Peter M Rothwell

Oxford University Hospitals NHS Trust, Oxford, England, United Kingdom

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Publications (495)4961.3 Total impact

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    ABSTRACT: Objectives: We aimed to determine age-specific rates of delirium and associated factors in acute medicine, and the impact of delirium on mortality and re-admission on long-term follow-up. Design: Observational study. Consecutive patients over two 8-week periods (2010, 2012) were screened for delirium on admission, using the confusion assessment method (CAM), and reviewed daily thereafter. Delirium diagnosis was made using the Diagnostic and Statistical Manual Fourth Edition (DSM IV) criteria. For patients aged ≥65 years, potentially important covariables identified in previous studies were collected with follow-up for death and re-admission until January 2014. Participants: 503 consecutive patients (age median=72, range 16-99 years, 236 (48%) male). Setting: Acute general medicine. Results: Delirium occurred in 101/503 (20%) (71 on admission, 30 during admission, 17 both), with risk increasing from 3% (6/195) at <65 years to 14% (10/74) for 65-74 years and 36% (85/234) at ≥75 years (p<0.0001). Among 308 patients aged >65 years, after adjustment for age, delirium was associated with previous falls (OR=2.47, 95% CI 1.45 to 4.22, p=0.001), prior dementia (2.08, 1.10 to 3.93, p=0.024), dependency (2.58, 1.48 to 4.48, p=0.001), low cognitive score (5.00, 2.50 to 9.99, p<0.0001), dehydration (3.53, 1.91 to 6.53, p<0.0001), severe illness (1.98, 1.17 to 3.38, p=0.011), pressure sore risk (5.56, 2.60 to 11.88, p<0.0001) and infection (4.88, 2.85 to 8.36, p<0.0001). Patients with delirium were more likely to fall (OR=4.55, 1.47 to 14.05, p=0.008), be incontinent of urine (3.76, 2.15 to 6.58, p<0.0001) or faeces (3.49, 1.81-6.73, p=0.0002) and be catheterised (5.08, 2.44 to 10.54, p<0.0001); and delirium was associated with stay >7 days (2.82, 1.68 to 4.75, p<0.0001), death (4.56, 1.71 to 12.17, p=0.003) and an increase in dependency among survivors (2.56, 1.37 to 4.76, p=0.003) with excess mortality still evident at 2-year follow-up. Patients with delirium had fewer re-admissions within 30-days (OR=0.32, 95% CI 0.09 to 1.1, p=0.07) and in total (median, IQR total re-admissions=0, 0-1 vs 1, 0-2, p=0.01). Conclusions: Delirium affected a fifth of acute medical admissions and a third of those aged ≥75 years, and was associated with increased mortality, institutionalisation and dependency, but not with increased risk of re-admission on follow-up.
    BMJ Open 11/2015; 5(11):e007808. DOI:10.1136/bmjopen-2015-007808 · 2.27 Impact Factor
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    ABSTRACT: Background: Prevalence of atrial fibrillation (AF) is increasing, due partly to the aging population. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) Trial, published in 2007, provided strong evidence of the effectiveness of warfarin at age≥80 years, but the impact on incidence of AF-related stroke and peripheral embolic vascular events (PVEs) is uncertain. Methods: We studied age-specific incidence and outcome of all AF-related incident strokes and systemic emboli from 2002-2012 in the Oxford Vascular Study. Results: Of 3096 acute cerebral or peripheral vascular events, 748 (24.2%) were AF-related. Of the 597 disabling/fatal incident ischaemic strokes, 369 occurred at age ≥80 years, of which 124 (33.6%) were in non-anticoagulated patients with known prior AF. There was no reduction in incident AF-related events after 2007 at all ages (n=231 vs 211; adjusted RR=1.11, 0.91-1.36, p=0.29) or at age ≥80 (137 vs 135, RR=1.15, 0.94-1.40, p=0.17). Scope for improved prevention at older ages was considerable. Among 208 patients with incident AF-related events at age ≥80 and known prior AF, only 19 (9.1%) were anticoagulated. Of the 189 patients not anticoagulated, 166 (87.8%) had no major disability prior to the event and 167 (88·4%) had a high embolism risk score, of whom 139 (83.2%) were also at low risk of complications. Yet, 125/167 (74.9%) were dead or institutionalised after the event. Potentially preventable embolic events outnumbered warfarin-related intracerebral haemorrhages by about 15-fold (280 vs 19), rising to 50-fold (189 vs 4) at age ≥80 years. Conclusion: We found no reduction in incidence of AF-related vascular events since publication of the BAFTA trial. A third of all disabling/fatal strokes occur in non-anticoagulated patients with known prior AF.
