Elevated lipoprotein(a) and associated oxidized phospholipids are implicated in approximately one-third of aortic stenosis cases, presenting a potential target for emerging medical therapies.
Does lowering Lp(a) reduce progression of aortic stenosis and the need for aortic valve replacement in patients with calcific aortic valve disease?
Elevated Lp(a) and oxidized phospholipids are potentially causal mediators in calcific aortic valve disease, offering a novel therapeutic target to prevent disease progression and avoid valve replacement.
The prevalence of calcific aortic valve disease is increasing with aging of the population. Current treatment options for advanced or symptomatic aortic stenosis are limited to traditional surgical or percutaneous aortic valve replacement. Medical therapies that impact the progression of calcific aortic valve disease do not currently exist. New pathophysiological insights suggest that the processes leading to calcific aortic valve disease are metabolically active for many years before and during the clinical expression of disease. The identification of genetic and potentially causal mediators of calcific aortic valve disease allows opportunities for therapies that may slow progression to the point where aortic valve replacement can be avoided. Recent studies suggest that approximately one-third of aortic stenosis cases are associated with highly elevated lipoprotein(a) Lp(a) and pathways related to the metabolism of procalcifying oxidized phospholipids. Oxidized phospholipids can be carried by Lp(a) into valve leaflets but can also be formed in situ from cell membranes, lipoproteins, and apoptotic cells. This review will summarize the clinical data implicating the potential causality of Lp(a)/oxidized phospholipids, describe emerging therapeutic agents, and propose clinical trial designs to test the hypothesis that lowering Lp(a) will reduce progression aortic stenosis and the need for aortic valve replacement.
Sotirios Tsimikas (Thu,) conducted a review in Calcific Aortic Valve Stenosis. Lipoprotein(a) lowering therapies was evaluated. Elevated lipoprotein(a) and associated oxidized phospholipids are implicated in approximately one-third of aortic stenosis cases, presenting a potential target for emerging medical therapies.
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