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.

A simple score (ABCD) to identify individuals at high early risk of stroke after transient ischaemic attack.

BACKGROUND: Effective early management of patients with transient ischaemic attacks (TIA) is undermined by an inability to predict who is at highest early risk of stroke. METHODS: We derived a score for 7-day risk of stroke in a population-based cohort of patients (n=209) with a probable or definite TIA (Oxfordshire Community Stroke Project; OCSP), and validated the score in a similar population-based cohort (Oxford Vascular Study; OXVASC, n=190). We assessed likely clinical usefulness to front-line health services by using the score to stratify all patients with suspected TIA referred to OXVASC (n=378, outcome: 7-day risk of stroke) and to a hospital-based weekly TIA clinic (n=210; outcome: risk of stroke before appointment). RESULTS: A six-point score derived in the OCSP (age [> or =60 years=1], blood pressure [systolic >140 mm Hg and/or diastolic > or =90 mm Hg=1], clinical features [unilateral weakness=2, speech disturbance without weakness=1, other=0], and duration of symptoms in min [> or =60=2, 10-59=1, <10=0]; ABCD) was highly predictive of 7-day risk of stroke in OXVASC patients with probable or definite TIA (p<0.0001), in the OXVASC population-based cohort of all referrals with suspected TIA (p<0.0001), and in the hospital-based weekly TIA clinic-referred cohort (p=0.006). In the OXVASC suspected TIA cohort, 19 of 20 (95%) strokes occurred in 101 (27%) patients with a score of 5 or greater: 7-day risk was 0.4% (95% CI 0-1.1) in 274 (73%) patients with a score less than 5, 12.1% (4.2-20.0) in 66 (18%) with a score of 5, and 31.4% (16.0-46.8) in 35 (9%) with a score of 6. In the hospital-referred clinic cohort, 14 (7.5%) patients had a stroke before their scheduled appointment, all with a score of 4 or greater. CONCLUSIONS: Risk of stroke during the 7 days after TIA seems to be highly predictable. Although further validations and refinements are needed, the ABCD score can be used in routine clinical practice to identify high-risk individuals who need emergency investigation and treatment.

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.

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.