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(Circulation. 2004;110:3143-3148.)
© 2004 American Heart Association, Inc.

Valvular Heart Disease

Evidence for a Heritable Component in Death Resulting From Aortic and Mitral Valve Diseases

Benjamin D. Horne, MStat, MPH; Nicola J. Camp, PhD; Joseph B. Muhlestein, MD; Lisa A. Cannon-Albright, PhD

From the Genetic Epidemiology Division, Department of Medical Informatics (B.D.H., N.J.C., L.A.C.-A.) and Cardiology Division (J.B.M.), University of Utah, and Cardiovascular Department, LDS Hospital (B.D.H., J.B.M.) and Genetic Research (N.J.C., L.A.C.-A.), Intermountain Health Care, Salt Lake City, Utah.

Correspondence to Benjamin D. Horne, Genetic Epidemiology, University of Utah, 391 Chipeta Way, Suite D, Salt Lake City, UT 84108-1266. E-mail benjamin{at}genepi.med.utah.edu

Received April 19, 2004; revision received July 27, 2004; accepted August 12, 2004.

Background— Cardiac valvular diseases contribute to >42 000 deaths yearly in the United States, but the role of genetics in these deaths is unknown. This study evaluated the familiality of death resulting from aortic, mitral, and all valvular diseases using a population-based genealogy linked to death records.

Methods and Results— The Utah Population Database contains >2 million individual records with genealogy data and 250 000 linked death certificates. Nonrheumatic aortic (n=932), mitral (n=1165), and all valvular (n=2504) disease deaths and rheumatic heart disease deaths (n=4713) were studied. Familial relative risks (FRRs) were assessed for first- and second-degree relatives. Familiality was also evaluated with the genealogical index of familiality, which considers all relationships in the Utah Population Database. FRRs were increased only for mitral valve death in both first-degree (FRR, 2.55; P<0.0001) and second-degree (FRR, 1.67; P<0.0001) relatives. Genealogical index of familiality analysis showed significant excess relatedness for all groups (P<0.001). Genealogical index of familiality results (P<0.001) for early age at death cases showed higher mean relatedness, a common characteristic of heritable disorders. Excess familiality extended to distant relatives for mitral (second-degree relatives) and aortic (beyond second-degree relatives) valve death.

Conclusions— Deaths resulting from nonrheumatic mitral and aortic diseases clustered among both close and distant relatives, especially among early age at death cases, suggesting a significant genetic component in death resulting from valvular diseases. Future studies should focus on gene discovery.

Key Words: databases • genealogy and heraldry • genetics • pedigree • valves

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