    Journal of neurology, neurosurgery, and psychiatry 10/2015; DOI:10.1136/jnnp-2015-311947 · 6.81 Impact Factor
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    ABSTRACT: Background and purpose: Cognitive assessment is recommended after stroke but there are few data on the applicability of short cognitive tests to the full spectrum of patients. We therefore determined the rates, causes, and associates of untestability in a population-based study of all transient ischemic attack (TIA) and stroke. Methods: Patients with TIA or stroke prospectively recruited (2002-2007) into the Oxford Vascular Study had ≥1 short cognitive test (mini-mental state examination, telephone interview of cognitive status, Montreal cognitive assessment, and abbreviated mental test score) at baseline and on follow-up to 5 years. Results: Among 1097 consecutive assessed survivors (mean: age/SD, 74.8/12.1 years; 378 TIA), numbers testable with a short cognitive test at baseline, 1, 6, 12, and 60 months were 835/1097 (76%), 778/947 (82%), 756/857 (88%), 692/792 (87%), and 472/567 (83%). Eighty-eight percent (331/378) of assessed patients with TIA were testable at baseline compared with only 46% (133/290) of major stroke (P<0.001). Untestability was also associated with older age, premorbid dependency, death on follow-up, and with both pre- and postevent dementia (all P<0.01). Untestability (and problems with testing) were commonly caused by acute stroke effects at baseline (153/262 [58%]: dysphasia/anarthria/hemiparesis=84 [32%], drowsiness=58 [22%], and acute confusion=11 [4%]), whereas sensory deficits caused relatively more problems with testing at later time points (24/63 [38%] at 5 years). Conclusions: Substantial numbers of patients with TIA and stroke are untestable with short cognitive tests. Future studies should report data on untestable patients and those with problems with testing in whom the likelihood of dementia is high.
    Stroke 10/2015; DOI:10.1161/STROKEAHA.115.010290 · 5.72 Impact Factor
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    ABSTRACT: Background and purpose: Copeptin, the c-terminal portion of provasopressin, is a useful prognostic marker in patients after myocardial infarction and heart failure. More recently, high levels of copeptin have also been associated with worse functional outcome and increased mortality within the first year after ischemic stroke and transient ischemic attack (TIA). However, to date, there are no published data on whether copeptin predicts long-term risk of vascular events after TIA and stroke. Methods: We measured copeptin levels in consecutive patients with TIA or ischemic stroke in a population-based study (Oxford Vascular Study) recruited from 2002 to 2007 and followed up to 2014. Associations with risk of recurrent vascular events were determined by Cox-regression. Results: During ≈6000 patient-years in 1076 patients, there were 357 recurrent vascular events, including 174 ischemic strokes. After adjustment for age, sex, and risk factors, copeptin was predictive of recurrent vascular events (adjusted hazard ratio per SD, 1.47; 95% confidence interval, 1.31-1.64; P=0.0001), vascular death (1.85; 1.60-2.14; P<0.0001), all-cause death (1.75; 1.58-1.93; P<0.0001), and recurrent ischemic stroke (1.22; 1.04-1.44; P=0.017); and improved model-discrimination significantly: net reclassification improvement for recurrent vascular events (32%; P<0.0001), vascular death (55%; P<0.0001), death (66%; P<0.0001), and recurrent stroke (16%; P=0.044). The predictive value of copeptin was largest in patients with cardioembolic index events (adjusted hazard ratio, 1.84; 95% confidence interval, 1.53-2.20 versus 1.31, 1.14-1.50 in noncardioembolic stroke; P=0.0025). In patients with cardioembolic stroke, high copeptin levels were associated with a 4-fold increased risk of vascular events within the first year of follow-up (adjusted hazard ratio, 4.02; 95% confidence interval, 2.13-7.70). Conclusions: In patients with TIA and ischemic stroke, copeptin predicted recurrent vascular events and death, particularly after cardioembolic TIA/stroke. Further validation is required, in particular, in studies using more extensive cardiac evaluation.
