Linda Bull

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.

Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison.

BACKGROUND The risk of recurrent stroke is up to 10% in the week after a transient ischaemic attack (TIA) or minor stroke. Modelling studies suggest that urgent use of existing preventive treatments could reduce the risk by 80-90%, but in the absence of evidence many health-care systems make little provision. Our aim was to determine the effect of more rapid treatment after TIA and minor stroke in patients who are not admitted direct to hospital. METHODS We did a prospective before (phase 1: April 1, 2002, to Sept 30, 2004) versus after (phase 2: Oct 1, 2004, to March 31, 2007) study of the effect on process of care and outcome of more urgent assessment and immediate treatment in clinic, rather than subsequent initiation in primary care, in all patients with TIA or minor stroke not admitted direct to hospital. The study was nested within a rigorous population-based incidence study of all TIA and stroke (Oxford Vascular Study; OXVASC), such that case ascertainment, investigation, and follow-up were complete and identical in both periods. The primary outcome was the risk of stroke within 90 days of first seeking medical attention, with independent blinded (to study period) audit of all events. FINDINGS Of the 1278 patients in OXVASC who presented with TIA or stroke (634 in phase 1 and 644 in phase 2), 607 were referred or presented direct to hospital, 620 were referred for outpatient assessment, and 51 were not referred to secondary care. 95% (n=591) of all outpatient referrals were to the study clinic. Baseline characteristics and delays in seeking medical attention were similar in both periods, but median delay to assessment in the study clinic fell from 3 (IQR 2-5) days in phase 1 to less than 1 (0-3) day in phase 2 (p<0.0001), and median delay to first prescription of treatment fell from 20 (8-53) days to 1 (0-3) day (p<0.0001). The 90-day risk of recurrent stroke in the patients referred to the study clinic was 10.3% (32/310 patients) in phase 1 and 2.1% (6/281 patients) in phase 2 (adjusted hazard ratio 0.20, 95% CI 0.08-0.49; p=0.0001); there was no significant change in risk in patients treated elsewhere. The reduction in risk was independent of age and sex, and early treatment did not increase the risk of intracerebral haemorrhage or other bleeding. INTERPRETATION Early initiation of existing treatments after TIA or minor stroke was associated with an 80% reduction in the risk of early recurrent stroke. Further follow-up is required to determine long-term outcome, but these results have immediate implications for service provision and public education about TIA and minor stroke.

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.

MoCA, ACE-R, and MMSE Versus the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Neuropsychological Battery After TIA and Stroke

Background and Purpose— The Montreal Cognitive Assessment (MoCA) and Addenbrookes Cognitive Examination–Revised (ACE-R) are proposed as short cognitive tests for use after stroke, but there are few published validations against a neuropsychological battery. We studied the relationship between MoCA, ACE-R, Mini-Mental State Examination (MMSE) and mild cognitive impairment (MCI) in patients with cerebrovascular disease and mild cognitive impairment (MCI). Methods— One hundred consecutive non-institutionalized patients had the MMSE, MoCA, ACE-R, and National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Neuropsychological Battery ≥1 year after transient ischemic attack or stroke in a population-based study. MCI was diagnosed using modified Petersen criteria in which subjective cognitive complaint is not required (equivalent to cognitive impairment–no dementia) and subtyped by number and type of cognitive domains affected. Results— Among 91 nondemented subjects completing neuropsychological testing (mean/SD age, 73.4/11.6 years; 44% female; 56% stroke), 39 (42%) had MCI (amnestic multiple domain=10, nonamnestic multiple domain=9, nonamnestic single domain=19, amnestic single domain=1). Sensitivity and specificity for MCI were optimal with MoCA <25 (sensitivity=77%, specificity=83%) and ACE-R <94 (sensitivity=83%, specificity=73%). Both tests detected amnestic MCI better than nonamnestic single-domain impairment. MMSE only achieved sensitivity >70% at a cutoff of <29, mainly due to relative insensitivity to single-domain impairment. Conclusions— The MoCA and ACE-R had good sensitivity and specificity for MCI defined using the Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Battery ≥1 year after transient ischemic attack and stroke, whereas the MMSE showed a ceiling effect. However, optimal cutoffs will depend on use for screening (high sensitivity) or diagnosis (high specificity). Lack of timed measures of processing speed may explain the relative insensitivity of the MoCA and ACE-R to single nonmemory domain impairment.

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.

Population-Based Study of Disability and Institutionalization After Transient Ischemic Attack and Stroke 10-Year Results of the Oxford Vascular Study

Background and Purpose— Long-term outcome information after transient ischemic attack (TIA) and stroke is required to help plan and allocate care services. We evaluated the impact of TIA and stroke on disability and institutionalization over 5 years using data from a population-based study. Methods— Patients from a UK population-based cohort study (Oxford Vascular Study) were recruited from 2002 to 2007 and followed up to 2012. Patients were followed up at 1, 6, 12, 24, and 60 months postevent and assessed using the modified Rankin scale. A multivariate regression analysis was performed to assess the predictors of disability postevent. Results— A total of 748 index stroke and 440 TIA cases were studied. For patients with TIA, disability levels increased from 14% (63 of 440) premorbidly to 23% (60 of 256) at 5 years (P=0.002), with occurrence of subsequent stroke being a major predictor of disability. For stroke survivors, the proportion disabled (modified Rankin scale >2) increased from 21% (154 of 748) premorbidly to 43% (273 of 634) at 1 month (P<0.001), with 39% (132 of 339) of survivors disabled 5 years after stroke. Five years postevent, 70% (483 of 690) of patients with stroke and 48% (179 of 375) of patients with TIA were either dead or disabled. The 5-year risk of care home institutionalization was 11% after TIA and 19% after stroke. The average 5-year cost per institutionalized patient was

Acute post-stroke blood pressure relative to premorbid levels in intracerebral haemorrhage versus major ischaemic stroke: a population-based study

99 831 (SD, 67 020) for TIA and

Quality of life after TIA and stroke Ten-year results of the Oxford Vascular Study

125 359 (SD, 91 121) for stroke. Conclusions— Our results show that 70% of patients with stroke are either dead or disabled 5 years after the event. Thus, there remains considerable scope for improvements in acute treatment and secondary prevention to reduce postevent disability and institutionalization.

