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Published on: January 20, 2015
Familial clustering of mitral valve prolapse in the community
Francesca N Delling1, Jian Rong2, Martin G Larson2
1From Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (F.N.D., J.R., M.G.L., B.L., E.O., P.S., E.J.B., R.S.V.); Department of Medicine (Cardiovascular Division), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (F.N.D.); Section of Neurology (J.R.), Section of Cardiology (E.J.B., R.S.V.), and Preventive Medicine (E.J.B., R.S.V.) sections in the Department of Medicine, Boston University School of Medicine, Boston, MA; Section of Mathematics and Statistics, Boston University, Boston, MA (M.G.L.); and Center for Human Genetic Research (S.A.S.) and Cardiac Ultrasound Laboratory, Department of Medicine (R.A.L.), Massachusetts General Hospital, Harvard Medical School, Boston. fdelling@bidmc.harvard.edu.
Background:
Knowledge of mitral valve prolapse (MVP) inheritance is based on pedigree observation and M-mode echocardiography. The extent of familial clustering of MVP among unselected individuals in the community using current, more specific echocardiographic criteria is unknown. In addition, the importance of nondiagnostic MVP morphologies (NDMs; first described in large pedigrees) has not been investigated in the general population. We hypothesized that parental MVP and NDMs increase the risk of offspring MVP.
Methods And Results:
Study participants were 3679 Generation 3 individuals with available parental data in the Offspring or the New Offspring Spouse cohorts. MVP and NDMs were distinguished by leaflet displacement >2 versus ≤2 mm beyond the mitral annulus, respectively. We compared MVP prevalence in Generation 3 participants with at least 1 parent with MVP (n=186) with that in individuals without parental MVP (n=3493). Among 3679 participants (53% women; mean age, 40±9 years), 49 (1%) had MVP. Parental MVP was associated with a higher prevalence of MVP in Generation 3 participants (10 of 186, 5.4%) compared with no parental MVP (39 of 3493, 1.1%; adjusted odds ratio, 4.51; 95% confidence interval, 2.13-9.54; P<0.0001). When parental NDMs were examined alone, the prevalence of Generation 3 MVP remained higher (12 of 484, 2.5%) compared with those without parental MVP or NDMs (27 of 3009, 0.9%; adjusted odds ratio, 2.52; 95% confidence interval, 1.25-5.10; P=0.01).
Conclusions:
Parental MVP and NDMs are associated with increased prevalence of offspring MVP, highlighting the genetic substrate of MVP and the potential clinical significance of NDMs in the community.
Insights
Parental mitral valve prolapse (MVP) and nondiagnostic MVP morphologies increase the risk of offspring MVP. This study highlights the genetic basis of MVP and the importance of these less defined conditions.
Area of Science:
- Cardiology
- Genetics
- Echocardiography
Background:
- Mitral valve prolapse (MVP) inheritance is traditionally studied through pedigrees and M-mode echocardiography.
- The familial clustering of MVP using current echocardiographic criteria in the general population remains unclear.
- The significance of nondiagnostic MVP morphologies (NDMs) in the broader community has not been assessed.
Purpose of the Study:
- To investigate the association between parental MVP and NDMs and the prevalence of MVP in their offspring.
- To determine if parental MVP and NDMs are risk factors for MVP in the general population.
Main Methods:
- Analysis of 3679 Generation 3 participants from the Offspring and New Offspring Spouse cohorts with parental data.
- MVP defined as leaflet displacement >2 mm; NDMs as displacement ≤2 mm.
- Comparison of MVP prevalence in offspring with and without parental MVP or NDMs.
Main Results:
- MVP was present in 1% (49 of 3679) of Generation 3 participants.
- Offspring with parental MVP had a significantly higher MVP prevalence (5.4%) compared to those without (1.1%; aOR, 4.51).
- Offspring with parental NDMs also showed a higher MVP prevalence (2.5%) compared to those without (0.9%; aOR, 2.52).
Conclusions:
- Parental MVP is a significant risk factor for MVP in offspring.
- NDMs are also associated with an increased prevalence of MVP in offspring.
- These findings underscore the genetic component of MVP and the clinical relevance of NDMs.
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