title: Familial clustering of mitral valve prolapse in the community.
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.
  
  
  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.affiliation: 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.
authors.forename: Francesca N
authors.initials: FN
authors.lastname: Delling
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Rong
authors.affiliation: 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.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.affiliation: 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.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Lehman
authors.affiliation: 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.
authors.forename: Ewa
authors.initials: E
authors.lastname: Osypiuk
authors.affiliation: 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.
authors.forename: Plamen
authors.initials: P
authors.lastname: Stantchev
authors.affiliation: 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.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Slaugenhaupt
authors.affiliation: 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.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: 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.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Levine
authors.affiliation: 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.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D000328:Adult; D016000:Cluster Analysis; D015331:Cohort Studies; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008945:Mitral Valve Prolapse / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D012111:Residence Characteristics
keywords: echocardiography; epidemiology; genetics; mitral valve prolapse