Hypertensive Disorders of Pregnancy and Subsequent Risk of Premature Mortality

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Hypertensive disorders of pregnancy (gestational hypertension and preeclampsia) (n=88395). Intervention: Hypertensive disorders of pregnancy (gestational hypertension or preeclampsia) vs. Parous women without hypertensive disorders of pregnancy (normotensive pregnancies). Primary outcome: All-cause premature mortality (death before age 70 years) (HR 1.31, 95% CI 1.18, 1.46).

Q: What does this research mean for the field?

Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are associated with an increased risk of premature mortality before age 70, particularly from cardiovascular disease, even in the absence of subsequent chronic hypertension. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Yixin Wang; Mariel Arvizu; Janet Wilson Rich-Edwards; Liang Wang; BERNARD A. ROSNER; Jennifer J. Stuart; Kathryn M. Rexrode; Jorge E. Chavarro

doi:10.1016/j.jacc.2021.01.018

March 1, 2021Journal of the American College of CardiologyOpen Access

Hypertensive Disorders of Pregnancy and Subsequent Risk of Premature Mortality

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Key result

Hypertensive disorders of pregnancy linked to ~31% higher risk of premature mortality before age 70.

HR 1.31
95% CI 1.18, 1.46
n=88,395

Why the study?

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

Are hypertensive disorders of pregnancy (gestational hypertension or preeclampsia) associated with an increased risk of premature mortality before age 70 in parous women?

Key Points

To evaluate whether hypertensive disorders of pregnancy, specifically gestational hypertension and preeclampsia, are associated with premature mortality before age 70.
Followed 88,395 parous female nurses participating in the Nurses' Health Study II between 1989 and 2017.
Tracked gestational hypertension and preeclampsia across 2,355,049 person-years of follow-up.
Estimated hazard ratios for all-cause and cause-specific premature death using Cox proportional hazards models adjusting for confounders and time-varying lifestyle factors.
Documented 2,387 premature deaths before age 70, with hypertensive disorders of pregnancy associated with an increased risk of all-cause premature mortality (HR=1.31, 95% CI: 1.18 to 1.46).
Observed the strongest association for cardiovascular disease mortality (HR=2.26, 95% CI: 1.67 to 3.07), while cancer mortality was unrelated (HR=0.97, 95% CI: 0.82 to 1.15).
Elevated premature mortality persisted among women with hypertensive disorders of pregnancy alone (HR=1.20, 95% CI: 1.02 to 1.40) and rose higher with subsequent chronic hypertension (HR=2.02, 95% CI: 1.75 to 2.33).

Study Design

Type

Cohort (n=88,395)

Structured PICO

Are hypertensive disorders of pregnancy (gestational hypertension or preeclampsia) associated with an increased risk of premature mortality before age 70 in parous women?

P

Population

88,395 parous female US nurses from the Nurses' Health Study II (mean age at first birth 26.7 years), free of baseline CVD, cancer, or type 2 diabetes, followed for 28 years.

E

Exposure

Occurrence of hypertensive disorders of pregnancy (HDPs), specifically gestational hypertension or preeclampsia (n=12,405, 14.0%)

C

Comparator

Parous women without hypertensive disorders of pregnancy (normotensive pregnancies)

O

Outcome

All-cause premature mortality (defined as death before age 70 years) over 28 years of follow-up (1989-2017)hard clinical

Main Result

Hazard Ratio: 1.31 (95% CI 1.18–1.46)

Limitations

Self-reported diagnosis of HDPs and chronic hypertension could result in misclassification of disease status and biased risk estimates
Residual confounding from unadjusted covariates cannot be completely ruled out
Study population mainly consisted of professional non-Hispanic white women, limiting generalizability to ethnic/racial minority groups
Cause of death was uncertain in 15% of women, which may have resulted in imprecise estimates for disease-specific mortality
Self-reported diagnosis of HDPs and chronic hypertension may result in misclassification of disease status
Limited generalizability to ethnic/racial minority groups as the cohort mainly consisted of professional non-Hispanic white women
Uncertain cause of death in 15% of women may have resulted in imprecise estimates for disease-specific mortality

Key expert perspectives

Captured external expert commentary on this paper, strongest first. Original sources are linked where available.

GS Garima SharmaAssistant professor of medicine (cardiology), Johns Hopkins

“The authors should be applauded on raising a biologic plausibility of HDP's independent association with premature all-cause mortality. Contemporary management of women with HDPs will need better risk assessment tools informed by precision medicine to appropriately identify those women who are at greatest risk of premature CVD and to develop algorithms for early intervention in order to change the trajectory of these”

Johns Hopkins University School of MedicineNews Coverage

JE Jorge E. ChavarroAssociate professor of nutrition and epidemiology, Harvard T.H. Chan School of Public Health

“Our results suggest that HDPs, either GHTN or preeclampsia, was associated with a greater risk of premature mortality, especially CVD-related deaths, even in the absence of chronic hypertension. Our results highlight the need for clinicians to screen for the history of HDPs when evaluating CVD morbidity and mortality risk of their patients.”

Harvard T.H. Chan School of Public Health; Brigham and Women's HospitalNews Coverage

Implication

Gestational hypertension and preeclampsia are independently associated with an elevated risk of premature death before age 70, particularly from cardiovascular disease, even in women who do not subsequently develop chronic hypertension.

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: To evaluate whether HDPs are associated with premature mortality. METHODS: Between 1989 and 2017, we followed 88,395 parous female nurses participating in the Nurses’ Health Study II. We focused on gestational hypertension and preeclampsia within the term HDPs. Hazard ratios (HR) and 95% confidence intervals (CI) for the associations between HDPs and premature mortality were estimated using Cox proportional hazards models, adjusting for relevant confounders. RESULTS: We documented that 2,387 women died before age 70, including 1,141 cancer deaths and 212 CVD deaths. The occurrence of HDPs, either gestational hypertension or preeclampsia, was associated with an HR of 1.31 (95% CI:1.18, 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 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 preeclampsia, was associated with an increased risk of premature mortality, particularly CVD mortality, even in the absence of chronic hypertension.

Discussion

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Cite This Study

Wang et al. (2021) conducted a cohort in Hypertensive disorders of pregnancy (gestational hypertension and preeclampsia) (n=88,395). Hypertensive disorders of pregnancy (gestational hypertension or preeclampsia) vs. Parous women without hypertensive disorders of pregnancy (normotensive pregnancies) was evaluated on All-cause premature mortality (death before age 70 years) (HR 1.31, 95% CI 1.18, 1.46). Hypertensive disorders of pregnancy (gestational hypertension or preeclampsia) were associated with an increased risk of premature mortality before age 70 (HR 1.31, 95% CI 1.18-1.46).

synapsesocial.com/papers/6ae265fb8ae57796c567dd71 https://doi.org/10.1016/j.jacc.2021.01.018

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Hypertensive Disorders of Pregnancy and Subsequent Risk of Premature Mortality

Key Points

Study Design

Structured PICO

Main Result

Limitations

Key expert perspectives

Implication

Abstract

Discussion

Cite This Study

Hypertensive Disorders of Pregnancy and Subsequent Risk of Premature Mortality

Key Points

Study Design

Structured PICO

Main Result

Limitations

Key expert perspectives

Implication

Abstract

Discussion

Cite This Study

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