The metabolic syndrome and vascular disease

In the Western population cardiovascular diseases are the most common cause of mortality and morbidity. There are several important risk factors for cardiovascular diseases, among them hypertension, hypercholesterolemia, diabetes and obesity. The clustering of cardiovascular risk factors associated with central obesity is often referred to as the metabolic syndrome. Due to different visions regarding the definitions, the underlying pathophysiology and the clinical usefulness, the metabolic syndrome attracts much attention of clinical research and clinicians. It has been shown that in apparently healthy individuals the prevalence of the metabolic syndrome is 20-25%, and the coming years the prevalence is expected to increase due to an increased prevalence of obesity. The metabolic syndrome is associated with a 2 to 3 fold increased risk for the development of cardiovascular disease and type 2 diabetes. In this thesis it is shown that in patients with manifest vascular disease the prevalence of the metabolic syndrome is nearly 50%. We also conclude that in patients with already manifest vascular diseases, the metabolic syndrome is associated with more advanced vascular damage as measured by indicators for increased (cardio)vascular risk. Adiponectin, produced by adipocytes, is involved in glucose metabolism and also has direct anti-atherogenic properties. The relationship between adiponectin and the metabolic syndrome and several estimates of obesity was demonstrated in patients with coronary artery disease in this thesis. Elevated iron stores are associated with type 2 diabetes mellitus and the metabolic syndrome, but the mechanistic link is not clear yet. Adipose tissue could be involved in the development of insulin resistance by the changed production of adipokines, so it could be hypothesized that elevated iron concentrations are involved in the development of the metabolic syndrome by interfering in adipocyte function. We indeed demonstrate that body iron stores, as reflected by ferritin levels, are significantly associated with the metabolic syndrome and adipocyte dysfunction, as measured by decreased adiponectin levels. The presence of coronary collaterals may have beneficial effects during myocardial ischemia and may improve cardiovascular outcome in patients with coronary artery disease. Impaired collateral formation could be one of the reasons for the increased cardiovascular risk in patients with the metabolic syndrome. However, we show that there is no significant association between the metabolic syndrome or insulin resistance and the presence of coronary collaterals in patients with documented coronary artery disease. Furthermore, we show that in patients with the metabolic syndrome combination therapy of low-dose simvastatin and ezetimibe preserves postprandial endothelial function contrary to high dose simvastatin monotherapy, whereas the same reduction in (fasting) plasma LDL-cholesterol is obtained after 6 weeks treatment. We also find that allowance for the use of lipid-lowering drugs in the NCEP-definition may identify an additional group of patients at elevated risk for cardiovascular diseases and diabetes and that the NCEP and IDF definitions identify metabolic syndrome patients with different cardiovascular risk profiles.