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P M Rothwell

Publications and source records attributed to P M Rothwell.

At least 19 recordsLinked to original sources
PubMed2006

Effect of nonoptimal imaging on the relationship between the measured degree of symptomatic carotid stenosis and risk of ischemic stroke.

BACKGROUND AND PURPOSE: Some recent studies of noninvasive carotid imaging have identified high rates of inappropriate decision-making about endarterectomy compared with conventional arterial angiography (CAA), but there is substantial inconsistency across the published literature. CAA is usually regarded as the gold standard for carotid imaging, partly because the degree of angiographic stenosis is a powerful predictor of ischemic stroke and hence of benefit from endarterectomy. However, there are very few published data on the extent to which predictive power varies with type of CAA or the number and quality of views of the stenosis obtained. METHODS: We analyzed measurements of stenosis made by 2 independent observers on 967 consecutive patients randomized to medial treatment alone in the European Carotid Surgery Trial (ECST). We determined prediction of 3-year risk of ipsilateral ischemic stroke (as a hazard ratio from a Cox model and as the area under a receiver operating characteristic curve [AUC]) in relation to the technique of angiography, the number and quality of views of the stenosis, and the use of 2 independent measurements. RESULTS: Using 2 independent measurements of stenosis increased predictive power slightly, but the effect was much smaller than that attributable to the type of CAA and the number of views of the stenosis. Prognostic value was greater in patients who had selective carotid injection CAA and at least biplane views (AUC, 0.75; 0.68 to 0.82) than in patients with only a single view or aortic arch injection CAA (AUC, 0.65; 0.56 to 0.73; P=0.03). CONCLUSIONS: The dependence of the prognostic value of CAA on the type of angiography and the number of views of the stenosis obtained has implications for the future development and validation of noninvasive methods of carotid imaging.

Aged↗
PubMed2006

Histological assessment of 526 symptomatic carotid plaques in relation to the nature and timing of ischemic symptoms: the Oxford plaque study.

BACKGROUND: Atherosclerotic plaque at the carotid bifurcation is often associated with transient ischemic attack (TIA) and ischemic stroke, but the mechanisms are not completely understood. Previous histological studies have been too small or insufficiently detailed to reliably determine the temporal course of features of plaque instability or to stratify analyses by the nature of presenting symptoms. METHODS AND RESULTS: We performed the largest-ever histological study of symptomatic carotid plaques from consecutive patients (n=526) undergoing endarterectomy and related detailed reproducible histological assessments to the nature and timing of presenting symptoms. There was a high prevalence of many features of coronary-type plaque instability. Dense plaque inflammation (especially infiltration with macrophages) was the feature most strongly associated with both cap rupture (odds ratio 3.39, 95% confidence interval 2.31 to 4.98, P<0.001) and time since stroke (P=0.001). Strong negative associations with time since stroke were also seen for cap rupture (P=0.02), overall plaque inflammation (P=0.003), and "unstable plaque" (P=0.001). Although plaques removed < or =60 days after the most recent event were more unstable after a stroke than after a TIA, the instability persisted after a TIA, and plaques removed >180 days after most recent event were less unstable after a stroke than after a TIA (plaque inflammation: < or =60 days, odds ratio 2.33 [95% confidence interval 0.76 to 7.19]; >180 days, 0.36 [0.16 to 0.84]; P=0.008; unstable plaque: odds ratio 3.27 [95% confidence interval 0.93 to 11.50] versus 0.74 [0.33 to 1.69], P=0.05). CONCLUSIONS: Pathology of recently symptomatic carotid plaques is similar to that of culprit coronary plaques, with strong correlations between macrophage infiltration and plaque instability. The tendency for plaque inflammation and overall instability to persist with time after a TIA but to decrease with time after a stroke suggests that the nature of the underlying pathology may differ.

Aged↗
PubMed2006

Apolipoproteins as predictors of ischaemic stroke in patients with a previous transient ischaemic attack.

