Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Associate professor Antonio Gallo, Hôpital Pitié-Salpétriêre,
- Second opponent: Professor Anja Bye, NTNU - Norwegian University of Science and Technology,
- Third member and chair of the evaluation committee: Associate professor Rune Enger, University of Oslo
Chair of the Defence
Professor Tore Julsrud Berg, University of Oslo
Principal Supervisor
Professor Kirsten B. Holven, University of Oslo
Summary
Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) from birth, increasing the risk of premature coronary heart disease (CHD) without early treatment.
Despite effective lipid-lowering therapies like statins, many FH patients start treatment late or do not reach their LDL-C goals. Elderly FH patients having lived many years before the statin era, face high CHD risk due to prolonged LDL-C exposure. Surprisingly, some elderly FH patients remain CHD event-free.
The aims of this PhD project were therefore to identify potential cardioprotective markers in elderly event-free FH patients and examine the association between CHD and cumulative LDL-C exposure, also called LDL-C burden.
The research involved a cross-sectional study of elderly FH patients with and without CHD, focusing on lipoprotein and gene expression profiling. In addition, LDL-C burden was estimated based on repeated LDL-C measures from medical records at the Lipid Clinic in Oslo.
Findings revealed that event-free FH patients had higher levels of large high-density lipoprotein (HDL) particles, but not small HDLs. They also had slightly different gene expression profiles, with higher expression of ABCA1 and ABCG1, genes involved in HDL maturation and cholesterol efflux, and lower expression of the inflammatory genes STAT1 and STAT3.
Additionally, FH patients with CHD had higher estimated LDL-C burden compared to those without CHD due to higher estimated LDL-C exposure earlier in life. Finally, higher LDL-C in women compared to men during follow-up at the Lipid Clinic indicates less intensive treatment of female FH patients.
Overall, the results of this PhD project suggest that HDL size separation, gene expression profiling, and estimation of LDL-C burden could improve risk prediction in high-risk individuals. Although more research is needed, the findings emphasize the importance of early LDL-C management.
Additional information
Contact the research support staff.