    Stroke 10/2015; DOI:10.1161/STROKEAHA.115.011021 · 5.72 Impact Factor
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    ABSTRACT: Background and purpose: Evidence from epidemiological studies points to differences in factors predisposing to stroke by age and sex. Whether these arise because of different genetic influences remained untested. Here, we use data from 4 genome-wide association data sets to study the relationship between genetic influence on stroke with both age and sex. Methods: Using genomic-relatedness-matrix restricted maximum likelihood methods, we performed 4 analyses: (1) we calculated the genetic correlation between groups divided by age and (2) by sex, (3) we calculated the heritability of age-at-stroke-onset, and (4) we evaluated the evidence that heritability of stroke is greater in women than in men. Results: We found that genetic factors influence age at stroke onset (h(2) [SE]=18.0 [6.8]; P=0.0038), with a trend toward a stronger influence in women (women: h(2) [SE]=21.6 [3.5]; Men: h(2) [SE]=13.9 [2.8]). Although a moderate proportion of genetic factors was shared between sexes (rG [SE]=0.68 [0.16]) and between younger and older cases (rG [SE]=0.70 [0.17]), there was evidence to suggest that there are genetic susceptibility factors that are specific to sex (P=0.037) and to younger or older groups (P=0.056), particularly for women (P=0.0068). Finally, we found a trend toward higher heritability of stroke in women although this was not significantly greater than in men (P=0.084). Conclusions: Our results indicate that there are genetic factors that are either unique to or have a different effect between younger and older age groups and between women and men. Performing large, well-powered genome-wide association study analyses in these groups is likely to uncover further associations.
    Stroke 10/2015; DOI:10.1161/STROKEAHA.115.009816 · 5.72 Impact Factor
  • Linxin Li · Ursula G Schulz · Wilhelm Kuker · Peter M Rothwell ·
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    ABSTRACT: Objective: To determine whether there is an association between previous migraine and cryptogenic TIA or ischemic stroke at older ages. Methods: We determined the age-specific associations of history of migraine and Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtype of TIA and ischemic stroke in a population-based cohort study (Oxford Vascular Study; 2002-2012). Results: Among 1,810 eligible patients with TIA or ischemic stroke, 668 (36.9%) had cryptogenic events, of whom 187 (28.0%) had previous migraine. Migraine was more commonly associated with cryptogenic events than with those of known etiology (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.38-2.16, p < 0.0001; cardioembolic 2.00, 1.50-2.66, p < 0.0001; large artery 1.75, 1.20-2.53, p = 0.003; small vessel 1.32, 0.95-1.83, p = 0.096). The association of migraine with cryptogenic events was independent of age, sex, and all measured vascular risk factors (RFs) (adjusted OR 1.68, 1.33-2.13, p < 0.0001) and was strongest at older ages (<55 years, OR 1.11, 0.55-2.23; 55-64 years, 1.48, 0.83-2.63; ≥65 years, 1.81, 1.39-2.36) and in patients without vascular RFs (0 RFs OR 2.62, 1.33-5.15; 1 RF 2.01, 1.35-3.01; 2 RFs 1.80, 1.21-2.68; 3 RFs 1.21, 0.71-2.07; 4 RFs 0.92, 0.28-2.99). Results were consistent for migraine with or without aura and for analyses excluding TIA or stratified by sex or vascular territory of event. Conclusions: In this population-based study of stroke etiology stratified by age, migraine was most strongly associated with cryptogenic TIA and ischemic stroke, particularly at older ages, suggesting a causal role or a shared etiology.