BACKGROUND: Weak associations between total and LDL cholesterol and ischaemic stroke compared with coronary heart disease (CHD) are at odds with the similar effectiveness of statin drugs in preventing ischaemic stroke and CHD, suggesting that other lipid sub-fractions that are affected by statins might be better predictors of ischaemic stroke. Apolipoprotein B levels are reduced by statins and are a stronger predictor of CHD than total and LDL cholesterol in patients both on and off statins. However, there are very few published data on apolipoproteins and stroke risk and no studies in patients with previous transient ischaemic attack (TIA). METHODS: We performed a prospective cohort study of the associations of baseline total cholesterol, LDL, HDL, apolipoproteins A1 and B (apo A1; apo B) and risk of ischaemic stroke in 261 patients with previous TIA. Cox proportional hazards models were used to determine crude and multivariate-adjusted hazard ratios (HR) above versus below median values at 10-years follow-up. RESULTS: The apo B/apo A1 ratio was the strongest independent predictor of ischaemic stroke (HR=2.94, 95% CI 1.43-5.88, p=0.003) followed by apo B (HR=2.26, 95% CI 1.16-4.38, p=0.02). The associations between total cholesterol, LDL, HDL, LDL/HDL ratio and apo A1 and ischaemic stroke risk did not reach statistical significance. CONCLUSIONS: Apo B and the apo B/apo A1 ratio are predictive of ischaemic stroke in patients with previous TIA. Further studies are required to determine whether the prognostic value of apolipoprotein levels is maintained in patients on statins.

Aged↗
PubMed2006

Predictors of risk of intracerebral haemorrhage in patients with a history of TIA or minor ischaemic stroke.

We developed a model identifying patients with previous cerebral ischaemia at increased risk of intracerebral haemorrhage (ICH). Based on data from eight cohorts, 107 ICHs were found to have occurred among 12 648 patients. Multivariate Cox regression analysis identified the following predictors: age (> or = 60 years, hazard ratio (HR) 2.07), blood glucose level (> or = 7 mmol/l, HR 0.33), systolic blood pressure (> or = 140 mm Hg, HR 2.17), and antihypertensive drugs (HR 1.53). The highest risk quartile was associated with five times more ICHs than the lowest quartile.

Adult↗
PubMed2005

Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study).

BACKGROUND: Acute coronary, cerebrovascular, and peripheral vascular events have common underlying arterial pathology, risk factors, and preventive treatments, but they are rarely studied concurrently. In the Oxford Vascular Study, we determined the comparative epidemiology of different acute vascular syndromes, their current burdens, and the potential effect of the ageing population on future rates. METHODS: We prospectively assessed all individuals presenting with an acute vascular event of any type in any arterial territory irrespective of age in a population of 91 106 in Oxfordshire, UK, in 2002-05. FINDINGS: 2024 acute vascular events occurred in 1657 individuals: 918 (45%) cerebrovascular (618 stroke, 300 transient ischaemic attacks [TIA]); 856 (42%) coronary vascular (159 ST-elevation myocardial infarction, 316 non-ST-elevation myocardial infarction, 218 unstable angina, 163 sudden cardiac death); 188 (9%) peripheral vascular (43 aortic, 53 embolic visceral or limb ischaemia, 92 critical limb ischaemia); and 62 unclassifiable deaths. Relative incidence of cerebrovascular events compared with coronary events was 1.19 (95% CI 1.06-1.33) overall; 1.40 (1.23-1.59) for non-fatal events; and 1.21 (1.04-1.41) if TIA and unstable angina were further excluded. Event and incidence rates rose steeply with age in all arterial territories, with 735 (80%) cerebrovascular, 623 (73%) coronary, and 147 (78%) peripheral vascular events in 12 886 (14%) individuals aged 65 years or older; and 503 (54%), 402 (47%), and 105 (56%), respectively, in the 5919 (6%) aged 75 years or older. Although case-fatality rates increased with age, 736 (47%) of 1561 non-fatal events occurred at age 75 years or older. INTERPRETATION: The high rates of acute vascular events outside the coronary arterial territory and the steep rise in event rates with age in all territories have implications for prevention strategies, clinical trial design, and the targeting of funds for service provision and research.

Adult↗
PubMed2005

Population-based study of delays in carotid imaging and surgery and the risk of recurrent stroke.

