New insight into biology, molecular diagnostics and treatment options of unstable carotid atherosclerotic plaque: a narrative review

Abstract

Indications for intervention in hemodynamically relevant carotid artery stenosis (carotid endarterectomy or stenting) are primarily based on a degree of stenosis and symptomatology. To date the plaque vulnerability is rarely taken into account in clinical decision making although development of molecular imaging allows a better understanding of plaque biology and provides new techniques detecting potentially vulnerable plaque at risk. A significant number of reports describing the mechanisms of unstable plaque formation suggest that it is a multifactorial process. Inflammation, lipid accumulation, apoptosis, proteolysis, the thrombotic process and angiogenesis are among the main factors of carotid plaque destabilization. Although inflammation is a key process in development of plaque vulnerability, the hemostasis and neoangiogenesis should be regarded as equally important. Only a small group of asymptomatic patients may benefit from the invasive treatment and it remains a challenge to determine whether initially asymptomatic carotid plaque become unstable or vulnerable. Currently, the main task of research on atherosclerotic lesion imaging is focused on functional state of the plaque. The presence of one or more features such as stenosis progression, large plaque area, large juxta-luminal black area, plaque echolucency, intra-plaque hemorrhage, impaired cerebral vascular reserve and spontaneous embolization may indicate patients at higher risk for stroke suitable for revascularization. Treatment of carotid stenosis as one of the manifestations of generalized atherosclerosis requires a broad approach. Nowadays pharmacological treatment options for the atherosclerotic process are largely aimed at stimulating the plaque stabilization, but in symptomatic patients and selected asymptomatic patients, carotid plaque should be removed as a potential source of embolism.

The Correlation between Increased Expressions of NLRP3 Inflammasome Components in Peripheral Blood Mono-Nuclear Cells and Plaque Vulnerability in Human Carotid Atherosclerosis

“…Identification of potential biomarkers for high-risk or vulnerable carotid plaque has been clinically important ( 5 , 25 ). Morphologic features of carotid plaques assessed by imaging methods can be obtained to evaluate plaque vulnerability, but with limitation of wide usage ( 12 , 26 , 27 ).…”

Markers of Carotid Plaque Destabilization in Patients With Sleep-Disordered Breathing

“…Carotid plaque stenosis, one of the leading causes of ischemic stroke, is a multifactorial and complex process. It involves fundamental mechanisms of atherosclerosis, such as oxidative stress, inflammation, lipid accumulation, angiogenesis, apoptosis, proteolysis, and thrombotic processes which are among the main factors of carotid plaque vulnerability and rupture ( 34 , 35 ).…”

“…The 2-fold higher levels of intracellular lipids' content in plaques of the patients with SDB also indicate that the plaques of patients with SDB are potentially more atherogenic and vulnerable than plaques of patients with non-SDB. This lipid accumulation is among the main factors of carotid plaque destabilization ( 35 ).…”

A new approach of statin therapy in carotid atherosclerosis: Targeting indices of plaque vulnerability on the top of lipid-lowering. A narrative review

“…In all aforementioned algorithms with statins, their prescription is entirely guided by LDL-C levels. However, their efficacy is dose-dependent, and it is attributed not only to their lipid-lowering effects but additionally to the pleiotropic actions leading to the improvement of carotid plaque texture and the reduction of the overall cardiovascular risk [20]. Therefore, it is wise to modify the therapeutic target of statin therapy to a composite end-point combining LDL-C reduction with favorable changes in plaque stability and the patient's risk profile quantified by imaging techniques and biomarkers.…”