Lipoprotein(a) – impact on cardiovascular disease, public health and potential as preventive health measure

Lipoprotein(a) [Lp(a)] is an important risk factor for cardiovascular disease and may be responsible for much of the cardiovascular risk that cannot be explained by other risk factors. Lp(a) levels are mainly determined by genes, and approximately 20% of the population has elevated levels of Lp(a). Unfortunately, there is still much we do not know about how Lp(a) affects the risk of different types of cardiovascular disease. In this research project, we will study how Lp(a) affects the risk of different types of cardiovascular diseases. At the same time, we will investigate which levels of Lp(a) give the greatest increase in the risk of cardiovascular disease and which factors can make Lp(a) more dangerous. This is knowledge that will help us identify people who will benefit from treatment against elevated Lp(a) levels. We will also investigate whether factors other than genes can affect Lp(a) levels and study biological mechanisms for how Lp(a) increases the risk of cardiovascular disease. If we obesrve that factors other than genes affect Lp(a) levels, we could potentially reduce Lp(a) by modifying these factors, and if we find that Lp(a)'s effect on cardiovascular disease is mediated by specific biochemical factors, it will also be possible to prevent Lp(a) from causing cardiovascular disease by manipulating these factors. Although Lp(a) appears to increase the risk of cardiovascular disease, it is not certain that Lp(a) has the same effect on other diseases. This is something we will also investigate in our project since this is important knowledge that can reveal whether reducing Lp(a) can have side effects in the form of increasing the risk of other diseases. In order to generate this essential knowledge about Lp(a), we use will the largest and most comprehensive population study in Norway, the Trøndelag Health Study, and the latest and most advanced methods in the field of epidemiology.

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein and risk factor for CVD that was discovered in 1963 by the Norwegian scientist Kåre Berg. Levels of Lp(a) are largely genetically determined and have not been observed to be affected by lifestyle or diet. CVD is the leading cause of death worldwide, representing 31% of all global deaths. Up to 90% of CVD may be preventable and lowering levels of atherogenic lipids has been considered one effective way of preventing CVD. Despite the progress in CVD prevention and treatment, there remains substantial residual CVD risk, even among well-treated groups. It is hypothesized that Lp(a) is responsible for residual risk of CVD not attenuated by standard lifestyle modification and lipid-lowering treatment, and it is therefore an ideal candidate for research aiming to improve CVD prevention, risk prediction and treatment. Treatments that reduce Lp(a) are about to become available in a context where knowledge about the role of Lp(a) in CVD is limited, leaving patients with elevated Lp(a) and their clinicians without the necessary knowledge needed for integrating Lp(a) in CVD prevention. This project aims to fill the knowledge gaps on the role of Lp(a) in CVD that are crucial for the implementation of Lp(a) in CVD prevention by performing state of the art observational and genetic epidemiological studies. These studies will examine the distribution and determinants of Lp(a) levels, estimate the impact of Lp(a) levels on different forms of CVD and evaluate the potential for Lp(a) to improve CVD risk prediction. Additionally, our studies of Lp(a) will fill the knowledge gaps on Lp(a) by investigating if potentially modifiable factors affect Lp(a) levels, by examining the complex interplay between Lp(a) and inflammation and by estimating the effect of Lp(a) on other conditions than CVD.