Cardiovascular disease is the principal cause of mortality in patients with type 2 diabetes mellitus. The present thesis describes a study, designed at a time-point when no primary prevention trial... Show moreCardiovascular disease is the principal cause of mortality in patients with type 2 diabetes mellitus. The present thesis describes a study, designed at a time-point when no primary prevention trial had yet been performed to investigate the effects of statin therapy on patients with type 2 diabetes without cardiovascular disease. We have performed a randomized, double-blind placebo-controlled trial in 250 type 2 diabetic patients without manifest cardiovascular disease. The aim of the study was to study non-invasively the effect of two year statin therapy on the vessel wall. We found no effect of two year statin therapy on carotid IMT as a reflection of the progress of atherosclerosis. We found no effect on endothelial function as assessed by FMD. The effect of statin therapy on CRP, as a marker for low grade inflammation, was only significant in a high- risk subgroup with the metabolic syndrome and a high LDL-cholesterol. There was no effect of two-year statin therapy on the prevalence of silent myocardial ischemia. In spite of these findings, we observed a lower cardiovascular event rate in patients on statin therapy, which is in line with other clinical trials. Show less
Cardiovascular diseases are the major cause of morbidity and mortality in western societies. The most common clinical manifestations are stroke and acute myocardial infarction and in both ailments... Show moreCardiovascular diseases are the major cause of morbidity and mortality in western societies. The most common clinical manifestations are stroke and acute myocardial infarction and in both ailments atherosclerosis is the underlying culprit. Atherosclerosis is a lipid-mediated chronic inflammatory disease, which is accompanied by leukocyte infiltration into the vessel wall. The migration of leukocytes from the circulation to the vessel wall is directed by a specific class of proteins, the chemokines. Therefore it is likely that chemokines have a distinctive role in leukocyte homeostasis at specific stages of atherosclerotic disease progression and during ischemia-reperfusion injury. This thesis encompasses of number of human and experimental mouse studies on the role of chemokines in cardiovascular diseases and atherosclerosis, from which several new targets were identified. For instance it is evident that patients with high levels of the chemokine CCL3 are 10 times more likely to develop severe cardiovascular events in the future. In conclusion, the research described in this thesis provided novel candidates that might be of value for the early prediction of high risk patients. Moreover, the identified candidates may also represent valuable targets for modulation of leukocyte homeostasis in the plaque that could improve atherosclerotic plaque progression and stability. Show less
