Association of Triglyceride-Related Genetic Variants With Mitral Annular Calcification

• Published in: Journal of the American College of Cardiology Vol. 69; no. 24; pp. 2941 - 2948
• Main Authors: Afshar, Mehdi, Luk, Kevin, Do, Ron, Dufresne, Line, Owens, David S., Harris, Tamara B., Peloso, Gina M., Kerr, Kathleen F., Wong, Quenna, Smith, Albert V., Budoff, Mathew J., Rotter, Jerome I., Cupples, L. Adrienne, Rich, Stephen S., Engert, James C., Gudnason, Vilmundur, O’Donnell, Christopher J., Post, Wendy S., Thanassoulis, George
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.06.2017; Elsevier Limited
• Subjects: Age; Aged; Apolipoproteins; Arteriosclerosis; Atherosclerosis; Calcification; Calcification (ectopic); Calcinosis - diagnosis; Calcinosis - genetics; Calcinosis - metabolism; Calcium; Cardiology; Cardiovascular; Cardiovascular disease; Cholesterol; Consortia; Estimates; Ethnicity; Female; Follow-Up Studies; Gene expression; Genetic Predisposition to Disease; Genetic Variation; Genetics; Health risk assessment; Heart; Heart diseases; Hispanic Americans; Humans; Incidence; Lipids; Low density lipoprotein; Male; Medical imaging; Mendelian randomization; Metabolism; Middle Aged; Minority & ethnic groups; Mitral valve; Mitral Valve - diagnostic imaging; Mitral Valve Insufficiency - diagnosis; Mitral Valve Insufficiency - genetics; Mitral Valve Insufficiency - metabolism; Pleiotropy; Polymorphism, Genetic; prevention; Prospective Studies; Regurgitation; Replication; Rheumatic heart disease; Risk Factors; single nucleotide polymorphism; Stenosis; Studies; Tomography, X-Ray Computed; Triglycerides; Triglycerides - blood; Triglycerides - genetics; Womens health; lipids; GWAS; OR; single nucleotide polymorphism; LDL-C; MR; CI; GRS; MV; Mendelian randomization; MAC; HDL-C; CT; SNP; mitral valve; prevention; computed tomography; mitral annular calcium; low-density lipoprotein cholesterol; genetic risk score; odds ratio; genome-wide association study; high-density lipoprotein cholesterol; confidence interval
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2017.04.051

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. The authors sought to evaluate whether a genetic predisposition to elevations in plasma lipids is associated with the presence of MAC. 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. 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. 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. [Display omitted]