Clinical Risk Factors and Plaque Characteristics Associated with New Development of Contralateral Stenosis in Patients Undergoing Carotid Endarterectomy

Abstract

Background: Following carotid endarterectomy (CEA), cerebrovascular hemodynamic may be hampered by ipsilateral restenosis or development of contralateral stenosis. It remains to be clarified if these patients need follow-up for identifying development of contralateral stenosis. Identification of risk factors contributing to development of contralateral stenosis could allow more specific follow-up. In this current study, we assessed clinical risk factors and plaque characteristics of patients undergoing CEA with development of new contralateral stenosis during mid-term follow-up. Methods: Seven hundred and sixty patients undergoing CEA between 2003 and 2011 at UMC Utrecht were included. Atherosclerotic plaques were excised and analyzed for smooth muscle cells (SMCs), collagen, macrophages, lipid core, plaque hemorrhage and vessel density. Patients underwent clinical and duplex ultrasound follow-up at 3 and 12 months and yearly thereafter. Association between plaque- and patient characteristics with development of contralateral stenosis ≥50% was assessed with univariate and multivariate analysis. Clinical outcome during follow-up was associated with development of new contralateral stenosis. Results: After a median follow-up time of 2.5 years, development of contralateral stenosis was observed in 108 patients (20%). Presence of high collagen (p = 0.025) and high SMC (p = 0.027) was associated with development of new contralateral stenosis, whereas large lipid core was negatively associated with new development of contralateral stenosis (p = 0.034). The same plaque characteristics were related to contralateral occlusion. History of coronary artery disease (p = 0.031) and asymptomatic presentation (p = 0.000) were univariably associated with development of contralateral stenosis. Multiple regression analysis indicated that asymptomatic status was independently associated with contralateral stenosis (p = 0.001). Patients with new development of contralateral stenosis more often showed symptoms during follow-up (p = 0.049). Conclusion: Dissection of a lipid-poor, collagen-rich or SMC-rich plaque yielded an association with development of new contralateral stenosis during mid-term follow-up after CEA. Asymptomatic patients had a significantly higher risk for development of contralateral stenosis. New contralateral stenosis was related to the presence of new cerebral symptoms. These findings may help to develop individual treatment algorithms for patients with cerebrovascular atherosclerotic burden.

Vascular Macrophages in Atherosclerosis

“…In addition, modified low-density lipoprotein (LDL), such as oxidized LDL (oxLDL), further induces the necrosis of foam cells, which can form a necrotic core, a typical feature of the instability of advanced plaques, leading to the rupture of plaques and further acute life-threatening clinical cardiovascular events [9]. Studies have concluded that increased lesional CD68 + macrophages are associated with a higher risk of CVD and stroke events, while presenting a weak relationship with stenosis [10, 11]. Therefore, clarifying the macrophage-dependent inflammatory processes in atherosclerosis progression and exploring macrophage-targeted strategies to reduce the residual risk of atherosclerotic CVD have become a hot research topic in recent years.…”

Macrophage complexity in human atherosclerosis: opportunities for treatment?

“…Table 1 provides an overview of studies linking human plaque macrophages with clinical outcome. Total plaque macrophage burden, defined by CD68-positive staining, associates with increased risk of stroke [16] and platelet reactivity [17], whereas associations with stenosis were less clear [18,19].…”

Botanical Antcin K Alleviates High-Fat Damage in Palm Acid Oil-Treated Vascular Endothelial Cells and Macrophages

“…Macrophages can pass through activated vascular endothelial cells, enter the subendothelial cell space to accumulate, and then proliferate into advanced plaques at the lesion site [ 20 ] (Robbins et al, 2013). The foam cells induce a series of inflammatory responses, resulting in more lipoprotein retention and persistent chronic inflammation, and finally increase the risk of atherosclerosis [ 21 , 22 , 23 ] (Hellings et al, 2008; Libby et al, 2000; Merckelbach et al, 2016).…”