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Peter M Rothwell

Publications and source records attributed to Peter M Rothwell.

At least 55 records · Page 3Linked to original sources
PubMed2004

Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5113 patients with transient ischemic attack and minor ischemic stroke.

BACKGROUND AND PURPOSE: Fibrinogen is an independent risk factor for coronary events in population-based studies and in patients with coronary heart disease, but there is uncertainty about prediction of stroke, particularly in secondary prevention. METHODS: We studied unpublished data from 3 prospective studies of patients with recent transient ischemic attack (TIA) or minor ischemic stroke: the United Kingdom TIA Aspirin (UK-TIA) trial (n=1860); the Dutch TIA trial (n=2960); and the Oxford TIA Study (n=293). By separate and pooled analysis, we used Cox models to determine the relationship between fibrinogen and risk of ischemic stroke and other vascular events during 23,272 patient-years of follow-up and adjusted for other risk factors. RESULTS: There was no significant heterogeneity in fibrinogen risk associations between studies. Fibrinogen predicted subsequent ischemic stroke, with a pooled hazard ratio (HR) for values above the median of 1.34 (95% CI, 1.13 to 1.60; P=0.001). The association tended to be stronger in patients with nonlacunar (HR=1.42; 95% CI, 1.13 to 1.78; P=0.002) than lacunar syndromes (HR=1.09; 95% CI, 0.80 to 1.49; P=0.58), but was not significantly so (P=0.18). There was no association with hemorrhagic stroke (adjusted HR=1.09; 95% CI, 0.55 to 2.17; P=0.81). Fibrinogen predicted acute coronary events (adjusted HR=1.42; 95% CI, 1.18 to 1.70; P<0.001) and all ischemic vascular events (adjusted HR=1.31; 95% CI, 1.15 to 1.49; P<0.001), but not nonvascular death (adjusted HR=1.24; 95% CI, 0.90 to 1.70; P=0.19). CONCLUSIONS: In patients with a previous TIA or ischemic stroke, risks of recurrent ischemic stroke and acute coronary events increase linearly with fibrinogen levels, but the relationships are weaker than in some previous population-based studies.

Aged↗
PubMed2004

Underfunding of stroke research: a Europe-wide problem.

BACKGROUND AND PURPOSE: Previous studies in the United States and the United Kingdom have shown that stroke research is underfunded compared with coronary heart disease (CHD) and cancer research despite the high clinical and financial burden of stroke. We aimed to determine whether underfunding of stroke research is a Europe-wide problem. METHODS: Data for the financial year 2000 to 2001 were collected from 9 different European countries. Information on stroke, CHD, and cancer research funding awarded by disease-specific charities and nondisease-specific charity or government- funded organizations was obtained from annual reports, web sites, and by direct communication with organizations. RESULTS: There was marked and consistent underfunding of stroke research in all the countries studied. Stroke funding as a percentage of the total funding for stroke, CHD, and cancer was uniformly low, ranging from 2% to 11%. Funding for stroke was less than funding for cancer, usually by a factor of > or =10. In every country except Turkey, funding for stroke research was less than that for CHD. CONCLUSIONS: This study confirms that stroke research is grossly underfunded, compared with CHD and cancer, throughout Europe. Similar data have been obtained from the United States suggesting that relative underfunding of stroke research is likely to be a worldwide phenomenon.

Biomedical Research↗
PubMed2004

Underestimation of the early risk of recurrent stroke: evidence of the need for a standard definition.

BACKGROUND: There is considerable variation in the definitions used for recurrent stroke. Most epidemiological studies exclude events within the first 28 days (eg, Monitoring Trends and Determinants in Cardiovascular Disease [MONICA]) or events within 21 days in the same territory as the presenting event (eg, most stroke incidence studies). However, recurrence is most common during this early period and these restrictive definitions could underestimate the benefits of early prevention. METHODS: We determined the 90-day risk of recurrence after incident ischemic stroke in 2 population-based cohorts (Oxford Vascular Study [OXVASC] and Oxfordshire Community Stroke Project [OCSP]) with the 3 most common definitions: any stroke > or =24 hours after the incident event excluding early deterioration not caused by a stroke (definition A); as above, but excluding any stroke within 21 days in the same territory as the incident event (definition B); and any stroke > or =28 days after the incident event (definition C). RESULTS: 657 patients had 93 recurrent strokes between 24 hours and 90 days after the incident event. The 90-day recurrence risks (95% CI) using definition A were 14.5% (11.5 to 17.5) in the OCSP and 18.3% (10.8 to 25.8) in the OXVASC. The equivalent risks using definitions B and C were 8.3% (5.9 to 10.8) and 4.8% (2.8 to 6.7), respectively, in the OCSP and 7.0% (1.6 to 12.4) and 5.9% (1.0 to 10.9) in the OXVASC. The definition A risk of recurrence was particularly high after partial anterior (22.9%,17.5 to 28.2) and posterior (19.5%,13.0 to 25.9) circulation strokes. CONCLUSIONS: The 3 most widely used definitions of recurrent stroke yield markedly different 90-day risks. We suggest that, where possible, definition A be adopted as the standard to avoid underestimation of risk and to allow valid comparison of different studies.

