Lipoprotein(a) and calcific aortic valve disease: current evidence and future directions

Abstract

Purpose of review Calcific aortic valve disease (CAVD), the most common cause of aortic stenosis (AS), is characterized by slowly progressive fibrocalcific remodelling of the valve cusps. Once symptomatic, severe AS is associated with poor survival unless surgical or transcatheter valve replacement is performed. Unfortunately, no pharmacological interventions have been demonstrated to alter the natural history of CAVD. Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle, has been implicated in the pathophysiology of CAVD. Recent findings The mechanisms by which Lp(a) results in CAVD are not well understood. However, the oxidized phospholipids carried by Lp(a) are considered a crucial mediator of the disease process. An increasing number of studies demonstrate a causal association between plasma Lp(a) levels and frequency of AS and need for aortic valve replacement, which is independent of inflammation, as measured by plasma C-reactive protein levels. However, not all studies show an association between Lp(a) and increased progression of calcification in individuals with established CAVD. Summary Epidemiologic, genetic, and Mendelian randomization studies have collectively suggested that Lp(a) is a causal risk factor for CAVD. Whether Lp(a)-lowering can prevent initiation or slow progression of CAVD remains to be demonstrated.