BACKGROUND: Benefit from carotid endarterectomy is greatest when performed within 2 weeks of a presenting TIA or stroke and decreases rapidly thereafter. OBJECTIVE: To determine the delays to carotid imaging and endarterectomy in Oxfordshire, UK, and the consequences for the effectiveness of stroke prevention. METHODS: All patients undergoing carotid imaging for ischemic retinal or cerebral TIA or stroke were identified in two populations: the population of Oxfordshire, UK (n = 680,772), from April 1, 2002, to March 31, 2003, and the Oxford Vascular Study (OXVASC) subpopulation (n = 92,000) from April 1, 2002, to March 31, 2004. The times from presenting event to referral, scanning, and endarterectomy (Oxfordshire population) and the risk of stroke prior to endarterectomy in patients with > or = 50% symptomatic carotid stenosis (OXVASC population) were determined. RESULTS: Among 853 patients who had carotid imaging in the Oxfordshire population, median (interquartile range) times from presenting event to referral, scanning, and endarterectomy were 9 (3 to 30), 33 (12 to 62), and 100 (59 to 137) days. Eighty-five patients were found to have 50 to 99% symptomatic stenosis, of whom 49 had endarterectomy. Only 3 (6%) had surgery within 2 weeks of their presenting event and only 21 (43%) within 12 weeks. The risk of stroke prior to endarterectomy in the OXVASC subpopulation with > or = 50% stenosis was 21% (8 to 34%) at 2 weeks and 32% (17 to 47%) at 12 weeks, in half of which strokes were disabling or fatal. CONCLUSION: Delays to carotid imaging and endarterectomy after TIA or stroke in the United Kingdom are similar to those reported in several other countries and are associated with very high risks of otherwise preventable early recurrent stroke.

Aged↗
PubMed2005

A systematic review of the associations between age and sex and the operative risks of carotid endarterectomy.

BACKGROUND: Randomized trials of carotid endarterectomy (CEA) for both symptomatic and asymptomatic carotid stenosis have demonstrated that benefit is decreased in women, due partly to a high operative risk, which is independent of age. However, it is uncertain whether these trial-based observations are generalisable to routine clinical practice. METHODS: We performed a systematic review of all publications reporting data on the association between age and/or sex and procedural risk of stroke and/or death following CEA from 1980 to 2004. RESULTS: 62 eligible papers reported relevant data. Females had a higher rate of operative stroke and death (25 studies, OR = 1.31, 95% CI = 1.17-1.47, p < 0.001) than males, but no increase in operative mortality (15 studies, OR = 1.05, 95% CI = 0.81-0.86, p = 0.78). Compared with younger patients, operative mortality was increased at > or =75 years (20 studies, OR = 1.36, 95% CI = 1.07-1.68, p = 0.02), at age > or =80 years (15 studies, OR = 1.80, 95% CI = 1.26-2.45, p < 0.001) and in older patients overall (35 studies, OR = 1.50, 95% CI = 1.26-1.78, p < 0.001). In contrast, risk of non-fatal stroke did not increase with age and so the combined perioperative risk was only slightly increased at age > or =75 years (21 studies, OR = 1.18, 95% CI = 0.94-1.44, p = 0.06), at age > or =80 years (10 studies, OR = 1.14, 95% CI = 0.92-1.36, p = 0.34) and in older patients overall (36 studies, OR = 1.17, 95% CI = 1.04-1.31, p = 0.01). CONCLUSIONS: The effects of age and sex on the operative risk of CEA in published case series are consistent with those observed in the trials. Operative risk of stroke is increased in women and operative mortality is increased in patients aged > or =75 years.

Adult↗
PubMed2005

A critical appraisal of the performance, reporting, and interpretation of studies comparing carotid plaque imaging with histology.

