Risk factors for aortic valve disease in bicuspid aortic valve: A family-based study

Troy J. Calloway, Lisa J. Martin, Xue Zhang, Animesh Tandon, D. Woodrow Benson, Robert B. Hinton

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Bicuspid aortic valve (BAV) is the most common cardiovascular malformation and is a risk factor for aortic valve disease (AVD). AVD typically manifests later in life, and the majority of cases have BAV. The purpose of this study was to identify risk factors for AVD in individuals with BAV. Families enriched for BAV were identified in a pediatric population, and echocardiography was performed on all family members. AVD was identified as stenosis and/or insufficiency, and BAV morphology was defined as right-left (RL), right-non (RN) or indeterminate. Heritability (h2) of AVD and BAV morphology was estimated using variance components analysis (SOLAR). To assess AVD risk over time, we used Generalized Estimating Equations methodology (SAS) adjusting for age and gender. A total of 1,128 individuals from 226 families were evaluated. BAV was identified in 281 individuals (25%), and AVD was identified in 167 (59%) individuals with BAV. Previously, we identified a high heritability for BAV (h2=0.89±0.06, P<0.00001), but the heritability of AVD in the present study (0.07±0.17, P=0.33) was low. AVD was significantly associated with BAV morphology (P=0.0027) and age (P=0.0068). Children with RN BAV and adults with RL BAV were more likely to develop AVD. BAV is determined largely by genetic effects, but the phenotypic variability of AVD is primarily determined by nongenetic factors. BAV morphology may have predictive value for the time course of AVD.

Original languageEnglish (US)
Pages (from-to)1015-1020
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Issue number5
StatePublished - May 2011


  • Aortic valve morphology
  • Cardiovascular malformation
  • Heritability

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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