Age-Specific Incidence, Outcome, Cost, and Projected Future Burden of Atrial Fibrillation–Related Embolic Vascular Events A Population-Based Study

Summary Background It is often assumed that blood pressure increases acutely after major stroke, resulting in so-called post-stroke hypertension. In view of evidence that the risks and benefits of blood pressure-lowering treatment in acute stroke might differ between patients with major ischaemic stroke and those with primary intracerebral haemorrhage, we compared acute-phase and premorbid blood pressure levels in these two disorders. Methods In a population-based study in Oxfordshire, UK, we recruited all patients presenting with stroke between April 1, 2002, and March 31, 2012. We compared all acute-phase post-event blood pressure readings with premorbid readings from 10-year primary care records in all patients with acute major ischaemic stroke (National Institutes of Health Stroke Scale >3) versus those with acute intracerebral haemorrhage. Findings Of 653 consecutive eligible patients, premorbid and acute-phase blood pressure readings were available for 636 (97%) individuals. Premorbid blood pressure (total readings 13 244) had been measured on a median of 17 separate occasions per patient (IQR 8–31). In patients with ischaemic stroke, the first acute-phase systolic blood pressure was much lower than after intracerebral haemorrhage (158·5 mm Hg [SD 30·1] vs 189·8 mm Hg [38·5], p<0·0001; for patients not on antihypertensive treatment 159·2 mm Hg [27·8] vs 193·4 mm Hg [37·4], p<0·0001), was little higher than premorbid levels (increase of 10·6 mm Hg vs 10-year mean premorbid level), and decreased only slightly during the first 24 h (mean decrease from <90 min to 24 h 13·6 mm Hg). By contrast with findings in ischaemic stroke, the mean first systolic blood pressure after intracerebral haemorrhage was substantially higher than premorbid levels (mean increase of 40·7 mm Hg, p<0·0001) and fell substantially in the first 24 h (mean decrease of 41·1 mm Hg; p=0·0007 for difference from decrease in ischaemic stroke). Mean systolic blood pressure also increased steeply in the days and weeks before intracerebral haemorrhage (regression p<0·0001) but not before ischaemic stroke. Consequently, the first acute-phase blood pressure reading after primary intracerebral haemorrhage was more likely than after ischaemic stroke to be the highest ever recorded (OR 3·4, 95% CI 2·3–5·2, p<0·0001). In patients with intracerebral haemorrhage seen within 90 min, the highest systolic blood pressure within 3 h of onset was 50 mm Hg higher, on average, than the maximum premorbid level whereas that after ischaemic stroke was 5·2 mm Hg lower (p<0·0001). Interpretation Our findings suggest that systolic blood pressure is substantially raised compared with usual premorbid levels after intracerebral haemorrhage, whereas acute-phase systolic blood pressure after major ischaemic stroke is much closer to the accustomed long-term premorbid level, providing a potential explanation for why the risks and benefits of lowering blood pressure acutely after stroke might be expected to differ. Funding Wellcome Trust, Wolfson Foundation, UK Medical Research Council, Stroke Association, British Heart Foundation, National Institute for Health Research.

Impact of different operational definitions on mild cognitive impairment rate and MMSE and MoCA performance in transient ischaemic attack and stroke.

Objective: To evaluate the 5-year impact of stroke and TIA on utility and quality-adjusted survival. Methods: TIA and stroke patients from a UK population-based study (Oxford Vascular Study) were recruited from 2002 to 2007, and followed up until 2012. Quality of life was assessed over 5 years using the EQ-5D (EuroQol-5 Dimensions), with responses converted into utilities ranging from −0.59 (worse than death) to 1 (perfect health), using UK population valuations. Utilities for stroke and TIA patients were compared with those in matched controls obtained from the 2006 Health Survey for England. Five-year quality-adjusted life years were estimated by combining utility and survival information. Results: Four hundred forty TIA and 748 stroke patients were ascertained and included. Utility remained constant at approximately 0.78 over the 5 years after TIA. Utility improved from 0.64 one month after stroke to 0.70 at 6 months (p = 0.006), remaining at approximately 0.70 thereafter. Matched controls had considerably higher utility levels than stroke/TIA patients (0.85, p < 0.001). Event severity and recurrent stroke were significant predictors of decreased long-term utility. Five-year quality-adjusted life expectancy was 3.32 (95% confidence interval: 3.22–3.48) quality-adjusted life years after TIA and 2.21 (2.15–2.37) after stroke, varying considerably by severity (minor: 2.94; moderate: 1.65; and severe: 0.70). Conclusion: Quality-adjusted survival is low over the 5 years after stroke and TIA, with severity and recurrent stroke being major predictors. There remains considerable scope for improvements in acute treatment and secondary prevention to improve the quality of life after TIA and stroke.