BACKGROUND AND PURPOSE: Carotid plaque instability is an important determinant of stroke risk. There are now a number of different imaging techniques that provide information on carotid plaque morphology. However, it is unclear how they compare with one another or whether they can reliably assess plaque instability. Studies comparing imaging with pathology have shown highly variable results, even for similar imaging techniques. This may be because of variable pathology techniques rather than differences in imaging. METHODS: We performed a systematic review of studies that compared carotid imaging with histology of the excised plaque published between January 1995 and September 2004. We assessed the quality and comparability of these studies. In particular, we determined which histology methods were used and whether observer reproducibility of the histology assessment was reported. RESULTS: Among 73 eligible studies, histological methods were poorly reported and highly variable; 23% reported reproducibility data for imaging and only 12% reported reproducibility data for histology. Of 29 studies that reported quantitative results of blinded comparisons, there were methodological deficiencies and the results were highly variable. No study considered the extent to which the lack of reproducibility influenced the imaging-pathological correlations reported. CONCLUSIONS: Pathological correlation in studies of carotid plaque imaging cannot be reliably interpreted or compared because of incomparable and poorly reported histology methods. We make recommendations for the performance, reporting, and interpretation of imaging-pathological correlation studies and highlight the need for consensus guidelines.

Carotid Arteries↗
PubMed2004

Sex difference in the effect of time from symptoms to surgery on benefit from carotid endarterectomy for transient ischemic attack and nondisabling stroke.

BACKGROUND AND PURPOSE: Early studies showed that carotid endarterectomy (CEA) carried a high risk if performed within days after a large ischemic stroke. Therefore, many surgeons delay CEA for 4 to 6 weeks after any stroke. To determine the effect of delay to CEA on operative risk and benefit, we pooled data from the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial. METHODS: Risk of ipsilateral ischemic stroke in the medical group, operative risk of stroke and death, and overall benefit from surgery were determined in relation to the time from the last symptomatic event to randomization. Operative risk of stroke and death was also determined in relation to the time to surgery. Analyses were stratified by sex and type of presenting event. RESULTS: The 30-day perioperative risk of stroke and death was unrelated to the time since the last symptomatic event and was not increased in patients operated <2 weeks after nondisabling stroke. In contrast, the risk of ipsilateral ischemic stroke in the medical group fell rapidly with time since event (P<0.001), as did the absolute benefit from surgery (P=0.001). This decline in benefit with time was unrelated to the type of presenting event but was more pronounced in women than men (difference P<0.001). Benefit in women was confined to those randomized <2 weeks after their last event, irrespective of severity of stenosis. CONCLUSIONS: CEA can be performed safely within 2 weeks of nondisabling ischemic stroke. Benefit from endarterectomy declines rapidly with increasing delay, particularly in women.

Aged↗
PubMed2004

Histological correlates of carotid plaque surface morphology on lumen contrast imaging.

BACKGROUND: Carotid angiographic plaque surface morphology is a powerful risk factor for stroke and systemic vascular risk. However, the underlying pathology is unclear, and a better understanding is required both to evaluate other forms of carotid imaging and to develop new treatments. Previous studies comparing angiographic plaque surface morphology with pathology have been small and unblinded, and the vast majority assessed only the crude macroscopic appearance of the plaque. We performed the first large study comparing angiographic surface morphology with detailed histology. METHODS AND RESULTS: Carotid plaque surface morphology was classified as ulcerated, irregular, or smooth on 128 conventional selective carotid artery angiograms from consecutive patients undergoing endarterectomy for severe symptomatic stenosis. Blinded angiographic assessments were compared with 10 histological features recorded on detailed microscopy of the plaque using reproducible semiquantitative scales. Angiographic ulceration was associated with plaque rupture (P=0.001), intraplaque hemorrhage (P=0.001), large lipid core (P=0.005), less fibrous tissue (P=0.003), and increased instability overall (P=0.001). For example, angiographically ulcerated plaques were much more likely than smooth plaques to be ruptured (OR=15.4, 95% CI=2.7 to 87.3, P<0.001), show a large lipid core (OR=26.7, 95% CI=2.6 to 270, P<0.001) or a large hemorrhage (OR=17.0, 95% CI=2.0 to 147, P=0.02). The equivalent odds ratios for angiographically irregular versus smooth plaque were 6.3 (1.3 to 31, P=0.02), 6.7 (1.5 to 30, P=0.008), and 9.2 (1.1 to 77, P=0.02), respectively. CONCLUSIONS: In contrast to previous studies based on macroscopic assessment, we found very strong associations between detailed histology and carotid angiographic plaque surface morphology. Plaque surface morphology on carotid angiography is a highly sensitive marker of plaque instability. Studies of the predictive value of MR- and CT-based lumen contrast plaque surface imaging are required.

