Popular Summary of my PhD Thesis

The index of this PhD thesis is available here. 

What is the significance of this PhD thesis?

         When you come to a doctor, the doctor will usually ask for two types of cholesterol to be measured: the ‘good’ HDL cholesterol and the ‘bad’ LDL cholesterol. From a technical point of view, this approach is outdated, since for quite some time we have been able to measure many more types or ‘subfractions’ of cholesterol; now measurements can distinguish up to forty such subfractions. Yet from a medical perspective, these detailed measurements are hard to relate to cardiovascular risk in a straightforward way. So if any of this detailed information is reported to a doctor, it is reported in a simplified fashion.

         The research in this PhD thesis set out to construct a mathematical model that is able to make the most out of the information contained in the detailed cholesterol measurements. The model is able to report information about the status of cholesterol metabolism, in a form we call ‘lipoprotein metabolic ratios’. We have found that by using a combination of two such ratios, we are able to significantly improve cardiovascular risk prediction. The one ratio, called the ‘extrahepatic lipolysis ratio’ is especially important to determine risk when someone is taking blood pressure medication. If someone takes such medication, but the body is not handling fat well, that person might be at high risk for a cardiovascular event. The second ratio, the ‘hepatic turnover ratio’, indicates how well the liver works. If someone is on the border between low and medium risk, this ratio can make the difference between having to take cholesterol-lowering medication yes or no. 

         We have shown this improved risk prediction using subjects from the classical ‘Framingham Heart Study’ cohort; the results will need to be replicated in other trials.