Stellingen Proefschrift

Stellingen

Behorende bij het proefschrift

Computational Modeling of Lipoprotein Metabolism

to Improve Cardiovascular Risk Prediction

1. The rate constants of metabolic lipolysis and uptake processes affecting apoB-containing lipoproteins can be expressed as a continuous function of lipoprotein particle size (Chapter 2).
2. The model-based diagnostic 'VLDL performance' efficiently distinguishes normolipidemic from dyslipidemic subjects (Chapter 3).
3. The difference in lipoprotein metabolism after medium chain fatty acid versus C18:2n-6 supplementation is consistent with the mechanism of PPAR activation due to the latter fatty acid (Chapter 4).
4. The ‘extrahepatic lipolysis ratio’ and the ‘hepatic turnover ratio’ of VLDL metabolism improve cardiovascular risk prediction when added to a multivariate model including classical and NMR-based risk markers (Chapter 6).
5. The Net Reclassification Index is a sensitive and clinically relevant statistic for comparison of diagnostics (see Pencina et al 2009, Stat Med).
6. Comparing different lipoprotein profile measurement methods is made difficult both by differences in the particle size definition and by differences in the subclass size range definition (see Otvos et al. 1999, Clin Chem; Usui et al. 2002, J Lipid Res).
7. Overproduction of large VLDL particles is driven by liver fat content rather than by liver cholesterol content (see Adiels et al. 2006, Diabetologia).
8. So far the only useful alternative to LDL cholesterol and HDL cholesterol diagnostics derived from detailed lipoprotein profiles are LDL and HDL particle number, that use little of the detailed size information contained in the profile (see Cromwell et all, 2007, J Clin Lipidol).
9. Systematic reflection about the fact that the universe develops along the road of natural laws reveals the presence of a living spirit, a 'Road Worker'.
10. Working time and facilities are essential for innovation, but above all it requires the scientist’s free choice to pursue the practical application of the new idea.
11. A new human organism comes into being at the very moment of fertilization of a human ovule, when all relevant genes and systems for development are in place.
12. What an affectionate greeting does communicate, no mathematical model can relate.

Note: At Leiden University, it is customary that the PhD candidate presents twelve 'stellingen' that he is willing to discuss during the public defence of his PhD thesis. The first four concern the PhD thesis itself, the second four the scientific literature of the corresponding field, and the last four are freely electable. All should be defensible with reasoned arguments.