The first part of this thesis identified patients at low risk for recurrent events or death after STEMI. It was observed that asymptomatic patients with a LVEF>45% after one year can safely be... Show moreThe first part of this thesis identified patients at low risk for recurrent events or death after STEMI. It was observed that asymptomatic patients with a LVEF>45% after one year can safely be referred to the GP with mortality rates after STEMI that come close to the rate in the general population.The second part focused to identify high-risk subpopulations to improve risk stratification. Despite current standards of care aimed at achieving targets for LDLc and other traditional risk factors, STEMI patients remain at high risk of new cardiovascular events. Valuable effort should therefore be made to further reduce residual cardiovascular risk by using additional more discriminating and more refined treatments targets like apoB and apoB/apoA1 ratio. Furthermore, novel biomarkers were identified to improve risk stratification and select high risk sub-populations. GDF-15, a more general marker for disease severity in STEMI patient demonstrated to have an additional prognostic value beyond identified risk factors and other cardiac biomarkers such as cTn and NT-proBNP.Lastly, the third part of this thesis showed that a dedicated pre-hospital triage protocol is an effective tool to select patients for admission at the cardiac emergency department. Overcrowding is a major public health problem and this thesis shows that the introduction of dedicated cardiac emergency departments can potentially reduce the caseload of the general emergency department. Show less
Mast cells (MCs) are potent innate immune cells that aggravate atherosclerosis through the release of proinflammatory mediators inside atherosclerotic plaques. Similarly, CD4+ T cells are... Show moreMast cells (MCs) are potent innate immune cells that aggravate atherosclerosis through the release of proinflammatory mediators inside atherosclerotic plaques. Similarly, CD4+ T cells are constituents of the adaptive immune response and accumulate within the plaques following lipid-specific activation by APCs. Recently it has been proposed that these two cell types can interact in a direct manner. However, no indication of such an interaction has been investigated in the context of atherosclerosis. In our study, we aimed to examine whether MCs can act as APCs in atherosclerosis, thereby modulating CD4+ T cell responses. We observed that MCs increased their MHC class II expression under hyperlipidemic conditions both in vivo and in vitro. Furthermore, we showed that MCs can present Ags in vivo via MHC class II molecules. Serum from high-fat diet–fed mice also enhanced the expression of the costimulatory molecule CD86 on cultured MCs, whereas OVA peptide–loaded MCs increased OT-II CD4+ T cell proliferation in vitro. The aortic CD4+ and TH1 cell content of atherosclerotic mice that lack MCs was reduced as compared with their wild-type counterparts. Importantly, we identified MCs that express HLA-DR in advanced human atheromata, indicating that these cells are capable of Ag presentation within human atherosclerotic plaques. Therefore, in this artice, we show that MCs may directly modulate adaptive immunity by acting as APCs in atherosclerosis. Show less
