skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Lipid-Altering Therapies and the Progression of Atherosclerotic Disease

Abstract

Lipids play a key role in the progression of atherosclerosis, and lipid-lowering therapies have been studied for 30 years in coronary disease. Measurement of the progression of atherosclerosis through carotid intima-media thickness, coronary mean lumen diameter, and, mostly recently, intravascular ultrasound is generally accepted. This article reviews the role of lipid-lowering therapies in changing the rate of atherosclerosis progression in the coronary and carotid circulations. Statins are the primary therapy used to reduce atherosclerosis and cardiovascular events, including strokes and transient ischemic attacks, and have benefits in reducing events in patients undergoing carotid endarterectomy. In contrast, data for other agents, including fibrates and nicotinic acid, in reducing the progression of atherosclerosis are less extensive and not as well known. There is increasing interest in optimizing the whole lipid profile, as this might deliver extra benefits over and above statin therapy alone. Initial proof of this concept has recently come from studies that measured the progression of atherosclerosis and showed that adding nicotinic acid to statin therapy and, more directly, infusion of high-density lipoprotein-like particles reduced progression and indeed might induce regression of the disease. It is likely that the management of significant carotid stenosis will become ever more drug focusedmore » and will be customized to the lipid profile of each patient with intervention reserved only for late-stage symptomatic disease.« less

Authors:
 [1]
  1. St. Thomas' Hospital, Department of Chemical Pathology (United Kingdom), E-mail: Anthony.Wierzbicki@kcl.ac.uk
Publication Date:
OSTI Identifier:
21091019
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cardiovascular and Interventional Radiology; Journal Volume: 30; Journal Issue: 2; Other Information: DOI: 10.1007/s00270-006-0183-8; Copyright (c) 2007 Springer Science+Business Media, Inc.; www.springer-ny.com; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ARTERIOSCLEROSIS; CORONARIES; DRUGS; INFUSION; LIPOPROTEINS; NICOTINIC ACID; OPTIMIZATION; THERAPY

