David Calvet

Addition of brain and carotid imaging to the ABCD² score to identify patients at early risk of stroke after transient ischaemic attack: a multicentre observational study.

BACKGROUND The ABCD² score improves stratification of patients with transient ischaemic attack by early stroke risk. We aimed to develop two new versions of the score: one that was based on preclinical information and one that was based on imaging and other secondary care assessments. METHODS We analysed pooled data from patients with clinically defined transient ischaemic attack who were investigated while in secondary care. Items that contribute to the ABCD² score (age, blood pressure, clinical weakness, duration, and diabetes), other clinical variables, carotid stenosis, and abnormal acute diffusion-weighted imaging (DWI) were recorded and were included in multivariate logistic regression analysis of stroke occurrence at early time intervals after onset of transient ischaemic attack. Scores based on the findings of this analysis were validated in patients with transient ischaemic attack from two independent population-based cohorts. FINDINGS 3886 patients were included in the study: 2654 in the derivation sample and 1232 in the validation sample. We derived the ABCD³ score (range 0-9 points) by assigning 2 points for dual transient ischaemic attack (an earlier transient ischaemic attack within 7 days of the index event). C statistics (which indicate discrimination better than chance at >0·5) for the ABCD³ score were 0·78 at 2 days, 0·80 at 7 days, 0·79 at 28 days, and 0·77 at 90 days, compared with C statistics for the ABCD² score of 0·71 at 2 days (p=0·083), 0·71 at 7 days (p=0·012), 0·71 at 28 days (p=0·021), and 0·69 at 90 days (p=0·018). We included stenosis of at least 50% on carotid imaging (2 points) and abnormal DWI (2 points) in the ABCD³-imaging (ABCD³-I) score (0-13 points). C statistics for the ABCD³-I score were 0·90 at 2 days (compared with ABCD² score p=0·035), 0·92 at 7 days (p=0·001), 0·85 at 28 days (p=0·028), and 0·79 at 90 days (p=0·073). The 90-day net reclassification improvement compared with ABCD² was 29·1% for ABCD³ (p=0·0003) and 39·4% for ABCD³-I (p=0·034). In the validation sample, the ABCD³ and ABCD³-I scores predicted early stroke at 7, 28, and 90 days. However, discrimination and net reclassification of patients with early stroke were similar with ABCD³ compared with ABCD². INTERPRETATION The ABCD³-I score can improve risk stratification after transient ischaemic attack in secondary care settings. However, use of ABCD³ cannot be recommended without further validation. FUNDING Health Research Board of Ireland, Irish Heart Foundation, and Irish National Lottery.

Carotid and Aortic Stiffness: Determinants of Discrepancies

Several studies have shown that aortic stiffness was an independent predictor for cardiovascular events. However, data are less consistent concerning carotid stiffness. We analyzed the determinants of the discrepancies between aortic and carotid stiffness in different populations with contrasting cardiovascular risk factors: 94 healthy normotensives (NT), 243 nondiabetic hypertensives (HT), and 126 patients with hypertension and type 2 diabetes (T2D). Aortic stiffness was measured with carotid-femoral pulse wave velocity. Common carotid stiffness was determined from the relative stroke change in diameter (measured with a high-resolution echotracking system) and carotid pulse pressure (measured with applanation tonometry) and was expressed in the same dimensions as pulse wave velocity (m/s). We identified the various factors explaining the discrepancies between aortic and carotid stiffness by multivariate analysis of the residuals of the correlation between aortic and carotid stiffness. The strength of the correlation between aortic and carotid stiffness became weaker as the number of cardiovascular risk factors increased (NT, r2=0.41; HT, r2=0.16; and T2D, r2=0.11), whereas we observed the opposite for the discrepancies (residuals) between aortic and carotid stiffness, of which an increasing part was explained (11% in NT, 22% in HT, and 45% in T2D) primarily by aging. In conclusion, although carotid-femoral pulse wave velocity and carotid stiffness provided similar information on the impact of aging on large artery stiffness in normal subjects, this was not the case for high blood pressure and/or diabetes. In these cases, the aorta stiffened more than the carotid artery with age and other cardiovascular risk factors.

