Lipid hypothesis of cardiovascular calcification.

Abstract

Prosthetic heart valve calcification can be a devastating event, especially in young children. In this issue of Circulation, Vyavahare et al1 make the important observation that bioprosthetic heart valve calcification is prevented by valvular pretreatment with ethanol. Not only do these findings have a direct impact on treatment of patients with valvular heart disease, they also provide clues about the fundamental mechanisms underlying calcification of bioprosthetic valves as well as native valve disease and atherosclerotic plaque in general. A particularly important question raised by this study is whether lipids and/or protein modification is an etiologic factor in cardiovascular calcification. To explain the negative effects of ethanol on bioprosthetic calcification, Vyavahare and colleagues1 identified three possible mechanisms: elimination of phospholipids and cholesterol, changes in collagen fiber conformation, and possible direct effects of ethanol on osteocalcin and/or the calcification process. Although they provide evidence for the first two possibilities, the following analysis suggests that the first mechanism predominates. ### Lipid Extraction Although ethanol treatment extracted almost all the lipid elements, the authors did not consider this the sole mechanism because the alternative method of lipid extraction, chloroform-methanol treatment, had less effect on calcification than ethanol despite an even more effective extraction. However, technical factors may need to be considered further because other investigators2 3 4 using chloroform-methanol extraction in a similar …