Aged↗
PubMed2004

Direct assessment of completeness of ascertainment in a stroke incidence study.

BACKGROUND AND PURPOSE: Validity of comparisons of stroke incidence between studies or time periods depends on the completeness of ascertainment. Ascertainment cannot be reliably assessed indirectly by statistical methods, such as capture-recapture. We report the first use of direct methods to determine the completeness of different ascertainment strategies in a population-based stroke incidence study (Oxford Vascular Study). METHODS: We assessed completeness of 2 different ascertainment strategies: the core methods common to most previous incidence studies and core plus supplementary methods used in some studies (including access to carotid and brain imaging referrals and assessment of patients referred as "transient ischemic attack" or "recurrent stroke"). We assessed completeness of ascertainment in 2 ways. First, we searched anonymized primary care electronic patient records of the whole study population (n=90,542). Second, we interviewed and followed-up a high-risk subset of our study population: all patients who had an acute coronary or peripheral vascular event or a related elective investigation or intervention. RESULTS: 126 strokes were ascertained by the core plus supplementary methods, of which only 108 were identified by the core methods alone. Only 2 additional incident strokes were identified by access to primary care electronic patient records of the whole study population. Assessment and follow-up of 1103 high-risk individuals (5.5% of our total study population aged older than 60 years) identified 16 incident strokes. However, all 16 had already been ascertained by the core plus supplementary methods. CONCLUSIONS: The core methods of ascertainment used in some stroke incidence studies lead to significant underascertainment. However, direct assessment of ascertainment suggests that the supplementary methods used in recent studies can lead to near-complete ascertainment.

Aged↗
PubMed2004

Reproducibility of histological assessment of carotid plaque: implications for studies of carotid imaging.

BACKGROUND: Thromboembolism from carotid plaque is an important cause of stroke. Identification of unstable plaque would therefore be clinically useful. Unfortunately, studies of carotid plaque imaging have shown poor agreement with histology. However, this may be due to inconsistent methods and the variability of assessments of carotid plaque histology, rather than inadequate imaging. METHODS: We assessed the reproducibility of histological assessment in 60 plaques, and section-to-section variability along the length of 26 plaques. RESULTS: Kappa values ranged from 0.35 to 0.89 and from 0.44 to 0.68, respectively, for intra- and inter-observer reproducibility. There was considerable section-to-section variability within plaques. CONCLUSIONS: The accuracy of imaging of carotid plaque morphology will be underestimated unless variability in the histology assessment is taken into account.

Carotid Arteries↗
PubMed2004

Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study).

BACKGROUND: The incidence of stroke is predicted to rise because of the rapidly ageing population. However, over the past two decades, findings of randomised trials have identified several interventions that are effective in prevention of stroke. Reliable data on time-trends in stroke incidence, major risk factors, and use of preventive treatments in an ageing population are required to ascertain whether implementation of preventive strategies can offset the predicted rise in stroke incidence. We aimed to obtain these data. METHODS: We ascertained changes in incidence of transient ischaemic attack and stroke, risk factors, and premorbid use of preventive treatments from 1981-84 (Oxford Community Stroke Project; OCSP) to 2002-04 (Oxford Vascular Study; OXVASC). FINDINGS: Of 476 patients with transient ischaemic attacks or strokes in OXVASC, 262 strokes and 93 transient ischaemic attacks were incident events. Despite more complete case-ascertainment than in OCSP, age-adjusted and sex-adjusted incidence of first-ever stroke fell by 29% (relative incidence 0.71, 95% CI 0.61-0.83, p=0.0002). Incidence declined by more than 50% for primary intracerebral haemorrhage (0.47, 0.27-0.83, p=0.01) but was unchanged for subarachnoid haemorrhage (0.83, 0.44-1.57, p=0.57). Thus, although 28% more incident strokes (366 vs 286) were expected in OXVASC due to demographic change alone (33% increase in those aged 75 or older), the observed number fell (262 vs 286). Major reductions were recorded in mortality rates for incident stroke (0.63, 0.44-0.90, p=0.02) and in incidence of disabling or fatal stroke (0.60, 0.50-0.73, p<0.0001), but no change was seen in case-fatality due to incident stroke (17.2% vs 17.8%; age and sex adjusted relative risk 0.85, 95% CI 0.57-1.28, p=0.45). Comparison of premorbid risk factors revealed substantial reductions in the proportion of smokers, mean total cholesterol, and mean systolic and diastolic blood pressures and major increases in premorbid treatment with antiplatelet, lipid-lowering, and blood pressure lowering drugs (all p<0.0001). INTERPRETATION: The age-specific incidence of major stroke in Oxfordshire has fallen by 40% over the past 20 years in association with increased use of preventive treatments and major reductions in premorbid risk factors.

