TY - JOUR
T1 - Association of Triglyceride-Related Genetic Variants With Mitral Annular Calcification
AU - CHARGE Extracoronary Calcium Working Group
AU - Afshar, Mehdi
AU - Luk, Kevin
AU - Do, Ron
AU - Dufresne, Line
AU - Owens, David S.
AU - Harris, Tamara B.
AU - Peloso, Gina M.
AU - Kerr, Kathleen F.
AU - Wong, Quenna
AU - Smith, Albert V.
AU - Budoff, Mathew J.
AU - Rotter, Jerome I.
AU - Cupples, L. Adrienne
AU - Rich, Stephen S.
AU - Engert, James C.
AU - Gudnason, Vilmundur
AU - O'Donnell, Christopher J.
AU - Post, Wendy S.
AU - Thanassoulis, George
N1 - Publisher Copyright:
© 2017 American College of Cardiology Foundation
PY - 2017/6/20
Y1 - 2017/6/20
N2 - Background Mitral annular calcium (MAC), commonly identified by cardiac imaging, is associated with cardiovascular events and predisposes to the development of clinically important mitral valve regurgitation and mitral valve stenosis. However, its biological determinants remain largely unknown. Objectives The authors sought to evaluate whether a genetic predisposition to elevations in plasma lipids is associated with the presence of MAC. Methods The authors used 3 separate Mendelian randomization techniques to evaluate the associations of lipid genetic risk scores (GRS) with MAC in 3 large patient cohorts: the Framingham Health Study, MESA (Multiethnic European Study of Atherosclerosis), and the AGE-RS (Age, Gene/Environment Susceptibility-Reykjavik Study). The authors provided cross-ethnicity replication in the MESA Hispanic-American participants. Results MAC was present in 1,149 participants (20.4%). In pooled analyses across all 3 cohorts, a triglyceride GRS was significantly associated with the presence of MAC (odds ratio [OR] per triglyceride GRS unit: 1.73; 95% confidence interval [CI]: 1.24 to 2.41; p = 0.0013). Neither low- nor high-density lipoprotein cholesterol GRS was significantly associated with MAC. Results were consistent in cross-ethnicity analyses among the MESA Hispanic-Americans cohort (OR per triglyceride GRS unit: 2.04; 95% CI: 1.03 to 4.03; p = 0.04). In joint meta-analysis across all included cohorts, the triglyceride GRS was associated with MAC (OR per triglyceride GRS unit: 1.79; 95% CI: 1.32 to 2.41; p = 0.0001). The results were robust to several sensitivity analyses that limit both known and unknown forms of genetic pleiotropy. Conclusions Genetic predisposition to elevated triglyceride levels was associated with the presence of MAC, a risk factor for clinically significant mitral valve disease, suggesting a causal association. Whether reducing triglyceride levels can lower the incidence of clinically significant mitral valve disease requires further study.
AB - Background Mitral annular calcium (MAC), commonly identified by cardiac imaging, is associated with cardiovascular events and predisposes to the development of clinically important mitral valve regurgitation and mitral valve stenosis. However, its biological determinants remain largely unknown. Objectives The authors sought to evaluate whether a genetic predisposition to elevations in plasma lipids is associated with the presence of MAC. Methods The authors used 3 separate Mendelian randomization techniques to evaluate the associations of lipid genetic risk scores (GRS) with MAC in 3 large patient cohorts: the Framingham Health Study, MESA (Multiethnic European Study of Atherosclerosis), and the AGE-RS (Age, Gene/Environment Susceptibility-Reykjavik Study). The authors provided cross-ethnicity replication in the MESA Hispanic-American participants. Results MAC was present in 1,149 participants (20.4%). In pooled analyses across all 3 cohorts, a triglyceride GRS was significantly associated with the presence of MAC (odds ratio [OR] per triglyceride GRS unit: 1.73; 95% confidence interval [CI]: 1.24 to 2.41; p = 0.0013). Neither low- nor high-density lipoprotein cholesterol GRS was significantly associated with MAC. Results were consistent in cross-ethnicity analyses among the MESA Hispanic-Americans cohort (OR per triglyceride GRS unit: 2.04; 95% CI: 1.03 to 4.03; p = 0.04). In joint meta-analysis across all included cohorts, the triglyceride GRS was associated with MAC (OR per triglyceride GRS unit: 1.79; 95% CI: 1.32 to 2.41; p = 0.0001). The results were robust to several sensitivity analyses that limit both known and unknown forms of genetic pleiotropy. Conclusions Genetic predisposition to elevated triglyceride levels was associated with the presence of MAC, a risk factor for clinically significant mitral valve disease, suggesting a causal association. Whether reducing triglyceride levels can lower the incidence of clinically significant mitral valve disease requires further study.
KW - Mendelian randomization
KW - lipids
KW - mitral valve
KW - prevention
KW - single nucleotide polymorphism
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U2 - 10.1016/j.jacc.2017.04.051
DO - 10.1016/j.jacc.2017.04.051
M3 - Article
C2 - 28619195
AN - SCOPUS:85020625421
SN - 0735-1097
VL - 69
SP - 2941
EP - 2948
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 24
ER -