Hypertensive Disorders of Pregnancy and Subsequent Risk of Premature Mortality

Abstract

Background: Hypertensive disorders of pregnancy (HDPs) are leading causes of maternal and perinatal morbidity and mortality. However, it is uncertain whether HDPs are associated with long-term risk of premature mortality (before age 70 years).

Objectives: The objective of this study was to evaluate whether HDPs were associated with premature mortality.

Methods: Between 1989 and 2017, the authors followed 88,395 parous female nurses participating in the Nurses' Health Study II. The study focused on gestational hypertension and pre-eclampsia within the term HDPs. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between HDPs and premature mortality were estimated by using Cox proportional hazards models, with adjustment for relevant confounders.

Results: The authors documented that 2,387 women died before age 70 years, including 1,141 cancer deaths and 212 CVD deaths. The occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an HR of 1.31 (95% CI: 1.18 to 1.46) for premature death during follow-up. When specific causes of death were examined, these relations were strongest for CVD-related mortality (HR: 2.26; 95% CI: 1.67 to 3.07). The association between HDPs and all-cause premature death persisted, regardless of the subsequent development of chronic hypertension (HR: 1.20 [95% CI: 1.02 to 1.40] for HDPs only and HR: 2.02 [95% CI: 1.75 to 2.33] for both HDPs and subsequent chronic hypertension).

Conclusions: An occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an increased risk of premature mortality, particularly CVD mortality, even in the absence of chronic hypertension.

Keywords: cardiovascular diseases; hypertensive disorders; mortality; pregnancy; women.

Conflict of interest statement

Funding Support and Author Disclosures This study was supported by grants U01-HL145386, U01-CA176726, R01-HL034594, and R01-HL088521 from the National Institutes of Health. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.. Multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for cause-specific premature mortality (before age 70 y) according to the occurrence of HDPs among 88,395 parous women (NHS-II, 1989–2017).

In the age-adjusted model, age in months at the start of follow-up and calendar year of the current questionnaire cycle was included as a stratified variable. Multivariable model 1 was further adjusted for White race/ethnicity, pre-pregnancy BMI, and time-varying menopausal status, current hormone therapy use, daily aspirin use, and parental history of MI or stroke. Multivariable model 2 was further adjusted for time-varying breastfeeding duration, parity, alcohol intake, smoking status, physical activity, AHEI-2010 dietary score, and current BMI. HDPs= Hypertensive disorders of pregnancy; GHTN=gestational hypertension; PY= person year; CI = Confidence intervals. The associations of GHTN and pre-eclampsia with premature mortality were assessed separately and always against normotensive pregnancies.

Central Illustration.. Hazard ratios (HRs) for the risk of all-cause premature mortality according to the occurrence of HDPs.

In the age-adjusted model, age in months at the start of follow-up and calendar year of the current questionnaire cycle was included as a stratified variable. Multivariable model 1 was further adjusted for White race/ethnicity, pre-pregnancy BMI, and time-varying menopausal status, current hormone therapy use, daily aspirin use, and parental history of MI or stroke. Multivariable model 2 was further adjusted for time-varying breastfeeding duration, parity, alcohol intake, smoking status, physical activity, AHEI-2010 dietary score, and current BMI. HDPs= Hypertensive disorders of pregnancy; GHTN=gestational hypertension; PY= person year; CI = Confidence intervals. The associations of GHTN and pre-eclampsia with premature mortality were assessed separately and always against normotensive pregnancies.