Adult↗
PubMed2004

Time trends in the published risks of stroke and death due to endarterectomy for symptomatic carotid stenosis.

BACKGROUND: Large randomised trials performed in the 1980s and early 1990s showed that carotid endarterectomy (CEA) is beneficial for patients with recently symptomatic severe stenosis. Some surgeons have argued that the operative risk of stroke and death has fallen over the last decade due to refinements in operative technique, and that the indications for surgery should therefore now be broadened. Yet, studies of routinely collected data report higher operative mortality than in the trials, and surgical case series without independent post-operative assessment by a neurologist may not provide reliable data on stroke risk. METHODS: We performed a systematic review of all studies published between 1994 and 2001 inclusive that which reported the risks of stroke and death for symptomatic carotid stenosis, and compared the reported risks and patient characteristics with those in the ECST and NASCET and with our previous review of studies published prior to 1995. Pooled estimates of the operative risk of stroke and death were obtained by Mantel-Haenszel meta-analysis. RESULTS: Of 383 studies published between 1994 and 2001, only 45 reported operative risks for patients with symptomatic stenosis separately. The pooled operative risk of stroke and death reported in studies published by surgeons only (4.2%, 95% CI = 2.9-5.5, 34 studies) was significantly lower (p < 0.0001) than that in the ECST and NASCET combined (7.0%, 95% CI = 6.2-8.0), whereas the pooled risk reported in studies that involved neurologists was similar (6.5%, 95% CI = 4.3-8.7, 11 studies, p = 0.6). In contrast, operative mortality in ECST and NASCET was significantly lower than in other studies published between 1994 and 2001. By comparison with our previous review, when stratified according to involvement of neurologists, we found no evidence of a reduction in published risks of death or stroke and death due to CEA between 1985 and 2001. CONCLUSIONS: There is no evidence of a systematic reduction over the last decade in the published risks of stroke and death due to CEA for symptomatic stenosis. Operative risks in studies with comparable outcome assessment are similar to ECST and NASCET. The surgical data from the large trials are still likely therefore to be applicable to routine clinical practice.

Carotid Stenosis↗
PubMed2004

Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery.

BACKGROUND: Carotid endarterectomy reduces the risk of stroke in patients with recently symptomatic stenosis. Benefit depends on the degree of stenosis, and we aimed to see whether it might also depend on other clinical and angiographic characteristics, and on the timing of surgery. METHODS: We analysed pooled data from the European Carotid Surgery Trial and North American Symptomatic Carotid Endarterectomy Trial. The risk of ipsilateral ischaemic stroke for patients on medical treatment, the perioperative risk of stroke and death, and the overall benefit from surgery were determined in relation to seven predefined and seven post hoc subgroups. RESULTS: 5893 patients with 33000 patient-years of follow-up were analysed. Sex (p=0.003), age (p=0.03), and time from the last symptomatic event to randomisation (p=0.009) modified the effectiveness of surgery. Benefit from surgery was greatest in men, patients aged 75 years or older, and those randomised within 2 weeks after their last ischaemic event, and fell rapidly with increasing delay. For patients with 50% or higher stenosis, the number of patients needed to undergo surgery (ie, number needed to treat) to prevent one ipsilateral stroke in 5 years was nine for men versus 36 for women, five for age 75 years or older versus 18 for younger than 65 years, and five for those randomised within 2 weeks after their last ischaemic event, versus 125 for patients randomised after more than 12 weeks. These results were consistent across the individual trials. INTERPRETATION: Benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other clinical characteristics such as delay to surgery after the presenting event. Ideally, the procedure should be done within 2 weeks of the patient's last symptoms.

Age Factors↗