Humans↗
PubMed2004

Effective stroke prevention in patients with symptomatic carotid stenosis.

Patients with recently symptomatic carotid stenosis require effective medical treatment, and some require surgical removal of the carotid plaque. Randomized controlled trials have shown that endarterectomy reduces the overall risk of stroke in patients with severe carotid stenosis and, to a lesser extent, in patients with moderate stenosis. However, operating on all patients is not necessarily the most effective approach. The effectiveness of endarterectomy could be improved by selecting patients more rigorously. To do this, we first need to use data from existing randomized controlled trials to precisely determine the overall effect of surgery for different degrees of stenosis, identify subgroups in which benefit is increased, and use risk modeling to identify individuals at particularly high risk of stroke without surgery. Such an approach will also be useful in targeting angioplasty and stenting in patients in whom endarterectomy is not possible.

Carotid Stenosis↗
PubMed2004

Risk of persistent cranial nerve injury after carotid endarterectomy.

OBJECT: Cranial nerve injuries, particularly motor nerve injuries, following carotid endarterectomy (CEA) can be disabling and therefore patients should be given reliable information about the risks of sustaining such injuries. The reported frequency of cranial nerve injury in the published literature ranges from 3 to 23%, and there have been few series in which patients were routinely examined before and after surgery by a neurologist. METHODS: The authors investigated the risk of cranial nerve injuries in patients who underwent CEA in the European Carotid Surgery Trial (ECST), the largest series of patients undergoing CEA in which neurological assessment was performed before and after surgery. Cranial nerve injury was assessed and recorded in every patient and persisting deficits were identified on follow-up examination at 4 months and 1 year after randomization. Risk factors for cranial nerve injury were examined by performing univariate and multivariate analyses. There were 88 motor cranial nerve injuries among the 1739 patients undergoing CEA (5.1% of patients; 95% confidence interval [CI] 4.1-6.2). In 23 patients, the deficit had resolved by hospital discharge, leaving 3.7% of patients (95% CI 2.9-4.7) with a residual cranial nerve injury: 27 hypoglossal, 17 marginal mandibular, 17 recurrent laryngeal, one accessory nerve, and three Homer syndrome. In only nine patients (0.5%; 95% CI 0.24-0.98) the deficit was still present at the 4-month follow-up examination; however, none of the persisting deficits resolved during the subsequent follow up. Only duration of operation longer than 2 hours was independently associated with an increased risk of cranial nerve injury (hazard ratio 1.56, p < 0.0001). CONCLUSIONS: The risk of motor cranial nerve injury persisting beyond hospital discharge after CEA is approximately 4%. The vast majority of neurological deficits resolve over the next few months, however, and permanent deficits are rare. Nevertheless, the risk of cranial nerve injury should be communicated to patients before they undergo surgery.

Aged↗
PubMed2003

Systematic review of methods and results of studies of the genetic epidemiology of ischemic stroke.

