Objectives To determine how soon after delivery the risk of post-pregnancy hypertension increases in women with hypertensive disorders of pregnancy and how the risk evolves over time. Design Nationwide register based cohort study. Setting Denmark. Populations 482 972 primiparous women with a first live birth or stillbirth between 1995 and 2012 (cumulative incidence analyses), and 1 025 118 women with at least one live birth or stillbirth between 1978 and 2012 (Cox regression analyses). Main outcome measures 10 year cumulative incidences of post-pregnancy hypertension requiring treatment with prescription drugs, and hazard ratios estimated using Cox regression. Results Of women with a hypertensive disorder of pregnancy in a first pregnancy in their 20s, 14% developed hypertension in the first decade post partum, compared with 4% of women with normotensive first pregnancies in their 20s. The corresponding percentages for women with a first pregnancy in their 40s were 32% and 11%, respectively. In the year after delivery, women with a hypertensive disorder of pregnancy had 12-fold to 25-fold higher rates of hypertension than did women with a normotensive pregnancy. Rates in women with a hypertensive disorder of pregnancy were threefold to 10-fold higher 1-10 years post partum and remained twice as high even 20 or more years later. Conclusions The risk of hypertension associated with hypertensive disorders of pregnancy is high immediately after an affected pregnancy and persists for more than 20 years. Up to one third of women with a hypertensive disorder of pregnancy may develop hypertension within a decade of an affected pregnancy, indicating that cardiovascular disease prevention in these women should include blood pressure monitoring initiated soon after pregnancy.

Linked pathophysiological mechanisms may be involved in some congenital heart defects and preterm preeclampsia. The strong associations across pregnancies support a predominantly maternal origin of effect.

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 PARTICIPANTSNationwide 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, 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,; 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 RELEVANCEWomen 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.

Background Peripartum cardiomyopathy (PPCM) is a serious cardiac disorder occurring late in pregnancy or early in the postpartum period. We examined associations between hypertensive disorders of pregnancy (HDP: preeclampsia and gestational hypertension) and PPCM, accounting for other pregnancy-related risk factors for PPCM. Methods Using nationwide Danish register data, we constructed a cohort of all women with ≥1 live birth or stillbirth in Denmark between 1978 and 2012. Using log-linear binomial regression and generalized estimating equations, we estimated risk ratios (RRs) for PPCM associated with HDP of varying severity. Results In a cohort of 1,088,063 women with 2,078,822 eligible pregnancies, 126 women developed PPCM (39 in connection with an HDP-complicated pregnancy). The risks of PPCM were significantly higher in women with HDP-complicated pregnancies than in women with normotensive pregnancies (severe preeclampsia, RR 21.2, 95% confidence interval [CI] 12.0–37.4; moderate preeclampsia, RR 10.2, 95% CI 6.18–16.9; gestational hypertension, RR 5.16, 95% CI 2.11–12.6). The RRs for moderate preeclampsia and gestational hypertension were not significantly different from one another (p = 0.18); the RR for severe preeclampsia was significantly different from the RR for moderate preeclampsia and gestational hypertension combined (p = 0.02). Conclusions Although 70% of PPCM occurred in women with normotensive pregnancies, HDPs were associated with substantial increases in PPCM risk that depended on HDP severity. The heart’s capacity to adapt to a normal pregnancy may be exceeded in some women already susceptible to cardiac insult, contributing to PPCM. HDPs, severe preeclampsia in particular, probably represent an additional cardiac stressor during pregnancy.

Women with hypertensive disorders of pregnancy (HDP) have higher levels of antiangiogenic growth factors during pregnancy than women with normotensive pregnancies. Since angiogenesis is necessary for solid cancer growth and spread, we hypothesized that women with a history of HDP might have a reduced risk of solid cancers (cancers other than lymphomas, hematologic cancers and nonmelanoma skin cancers) later in life. In a register-based cohort study of 1.08 million women giving birth at least once between 1978 and 2011, we used Cox regression to estimate hazard ratios (HRs) comparing solid cancer rates for women with and without a history of HDP. In this cohort, 68,236 women (6.3%) had 1 pregnancy complicated by HDP and 42,236 women (3.9%) developed solid tumors during follow-up. A history of HDP was not associated with a clinically meaningful reduction in the overall rate of solid cancer (HR 0.96, 95% confidence interval 0.92-1.00), regardless of HDP severity or time since HDP, nor was there a general tendency toward reduced solid cancer rates across organ sites. A history of HDP was only significantly associated with decreased rates of breast and lung cancers and with increased rates of endometrial and urinary tract cancers. Overall, our results do not support the hypothesis that women with a history of HDP have a reduced overall risk of solid cancer due to a persistent post-HDP antiangiogenic state or an innate tendency toward antiangiogenesis. Observed associations with specific cancers may instead be due to other pregnancy-related mechanisms or to residual/unmeasured confounding.Hypertensive disorders of pregnancy (HDP) are a group of disorders that affect up to 10% of pregnancies worldwide; the preeclampsia syndrome alone complicates 2-8% of pregnancies.1,2 While the various disorders classified as HDP share clinical features, their etiology is unclear, and although pathophysiologic pathways may overlap, there is likely etiologic heterogeneity.A balance between proangiogenic factors (e.g., vascular endothelial growth factor [VEGF], placental growth factor [PlGF]) and antiangiogenic factors (e.g., soluble fms-like tyrosine kinase-1 [sFlt1] and soluble endoglin [sEng]) is required to maintain vascular endothelial function. An imbalance toward antiangiogenesis likely contributes to the symptoms of preeclampsia 3 ; antiangiogenic factor levels rise earlier and reach higher levels in preeclamptic pregnancies (particularly in early-onset, severe preeclampsia) than in normal pregnancies. [4][5][6][7][8] However, whether the antiangiogenic imbalance in these women is pregnancyinduced, or women who develop preeclampsia have an innate tendency to antiangiogenesis, is unclear. Angiogenesis is also necessary for the growth and spread of solid cancers 10

(JAMA 2016;315(10):1026–1033) Hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension, are common, occurring in approximately 10% of parturients worldwide. Women with preeclampsia have been shown to be at increased risk for peripartum cardiomyopathy as well as cardiovascular disease later in life. It has not yet been determined if these women are also at greater risk for developing cardiomyopathy beyond the peripartum period. However, recent research has suggested women with preeclampsia may undergo some degree of cardiac remodeling that results in persistent cardiac dysfunction. The aim of this study was to investigate the association between HDP and cardiomyopathy after the peripartum period.

Certain pregnancy losses and atherosclerotic diseases in both heart and brain may have a common aetiologic mechanism. Women in families with atherosclerotic disease may be predisposed to pregnancy loss; conversely, pregnancy losses in first-degree relatives may have implications for atherosclerotic disease risk.

No abstract