    Neurology 10/2015; DOI:10.1212/WNL.0000000000002059 · 8.29 Impact Factor
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    ABSTRACT: Background: Incidence and prevalence studies of neurological disorders play an extremely important role in hypothesis-generation, assessing the burden of disease and planning of health services. However, the assessment of disease estimates is hindered by the poor quality of reporting for such studies. We developed the Standards of Reporting of Neurological Disorders (STROND) guideline in order to improve the quality of reporting of neurological disorders from which prevalence, incidence, and outcomes can be extracted for greater generalisability. Methods: The guideline was developed using a 3-round Delphi technique in order to identify the 'basic minimum items' important for reporting, as well as some additional 'ideal reporting items.' An e-consultation process was then used in order to gauge opinion by external neuroepidemiological experts on the appropriateness of the items included in the checklist. Findings: The resultant 15 items checklist and accompanying recommendations were developed using a similar process and structured in a similar manner to the Strengthening of the Reporting of Observational Studies in Epidemiology checklist for ease of use. This paper presents the STROND checklist with an explanation and elaboration for each item, as well as examples of good reporting from the neuroepidemiological literature. Conclusions: The introduction and use of the STROND checklist should lead to more consistent, transparent and contextualised reporting of descriptive neuroepidemiological studies that should facilitate international comparisons, and lead to more accessible information for multiple stakeholders, ultimately supporting better healthcare decisions for neurological disorders.
    Neuroepidemiology 09/2015; 45(2):113-137. DOI:10.1159/000439132 · 2.56 Impact Factor
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    ABSTRACT: Background: Assessment of antihypertensive treatment is normally based on the mean value of a number of blood pressure (BP) measurements. However, it is uncertain whether high in-treatment visit-to-visit BP variability may be harmful in hypertensive patients with left ventricular hypertrophy (LVH). Methods: In 8505 patients randomized to losartan vs. atenolol-based treatment in the LIFE study, we tested whether BP variability assessed as SD and range for BP6-24months measured at 6, 12, 18 and 24 months of treatment was associated with target organ damage (TOD) defined by LVH on ECG and urine albumin/creatinine ratio at 24 months, and predicted the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction (MI) or stroke occurring after 24 months (CEP = 630 events). Results: In multiple regression models adjusted for mean BP6-24months and treatment allocation, neither high BP6-24months SD nor wide range were related to TOD at 24 months, except for a weak association between Sokolow-Lyon voltage and DBP6-24months SD and range (both β = 0.04, P < 0.01). Independently of mean BP6-24months, treatment allocation, TOD and baseline characteristics in Cox regression models, CEP after 24 months was associated with DBP6-24months SD [hazard ratio per 1 mmHg increase1.04, 95% confidence interval (95% CI) 1.01-1.06, P = 0.005], range (hazard ratio 1.02, 95% CI 1.01-1.03, P = 0.004), SBP6-24months SD (hazard ratio 1.01, 95% CI 0.99-1.02, P = 0.07) and range (hazard ratio 1.006, 95% CI 1.001-1.01, P = 0.04). Adjusted for the same factors, stroke was associated with DBP6-24months SD (hazard ratio 1.06, 95% CI 1.02-1.10, P = 0.001), range (hazard ratio 1.03, 95% CI 1.01-1.04, P = 0.001), SBP6-24months SD (hazard ratio 1.02, 95% CI 1.002-1.04, P = 0.04) and range (hazard ratio 1.008, 95% CI 1.001-1.02, P = 0.05), but MI was not. Conclusion: In LIFE patients, higher in-treatment BP6-24months variability was independently of mean BP6-24months associated with later CEP and stroke, but not with MI or TOD after 24 months.
