Biomedical subjects

Marc-André Lavoie

Publications and source records attributed to Marc-André Lavoie.

4 recordsLinked to original sources

PubMed2006

Effect of atherosclerotic regression on total luminal size of coronary arteries as determined by intravascular ultrasound.

We assessed vascular changes during atherosclerosis regression. Compensatory enlargement of coronary arteries accommodates plaque burden during atherosclerosis development. Lipid-lowering therapy has altered the natural history of coronary atherosclerosis, but the arterial changes that occur during disease regression need to be clarified. Intravascular ultrasound was performed at baseline and after approximately 18 months in 432 patients with coronary disease. Mean plaque, lumen, and total vessel area were computed in a 30-mm coronary segment of interest. Mean low-density lipoprotein cholesterol level was 2.4 mmol/L, and 88% of patients received statins. Overall, changes in plaque and total vessel areas were highly correlated (r = 0.82, p <0.0001). Among the 227 patients with plaque regression, the plaque area decrease was -0.58 +/- 0.54 mm(2), and changes in total vessel and lumen areas were -1.02 +/- 1.10 and -0.44 +/- 0.86 mm(2), respectively. The decrease in plaque area correlated better with the change in total vessel area (r = 0.64, p <0.0001) than with the change in lumen area (r = 0.20, p = 0.003). The relation between plaque regression and decrease in total vessel area was significantly better (p = 0.019) for patients with a >40% atheroma area (r = 0.72; p <0.0001) than for those with <or=40% (r = 0.48; p = 0.0004). In conclusion, regression of atherosclerotic plaque is generally accompanied by a decrease in total vessel size, without an increase in luminal dimensions. This reverse vascular remodeling may be responsible for the "regression paradox," whereby secondary prevention is associated with clinical benefits despite minimal improvement in coronary lumen dimensions.

Acetamides↗

PubMed2003

Pharmacologic prevention of both restenosis and atherosclerosis progression: AGI-1067, probucol, statins, folic acid and other therapies.

PURPOSE OF REVIEW: In this article, the authors intend to provide an update on clinical trials of pharmacologic prevention of restenosis after percutaneous coronary interventions, placed in the perspective of the use of orally administered therapy for the prevention of atherosclerosis progression and clinical events. RECENT FINDINGS: AGI-1067, the mono-succinic acid ester of probucol, is a phenolic antioxidant member of a novel class of agents termed v-protectants. It has strong antioxidant properties equipotent to those of probucol and antiinflammatory properties. It inhibits gene expression of VCAM-1 and MCP-1 and has been effective at preventing atherosclerosis in all tested animal models including the non-human primate. In the Canadian Antioxidant Restenosis Trial (CART) 1, AGI-1067 and probucol improved lumen dimensions at the site of percutaneous coronary intervention. AGI-1067 also improved luminal dimensions of non-intervened coronary reference segments in the Canadian Antioxidant Restenosis Trial, which suggests a direct antiatherosclerosis effect. Probucol reduced post-percutaneous coronary intervention restenosis and progression of carotid atherosclerosis in other clinical trials. Although statins reduce atherosclerotic events, they do not appear to have a significant effect on restenosis. The failure of folate therapy to protect against restenosis in the Folate After Coronary Intervention Trial (FACIT) occurred despite significant reductions in homocysteine levels. SUMMARY: Prevention of both post-percutaneous coronary intervention restenosis and atherosclerosis progression with a pharmacologic agent such as AGI-1067 may be an attractive treatment paradigm. Two important trials that test the antioxidant/antiinflammatory hypothesis are ongoing with AGI-1067: the Canadian Atherosclerosis and Restenosis Trial 2, which assesses its value for the reduction of both atherosclerosis progression and post-percutaneous coronary interventions restenosis, and the Aggressive Reduction of Inflammation Stops Events (ARISE) trial which is evaluating its effects on cardiovascular events.

Anti-Inflammatory Agents↗

PubMed2003

Vascular protectants for the treatment of atherosclerosis.

AGI-1067, the monosuccinic acid ester of probucol, is a phenolic antioxidant member of a novel class of agents termed vascular protectants. It has strong antioxidant properties, equipotent to those of probucol, and anti-inflammatory properties. It inhibits gene expression of vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and has been effective at preventing atherosclerosis in all tested animal models. It also improved luminal dimensions of reference segments in the percutaneous coronary intervention (PCI) vessels in the CART-1 clinical trial, which suggests a direct anti-atherosclerosis effect. Two important trials that test the antioxidant/anti-inflammatory hypothesis are ongoing with AGI-1067: the Canadian Atherosclerosis and Restenosis Trial, which assesses its value for the reduction of both atherosclerosis progression in non-PCI vessels and post-PCI restenosis, and the Aggressive Reduction of Inflammation Stops Events trial, which is evaluating the effects of AGI-1067 on hard cardiovascular outcomes.

Antioxidants↗

PubMed2003

Ezetimibe and cholesterol absorption.

Cholesterol, an important biological lipid and excessive dietary intake, is associated with hypercholesterolemia, a prevalent cardiovascular risk factor. Because cholesterol is essentially a water insoluble molecule, its transport within and absorption from the aqueous medium of the intestine is rather complex. This takes place in a series of orderly and interrelated steps, including emulsification, hydrolysis by specific pancreatic esterases, micellar transport, mucosal absorption, resynthesis in enterocytes and assembly with apolipoproteins to form chylomicrons. Many of these processes are not well characterized at the molecular level. Besides being generally inefficient, cholesterol absorption is highly variable with a between-subject variability that depends in part on genetic factors and an intraindividual variability, which may be modulated by physiological and dietary conditions. All of the sequential steps in intestinal cholesterol absorption can be interfered with by dietary components or drugs and therefore are potential therapeutic targets for rendering cholesterol absorption even more inefficient in an attempt to lower cholesterol levels.

Anticholesteremic Agents↗