Background and aims: Familial hypercholesterolemia (FH) is a metabolic autosomal dominant disorder. It is characterised by elevated plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels usually due to a genetic mutation in the LDL receptor gene and have therefore a higher risk of non-fatal or fatal coronary heart disease (CHD). Yet, there is a substantial variation between individuals with FH, even among FH subjects with the same genetic mutations, in susceptibility to CHD in terms of the age of onset and severity. The aim of this thesis was to increase the knowledge about which factors that may affect the onset of CHD in FH subjects. This is an important knowledge in order to determine how intense the treatment the various patients should be offered and how early treatment should be initiated.
Subjects and methods: Two different studies were included in this thesis. The first study, a retrospective data collection study, characterised and compared clinical and biochemical parameters from the medical records of 71 FH subjects with early CHD event and 76 FH subjects with late or no CHD event. In addition, 14 deceased FH subjects with early CHD event and 14 deceased FH subjects with late or no CHD event were compared with each other and with the non-deceased FH groups. In the second study, a case-control study administered by the master student, clinical and biochemical parameters in a smaller group of FH subjects with more strict inclusion criteria than the first study were compared, with special regard to different coagulation factors, CRP and fibrinogen. The case-control study included 19 FH subjects with early CHD event, 15 FH subjects with late or no CHD event and 10 control subjects. All groups except from the control group were subdivided into gender.
Results: FH subjects with early onset of CHD seems to have a more severe risk factor profile compared with FH subjects with late or no CHD event, even though they are more intensively medically treated. Female FH subjects seem to have a more severe risk factor profile in comparison with male FH subjects, suggesting that they are not well enough medically treated. However, in general, today’s lipid-lowering treatment seems to be more effective than the lipid-lowering treatment ten years ago, reducing the risk of fatal CHD in FH subjects. In our study, coagulation markers do not appear to play a determining role in susceptibility to CHD in FH subjects.
Conclusion: Even though the treatment in FH subjects seems to have improved substantially, there is still a potential for improvement concerning reaching the treatment goals for blood lipid levels. Our results may also indicate that female FH subjects may need to be followed up more closely, and to be more extensively treated with lipid-lowering medication and combination medication. The contribution of lipoprotein (a) in particular but also supplementation with omega-3 fatty acids with regard to CHD risk and death in FH subjects should be examined to a greater extent.