Grant: Travel Awards - Institute Community Support

Calcific aortic valve stenosis (CAVS) is the narrowing of the exit of the left ventricle of the heart and is the most common form of heart valve diseases. Surgical replacement of the aortic valve is the only effective treatment for CAVS. The circulating level of Lipoprotein(a) (Lp[a]) is largely determined by genetic variation in the gene coding for the apolipoprotein(a), an essential component of Lp(a). Previous studies have identified that gene variants impacting on Lp(a) levels were associated with CAVS and coronary artery disease (CAD) risk. The objective of this study was to test the association between genetically elevated Lp(a) levels and the risk of CAVS in a cohort of patients undergoing a heart surgery including controls with CAD. We performed a genetic association study in the Quebec City Case-Control Calcific Aortic Valve Stenosis Cohort (QUEBEC-CAVS), which includes patients undergoing cardiac surgery. The cohort included 1001 patients undergoing aortic valve replacements (AVR) for CAVS and 1017 control patients with CAD undergoing coronary artery bypass grafting and without valvulopathy. In patients with CAVS, 58,1% had concomitant CAD. A weighted genetic risk score (GRS) based on three genetic variants known to affect Lp(a) levels was used. Increase of the GRS was associated with a 2 folds higher risk of CAVS. In sensitivity analysis including only CAVS cases with CAD, the GRS remained associated with the risk of CAVS. This study shows that genetically elevated Lp(a) level is causally associated with the risk of CAVS, independently of the presence/absence of CAD. Targeting Lp(a) could be an effective strategy for CAVS prevention and/or treatment, including in individuals with documented CAD.