Addition of Brain Infarction to the ABCD2 Score (ABCD2I) A Collaborative Analysis of Unpublished Data on 4574 Patients

Background and Purpose— The ABCD system was developed to predict early stroke risk after transient ischemic attack. Incorporation of brain imaging findings has been suggested, but reports have used inconsistent methods and been underpowered. We therefore performed an international, multicenter collaborative study of the prognostic performance of the ABCD2 score and brain infarction on imaging to determine the optimal weighting of infarction in the score (ABCD2I). Methods— Twelve centers provided unpublished data on ABCD2 scores, presence of brain infarction on either diffusion-weighted imaging or CT, and follow-up in cohorts of patients with transient ischemic attack diagnosed by World Health Organization criteria. Optimal weighting of infarction in the ABCD2I score was determined using area under the receiver operating characteristic curve analyses and random effects meta-analysis. Results— Among 4574 patients with TIA, acute infarction was present in 884 (27.6%) of 3206 imaged with diffusion-weighted imaging and new or old infarction was present in 327 (23.9%) of 1368 imaged with CT. ABCD2 score and presence of infarction on diffusion-weighted imaging or CT were both independently predictive of stroke (n=145) at 7 days (after adjustment for ABCD2 score, OR for infarction=6.2, 95% CI=4.2 to 9.0, overall; 14.9, 7.4 to 30.2, for diffusion-weighted imaging; 4.2, 2.6 to 6.9, for CT; all P<0.001). Incorporation of infarction in the ABCD2I score improved predictive power with an optimal weighting of 3 points for infarction on CT or diffusion-weighted imaging. Pooled areas under the curve increased from 0.66 (0.53 to 0.78) for the ABCD2 score to 0.78 (0.72 to 0.85) for the ABCD2I score. Conclusions— In secondary care, incorporation of brain infarction into the ABCD system (ABCD2I score) improves prediction of stroke in the acute phase after transient ischemic attack.

DWI Lesions and TIA Etiology Improve the Prediction of Stroke After TIA

Background and Purpose— The ABCD2 score has been shown to predict the early risk of stroke after transient ischemic attack (TIA). The additional predictive value of diffusion-weighted imaging (DWI) and TIA etiology is not well known. Methods— From January 2003 to June 2007, 343 consecutive patients (mean±SD age, 62.4±15.4 years) with TIA were admitted to our stroke unit. Most (339) patients underwent DWI and all had an etiologic work-up and were followed up for 3 months. The predictive value of the ABCD2 score, positive DWI findings, large-artery atherosclerosis (LAA), and atrial fibrillation (AF) with respect to occurrence of ischemic stroke at 1 week and 3 months was assessed. Results— DWI was positive in 136 (40%) patients. Sixty (17%) patients had LAA and 27 (8%) had AF. Patients with positive DWI findings were more likely to have unilateral weakness (odds ratio [OR]=2.2; 95% CI, 1.3 to 3.7), TIA duration ≥60 minutes (OR=2.6; 95% CI, 1.3 to 5.2), ABCD2 >5 (OR=4.7; 95% CI, 2.0 to 11.0), LAA (OR=1.8; 95% CI, 1.0 to 3.1), and AF (OR=3.5; 95% CI, 1.5 to 8.0). During follow-up, 5 patients had a stroke within 7 days (absolute risk=1.5%, 95% CI, 0.3% to 2.7%), and 10 had a stroke within 3 months (absolute risk=2.9%; 95% CI, 1.1% to 4.7%). All early strokes but 1 occurred in patients with positive DWI findings. ABCD2 score and positive DWI findings were associated with an increased 7-day and 3-month risk of stroke. At 3 months, ABCD2 score >5 (hazard ratio=10.1; 95% CI, 1.1 to 93.4), positive DWI result (hazard ratio=8.7; 95% CI, 1.1 to 71.0), and LAA (hazard ratio=3.4; 95% CI, 1.0 to 11.8) were independently associated with an increased risk of stroke. There was no association with AF. Conclusions— Taking DWI and TIA etiology into account in addition to the ABCD2 score improves the prediction of the early risk of stroke after TIA.

