Calcific aortic valve disease: mechanisms, prevention and treatment

Nat Rev Cardiol. 2023 Aug;20(8):546-559. doi: 10.1038/s41569-023-00845-7. Epub 2023 Feb 24.


Calcific aortic valve disease (CAVD) is the most common disorder affecting heart valves and is characterized by thickening, fibrosis and mineralization of the aortic valve leaflets. Analyses of surgically explanted aortic valve leaflets have shown that dystrophic mineralization and osteogenic transition of valve interstitial cells co-occur with neovascularization, microhaemorrhage and abnormal production of extracellular matrix. Age and congenital bicuspid aortic valve morphology are important and unalterable risk factors for CAVD, whereas additional risk is conferred by elevated blood pressure and plasma lipoprotein(a) levels and the presence of obesity and diabetes mellitus, which are modifiable factors. Genetic and molecular studies have identified that the NOTCH, WNT-β-catenin and myocardin signalling pathways are involved in the control and commitment of valvular cells to a fibrocalcific lineage. Complex interactions between valve endothelial and interstitial cells and immune cells promote the remodelling of aortic valve leaflets and the development of CAVD. Although no medical therapy is effective for reducing or preventing the progression of CAVD, studies have started to identify actionable targets.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aortic Valve
  • Aortic Valve Stenosis* / metabolism
  • Aortic Valve Stenosis* / prevention & control
  • Calcinosis* / genetics
  • Calcinosis* / prevention & control
  • Humans

Supplementary concepts

  • Aortic Valve, Calcification of