Francesca N Delling1, Jian Rong2, Martin G Larson2, Birgitta Lehman2, Ewa Osypiuk2, Plamen Stantchev2, Susan A Slaugenhaupt2, Emelia J Benjamin2, Robert A Levine2, Ramachandran S Vasan2. 1. From 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. 2. From 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.
Abstract
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.
RCT Entities:
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.
Authors: L H Ling; M Enriquez-Sarano; J B Seward; A J Tajik; H V Schaff; K R Bailey; R L Frye Journal: N Engl J Med Date: 1996-11-07 Impact factor: 91.245
Authors: L A Freed; D Levy; R A Levine; M G Larson; J C Evans; D L Fuller; B Lehman; E J Benjamin Journal: N Engl J Med Date: 1999-07-01 Impact factor: 91.245
Authors: Robert A Levine; Albert A Hagége; Daniel P Judge; Muralidhar Padala; Jacob P Dal-Bianco; Elena Aikawa; Jonathan Beaudoin; Joyce Bischoff; Nabila Bouatia-Naji; Patrick Bruneval; Jonathan T Butcher; Alain Carpentier; Miguel Chaput; Adrian H Chester; Catherine Clusel; Francesca N Delling; Harry C Dietz; Christian Dina; Ronen Durst; Leticia Fernandez-Friera; Mark D Handschumacher; Morten O Jensen; Xavier P Jeunemaitre; Hervé Le Marec; Thierry Le Tourneau; Roger R Markwald; Jean Mérot; Emmanuel Messas; David P Milan; Tui Neri; Russell A Norris; David Peal; Maelle Perrocheau; Vincent Probst; Michael Pucéat; Nadia Rosenthal; Jorge Solis; Jean-Jacques Schott; Ehud Schwammenthal; Susan A Slaugenhaupt; Jae-Kwan Song; Magdi H Yacoub Journal: Nat Rev Cardiol Date: 2015-10-20 Impact factor: 32.419
Authors: Mengyao Yu; Adrien Georges; Nathan R Tucker; Sergiy Kyryachenko; Katelyn Toomer; Jean-Jacques Schott; Francesca N Delling; Leticia Fernandez-Friera; Jorge Solis; Patrick T Ellinor; Robert A Levine; Susan A Slaugenhaupt; Albert A Hagège; Christian Dina; Xavier Jeunemaitre; David J Milan; Russell A Norris; Nabila Bouatia-Naji Journal: Circ Genom Precis Med Date: 2019-05
Authors: Francesca N Delling; Jian Rong; Martin G Larson; Birgitta Lehman; Ewa Osypiuk; Plamen Stantchev; Susan A Slaugenhaupt; Emelia J Benjamin; Robert A Levine; Ramachandran S Vasan Journal: Circulation Date: 2015-10-06 Impact factor: 29.690
Authors: Mir Henglin; Gillian Stein; Pavel V Hushcha; Jasper Snoek; Alexander B Wiltschko; Susan Cheng Journal: Circ Cardiovasc Imaging Date: 2017-10 Impact factor: 7.792
Authors: Thierry Le Tourneau; Jean Mérot; Antoine Rimbert; Solena Le Scouarnec; Vincent Probst; Hervé Le Marec; Robert A Levine; Jean-Jacques Schott Journal: Heart Date: 2018-01-19 Impact factor: 5.994