title: Association Between Hypertensive Disorders of Pregnancy and Later Risk of Cardiomyopathy.
abstract: OBJECTIVE
  Women with hypertensive disorders of pregnancy, preeclampsia in particular, have an increased risk of cardiomyopathy during the peripartum period. Whether hypertensive disorders of pregnancy are also associated with cardiomyopathy later in life is unknown.
  
  
  OBJECTIVE
  To determine whether hypertensive disorders of pregnancy are associated with cardiomyopathy beyond the peripartum period.
  
  
  METHODS
  Nationwide register-based cohort study using Cox regression to compare rates of cardiomyopathy in women with and without a history of hypertensive disorders of pregnancy in a cohort of 1,075,763 women with at least 1 pregnancy ending in live birth or stillbirth in Denmark, 1978-2012, with follow-up through December 31, 2012.
  
  
  METHODS
  A hypertensive disorder of pregnancy (severe or moderate preeclampsia or gestational hypertension) registered in the National Patient Register.
  
  
  METHODS
  Cardiomyopathy more than 5 months after delivery (outside the peripartum period) up to 34 years 7 months.
  
  
  RESULTS
  The women in the primary cohort had 2,067,633 eligible pregnancies during the study period, 76,108 of which were complicated by a hypertensive disorder of pregnancy. During follow-up, 1577 women (mean age, 48.5 years at cardiomyopathy diagnosis; 2.6% with multiple pregnancies) developed cardiomyopathy. Compared with women with normotensive pregnancies (18,211,603 person-years of follow-up; n = 1408 cardiomyopathy events, 7.7/100,000 person-years [95% CI, 7.3-8.2]), women with a history of hypertensive disorders of pregnancy had significantly increased rates of cardiomyopathy (in 173,062 person-years of follow-up among women with severe preeclampsia, n = 27 cardiomyopathy events; 15.6/100,000 person-years [95% CI, 10.7-22.7]; adjusted hazard ratio [HR], 2.20 [95% CI, 1.50-3.23]; in 697,447 person-years of follow-up among women with moderate preeclampsia, n = 102 cardiomyopathy events; 14.6/100,000 person-years [95% CI, 12.0-17.8]; adjusted HR, 1.89 [95% CI, 1.55-2.23]; in 213,197 person-years of follow-up among women with gestational hypertension, n = 40 cardiomyopathy events; 17.3/100,000 person-years [95% CI, 12.7-23.6]; adjusted HR, 2.06 [95% CI, 1.50-2.82]). These increases persisted more than 5 years after the latest pregnancy. Mediation analyses suggested that only about 50% of the association was an indirect association through postpregnancy chronic hypertension. In this cohort, 11% of all cardiomyopathy events occurred in women with a history of hypertensive disorders of pregnancy.
  
  
  CONCLUSIONS
  Women with a history of hypertensive disorders of pregnancy, compared with women without such a history, had a small but statistically significant increased risk of cardiomyopathy more than 5 months after delivery. Further research is necessary to understand whether there is a causal mechanism behind this association.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Behrens
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Saima
authors.initials: S
authors.lastname: Basit
authors.affiliation: Department of Obstetrics, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Jacob Alexander
authors.initials: JA
authors.lastname: Lykke
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Mattis Flyvholm
authors.initials: MF
authors.lastname: Ranthe
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Wohlfahrt
authors.affiliation: Unit for Inherited Cardiac Diseases, The Heart Centre, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Bundgaard
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark4Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark5Department of Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Boyd
mesh_terms: D000328:Adult; D009202:Cardiomyopathies / Q000453:epidemiology* / Q000209:etiology; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000453:epidemiology*; D008875:Middle Aged; D049590:Postpartum Period; D011225:Pre-Eclampsia / Q000453:epidemiology; D011247:Pregnancy; D016016:Proportional Hazards Models; D012042:Registries; D012306:Risk; D013997:Time Factors; D055815:Young Adult