BACKGROUND AND PURPOSE: To design appropriate molecular genetic studies, we first need to understand the genetic epidemiology of stroke. We therefore performed a systematic review of the literature to assess the heritability of stroke according to methodological quality of studies and to determine any heterogeneity in findings between studies and possible publication bias. METHODS: We searched for twin studies and studies of family history of stroke using bibliographic databases and by hand-searching reference lists and journals. Odds ratios (ORs) for family history as a risk factor for stroke were calculated within studies and combined by meta-analysis. Heterogeneity between studies, methodological quality of studies, and the influence of the age at which stroke occurred in both probands and relatives were assessed. RESULTS: We identified 53 independent studies (3 twin, 33 case-control, and 17 cohort). Monozygotic twins were more likely to be concordant than dizygotic twins (OR, 1.65; 95% CI, 1.2 to 2.3; P=0.003). A positive family history was a risk factor for stroke in both case-control (OR, 1.76; 95% CI, 1.7 to 1.9; P<0.00001) and cohort (OR, 1.30; 95% CI, 1.2 to 1.5; P<0.00001) studies. However, there was major heterogeneity between studies (cohort P=0.0001; case-control P<0.00001), with much stronger associations in small studies and methodologically less rigorous studies. Moreover, studies that reported insufficient data to allow meta-analysis tended to have found weaker associations. Family history of stroke was more frequent in studies that were confined to probands or relatives aged <70 years. However, few studies considered the number of affected and unaffected relatives, only 2 studies considered stroke phenotypes in detail, and only 19 studies (38%) adjusted associations for intermediate phenotypes. No twin study, only 5 cohort studies (26%), and 20 case-control studies (61%) differentiated between ischemic and hemorrhagic stroke in the proband. Family history of stroke was more frequent in large- and small-vessel stroke than in cardioembolic stroke. There were very few data on the influence of family history on stroke severity and no data on stroke recovery. CONCLUSIONS: Twin studies suggest a small genetic contribution to stroke, but reliable interpretation of published family history studies is undermined by major heterogeneity, insufficient detail, and potential publication and reporting bias. More detailed large-scale genetic epidemiology is required.

Bias↗
PubMed2003

Prognosis of vertebrobasilar transient ischaemic attack and minor stroke.

Vertebrobasilar (VB) territory transient ischaemic attacks (TIAs) and minor strokes are perceived to have a better prognosis than carotid territory events, and are sometimes managed less aggressively. However, this notion stems mainly from a few small studies in the 1960s and 1970s, and has not been systematically tested. We therefore identified all published studies of prognosis after TIA or minor stroke using MEDLINE and EMBASE, and hand-searching reference lists and relevant journals. In addition, we attempted to include all available individual patient data (IPD) from studies that had not published outcome data by territory of presenting event. Odds of recurrent events were calculated within studies and combined by fixed-effects meta-analysis. Heterogeneity between studies was calculated using the chi2 method. We stratified the analysis by time interval between presenting event and inclusion in study, and by study setting (population-based, published hospital-based and unpublished hospital-based). Publication bias was tested for by linear regression of the standard normal deviate against precision. Eight hundred and twenty abstracts were reviewed, and 304 papers were considered in detail. Of these, 43 studies representing 36 independent cohorts (12,196 patients) reported outcomes by territory of presenting event. IPD from five studies (4643 patients) were also included. The following results compare relative risks of VB with carotid events. Studies including the acute phase (up to 7 days) after the presenting event found a higher relative risk of subsequent stroke in patients with VB events [odds ratio (OR) 1.47, 95% confidence interval (CI) 1.1-2.0, P = 0.014]. Conversely, studies mainly recruiting after the acute phase found a lower relative risk (OR 0.74, 95% CI 0.7-0.8, P = 0.00001). In published hospital-based studies, the risk of recurrent stroke was lower for patients presenting with VB events (OR 0.68, 95% CI 0.6-0.8, P < 0.00001). However, there was no difference in hospital-based IPD (OR 1.02, 95% CI 0.8-1.3, P = 0.91). Moreover, in population-based studies, patients with VB events had a higher risk of stroke (OR 1.48, 95% CI 1.1-2.0, P = 0.025). There was no within-stratum heterogeneity. There was no difference in the risk of fatal stroke (OR 1.04, 95% CI 0.8-1.4, P = 0.90). Therefore, we found no evidence that patients presenting with VB events have a lower risk of subsequent stroke or death compared with patients presenting with carotid TIA or minor stroke. Indeed, their risk of stroke is probably higher in the acute phase. Patients with VB events require active preventive treatment.

Humans↗
PubMed2003

Pulse pressure is independently associated with carotid plaque ulceration.

