Lipoprotein(a) as potential risk factor for atherosclerosis in children and young adults Awake and aware

Lipoprotein(a) [Lp(a)] is a cholesterol-like particle that is genetically determined. When Lp(a) levels are elevated, patients are exposed to a lifelong burden of high Lp(a) levels from young ages onwards. Given the scarcity of studies in young patients, this thesis focuses on enlarging the knowledge of Lp(a) in children and young adults and evaluated if high Lp(a) levels pose a risk for atherosclerosis at young ages already. In the first part of this thesis, we show that it is important to measure Lp(a) levels in children that are suspected of a genetic form of high cholesterol levels, familial hypercholesterolemia (FH), because high Lp(a) levels may underlie the clinical presentation of FH. Moreover, we found that Lp(a) levels do not remain stable during childhood and exhibit a significant increase with age and show large intra-individual fluctuations. Therefore, measuring Lp(a) more than once is recommended in selected cases. In the second part of this thesis, we show that elevated Lp(a) levels contribute significantly to arterial wall thickening, a sign of atherosclerosis, in children with FH that were followed-up for 20 years. We did not find a similar association in children without FH. Finally, we showed that statin therapy, a frequently prescribed drug for lowering LDL-cholesterol levels, do not change Lp(a) levels significantly. In contrast, other types of drugs, such as RNA-based therapies targeted at the LPA gene, do seem to lower Lp(a) levels effectively and might hold promise for the future.