Grant: Project Grant

Calcific aortic valve stenosis (CAVS) is the most common form of heart valve diseases, affecting almost 3% of the population older than 65. CAVS is caused by the calcification of cells in the aortic valve. In patients with CAVS, if the valve is not surgically removed and replaced, 4 out of 5 patients will die within 5 years. Unfortunately, no pharmacological agents have been proven effective in the treatment of CAVS. The identification of CAVS risk factors might give us insights about new treatment opportunities for these high-risk patients. Our team has contributed to the identification of a particle carried in the blood called lipoprotein(a) (Lp[a]) as one of the strongest genetic risk factor for CAVS. Between one in four and one in three patients with CAVS might have elevated Lp(a) levels. Lp(a) is also associated with the risk of developing a broad range of cardiovascular diseases such as coronary artery disease (CAD), peripheral artery disease, heart failure and stroke. Whether the measurement of blood Lp(a) levels in patients with CAVS would be clinically useful is unsure. Additionally, why Lp(a) causes aortic valve calcification and CAVS is still a mystery. The objective of this research project aims are twofold: First, we will determine whether Lp(a) is associated with CAVS risk independently of the presence or absence of CAD and test whether siblings of patients with CAVS and high Lp(a) levels are at increased risk of future CAVS using state-of-the-art cardiac imaging techniques. Second, we will perform experimental using blood and explanted aortic valves of patients who have had their aortic valve removed because of CAVS to determine specifically how Lp(a) increases aortic valve calcification and CAVS. On top of generating new knowledge on Lp(a) and CAVS biology, this study will contribute to identifying the key patients in whom Lp(a) should be assessed and targeted.