapid assessment although a wide variation in practice exists. Effective management of patients with transient ischemic attack or minor stroke, therefore, requires identification of individuals at the highest (and lowest) risk and initiation of appropriate secondary prevention. Risk can be stratified at initial presentation by the presence or absence of simple clinical features and following subsequent investigation. For transient ischemic attack patients, older age, diabetes, longer duration of symptoms and weakness or speech disturbance identify patients at highest risk, as does the presence of large artery atherosclerosis (mainly internal carotid artery stenosis) and lesions on diffusion-weighted magnetic resonance imaging. Strong evidence exists for the benefit of some early interventions (carotid endarterectomy and antiplatelet agents), but is circumstantial or awaited for others (statins and antihypertensives). In order for the public health challenge posed by transient ischemic attack and minor stroke to be met, considerable change is required in both public education (to ensure correct recognition of symptoms and swift presentation to medical attention) and the provision of clinical services to ensure the timely initiation of effective treatment.

Cerebral Angiography↗
PubMed2005

Identification, prognosis, and management of patients with carotid artery near occlusion.

BACKGROUND AND PURPOSE: Two large trials indicated that endarterectomy was less beneficial for symptomatic patients with internal carotid artery (ICA) near occlusion than for patients who had severe stenosis without near occlusion. Near occlusions complicate ratio calculations of ICA stenosis and require attention to detail for identification. The goal is to provide diagnostic criteria, illustrate identifying features, estimate accuracy of identification, and assess prognosis for patients with near occlusion. METHODS: We re-reviewed 1216 patients with severe (> or =70%) stenosis on angiography in the North American Symptomatic Carotid Endarterectomy Trial and European Carotid Surgery Trial. One of 5 (n = 262) had 2 or more criteria for near occlusion: (1) delayed cranial arrival of ICA contrast compared with external carotid artery (ECA); (2) intracranial collaterals seen as cross-filling of contralateral vessels or ipsilateral contrast dilution; (3) obvious diameter reduction of ICA compared with opposite ICA; or (4) ICA diameter reduction compared with ipsilateral ECA. RESULTS: Interrater agreement, sensitivity, and specificity were excellent (0.88, 90.6%, and 93.8%, respectively). By intention to treat, 3-year risks of ipsilateral stroke for medically treated patients with near occlusion was 15.1% versus 10.9% for surgically treated (absolute risk reduction [ARR] = 4.2%; P value = .33). Patients who continued to receive treatment in the medical arm for the trial's duration had a 3-year risk of 18.3% (ARR = 7.4%; P value = .13). Medically treated patients with severe stenosis but without near occlusion had a 3-year risk of 26.0% versus surgically treated of 8.2% (ARR = 17.8%; P value < .001). CONCLUSION: It is crucial to identify near occlusions on vascular imaging. Although it still is reasonable to consider endarterectomy for these patients, the benefit is muted.

Carotid Stenosis↗
PubMed2004

Timing of birth and risk of multiple sclerosis: population based study.

OBJECTIVES: To determine if risk of multiple sclerosis (MS) is associated with month of birth in countries in the northern hemisphere and if factors related to month of birth interact with genetic risk. DESIGN: Population based study with population and family based controls and a retrospective cohort identified from death certificates. A post hoc pooled analysis was carried out for large northern datasets including Sweden and Denmark. SETTING: 19 MS clinics in major cities across Canada (Canadian collaborative project on the genetic susceptibility to multiple sclerosis); incident cases of MS from a population based study in the Lothian and Border regions of Scotland; and death records from the UK Registrar General. POPULATIONS: 17,874 Canadian patients and 11,502 British patients with multiple sclerosis. MAIN OUTCOME MEASURE: Diagnosis of multiple sclerosis. RESULTS: In Canada (n = 17,874) significantly fewer patients with MS were born in November compared with controls from the population census and unaffected siblings. These observations were confirmed in a dataset of British patients (n = 11, 502), in which there was also an increase in the number of births in May. A pooled analysis of datasets from Canada, Great Britain, Denmark, and Sweden (n = 42,045) showed that significantly fewer (8.5%) people with MS were born in November and significantly more (9.1%) were born in May. For recent incident data, the effect of month of birth was most evident in Scotland, where MS prevalence is the highest. CONCLUSIONS: Month of birth and risk of MS are associated, more so in familial cases, implying interactions between genes and environment that are related to climate. Such interactions may act during gestation or shortly after birth in individuals born in the northern countries studied.

