BACKGROUND AND PURPOSE: Although symptomatic carotid stenosis is associated with 3-fold increased risk of early stroke recurrence, the pathophysiologic mechanisms of high early stroke risk have not been established. We aimed to investigate the relationship between early stroke recurrence after initial symptoms and histological features of plaque inflammation and instability in resected carotid plaque. METHODS: Carotid endarterectomy tissue from consecutive patients with ipsilateral stenosis≥50% and recent symptoms were analyzed using a validated histopathologic algorithm (Oxford Plaque Study [OPS] system). Nonprocedural stroke recurrence before carotid endarterectomy was ascertained at 7, 28, and 90 days after initial symptoms. RESULTS: Among 44 patients meeting eligibility criteria, 27.3% (12/44) had stroke recurrence after initial stroke/transient ischemic attack but before carotid endarterectomy. Compared with patients without recurrence, stroke recurrence was associated with dense macrophage infiltration (OPS grade≥3; 91.7% versus 37.5%; P=0.002), extensive (>25%) fibrous cap disruption (90.9% versus 37%; P=0.004), neovascularization (OPS grade≥2; 83.3% versus 43.8%; P=0.04), and low plaque fibrous content (OPS grade<2; 50% versus 6.3%; P=0.003). Early recurrence rates were 82.3% (confidence interval, 49.2%-98.8%) in patients with extensive plaque macrophage infiltration (OPS grade≥3) compared with 22.2% (confidence interval, 3.5%-83.4%) in those with OPS grade<3 (log-rank P=0.009). On multivariable Cox regression, including OPS macrophage grade (≥3 or <3), age, and severity of stenosis (50%-69% or ≥70%), plaque inflammation was the only variable independently predicting stroke recurrence (adjusted hazard ratio, 9; confidence interval, 1.1-70.6; P=0.04). CONCLUSIONS: Plaque inflammation and other vulnerability features were associated with highest risk of stroke recurrence and may represent therapeutic targets for future stroke prevention trials.
BACKGROUND AND PURPOSE: Although symptomatic carotid stenosis is associated with 3-fold increased risk of early stroke recurrence, the pathophysiologic mechanisms of high early stroke risk have not been established. We aimed to investigate the relationship between early stroke recurrence after initial symptoms and histological features of plaque inflammation and instability in resected carotid plaque. METHODS: Carotid endarterectomy tissue from consecutive patients with ipsilateral stenosis≥50% and recent symptoms were analyzed using a validated histopathologic algorithm (Oxford Plaque Study [OPS] system). Nonprocedural stroke recurrence before carotid endarterectomy was ascertained at 7, 28, and 90 days after initial symptoms. RESULTS: Among 44 patients meeting eligibility criteria, 27.3% (12/44) had stroke recurrence after initial stroke/transient ischemic attack but before carotid endarterectomy. Compared with patients without recurrence, stroke recurrence was associated with dense macrophage infiltration (OPS grade≥3; 91.7% versus 37.5%; P=0.002), extensive (>25%) fibrous cap disruption (90.9% versus 37%; P=0.004), neovascularization (OPS grade≥2; 83.3% versus 43.8%; P=0.04), and low plaque fibrous content (OPS grade<2; 50% versus 6.3%; P=0.003). Early recurrence rates were 82.3% (confidence interval, 49.2%-98.8%) in patients with extensive plaque macrophage infiltration (OPS grade≥3) compared with 22.2% (confidence interval, 3.5%-83.4%) in those with OPS grade<3 (log-rank P=0.009). On multivariable Cox regression, including OPS macrophage grade (≥3 or <3), age, and severity of stenosis (50%-69% or ≥70%), plaque inflammation was the only variable independently predicting stroke recurrence (adjusted hazard ratio, 9; confidence interval, 1.1-70.6; P=0.04). CONCLUSIONS: Plaque inflammation and other vulnerability features were associated with highest risk of stroke recurrence and may represent therapeutic targets for future stroke prevention trials.
Authors: Fabien Hyafil; Andreas Schindler; Dominik Sepp; Tilman Obenhuber; Anna Bayer-Karpinska; Tobias Boeckh-Behrens; Sabine Höhn; Marcus Hacker; Stephan G Nekolla; Axel Rominger; Martin Dichgans; Markus Schwaiger; Tobias Saam; Holger Poppert Journal: Eur J Nucl Med Mol Imaging Date: 2015-10-03 Impact factor: 9.236
Authors: Carol C Mitchell; James H Stein; Thomas D Cook; Shahriar Salamat; Xiao Wang; Tomy Varghese; Daren C Jackson; Carolina Sandoval Garcia; Stephanie M Wilbrand; Robert J Dempsey Journal: Ultrasound Med Biol Date: 2016-10-05 Impact factor: 2.998
Authors: L Saba; S Zucca; A Gupta; G Micheletti; J S Suri; A Balestrieri; M Porcu; P Crivelli; G Lanzino; Y Qi; V Nardi; G Faa; R Montisci Journal: AJNR Am J Neuroradiol Date: 2020-07-30 Impact factor: 3.825
Authors: Catherine N Steffel; Shahriar Salamat; Thomas D Cook; Stephanie M Wilbrand; Robert J Dempsey; Carol C Mitchell; Tomy Varghese Journal: Ultrasound Med Biol Date: 2020-04-11 Impact factor: 2.998
Authors: J J McCabe; E O'Reilly; S Coveney; R Collins; L Healy; J McManus; R Mulcahy; B Moynihan; T Cassidy; F Hsu; B Worrall; S Murphy; M O'Donnell; P J Kelly Journal: Eur Stroke J Date: 2021-01-05