    Journal of Hypertension 09/2015; DOI:10.1097/HJH.0000000000000739 · 4.72 Impact Factor
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    ABSTRACT: Background: -There are few published data on the incidence and long-term outcomes of critical limb ischemia (CLI), acute limb ischemia (ALI), or acute visceral ischemia (AVI) with which to inform health service planning, monitor prevention and enable risk prediction. Methods and results: -In a prospective population-based study (Oxfordshire, UK, 2002-2012), we determined incidence and outcome of all acute peripheral arterial events in a population of 92,728. Risk factors were assessed by comparison with the underlying population. 510 acute events occurred in 386 patients requiring 803 interventions. 221(59.3%) patients were aged ≥75yrs and 98(26.3%) ≥85 years. 230(62.3%) patients were independent prior to event, but 270(73.4%) were dead or dependent at 6 month follow-up and 328(88.9%) at 5 years. 30-day survival was lowest for AVI (28.2%) compared to ALI (75.3%) and CLI (92.6%) (p<0.001). Risk factors (all p<0.001) were hypertension (age-sex-adjusted RR 2.75,1.95-3.90), smoking (2.14,1.37-3.34), and diabetes (3.01, 1.69-5.35; particularly for CLI (5.96,3.15-11.26). 288(77.2%) patients had known prior cardiovascular disease and 361(96.8%) had vascular risk factors, but only 203(54.4%) were on an antiplatelet and only 166(44.5%) on a statin. Although 260(69.7%) patients were taking antihypertensives, 42.9% of all BPs recorded during the 5-years prior-to-event were >140/90. Of 88(23.6%) patients with incident cardio-embolic events, 62 had known AF (diagnosed prior-to-event), of whom only 14.5% were anticoagulated despite 82.3% having CHA2DS2VASC scores ≥2 without contraindications. Conclusions: -The clinical burden of peripheral arterial events is substantial. Although the vast majority of patients have known vascular disease in other territories and multiple treatable risk factors, premorbid control is poor.
    Circulation 09/2015; 132(19). DOI:10.1161/CIRCULATIONAHA.115.016424 · 14.43 Impact Factor
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    ABSTRACT: Current abdominal aortic aneurysm (AAA) screening in men age 65 might have limited impact on overall AAA death rates if incidence is moving to older ages. Up-to-date population-based studies of age-specific incidence, risk factors, and outcome of acute AAA are needed to inform screening policy. In a prospective, population-based study (Oxfordshire, UK, 2002-2014), the incidence and outcome of acute AAA events were determined. Based on population projections and current incidence trends, the impact of screening strategies in the UK was estimated. Over the 12-year period, 103 incident acute AAA events occurred in the study population of 92 728. Incidence/100 000/year was 55 in men ages 65 to 74 years, but increased to 112 at 75 to 85 and 298 at ≥85, with 66.0% of all events occurring at age ≥75 years. Incidence at ages 65 to 74 was highest in male smokers (274), with 96.4% of events in men <75 years occurring in ever-smokers. Extrapolating rates to the UK population, using trial evidence of screening efficacy, the current UK screening program would prevent 5.6% of aneurysm-related deaths (315 200 scans/year: 1426/death prevented, 121/year-of-life saved). Screening only male smokers age 65 and then all men at age 75 would prevent 21.1% of deaths (247 900 scans/year; 297/death prevented, 34/year-of-life saved). By 2030, 91.0% of deaths will occur at age ≥75, 61.6% at ≥85, and 28.6% in women. Given that two thirds of acute AAA occurred at ≥75 years of age, screening older age groups should be considered. Screening nonsmokers at age 65 is likely to have very little impact on AAA event rates. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Journal of the American Heart Association 08/2015; 4(8). DOI:10.1161/JAHA.115.001926 · 4.31 Impact Factor
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    ABSTRACT: Carotid angioplasty and stenting (CAS) is associated with higher risk of periprocedural stroke and death when compared with carotid endarterectomy (CEA). By contrast, the risk of myocardial infarction (MI) was higher after CEA than after CAS in randomized trials. However, numbers were small, and risk factors are unknown. We performed a systematic review and a meta-analysis of studies published from January 1980 to June 2014 and collected unpublished data. We extracted data on 9 predefined risk factors (age, contralateral carotid occlusion, coronary artery disease, diabetes mellitus, sex, hypertension, peripheral artery disease, type stenosis, and clinical presentation). We selected studies with data available on MI in at least 1 subgroup, calculated absolute and relative risks, and identified differential effects on risks of MI. The 30-day absolute risk of MI was 0.87% (95% confidence interval, 0.69-1.07) after CEA and 0.70% (95% confidence interval, 0.54-0.88) after CAS (Pint=0.38). After CAS, patients with symptomatic stenosis and restenosis were at higher risk of MI, whereas men were at lower risk. After CEA, age, history of coronary artery disease, peripheral artery disease, and restenosis increased the risk of MI. Only the effect of sex differed between CAS and CEA with men being at lower risk of MI than women after CAS, whereas there was no difference between after CEA (Pint=0.01). The risk of MI after CEA and CAS did not significantly differ. Risk factors for MI are overall similar in both techniques except that men are at lower risk of MI after CAS but not after CEA. © 2015 American Heart Association, Inc.
