Stabilization of symptomatic carotid atherosclerotic plaques by statins: a clinico-pathological analysis.

Human and animal studies have revealed a stabilization of atherosclerotic plaques by statins. However, the stabilization of human carotid plaques has not been thoroughly described pathologically. This analysis explored the relationship between statin therapy and plaque stability in carotid endarterectomy (CEA) specimens. We analyzed specimens harvested between May 2015 and February 2017, from 79 consecutive patients presenting with > 70% carotid artery stenoses, of whom 66 were untreated (group 1) and 13 treated (group 2) with a statin. Immunohistochemistry was performed, using an endothelial specific antibody to CD31, CD34 and platelet derived growth factor receptor-ß. The prevalence of plaque ruptures (P = 0.009), lumen thrombi (P = 0.009), inflammatory cells (P = 0.008), intraplaque hemorrhages (P = 0.030) and intraplaque microvessels (P < 0.001) was significantly lower in group 2 than in group 1. Among 66 patients presenting with strokes and infarct sizes > 1.0 cm3 on magnetic resonance imaging, the mean infarct volume was significantly smaller (P = 0.031) in group 2 (4.2 ± 2.5 cm3) than in group 1 (8.2 ± 7.1 cm3). The difference in mean concentration of low-density lipoprotein cholesterol between group 1 (121 ± 32 mg/dl) and group 2 (105 ± 37 mg/dl) was non-significant (P = 0.118). This analysis of plaques harvested from patients undergoing CEA suggests that statin therapy mitigates the plaque instability, which, in patients presenting with strokes, might decrease infarct volume.

Pathological Quantification of Carotid Artery Plaque Instability in Patients Undergoing Carotid Endarterectomy.

BACKGROUND: Unstable atherosclerotic carotid plaques cause cerebral thromboemboli and ischemic events. However, this instability has not been pathologically quantified, so we sought to quantify it in patients undergoing carotid endarterectomy (CEA).Methods and Results:Carotid plaques were collected during CEA from 67 symptomatic and 15 asymptomatic patients between May 2015 and August 2016. The specimens were stained with hematoxylin-eosin and elastica-Masson. Immunohistochemistry was performed using an endothelial-specific antibody to CD31, CD34 and PDGFRß. The histopathological characteristics of the plaques were studied. By multiple-variable logistic regression analysis, plaque instability correlated with the presence of plaque rupture [odds ratio (OR), 9.75; P=0.013], minimum fibrous cap thickness (OR per 10 µm 0.70; P=0.025), presence of microcalcifications in the fibrous cap (OR 7.82; P=0.022) and intraplaque microvessels (OR 1.91; P=0.043). Receiver-operating characteristics analyses showed that these factors combined into a single score diagnosed symptomatic carotid plaques in patients with carotid artery stenosis with a high level of accuracy (area under the curve 0.92; 95% confidence interval 0.85-0.99 vs. asymptomatic). CONCLUSIONS: This analysis of carotid plaque instability strongly suggested that the diagnostic scoring of carotid plaque instability improves the understanding and treatment of carotid artery disease in patients undergoing CEA.

[The efficiency of cilostazol for cerebral vasospasm following subarachnoid hemorrhage].

Delayed ischemic deficit following subarachnoid hemorrhage(SAH)is a major source of morbidity and mortality after rupture of an intracranial aneurysm. Once symptomatic cerebral vasospasm has occured, available treatments do not provide good outcomes for all patients. Symptomatic vasospasm results in serious sequelae for 10-15% of patients and the etiology and pathogenesis remain unclear. Cilostazol is a specific inhibitor of cAMP(cyclic adenosine monophosphate)phosphodiesterase, and is used for treating ischemic symptoms of peripheral vascular disease. Cilostazol has various actions, such as inhibiting vascular smooth muscle proliferation, and increasing nitric oxide(NO)levels derived from endothelial cells. The present study included 81 patients with SAH caused by ruptured cerebral aneurysms treated in two hospitals between June, 2008 and September, 2009. All patients were treated with clipping surgery, and were classified into two groups: 25 patients who received cilostazol from postoperative day 1 to 14 or 28; and 56 control patients. Clinical symptoms due to cerebral vasospasm and frequency of severe spasm were compared between each of the groups. The frequencies of severe spasm appearing on angiography(age>65)and symptomatic cerebral vasospasm were lower in the cilostazol group than in controls. These findings suggest that cilostazol may prevent symptomatic cerebral vasospasm after subarachnoid hemorrhage.