La maladie coronarienne est l’une des principales causes de mortalite dans le monde, la manifestation la plus connue etant l’infarctus du myocarde. Plus de 80 % des infarctus sont causes par la formation d’un thrombus occlusif dans une artere coronaire, decoulant de la destabilisation d’une plaque d’atherosclerose. Bien que la presence de facteurs de risque traditionnels majeurs (hypertension, diabete, dyslipidemie, tabagisme) augmente le risque coronarien, plus de 85 % des infarctus sont inexpliques par ceux-ci. L’atherosclerose, le mecanisme sous-jacent a la majorite des evenements coronariens, se caracterise par des depots de calcium, de tissu fibreux, ainsi que de lipides et de debris necrotiques, lesquels s’agglomerent pour former un noyau necrotique riche en lipides (LRNC) dans la paroi arterielle. Le LRNC est un determinant majeur de la vulnerabilite de l’atherosclerose etant associe a la survenue d’evenements coronariens. Les lipoproteines atherogenes sont tres impliquees dans le developpement du LRNC et sont influencees par plusieurs elements, dont l’adiposite viscerale. L’activite physique reduirait cette adiposite et pourrait egalement ralentir la progression de l’atherosclerose. Or, la relation entre l’atherosclerose et ces marqueurs cardiometaboliques est a clarifier. L’etude des arteres coronaires necessite des methodes d’imagerie invasives, peu applicables chez des sujets sains. Puisqu’il est suggere que l’atherosclerose est une maladie systemique, l’artere carotide representerait un temoin facilement accessible a l’imagerie par resonance magnetique, non invasive, et permettrait d’etudier ces relations. Les objectifs generaux de cette these sont de determiner si les mesures volumetriques du fardeau et des caracteristiques tissulaires de l’atherosclerose carotidienne sont associees au risque coronarien et de verifier leurs relations avec le gras visceral, les lipoproteines atherogenes et l’activite physique. D’abord, nous avons eclairci la relation entre l’atherosclerose carotidienne et coronarienne, montrant que les mesures volumetriques de l’atherosclerose carotidienne faisaient etat du risque coronarien. Ensuite, nous avons montre que les mesures cliniques de l’adiposite abdominale et des lipoproteines atherogenes, informant sur l’exces de gras visceral, amelioraient l’evaluation du risque en clinique et que l’inactivite physique et la progression du gras visceral etaient associees a l’evolution du LRNC dans les carotides. Enfin, nous avons etabli que l’amelioration de la condition cardiorespiratoire etait inversement associee a la progression de la proportion du LRNC dans les carotides. Nos travaux montrent donc que l’adiposite viscerale abdominale et la sedentarite affectent l’evolution de l’atherosclerose vulnerable, offrant des avenues de prevention tres prometteuses pour reduire l’incidence de la maladie coronarienne. / Coronary artery disease is one of the leading causes of mortality worldwide, myocardial infarction being the most common clinical manifestation. More than 80% of myocardial infarctions are caused by an occlusive thrombus in a coronary artery, resulting from the destabilization of an atherosclerotic plaque. Although the presence of traditional risk factors such as hypertension, diabetes, dyslipidemia and smoking increases the risk of coronary artery disease, more than 85% of myocardial infarction events remain unexplained by those risk factors. Atherosclerosis is characterized by an accumulation of calcium and fibrous tissue as well as necrotic and lipids debris, aggregated in a lipid-rich necrotic core (LRNC) within the artery wall. LRNC is a major determinant of atherosclerosis vulnerability, being associated with the occurrence of coronary events. Atherogenic lipoproteins are closely involved in the LRNC development, and are mediated through several mechanisms, but especially by visceral adiposity. Physical activity reduces the amount of visceral fat and the level of atherogenic lipoproteins, and may also slow atherosclerosis progression. However, the relationship between atherosclerosis characteristics and those cardiometabolic markers remains to be clarified. Imaging of coronary arteries requires invasive techniques, which are difficult to apply in otherwise healthy individuals. The carotid artery is easily accessible to magnetic resonance imaging, which is non-invasive, and may be used to study those relationships. The general objectives of this thesis are to determine whether volumetric measurements of carotid atherosclerosis burden and tissue features are associated with coronary risk, and if they are related to visceral adiposity, atherogenic lipoproteins and physical activity. First, we clarified the relationship between carotid and coronary atherosclerosis, and demonstrated that volumetric measurements of carotid atherosclerosis were good indicators of the clinical coronary risk. Then, we established that clinical measurements of visceral abdominal adiposity and atherogenic lipoproteins may improve risk evaluations by identifying individuals with high-risk atherosclerosis. We also demonstrated that physical inactivity and visceral abdominal adiposity progression are associated with the progression of the LRNC in the carotid artery. Finally, we observed that the improvement of cardiorespiratory fitness, generated by regular physical activity, is inversely associated with the change of LRNC proportion in the carotid artery. Our work therefore shows that physical inactivity and visceral abdominal adiposity are associated with the progression of high-risk atherosclerosis features, offering promising avenues to reduce the incidence of coronary artery disease.
| Identifer | oai:union.ndltd.org:LAVAL/oai:corpus.ulaval.ca:20.500.11794/35733 |
| Date | 02 August 2019 |
| Creators | LeBlanc, Stéphanie |
| Contributors | Larose, Éric, Després, Jean-Pierre |
| Source Sets | Université Laval |
| Language | French |
| Detected Language | French |
| Type | thèse de doctorat, COAR1_1::Texte::Thèse::Thèse de doctorat |
| Format | 1 ressource en ligne (xxi, 283 pages), application/pdf |
| Rights | http://purl.org/coar/access_right/c_abf2 |
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