Genetic Associations with Valvular Calcification and Aortic Stenosis

• Published in: The New England journal of medicine Vol. 368; no. 6; pp. 503 - 512
• Main Authors: Thanassoulis, George, Campbell, Catherine Y, Owens, David S, Smith, J. Gustav, Smith, Albert V, Peloso, Gina M, Kerr, Kathleen F, Pechlivanis, Sonali, Budoff, Matthew J, Harris, Tamara B, Malhotra, Rajeev, O'Brien, Kevin D, Kamstrup, Pia R, Nordestgaard, Børge G, Tybjaerg-Hansen, Anne, Allison, Matthew A, Aspelund, Thor, Criqui, Michael H, Heckbert, Susan R, Hwang, Shih-Jen, Liu, Yongmei, Sjogren, Marketa, van der Pals, Jesper, Kälsch, Hagen, Mühleisen, Thomas W, Nöthen, Markus M, Cupples, L. Adrienne, Caslake, Muriel, Di Angelantonio, Emanuele, Danesh, John, Rotter, Jerome I, Sigurdsson, Sigurdur, Wong, Quenna, Erbel, Raimund, Kathiresan, Sekar, Melander, Olle, Gudnason, Vilmundur, O'Donnell, Christopher J, Post, Wendy S
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 07.02.2013
• Subjects: Aged; Aortic Valve - diagnostic imaging; Aortic Valve - pathology; Aortic Valve Stenosis - diagnostic imaging; Aortic Valve Stenosis - ethnology; Aortic Valve Stenosis - genetics; Biological and medical sciences; Calcinosis - genetics; Cardiology and Cardiovascular Disease; Cardiology. Vascular system; Cardiovascular disease; Clinical Medicine; Endocardial and cardiac valvular diseases; Family medical history; Female; General aspects; Genome-Wide Association Study; Heart; Heart Valve Diseases - diagnostic imaging; Heart Valve Diseases - ethnology; Heart Valve Diseases - genetics; Humans; Kardiologi och kardiovaskulära sjukdomar; Klinisk medicin; Linear Models; Lipoprotein(a) - genetics; Male; Medical and Health Sciences; Medical imaging; Medical sciences; Medicin och hälsovetenskap; Mendelian Randomization Analysis; Middle Aged; Mitral Valve - diagnostic imaging; Mitral Valve - pathology; Polymorphism, Single Nucleotide; Tomography, X-Ray Computed; Veins & arteries; Medicine; Aortic stenosis; Association; Cardiac valvular disease; Calcification; Cardiovascular disease; Genetics
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1109034

In a genomewide association study, a SNP in the LPA locus was significantly associated with aortic-valve calcification; this SNP was prospectively associated with incident aortic stenosis. Mendelian randomization suggested a causal role for lipoprotein(a) in aortic-valve calcification. Valvular calcification precedes the development of valvular stenosis and may represent an important early phenotype for valvular heart disease. Although aortic sclerosis is frequently considered to be a benign condition, it is associated with progression to clinical aortic stenosis 1 , 2 and with increased cardiovascular morbidity and mortality. 3 In addition, mitral annular calcification is associated with a risk of cardiovascular disease that is increased by nearly 50%. 4 Currently, there are no treatments that prevent or slow the progression of valve disease. Although genetic factors may influence the development of valvular calcification, which tends to run in families, 5 the role of common . . .