Prevalence of Asymptomatic Coronary Artery Disease in Ischemic Stroke Patients. The PRECORIS Study

Background— Coronary artery disease (CAD) is a significant cause of morbidity and mortality in stroke patients. Some patients with asymptomatic CAD might benefit from specific prevention, but the prevalence of asymptomatic CAD is not well known. We assessed the prevalence of ≥50% asymptomatic CAD in patients with ischemic stroke or transient ischemic attack and whether the prevalence is related to traditional vascular risk factors and cervicocephalic atherosclerosis. Methods and Results— From January 2006 to February 2009, consecutive patients between 45 and 75 years of age with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack and no prior history of CAD were enrolled in the study. All patients had a 64-section computed tomography coronary angiography and a detailed cervicocephalic arterial workup. Risk factors were assessed individually and through the Framingham Risk Score. Among 300 patients included in the study, 274 had computed tomography coronary angiography. The prevalence of ≥50% asymptomatic CAD was 18% (95% confidence interval [CI], 14 to 23; n=50). Asymptomatic CAD was independently associated with traditional risk factors assessed individually and through the Framingham Risk Score (odds ratio [OR], 2.6; 95% CI, 1.0 to 7.6 for a 10-year risk of coronary heart disease of 10% to 19%; and OR, 7.3; 95% CI, 2.8 to 19.1 for a 10 year-risk of coronary heart disease ≥20%), the presence of at least 1 ≥50% cervicocephalic artery stenosis (OR, 4.0; 95% CI, 1.4 to 11.2), excessive alcohol consumption (OR, 3.1; 95% CI 1.3 to 7.3), and ankle brachial index <0.9 (OR, 2.2; 95% CI, 0.9 to 5.2). The prevalence of ≥50% asymptomatic CAD was also related to the extent of cervicocephalic atherosclerosis. Conclusions— About one fifth of patients with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack have ≥50% asymptomatic CAD. In addition to vascular risk factors, the presence of ≥50% cervicocephalic artery stenosis is strongly related to ≥50% asymptomatic CAD.

Multiaxial Mechanical Characteristics of Carotid Plaque Analysis by Multiarray Echotracking System

Background and Purpose— Carotid plaque rupture depends on the various types of mechanical stresses. Our objective was to determine the multiaxial mechanical characteristics of atherosclerotic plaque and adjacent segment of the common carotid artery. Methods— A novel noninvasive echotracking system was used to measure intima-media thickness, diameter, pulsatile strain, and distensibility at 128 sites on a 4-cm long common carotid artery segment. The study included 62 patients with recent cerebrovascular ischemic event and either a plaque on the far wall of common carotid artery (n=25) or no plaque (n=37). Results— The mechanical characteristics of the carotid segment devoid of plaque did not differ between the two groups. Among patients with plaque, 16 had a larger radial strain at the level of plaque than at the level of adjacent common carotid artery (pattern A: outward-bending strain). The eight patients who had an opposite pattern (inward-bending strain) were more often dyslipidemic (100% versus 56% P=0.03) and type 2 diabetic (63% versus 12%, P=0.04) than pattern A patients. Strain gradient significantly decreased in parallel with the presence of dyslipidemia and/or type 2 diabetes. Longitudinal gradients of distensibility and Youngs elastic modulus were consistent with strain gradients. Conclusions— Type 2 diabetes and dyslipidemia were associated with a stiffer carotid at the level of the plaque than in the adjacent common carotid artery leading to an inward-bending stress. The analysis of plaque mechanics along the longitudinal axis may afford useful information, because repetitive bending strain of an atherosclerotic plaque may fatigue the wall material and result in plaque rupture.