    Stroke 08/2015; 46(10). DOI:10.1161/STROKEAHA.115.010052 · 5.72 Impact Factor
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    ABSTRACT: Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes. Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N≈2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls-the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke. One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7×10(-04)); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8×10(-04)) and the cardioembolic subtype (smallest P=1.7×10(-04)). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=-0.71, P=0.01) and the cardioembolic subtype (rG=-0.80, P=0.03). Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype. © 2015 The Authors.
    Stroke 07/2015; 46(8). DOI:10.1161/STROKEAHA.115.009387 · 5.72 Impact Factor
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    ABSTRACT: Incidence and prevalence studies of neurologic disorders play an important role in assessing the burden of disease and planning services. However, the assessment of disease estimates is hindered by problems in reporting for such studies. Despite a growth in published reports, existing guidelines relate to analytical rather than descriptive epidemiologic studies. There are also no user-friendly tools (e.g., checklists) available for authors, editors, and peer reviewers to facilitate best practice in reporting of descriptive epidemiologic studies for most neurologic disorders. The Standards of Reporting of Neurological Disorders (STROND) is a guideline that consists of recommendations and a checklist to facilitate better reporting of published incidence and prevalence studies of neurologic disorders. A review of previously developed guidance was used to produce a list of items required for incidence and prevalence studies in neurology. A 3-round Delphi technique was used to identify the "basic minimum items" important for reporting, as well as some additional "ideal reporting items." An e-consultation process was then used in order to gauge opinion by external neuroepidemiologic experts on the appropriateness of the items included in the checklist. Of 38 candidate items, 15 items and accompanying recommendations were developed along with a user-friendly checklist. The introduction and use of the STROND checklist should lead to more consistent, transparent, and contextualized reporting of descriptive neuroepidemiologic studies resulting in more applicable and comparable findings and ultimately support better health care decisions. © 2015 American Academy of Neurology.
    European Journal of Epidemiology 06/2015; 85(9). DOI:10.1007/s10654-015-0034-5 · 5.34 Impact Factor
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    ABSTRACT: Family history of stroke is an established risk factor for stroke. We evaluated whether family history of stroke predisposed to certain stroke subtypes and whether it differed by sex in young patients with stroke. We used data from the Stroke in Fabry Patients study, a large prospective, hospital-based, screening study for Fabry disease in young patients (aged <55 years) with stroke in whom cardiovascular risk factors and family history of stroke were obtained and detailed stroke subtyping was performed. A family history of stroke was present in 1578 of 4232 transient ischemic attack and ischemic stroke patients (37.3%). Female patients more often had a history of stroke in the maternal lineage (P=0.027) than in the paternal lineage. There was no association with stroke subtype according to Trial of Org 10172 in Acute Stroke Treatment nor with the presence of white matter disease on brain imaging. Patients with dissection less frequently reported a family history of stroke (30.4% versus 36.3%; P=0.018). Patients with a parental history of stroke more commonly had siblings with stroke (3.6% versus 2.6%; P=0.047). Although present in about a third of patients, a family history of stroke is not specifically related to stroke pathogenic subtypes in patients with young stroke. Young women with stroke more often report stroke in the maternal lineage. URL: Unique identifier: NCT00414583. © 2015 American Heart Association, Inc.