BACKGROUND: Plaque rupture is the principal cause of acute coronary ischaemia, and unstable carotid plaques are associated with a high risk of ischaemic stroke. Carotid plaque ulceration also predicts acute coronary events, suggesting that systemic factors may determine plaque instability. One potentially important factor is pulse pressure. There is indirect evidence that cyclical haemodynamic forces affect plaque stability, and pulse pressure is a strong predictor of coronary events. OBJECTIVE: To study the association between pulse pressure and plaque ulceration. DESIGN AND METHODS: We studied angiograms from 3007 patients with recently symptomatic carotid stenosis in the European Carotid Surgery Trial. Presence of ulceration was related to the different components of blood pressure [pulse pressure, systolic blood pressure (SBP), mean arterial pressure (MAP), and diastolic blood pressure (DBP)], and adjustment was made for age, sex, diabetes, smoking, and the degree of vessel stenosis. RESULTS: Pulse pressure was the strongest independent predictor of ulceration of the symptomatic carotid plaque [adjusted odds ratio (OR) for the upper compared with the lower quintile 2.07, 95% confidence interval (CI) 1.25 to 3.44; P = 0.004]. This relationship was weaker for SBP (OR 1.66, 95% CI 1.05 to 2.62; P = 0.02), and non-significant for MAP (OR 1.58, 95% CI 1.01 to 2.48, P = 0.13) and DBP (OR 1.67, 95% CI 0.73 to 1.87, P = 0.50). CONCLUSIONS: Pulse pressure is independently associated with carotid plaque ulceration, supporting the hypothesis that pulsatile haemodynamic forces are an important cause of plaque rupture.

Aged↗
PubMed2003

Association between arterial bifurcation anatomy and angiographic plaque ulceration among 4,627 carotid stenoses.

Stability of atheromatous plaques is influenced by local mechanical and haemodynamic factors, such as plaque motion and shear stress. However, although blood vessel anatomy is an important determinant of haemodynamics, particularly at bifurcations, there have been no previous clinical studies of the association between arterial anatomy and plaque ulceration. We therefore studied arterial anatomy and plaque ulceration using angiograms of 4,627 carotid bifurcations with atheromatous disease from the European Carotid Surgery Trial (ECST). We studied the vessel diameter and area ratios that have been shown in flow models to affect local haemodynamics and shear stress, and which are known to vary widely between and within individuals (internal to common, external to common, external to internal carotid artery and outflow/inflow area). Angiographic plaque surface morphology was defined as ulcerated or not ulcerated. To avoid any potential bias due to selective inclusion of patients in the ECST, we studied the contralateral, and usually asymptomatic, as well as the symptomatic carotid artery. To correct for the effects of systemic factors that might influence plaque stability, we also studied the relationship between the degree of asymmetry of bifurcation anatomy within individuals and the presence of plaque ulceration. Despite considerable inter-individual variation in carotid anatomy, we found no association between the prevalence of angiographic plaque ulceration and any of the anatomical parameters studied in either symptomatic or contralateral carotid arteries. There were also no associations between ipsilateral bifurcation anatomy and plaque ulceration in individuals with unilateral plaque ulceration. Carotid arterial anatomy does not appear to be an important determinant of plaque stability. Other factors that influence local haemodynamics, such as the anatomy and composition of the plaque itself may be more important.

Carotid Artery, Common↗
PubMed2003

Incidence, risk factors and prognosis of stroke and TIA: the need for high-quality, large-scale epidemiological studies and meta-analyses.

Stroke is a considerable clinical, social and economic burden. In recent clinical trials, a number of strategies have been shown to reduce the risk of stroke and transient ischaemic attack (TIA) in both primary and secondary prevention settings. Whether these treatments are leading to a significant reduction in the incidence of first and recurrent stroke in the clinic, however, remains unclear due to a paucity of high-quality epidemiological data. A similar lack of reliable epidemiological studies has undermined our understanding of the relationship between many potentially important vascular risk factors and stroke risk. Improvement in our knowledge of stroke epidemiology is a prerequisite for the planning of stroke services, the effective application of current stroke prevention strategies, the development of new strategies, and our understanding of the mechanisms of stroke. Future studies must take into account the clinical and pathological heterogeneity of TIA and stroke, and must be powered to allow subtype differences in risk factor relationships and prognosis to be determined reliably. In many cases, this will require meta-analysis of detailed individual patient data from multiple independent studies.

Epidemiologic Studies↗
PubMed2003

Site of carotid plaque ulceration in relation to direction of blood flow: an angiographic and pathological study.

BACKGROUND: Rupture of atherosclerotic plaque is the main cause of acute coronary syndromes and carotid territory ischaemic stroke. Haemodynamic stress is important in early plaque formation and may affect the stability of mature plaques. There is some evidence that macrophage infiltration and plaque rupture tend to localise to the proximal (upstream) part of the plaque where shear stress is highest. However, previous studies have been too small to assess this reliably. We studied the site of ulceration in a large number of carotid plaques. METHODS: We studied angiograms of 3007 symptomatic carotid stenoses, and the pathological appearance of 119 carotid plaques (77 asymptomatic), to identify the presence and position of plaque ulceration. RESULTS: Angiographic ulceration, which was present in 421 patients (14%), was more likely to be PROXIMAL than DISTAL to the point of maximum stenosis (OR = 16.6, 95% CI = 11.6-26.9, p < 0.001). This trend increased with severity of stenosis (p = 0.002). Pathological examination of the 119 carotid plaques also showed that ulceration was more likely to occur proximal to the point of maximum stenosis (OR = 6.1, 95% CI = 2.8-13.6, p < 0.001). CONCLUSIONS: Ulceration of carotid plaques, visible on angiography or on pathological examination, is seen most often in the proximal (upstream) part where shear stress is highest.