Long-Term Follow-Up Study of Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis Trial

Background and Purpose— We aimed at comparing the long-term benefit–risk balance of carotid stenting versus endarterectomy for symptomatic carotid stenosis. Methods— Long-term follow-up study of patients included in Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S), a randomized, controlled trial of carotid stenting versus endarterectomy in 527 patients with recently symptomatic severe carotid stenosis, conducted in 30 centers in France. The main end point was a composite of any ipsilateral stroke after randomization or any procedural stroke or death. Results— During a median follow-up of 7.1 years (interquartile range, 5.1–8.8 years; maximum 12.4 years), the primary end point occurred in 30 patients in the stenting group compared with 18 patients in the endarterectomy group. Cumulative probabilities of this outcome were 11.0% (95% confidence interval, 7.9–15.2) versus 6.3% (4.0–9.8) in the endarterectomy group at the 5-year follow-up (hazard ratio, 1.85; 1.00–3.40; P=0.04) and 11.5% (8.2–15.9) versus 7.6% (4.9–11.8; hazard ratio, 1.70; 0.95–3.06; P=0.07) at the 10-year follow-up. No difference was observed between treatment groups in the rates of ipsilateral stroke beyond the procedural period, severe carotid restenosis (≥70%) or occlusion, death, myocardial infarction, and revascularization procedures. Conclusions— The long-term benefit–risk balance of carotid stenting versus endarterectomy for symptomatic carotid stenosis favored endarterectomy, a difference driven by a lower risk of procedural stroke after endarterectomy. Both techniques were associated with low and similar long-term risks of recurrent ipsilateral stroke beyond the procedural period. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00190398.

Reduction in Early Stroke Risk in Carotid Stenosis With Transient Ischemic Attack Associated With Statin Treatment

Background and Purpose— Statins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis. Methods— We analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded. Results— In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7–11.1) compared with 2.7% (CI, 2.0%–3.4%) without stenosis (P<0.0001; 90-day risks 17.8% and 5.7% [P<0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%–9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%–19.8%) in those not statin pretreated (P=0.01; 90-day risks 8.9% versus 20.8% [P=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37; CI, 0.17–0.82) but not nonstenosis patients (odds ratio, 1.3; CI, 0.8–2.24; P for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted P for interaction, 0.054). Conclusions— In acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required.

Management and Outcome of Patients with Transient Ischemic Attack Admitted to a Stroke Unit

Background: The way in which patients with transient ischemic attack (TIA) are investigated and treated varies substantially worldwide. There are no data on the management and outcome of TIA patients admitted to a stroke unit. We assessed to what extent rapid management of TIA patients admitted to a stroke unit led to specific treatments which can prevent stroke and evaluated the early risk and predictors of stroke in these patients. Methods: From January 2003 to November 2005, 203 consecutive patients with a recent (<48 h) TIA were admitted to our stroke unit. All patients had a diffusion-weighted imaging (DWI) on admission, a standardized etiological workup, and were followed up to 3 months. Results: The median (interquartile range) time from TIA onset to admission to the stroke unit was 12 h (5–25). DWI revealed acute lesions in 64 patients (32%). Of the 203 patients, 147 (72%) were treated by antiplatelet therapy and 56 (28%) with high doses of heparin, soon after their admission. In addition, 7 patients (3%) had a carotid revascularization. The risk of stroke was 2.5% (95% CI, 0.3–4.7) at 1 week, and 3.5% (1.0–6.1) at 3 months. In multivariate analysis, a score ≧5 at the previously validated ABCD score (HR = 5.0; 1.0–25.8; p = 0.06) and the presence of DWI abnormalities (HR = 10.3; 1.2–86.7; p = 0.03) were independent predictors of stroke at 3 months. Conclusion: Early management of TIA in a stroke unit leads to specific treatments in a significant proportion of cases. The presence of acute lesions on DWI and the ABCD score predict the 3-month risk of stroke after TIA.

Carotid Stenting: Is There an Operator Effect? A Pooled Analysis From the Carotid Stenting Trialists’ Collaboration

Background and Purpose— Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists’ Collaboration database. Methods— The Carotid Stenting Trialists’ Collaboration is a pooled individual patient database including all patients recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol. Results— Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience (P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was significantly higher in patients treated by operators with low (mean ⩽3.2 procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36–3.87]) and intermediate annual in-trial volumes (3.2–5.6 procedures/y; 8.4%; adjusted risk ratio=1.93 [1.14–3.27]) compared with patients treated by high annual in-trial volume operators (>5.6 procedures/y; 5.1%). Conclusions— Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year.