Abstract
Calcific aortic stenosis (AS) is the most common form of valve disease in the Western world and affects over 2.5 million individuals in North America. Despite the large burden of disease, there are no medical treatments to slow the development of AS, due at least in part to our incomplete understanding of its causes. The Cohorts for Heart and Aging Research in Genetic Epidemiology extra-coronary calcium consortium reported a genome-wide association study demonstrating that genetic variants in LPA are strongly associated with aortic valve (AV) calcium and clinical AS. Using a Mendelian randomization study design, it was demonstrated that the effect of this genetic variant is mediated by plasma lipoprotein (a) [Lp(a)], directly implicating elevations in Lp(a) as a cause of AV calcium and progression to AS. This discovery has sparked intense interest in Lp(a) as a modifiable cause for AV disease. Herein, we will review the mounting epidemiological and genetic findings in support of Lp(a)-mediated valve disease, discuss potential mechanisms underlying this observation, and outline the steps to translate this discovery to a much needed novel preventive and/or therapeutic strategy for AV disease.
Highlights
Calcific aortic stenosis (AS) is the most common form of valve disease in the Western world and affects over 2.5 million individuals in North America
Calcific aortic valve disease (CAVD) encompasses all forms of CAVD, including subclinical forms, such as the presence of aortic valve calcium (AVC), identified by computed
AS, which is defined as a progressive narrowing of the aortic valve (AV), affects over 2.5 million people [3] and leads to severe impairment in cardiac function consisting of heart failure, angina, and syncope when stenosis becomes severe
Summary
Calcific aortic stenosis (AS) is the most common form of valve disease in the Western world and affects over 2.5 million individuals in North America. AV sclerosis, which was long deemed a benign consequence of ageing, is known to confer a 40% increase in the risk of Abbreviations: AS, aortic stenosis; ATX, autotaxin; AV, aortic valve; AVC, aortic valve calcium; CAVD, calcific aortic valve disease; CHARGE, Cohorts for Heart and Aging Research in Genetic Epidemiology; CI, confidence interval; CT, computed tomography; CV, cardiovascular; HR, hazard ratio; Lp(a), lipoprotein (a); MDCS, Malmo Diet Cancer Study; OR, odds ratio; OxPL, oxidized phospholipid; PC, phosphocholine; TLR, toll-like receptor.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