Citation Formats

Wierzbicki, Anthony S. Lipid-Altering Therapies and the Progression of Atherosclerotic Disease. United States: N. p., 2007. Web. doi:10.1007/S00270-006-0183-8.
Wierzbicki, Anthony S. Lipid-Altering Therapies and the Progression of Atherosclerotic Disease. United States. doi:10.1007/S00270-006-0183-8.
Wierzbicki, Anthony S. Sun . "Lipid-Altering Therapies and the Progression of Atherosclerotic Disease". United States. doi:10.1007/S00270-006-0183-8.
@article{osti_21091019,
title = {Lipid-Altering Therapies and the Progression of Atherosclerotic Disease},
author = {Wierzbicki, Anthony S.},
abstractNote = {Lipids play a key role in the progression of atherosclerosis, and lipid-lowering therapies have been studied for 30 years in coronary disease. Measurement of the progression of atherosclerosis through carotid intima-media thickness, coronary mean lumen diameter, and, mostly recently, intravascular ultrasound is generally accepted. This article reviews the role of lipid-lowering therapies in changing the rate of atherosclerosis progression in the coronary and carotid circulations. Statins are the primary therapy used to reduce atherosclerosis and cardiovascular events, including strokes and transient ischemic attacks, and have benefits in reducing events in patients undergoing carotid endarterectomy. In contrast, data for other agents, including fibrates and nicotinic acid, in reducing the progression of atherosclerosis are less extensive and not as well known. There is increasing interest in optimizing the whole lipid profile, as this might deliver extra benefits over and above statin therapy alone. Initial proof of this concept has recently come from studies that measured the progression of atherosclerosis and showed that adding nicotinic acid to statin therapy and, more directly, infusion of high-density lipoprotein-like particles reduced progression and indeed might induce regression of the disease. It is likely that the management of significant carotid stenosis will become ever more drug focused and will be customized to the lipid profile of each patient with intervention reserved only for late-stage symptomatic disease.},
doi = {10.1007/S00270-006-0183-8},
journal = {Cardiovascular and Interventional Radiology},
number = 2,
volume = 30,
place = {United States},
year = {Sun Apr 15 00:00:00 EDT 2007},
month = {Sun Apr 15 00:00:00 EDT 2007}
}
  • Laser energy delivered through optical fibers can produce potent controlled thermal dissolution of human coronary obstructive disease, thus widening the stenotic vascular lumen. The ease of vaporization and penetration depends not only on the physical properties of the laser beam but also on the physical characteristics of the atherosclerotic plaque. Lipid-laden plaques are more easily vaporized compared with plaques that are heavily calcified. In atherosclerotic animal models studied in vivo, laser radiation produced a charred lining around the evacuated area and rapid regeneration of a new endothelial lining. After several weeks, the laser-induced crater was still evident, and thrombogenesis wasmore » not a significant complication. Focal aneurysmal dilatation may develop when there is thermal injury of the medial layer, and acute perforation can occur if severe laser burn is extended beyond the adventitial layer. Further technical advances and achievements are needed before laser recanalization becomes a clinical reality.« less
  • Nuclear magnetic resonance (NMR) images of 93 patients undergoing studies of the abdomen and pelvis were studied for evidence of lesions of the aorta and the iliac and femoral arteries; atherosclerotic lesions were present in 13 of them. The lesions consisted of eccentric and concentric mural thickening with luminal narrowing and discrete plaques protruding into the vessel lumen. This appearance was distinctly different from the morphology of the internal vessel surface and uniformly thin vessel wall in normal patients and volunteers under the age of 30 years. Intraluminal flow signals observed in atherosclerotic and nonatherosclerotic subjects could be distinguished frommore » mural lesions because of their lack of contiguity with the vessel wall and variation in appearance on multiple images obtained with the first and second spin echo. This initial experience suggests a potential role for NMR in the noninvasive imaging of atherosclerotic lesions. The natural contrast between flowing blood and the vessel wall indicates a distinct advantage of NMR for vascular imaging.« less
  • Radiolabeling of low-density lipoprotein (LDL) and external imaging with a gamma camera would offer a means of taking advantage of the metabolic activity of developing atherosclerotic lesions in order to noninvasively detect and determine the extent of atherosclerotic cardiovascular disease. Indium-111-({sup 111}In) labeled LDL was prepared and its purity demonstrated by agarose electrophoresis and ultracentrifugation. In vitro studies with cultured human fibroblasts demonstrated significant inhibition of iodine-125-({sup 125}I) LDL binding to LDL receptors by {sup 111}In-LDL, although this was less than the inhibition produced by unlabeled LDL. Adrenal gland uptake of {sup 111}In-LDL by hypercholesterolemic rabbits was reduced by 86%more » compared to the level of uptake observed in normal rabbits. These results were compatible with downregulation of adrenal LDL receptors in the hypercholesterolemic rabbits. Uptake of {sup 111}In-LDL in the atherosclerotic proximal aorta of hypercholesterolemic rabbits was 2.5 times higher than in normal rabbits. These results suggest that {sup 111}In-LDL has the potential to be a useful agent for external imaging of atherosclerotic lesions and lipoprotein biodistribution.« less
  • Atherosclerotic peripheral vascular disease (PVD) of the lower extremities deprives a person of the ability to exercise to their satisfaction, later of the ability to perform the activities of their daily life, and finally of their legs themselves. Peripheral vascular disease has long been managed by the vascular surgeon utilizing endarterectomy and peripheral arterial bypass. Patient acceptance of nonsurgical, percutaneous procedures such as percutaneous transluminal balloon angioplasty (PTA) is high. Increased utilization of these procedures has led to improved techniques and adjuncts to therapy, as well as more critical review of long-term results. This article will review the evaluation andmore » nonoperative management of PVD, with an emphasis on the newer modalities of management presently being investigated.« less