premature coronary atherosclerosis : risk factors, prognosis, prevention and novel mechanistics approaches ; Athérosclérose coronaire prématurée : facteurs de risque, pronostic, prévention et nouvelles approches mécanistiques

This thesis focused on premature coronary atherosclerosis, the clinical and biological profile of affected individuals, with a pathophysiological approach aiming to assess the contribution of inflammation and vascular age. Studies 1 and 2 described the very high-risk cardiovascular profile of these patients and the factors of poor long-term outcomes. These studies have demonstrated that premature coronary atherosclerosis is a progressive disease with a rapid multi-arterial involvement, leading to a mortality rate of 20% over 10 years. Study 3 demonstrated the significant contribution of subclinical inflammation to the genesis of coronary atherosclerosis in younger individuals, compared with older populations. This observation relied on the use of a new biomarker of chronic inflammation, GlycA, a composite signal of the glycosylation of proteins in the acute phase. Study 4 demonstrated the significant involvement of IL-1β in the post-myocardial infarction inflammatory cascade, and its association with short and long-term death. Study 5 evaluated the stiffness of the aortic root measured by MRI as a new risk marker for premature coronary artery disease, introduction a new tool for an integrative measure of vascular aging. Studies 6 and 7 have highlighted the lack of performance of American and European international guidelines in detecting and treating individuals at high risk of premature atherosclerosis, and the missed opportunities for intensive treatment after a first myocardial infarction. premature. ; Cette thèse s’est intéressée à la question de l’athérosclérose coronaire prématurée, du profil clinique et biologique des individus qui en sont touchés, avec une approche physiopathologique permettant d’évaluer la contribution de l’inflammation et l’âge vasculaire. Les études 1 et 2 ont décrit le profil cardiovasculaire à très haut risque de ces patients et les facteurs d’évolution péjorative sur le long-terme. Ces études ont démontré que l’athérosclérose coronaire est une maladie évolutive avec une atteinte ...