    Stroke 06/2015; 46(7). DOI:10.1161/STROKEAHA.115.009341 · 5.72 Impact Factor
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    Peter M Rothwell ·

    The Lancet 05/2015; 342(9988). DOI:10.1016/S0140-6736(15)60906-0 · 45.22 Impact Factor
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    ABSTRACT: The most common monogenic cause of cerebral small-vessel disease is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, caused by NOTCH3 gene mutations. It has been hypothesized that more common variants in NOTCH3 may also contribute to the risk of sporadic small-vessel disease. Previously, 4 common variants (rs10404382, rs1043994, rs10423702, and rs1043997) were found to be associated with the presence of white matter hyperintensity in hypertensive community-dwelling elderly. We investigated the association of common single nucleotide polymorphisms (SNPs) in NOTCH3 in 1350 patients with MRI-confirmed lacunar stroke and 7397 controls, by meta-analysis of genome-wide association study data sets. In addition, we investigated the association of common SNPs in NOTCH3 with MRI white matter hyperintensity volumes in 3670 white patients with ischemic stroke. In each analysis, we considered all SNPs within the NOTCH3 gene, and within 50-kb upstream and downstream of the coding region. A total of 381 SNPs from the 1000 genome population with a mean allele frequency >0.01 were included in the analysis. A significance level of P<0.0015 was used, adjusted for the effective number of independent SNPs in the region using the Galwey method. We found no association of any common variants in NOTCH3 (including rs10404382, rs1043994, rs10423702, and rs1043997) with lacunar stroke or white matter hyperintensity volume. We repeated our analysis stratified for hypertension but again found no association. Our study does not support a role for common NOTCH3 variation in the risk of sporadic small-vessel disease. © 2015 The Authors.
    Stroke 05/2015; 46(6). DOI:10.1161/STROKEAHA.114.008540 · 5.72 Impact Factor
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    ABSTRACT: Cognitive outcomes in cohorts and trials are often based only on face-to-face clinic assessment. However, cognitive impairment is strongly associated with increased morbidity and mortality, leading to substantial loss to clinic follow-up. In the absence of previous population-based data, we determined the effect of such attrition on measured risk of dementia after transient ischemic attack and stroke. Patients with transient ischemic attack or stroke prospectively recruited (2002-2007) into the Oxford Vascular (OXVASC) study had baseline clinical/cognitive assessment and follow-up to 2014. Dementia was diagnosed through face-to-face clinic interview, supplemented by home visits and telephone assessment in patients unable to attend clinic and by hand-searching of primary care records in uncontactable patients. Of 1236 patients (mean age/SD, 75.2/12.1 years; 582 men), 527 (43%) died by 5-year follow-up. Follow-up assessment rates (study clinic, home visit, or telephone) of survivors were 947 in 1026 (92%), 857 in 958 (89%), 792 in 915 (87%), and 567 in 673 (84%) at 1, 6, 12 months and 5 years. Dementia developed in 260 patients, of whom 110 (42%; n=50 primary care records, n=49 home visit, and n=11 telephone follow-up) had not been available for face-to-face clinic follow-up at the time of diagnosis. The 5-year cumulative incidence of postevent dementia was 29% (26%-32%) overall but was only 17% (14% to 19%) in clinic assessed versus 45% (39%-51%) in nonclinic-assessed patients (P difference<0.001). Exclusion of patients unavailable for clinic follow-up reduces the measured risk of postevent dementia. Use of multiple follow-up methods, including home visits, telephone assessments, and consent, to access primary care records substantially increases ascertainment of longer-term dementia outcomes. © 2015 American Heart Association, Inc.