Canada↗
PubMed2004

Potential confounding by intermediate phenotypes in studies of the genetics of ischaemic stroke.

BACKGROUND: Family history (FHx) of stroke is perceived to be an important risk factor for ischaemic stroke. However, there are several intermediate phenotypes that are often involved in the aetiology of ischaemic stroke and that have a substantial genetic component themselves. We studied FHx of ischaemic heart disease (IHD), hypertension (HTN) and diabetes mellitus (DM) as risk factors for ischaemic stroke. METHODS: We performed a systematic review of case-control and cohort studies reporting on FHx(IHD), FHx(HTN) or FHx(DM) as risk factors for stroke using bibliographic databases, and by hand searching reference lists and journals. Odds ratios of FHx as a risk factor for stroke were calculated within individual studies. We included unpublished data from two Oxfordshire population-based studies to assess effects on subtypes of ischaemic stroke. RESULTS: We identified 54 studies that investigated the odds of stroke conferred by a positive FHx, 24 of which reported data on FHx of one or more intermediate phenotypes in addition to FHx of stroke. Most studies reported an increased frequency of FHx(IHD) and FHx(HTN) in stroke patients versus controls. The association was significant in 6 out of 14 studies for FHx(IHD) and 4 out of 11 studies for FHx(HTN). In contrast, FHx(DM) was not associated with stroke. FHx(IHD) was particularly associated with large vessel strokes (OR 1.72, CI 1.3-2.2, p = 0.00004). CONCLUSIONS: FHx(IHD) and FHx(HTN) are both risk factors for stroke. It is likely that the apparent heritability of stroke is partly accounted for by heritability of HTN and large vessel atherosclerosis. Analyses of heritability of stroke and candidate gene studies should be adjusted accordingly.

Brain Ischemia↗
PubMed2004

Diffusion-weighted MRI in 300 patients presenting late with subacute transient ischemic attack or minor stroke.

BACKGROUND AND PURPOSE: Many patients with transient ischemic attack (TIA) or minor stroke present to medical attention after a delay of several days or weeks, at which time it may be more difficult to obtain a clear history and clinical signs may have resolved. Because ischemic lesions on diffusion-weighted MRI (DWI) often persist for several weeks, we hypothesized that adding DWI to a standard protocol with T2-weighted imaging might be useful in the management of patients presenting late. METHODS: We studied consecutive patients with TIA or minor stroke presenting > or =3 days after the event. Two independent observers recorded the presence or absence of recent ischemic lesions on 2 different occasions, first with the T2 scan only, and second with T2 and DWI. Each time, with the aid of a written clinical summary, the observers recorded their diagnosis and proposed management. RESULTS: 300 patients (159 men) were scanned at a median of 17 (interquartile range=10 to 23) days after symptom onset. DWI showed a high signal lesion in 114/164 (70%) minor strokes versus 17/136 (13%) TIAs (P<0.0001). The presence of high-signal lesions on DWI decreased nonlinearly with time since symptom onset (P<0.0001) and increased with National Institutes of Health Stroke Score (P=0.038) and with age (P=0.01). In 90/206 (43.7%) patients with 1 or multiple lesions on T2, DWI helped to clarify whether these were related to a recent ischemic event (79 [48%] strokes; 11 [31%] TIAs). Compared with T2 alone, DWI provided additional information in 108 (36%) patients (91 [56%] strokes and 17 [13%] TIAs), such as clarification of clinical diagnosis (18 patients, 6%) or vascular territory (28 patients, 9.3%), which was considered likely to influence management in 42 (14%) patients (32 [19%] strokes; 10 [7.4%] TIAs). CONCLUSIONS: The clinically useful information available from DWI provides a further justification for an MRI-based imaging protocol in patients with subacute TIA or minor stroke.

Aged↗