title: Gender-specific differences in major cardiac events and mortality in lamin A/C mutation carriers.
abstract: OBJECTIVE
  Mutations in the lamin A/C gene (LMNA) cause a variety of clinical phenotypes, including dilated cardiomyopathy. LMNA is one of the most prevalent mutated genes in dilated cardiomyopathy, and is associated with a high risk of arrhythmias, sudden cardiac death, and heart failure. There are few data on the impact of age and gender on cardiac disease penetrance and mortality.
  
  
  RESULTS
  In a multicentre cohort of 269 LMNA mutation carriers, we evaluated gender-specific penetrance of cardiac involvement and major cardiac events. All-cause mortality of mutation carriers [standardized mortality ratio (SMR)] was determined. Cardiac disease penetrance was age dependent and almost complete at the age of 70 years. The presence of an LVEF ≤45% was significantly higher in men (P < 0.001). However, there was no difference between genders in the prevalence of atrioventricular block, atrial tachyarrhythmias, and non-sustained ventricular tachycardia. Malignant ventricular arrhythmias (26% vs. 8%) and end-stage heart failure (28% vs. 14%) were more common in men than in women (P < 0.001 and P = 0.006, respectively). All-cause mortality of mutation carriers was significantly increased [SMR 4.0, 95% confidence interval (CI) 2.8-5.2] between the ages of 15 and 75 years. Mortality in men was higher than in women (hazard ratio 2.2, 95% CI 1.2-4.3).
  
  
  CONCLUSIONS
  This large cohort of LMNA mutation carriers demonstrates a high cardiac disease penetrance and a high mortality in mutation carriers. Male mutation carriers have a worse prognosis due to a higher prevalence of malignant ventricular arrhythmias and end-stage heart failure.
authors.affiliation: Department of Cardiology (Heart Failure Research Center), Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ingrid A W
authors.initials: IA
authors.lastname: van Rijsingen
authors.forename: Eline A
authors.initials: EA
authors.lastname: Nannenberg
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
authors.forename: Perry M
authors.initials: PM
authors.lastname: Elliott
authors.forename: Jens
authors.initials: J
authors.lastname: Mogensen
authors.forename: Johanna F
authors.initials: JF
authors.lastname: Hermans-van Ast
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: J Peter
authors.initials: JP
authors.lastname: van Tintelen
authors.forename: Maarten P
authors.initials: MP
authors.lastname: van den Berg
authors.forename: Maurizia
authors.initials: M
authors.lastname: Grasso
authors.forename: Alessandra
authors.initials: A
authors.lastname: Serio
authors.forename: Sharon
authors.initials: S
authors.lastname: Jenkins
authors.forename: Camilla
authors.initials: C
authors.lastname: Rowland
authors.forename: Pascale
authors.initials: P
authors.lastname: Richard
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: Andreas
authors.initials: A
authors.lastname: Perrot
authors.forename: Sabine
authors.initials: S
authors.lastname: Pankuweit
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Philippe
authors.initials: P
authors.lastname: Charron
authors.forename: Imke
authors.initials: I
authors.lastname: Christiaans
authors.forename: Yigal M
authors.initials: YM
authors.lastname: Pinto
mesh_terms: D000328:Adult; D000367:Age Factors; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000401:mortality; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D006333:Heart Failure / Q000235:genetics / Q000401:mortality; D006579:Heterozygote; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D012189:Retrospective Studies; D012737:Sex Factors
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A