Aged↗
PubMed2002

Long-term risk of stroke and other vascular events in patients with asymptomatic carotid artery stenosis.

CONTEXT: The annual risk of ischemic stroke in patients with asymptomatic carotid artery stenosis is about 2% during the short-term (2-3 years), but the long-term risks of stroke and other vascular events are unknown, although they may affect surgical decision making. OBJECTIVE: To evaluate the long-term risk of stroke and other vascular events in patients with asymptomatic carotid artery stenosis. DESIGN: Cohort study with a median follow-up of 10 years (range, 5-18 years). SETTING: The teaching hospital of the University of Toronto, Toronto, Ontario. PATIENTS: From the initial cohort of 500 patients, 106 patients with asymptomatic carotid artery stenosis were selected because they had completed at least 5 years of follow-up. MAIN OUTCOME MEASURES: Ipsilateral stroke, myocardial infarction, and nonstroke vascular death. RESULTS: The 10- and 15-year actuarial risks of ipsilateral stroke were 5.7% (95% confidence interval [CI], 0%-12%) and 8.7% (95% CI, 1%-17%), respectively, in patients with 0% to 49% internal carotid artery stenosis, and 9.3% (95% CI, 1%-18%) and 16.6% (95% CI, 1%-32%) in patients with 50% to 99% internal carotid artery stenosis. The 10- and 15-year risks of myocardial infarction and nonstroke vascular death were 10.1% (95% CI, 4%-16%) and 24.0% (95% CI, 14%-34%). Age (P =.02), diabetes mellitus (P =.02), and internal carotid artery stenosis of 50% or more (P =.04) were predictive of increased risks of myocardial infarction and nonstroke vascular death. Internal carotid artery stenosis of 50% or more did predict the risk of ipsilateral stroke (P =.003) when all 181 asymptomatic carotid arteries were included. CONCLUSIONS: The annual stroke risk in patients with asymptomatic carotid artery stenosis was low and remained stable during long-term follow-up. Any benefit from carotid surgery is therefore unlikely to increase significantly with long-term follow-up. The high long-term risks of myocardial infarction and nonstroke vascular death suggest that prevention strategies should concentrate on coronary risk more than stroke risk.

Aged↗
PubMed2002

Why do clinicians sometimes find it difficult to use the results of systematic reviews in routine clinical practice?

Reviews of systematic results have proved enormously useful in routine clinical practice. However, the uncritical application of the overall results of systematic reviews to clinical decisions about individual patients can sometimes do more harm than good. Clinical syndromes are often complex, with considerable pathological heterogeneity, and the likely balance of the risks and benefits of interventions can be difficult to judge on an individual patient basis. Active involvement of experienced clinicians is essential in the planning, reporting, and interpretation of reviews. Detailed consideration should be given to the possibility of diagnostic or pathological heterogeneity within the clinical trials included in the review or between the trial patients and patients seen in routine clinical practice. For treatments that have significant risk of harm or treatments that are particularly costly, meta-analysis of individual patient data with stratification by baseline risk is sometimes helpful in targeting treatment appropriately in routine clinical practice.

Attitude of Health Personnel↗
PubMedDate not supplied

External validity of randomised controlled trials: "to whom do the results of this trial apply?".

In making treatment decisions, doctors and patients must take into account relevant randomised controlled trials (RCTs) and systematic reviews. Relevance depends on external validity (or generalisability)--ie, whether the results can be reasonably applied to a definable group of patients in a particular clinical setting in routine practice. There is concern among clinicians that external validity is often poor, particularly for some pharmaceutical industry trials, a perception that has led to underuse of treatments that are effective. Yet researchers, funding agencies, ethics committees, the pharmaceutical industry, medical journals, and governmental regulators alike all neglect external validity, leaving clinicians to make judgments. However, reporting of the determinants of external validity in trial publications and systematic reviews is usually inadequate. This review discusses those determinants, presents a checklist for clinicians, and makes recommendations for greater consideration of external validity in the design and reporting of RCTs.

Data Interpretation, Statistical↗