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The low density lipoprotein (LDL) particle population is heterogeneous with regard to several structural and functional properties that may influence its atherogenic potential. A preponderance of small, dense LDL is associated with an increased risk of coronary heart disease (CHD), and also predicts future CHD events. However, the metabolic pathways for the formation of the small, dense LDL are not yet fully understood. There is strong evidence that the LDL particle size distribution is under genetic influence, although the major regulating genes remain unknown. The present studies were conducted to further elucidate the role of LDL heterogeneity in cardiovascular disease, and to evaluate the metabolic arid genetic determinants of LDL particle size distribution. In study I the influence of LDL particle size distribution on intima-media thickness (IMT) of the common carotid artery (CCA) was investigated in healthy 50-year-old men. A high-resolution non-denaturing polyacrylamide gradient (3-7.5%) gel electrophoresis (GGE) procedure was developed to measure LDL peak particle size (run), relative distribution (%) and plasma concentration (mg/L) of four LDL subfractions. The IMT of the CCA was measured by B-mode ultrasound. The results of this study show that the plasma concentration of small, dense LDL (LDL-III) is a strong and independent indicator of early atherosclerosis in healthy, middle-aged men. In study II the effects of artificial and exhaustive lipolysis on potentially atherogenic properties of LDL were investigated in healthy normotriglyceridaemic men. After in vitro and in vivo lipolysis of serum and plasma triglycerides, respectively, the LDL particle population was characterised with regard to size, composition, and susceptibility to oxidative modification The results of this study demonstrate that an exaggerated or efficient lipolysis of plasma triglycerides results in the generation of new LDL particles with an increased content of alpha-tocopherol and i