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

Abstract

Novel imaging techniques and biomarkers have emerged as surrogate markers of carotid plaque vulnerability. In parallel, statin administration in patients with established carotid atherosclerosis not requiring revascularization has reduced the number of consequent cerebrovascular events. This reduction is not only attributed to the lipid-lowering properties of statins but also to their pleiotropic actions. The present literature review aimed to summarize the stabilizing effects of statins on carotid plaques based on imaging modalities and biomarkers and propose an alternative approach to their implementation. Moreover, we assessed the perioperative use of statins in patients undergoing carotid revascularization and the impact of aggressive vs. conventional statin therapy. Recent studies using: (1) ultrasound indices of plaque echogenicity; (2) fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scans for plaque inflammation assessment; or (3) magnetic resonance imaging (MRI) scans quantifying intraplaque hemorrhage, and lipid-rich necrotic core (LRNC) have shown quite promising results in evaluation of carotid plaque vulnerability. Based on those imaging modalities, a growing number of studies have demonstrated a very modest carotid plaque regression due to/induced by statins, while their stabilizing impact is disproportionally higher. Other studies assaying several biomarkers (e.g. inflammation, etc.) have confirmed a statin-induced carotid plaque stabilization. All the aforementioned benefits followed a dose-dependent pattern of statins, on top of the low-density lipoprotein cholesterol (LDL-C) target in current guidelines. In the case of symptomatic patients with carotid atherosclerosis suitable for revascularization, robust evidence implicates a significant statin-related reduction of perioperative cardiovascular risk only in patients undergoing endarterectomy.

A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients—A Review PART II—Pharmacological Approach for Management of Elderly Patients with Peripheral Atherosclerotic Lesions outside Coronary Territory

“…Even if a statin does not result in regression of atherosclerotic plaque, achieving the recommended LDL cholesterol concentration is associated with a reduction in the rate of atherosclerotic progression. In patients with good tolerance, statins should not be discontinued because they have pleiotropic effects and significantly reduce the need for revascularization in this age group [ 85 ]. In turn, the avoidance of revascularization avoids complications caused by medication required for interventional treatment [ 86 , 87 , 88 ].…”

Classical and Novel Lipid-Lowering Therapies for Diabetic Patients with Established Coronary Artery Disease or High Risk of Coronary Artery Disease—A Narrative Clinical Review

“…Notably, in the same meta-analysis, statin therapy failed to significantly reduce all-cause mortality (RR: 0.85; 95% CI: 0.70, 1.03; p = 0.065) [23], which may be related to participants' backgrounds of CAD or other CVD. A possible explanation for the remarkable CV benefits of statins derives from their pleiotropic effects beyond lipid lowering [24,25], for instance, the favorable modification of the adipose tissue derivatives adipokines, significant amounts of which are found in the blood circulation of diabetic patients with CVD [26].…”

Cardiac microRNAs: diagnostic and therapeutic potential

“…The optimal point for early intervention would be during the identification of intima-media complex thickening or the presence of early plaques [127][128][129]. Increasing thickness of the carotid intima-media complex and carotid plaques is related to the extent and severity of atherosclerosis, in addition to polyvascular atherosclerosis [163][164][165][166][167][168][169][170][171]. Also, the role of mi-croRNAs in cardiovascular risk factor modification seems extremely important.…”