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Possible Role for Niacin and Vitamin K in Calcific Aortic Valve Stenosis

2/27/2018 1:37:31 PM
Calcific aortic valve stenosis (CAVS) is the most common cause of aortic stenosis in developed countries. CAVS is increasingly common in older adults and has a poor prognosis without intervention. Current guidelines do not recommend pharmacological interventions, leaving surgical valve replacement as the only treatment option for patients with severe and symptomatic CAVS. A clinical update, published in the European Heart Journal in 2017, summarized the latest research in the pathophysiology, potential pharmacological interventions, and new imaging techniques for CAVS.
The pathophysiology of CAVS progresses in 2 phases: initiation and propagation. Much like atherosclerosis, the initiation phase is marked by endothelial damage and an inflammatory response. The propagation phase is characterized by fibrosis, calcification, and valvular dysfunction. A fundamental step in promoting valvular calcification is a switch of valvular interstitial cells to an osteoblast-like phenotype. Inhibition of calcification relies on the presence of carboxylated matrix-Gla protein, a vitamin K-dependent protein.
Pharmacological interventions that have been evaluated for the treatment of CAVS but lack data from randomized controlled trials include angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, and statins. Bisphosphonates are being investigated in the ongoing SALTIRE 2 clinical trial. Niacin is being investigated in the EAVaLL clinical trial. Vitamin K has shown promise in slowing the progression of aortic stenosis, as reported in a randomized controlled trial published by Brandenburg et al. in 2017. The effect of vitamin K on slowing calcification in CAVS is being further investigated in multiple trials, including the iPACK-HD, VitaVasK, and VitaK-CAC trials.
As new therapeutic options are explored for CAVS, there is an increasing need for imaging techniques to monitor treatment response. Echocardiogram and computed tomography (CT) detect microcalcifications but cannot detect early disease activity. Positron emission tomography (PET) using F-sodium fluoride tracers offers a new approach to detecting microcalcifications from the earliest stages onwards.
Knowledge of the pathogenic mechanisms underlying CAVS opens opportunities for biomolecular approaches to diagnosis and treatment. This knowledge may lead to options (other than surgery) that have not existed in the past.    
Reference: Peeters, F. E. C. M. et al. Calcific aortic valve stenosis: hard disease in the heart: A biomolecular approach towards diagnosis and treatment. Eur Heart J (2017).