Histological features of symptomatic carotid plaques in relation to age and smoking: the oxford plaque study.

BACKGROUND AND PURPOSE: Rates of incident and recurrent cardiovascular events rise steadily with age, due partly to more extensive atherosclerotic burden. However, in patients with similarly severe symptomatic carotid stenosis, increasing age is associated with a greater risk of ipsilateral ischemic stroke. This effect may be due to age-related differences in the pathology of symptomatic carotid plaques. However, previous studies of plaque pathology in relation to age have not accounted for potential confounders, particularly smoking, which is often less prevalent in the elderly population undergoing endarterectomy. Method-We related patient age (<55, 55 to 64, 65 to 74, 75+ years) and smoking habit (never, exsmoker, recent smoker, and current smoker; and number of cigarettes smoked per day) to detailed histological assessments of 526 carotid plaques from consecutive patients undergoing carotid endarterectomy for symptomatic carotid stenosis. RESULTS: Three hundred seventy-nine (72.1%) patients were male (mean/SD age 66.6/8.7). Current/recent smokers were on average 7 years younger at carotid endarterectomy than ex-/never smokers (P<0.001), and age at carotid endarterectomy decreased with increasing number of cigarettes smoked per day (P trend=0.005). Plaques from current/recent smokers had a lower prevalence of intraplaque hemorrhage (P -trend=0.01), but histology was otherwise similar to that in ex-/never smokers, and both groups showed similar changes with age. With increasing age, plaque calcification and large lipid core increased (P<0.001 and P=0.01, respectively) and fibrous tissue (P=0.01) decreased, but lymphocyte infiltration of the plaque (P=0.03) and cap (P=0.002) and overall plaque inflammation (P=0.03) also decreased such that overall plaque instability was unrelated to age. CONCLUSIONS: Smoking is associated with a lower age at carotid endarterectomy suggesting that it may accelerate the development and/or progression of atherosclerosis. However, the mechanisms of plaque instability seem largely unrelated to smoking. Plaques from younger patients had greater inflammatory cell infiltration, whereas those from older patients had a larger lipid core, but there were no age trends in overall plaque instability suggesting the increased risk of stroke in the elderly with symptomatic carotid stenosis is due to other 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.

Systematic review of associations between the presence of acute ischemic lesions on diffusion-weighted imaging and clinical predictors of early stroke risk after transient ischemic attack.

BACKGROUND AND PURPOSE: Early risk of stroke after a transient ischemic attack can be reliably predicted with risk scores based on clinical features of the patient and of the ischemic event, but it is unclear how these features correlate with findings on brain imaging. METHODS: We performed a systematic review of the literature and identified all previous studies which reported patient characteristics and the nature of transient ischemic attack symptoms in relation to appearances on diffusion-weighted imaging (DWI). We then performed a meta-analysis of the associations between the components of the risk scores and positive DWI. Authors were contacted for additional unpublished data. RESULTS: Nineteen studies were identified by the systematic review, and additional unpublished data were obtained from 11 of these studies. On meta-analysis, several components of the risk scores were associated with positive DWI, including symptom duration > or =60 minutes (13 studies, odds ratio [OR], 1.50; 95% CI, 1.16 to 1.96; P=0.004), dysphasia (9 studies, OR, 2.25; 95% CI, 1.57 to 3.22; P<0.001), dysarthria (8 studies, OR, 1.73; 95% CI, 1.11 to 2.68; P=0.03) and motor weakness (9 studies, OR, 2.20; 95% CI, 1.56 to 3.10; P<0.001). However patient age, sex, hypertension and diabetes were not associated with the presence of DWI lesions. From an etiologic perspective, atrial fibrillation (9 studies, OR, 2.75; 95% CI, 1.78 to 4.25; P<0.001) and ipsilateral > or =50% carotid stenosis (10 studies, OR, 1.93; 95% CI, 1.34 to 2.76; P=0.001) were associated with positive DWI. CONCLUSIONS: Presence of acute ischemic lesions on DWI correlates with several clinical features known to predict stroke risk after transient ischemic attack. Large studies (sample size >1000) will therefore be required to determine the independent prognostic value of DWI and its interactions with these clinical characteristics.