Lipids and lipoproteins in calcific aortic valve disease

Purpose of review Lipids and lipoproteins have established roles in calcific atherosclerosis, but there is less awareness of their role in calcific aortic valve disease (CAVD). Clinical studies link CAVD with severe hypercholesterolemia, and genetic studies consistently link it with lipoprotein little (a) [Lp(a)], a major carrier of oxidized phospholipids. Given the remarkable similarities between calcific atherosclerotic plaques and calcific aortic valves, lipids are incriminated. Hence, lipid-lowering therapies used for atherosclerosis have been tested in CAVD, but results have been inexplicably disappointing. New evidence for the importance of lipids, despite failure of lipid-lowering, and new concepts in diagnostic and therapeutic approaches are discussed. Recent findings Evidence supports a key role of Lp(a) levels in CAVD. Potential diagnostic advances include pH-sensitive-fluorescence probes for visualizing lipid droplets in valves and identification of natural antibodies to modified LDL that associate inversely with CAVD. Potential therapeutic advances include Lp(a) lowering, SGLT2 inhibition, and reactivation of soluble guanylate cyclase. Trial outcomes currently remain mixed. Summary Recent studies clarify the mechanisms by which lipids, lipoproteins, and Lp(a) contribute to CAVD. New potential diagnostic techniques include screening for natural antibodies and visualizing lipid deposits. New therapeutic agents include oligonucleotides and nanoparticles. New clinical trials are underway.