TY - JOUR

T1 - Association Between Hypertensive Disorders of Pregnancy and Later Risk of Cardiomyopathy

AU - Behrens, Ida

AU - Basit, Saima

AU - Lykke, Jacob Alexander

AU - Ranthe, Mattis Flyvholm

AU - Wohlfahrt, Jan

AU - Bundgaard, Henning

AU - Melbye, Mads

AU - Boyd, Heather A

PY - 2016/3

Y1 - 2016/3

N2 - IMPORTANCE: 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.DESIGN, SETTING, AND PARTICIPANTS: 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.EXPOSURES: A hypertensive disorder of pregnancy (severe or moderate preeclampsia or gestational hypertension) registered in the National Patient Register.MAIN OUTCOMES AND MEASURES: Cardiomyopathy more than 5 months after delivery (outside the peripartum period) up to 34 years 7 months.RESULT: 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 AND RELEVANCE: 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.

AB - IMPORTANCE: 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.DESIGN, SETTING, AND PARTICIPANTS: 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.EXPOSURES: A hypertensive disorder of pregnancy (severe or moderate preeclampsia or gestational hypertension) registered in the National Patient Register.MAIN OUTCOMES AND MEASURES: Cardiomyopathy more than 5 months after delivery (outside the peripartum period) up to 34 years 7 months.RESULT: 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 AND RELEVANCE: 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.

KW - Adult

KW - Cardiomyopathies

KW - Cohort Studies

KW - Confounding Factors (Epidemiology)

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Hypertension, Pregnancy-Induced

KW - Middle Aged

KW - Postpartum Period

KW - Pre-Eclampsia

KW - Pregnancy

KW - Proportional Hazards Models

KW - Registries

KW - Risk

KW - Time Factors

KW - Young Adult

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1001/jama.2016.1869

DO - 10.1001/jama.2016.1869

M3 - Journal article

C2 - 26954411

VL - 315

SP - 1026

EP - 1033

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0098-7484

IS - 10

ER -