Dyslipidemia and atherosclerotic carotid artery stenosis

Abstract

Carotid artery atherosclerosis or stenosis is frequently present at the carotid bifurcation or the internal carotid artery, accounting for at least 20% of all ischemic strokes. High levels of serum total cholesterol and low-density lipoprotein cholesterol are established risk factors for genesis and progression of atherosclerotic lesions through various mechanisms. In addition, accumulating evidence has shown that a high level of triglyceride is associated with increased atherosclerosis risks. The so-called "vulnerable plaque" with a large lipid core, thin fibrous cap and intra-plaque hemorrhage tends to cause subsequent thromboembolic ischemic events. Statins are known not only to lower serum cholesterol levels but also to promote plaque stabilization via pleiotropic effects such as reducing subclinical systemic inflammation, endothelial activation, leukocyte intra-plaque infiltration, and increasing intimal smooth muscle cell migration. This article discusses the mechanisms of atherosclerosis formation induced by dyslipidemia and the role of lipid-lowering agents including statins in patients with symptomatic and asymptomatic atherosclerotic carotid artery stenosis.

Non-Fasting Hypertriglyceridemia Burden as a Residual Risk of the Progression of Carotid Artery Stenosis

“…The impact of elevated non-fasting TG levels on carotid artery stenosis can be explained by the following mechanisms [ 19 , 20 ]. In the postprandial state, chylomicrons are secreted from the intestines into the blood, and the resulting increased chylomicron remnants lead to the production of TG [ 20 ].…”

“…The impact of elevated non-fasting TG levels on carotid artery stenosis can be explained by the following mechanisms [ 19 , 20 ]. In the postprandial state, chylomicrons are secreted from the intestines into the blood, and the resulting increased chylomicron remnants lead to the production of TG [ 20 ]. In addition, under dyslipidemia with insulin-resistant states (obesity, metabolic syndrome and type-2 diabetes mellitus), free fatty acids are increased and promote the production of TG [ 20 ].…”

“…In the postprandial state, chylomicrons are secreted from the intestines into the blood, and the resulting increased chylomicron remnants lead to the production of TG [ 20 ]. In addition, under dyslipidemia with insulin-resistant states (obesity, metabolic syndrome and type-2 diabetes mellitus), free fatty acids are increased and promote the production of TG [ 20 ]. The resultant overproduction of TG enlarges VLDL associated with apolipoprotein C3, which delays the clearance of TG-rich lipoproteins (chylomicron and VLDL) from the blood [ 13 ].…”

“…As a result, the size and density of LDL further decrease, turning into small dense LDLs, which are more atherogenic than large buoyant LDLs, while antiatherogenic HDL decreases [ 13 ]. Thus, elevated levels of postprandial TG indicate accumulation of proatherogenic TG-rich remnant lipoproteins (derived from chylomicrons and VLDLs) and small dense LDLs in the circulation, as well as a decrease in antiatherogenic HDLs, contributing to proatherogenic and procoagulant processes including inflammation, oxidative stress, and endothelial dysfunction [ 20 , 23 , 24 ]. The proatherogenic mechanisms involving TG are rather complicated and need to be further explored.…”

Higher Non-fasting Serum Triglyceride Preceding the Carotid Stenosis Progression

“…9) TGs and TG-rich lipoproteins are known to accelerate atherogenesis via direct and indirect mechanisms. 12) TG is a major component of TG-rich lipoproteins that include chylomicrons, very low-density lipoproteins (LDLs) and their remnants created during metabolism of TG, and elevated non-fasting TG levels indicate the presence of increased levels of TG-rich remnant particles from chylomicrons and very LDLs. 7) Atherogenic dyslipidemia, a cardiovascular risk factor for atherosclerosis, is an imbalance between pro-atherogenic apolipoprotein B-containing lipoproteins (chylomicrons and very LDL remnants) and anti-atherogenic apolipoprotein A1-containing HDL.…”