    Stroke 05/2015; 46(6). DOI:10.1161/STROKEAHA.115.009065 · 5.72 Impact Factor
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    D P J Howard · A Banerjee · J F Fairhead · A Handa · L E Silver · P M Rothwell ·
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    ABSTRACT: Contemporary population-based data on age-specific incidence and outcome from acute abdominal aortic aneurysm (AAA) events are needed to understand the impact of risk factor modification and demographic change, and to inform AAA screening policy. In a prospective population-based study (Oxfordshire, UK, 2002-2014), event rates, incidence, early case fatality and long-term outcome from all acute AAA events were determined, both overall and in relation to the four main risk factors: smoking, hypertension, male sex and age. Over the 12-year interval, 103 incident acute AAA events occurred in the study population of 92 728 (men 72·8 per cent; 59·2 per cent 30-day case fatality rate). The incidence per 100 000 population per year was 55 in men aged 65-74 years, but increased to 112 at age 75-84 years and to 298 at age 85 years or above. Some 66·0 per cent of all events occurred in those aged 75 years or more. The incidence at 65-74 years was highest in male smokers (274 per 100 000 population per year); 27 (96 per cent) of 28 events in men aged less than 75 years occurred in ever-smokers. Mean(s.d.) age at event was lowest in current smokers (72·2(7·2) years), compared with that in ex-smokers (81·2(7·0) years) and never-smokers (83·3(7·9) years) (P < 0·001). Hypertension was the predominant risk factor in women (diagnosed in 93 per cent), with 20 (71 per cent) of all 28 events in women occurring in those aged 75 years or above with hypertension. The 30-day case fatality rate increased from 40 per cent at age below 75 years to 69 per cent at age 75 years or more (P = 0·008). Two-thirds of acute AAA events occurred at age 75 years or above, and more than 25 per cent of events were in women. Taken with the strong associations with smoking and hypertension, these findings could have implications for AAA screening. © 2015 The Authors. BJS published by JohnWiley & Sons Ltd on behalf of BJS Society Ltd..
    British Journal of Surgery 05/2015; 102(8). DOI:10.1002/bjs.9838 · 5.54 Impact Factor
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    ABSTRACT: Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10(-28) for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10(-20) for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.
    Neurology 05/2015; 84(21). DOI:10.1212/WNL.0000000000001606 · 8.29 Impact Factor

Publication Stats

25k Citations
4,961.30 Total Impact Points


  • 2008-2015
    • Oxford University Hospitals NHS Trust
      • Department of Clinical Neurology
      Oxford, England, United Kingdom
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany
  • 1999-2015
    • University of Oxford
      • • Nuffield Department of Clinical Neurosciences
      • • Weatherall Institute of Molecular Medicine
      Oxford, England, United Kingdom
  • 2013
    • NIHR Oxford Biomedical Research
      Oxford, England, United Kingdom
    • University of Cambridge
      • Department of Clinical Neurosciences
      Cambridge, England, United Kingdom
  • 2012
    • St George's, University of London
      • Stroke and Dementia Research Centre
      Londinium, England, United Kingdom
  • 2011
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      Newcastle-on-Tyne, England, United Kingdom
  • 1994-2009
    • Western General Hospital
      Edinburgh, Scotland, United Kingdom
    • The University of Edinburgh
      • Division of Clinical Neurosciences
      Edinburgh, Scotland, United Kingdom
  • 2007
    • The University of Calgary
      Calgary, Alberta, Canada
    • VU University Medical Center
      • Department of Neurology
      Amsterdamo, North Holland, Netherlands
  • 2006
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 2005
    • University of Toronto
      • Department of Medical Imaging
      Toronto, Ontario, Canada