# Early Mortality, Cardiovascular, and Renal Diseases in Women's Lives Following Hypertensive Disorders of Pregnancy: The Prospective Nationwide Study

Gregory Lailler, Clemence Grave, Amelie Gabet, Pierre Joly, Nolwenn Regnault, Catherine Deneux-Tharaux, Vassilis Tstsaris, Genevieve Plu-Bureau, Sandrine Kretz, Jacques Blacher, et al.

<figure><img src="image_1.png" /></figure>

## To cite this version:

Gregory Lailler, Clemence Grave, Amelie Gabet, Pierre Joly, Nolwenn Regnault, et al. Early Mortality, Cardiovascular, and Renal Diseases in Women's Lives Following Hypertensive Disorders of Pregnancy: The Prospective Nationwide Study CONCEPTION. Journal of the American Heart Association, 2024, 13 (8), pp.e033252. 10.1161/jaha.123.033252. hal-04619977

HAL Id: hal-04619977

https://hal.science/hal-04619977

Submitted on 21 Jun 2024

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# Early Mortality, Cardiovascular, and Renal Diseases in Women's Lives Following Hypertensive Disorders of Pregnancy: The Prospective Nationwide Study

Gregory Lailler, Clemence Grave, Amelie Gabet, Pierre Joly, Nolwenn Regnault, Catherine Deneux-Tharaux, Vassilis Tstsaris, Genevieve Plu-Bureau, Sandrine Kretz, Jacques Blacher, et al.

► To cite this version:

Gregory Lailler, Clemence Grave, Amelie Gabet, Pierre Joly, Nolwenn Regnault, et al. Early Mortality, Cardiovascular, and Renal Diseases in Women's Lives Following Hypertensive Disorders of Pregnancy: The Prospective Nationwide Study CONCEPTION. Journal of the American Heart Association, 2024, 13 (8), pp.e033252. 10.1161/jaha.123.033252. hal-04619977

HAL Id: hal-04619977

https://hal.science/hal-04619977v1

Submitted on 21 Jun 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
<figure><img src="image_3.png" /></figure>

ORIGINAL RESEARCH

Early Mortality, Cardiovascular, and Renal
Diseases in Women's Lives Following
Hypertensive Disorders of Pregnancy:
The Prospective Nationwide Study
CONCEPTION

Grégory Lailler <sup>1, ID</sup>, MD, PhD; Clémence Grave <sup>1, ID</sup>, MD; Amélie Gabet <sup>1, ID</sup>, PhD; Pierre Joly, PhD; Nolwenn Regnault <sup>1, ID</sup>, PhD; Catherine Deneux-Tharaux <sup>1, ID</sup>, MD, PhD; Vassilis Tstsaris <sup>1, ID</sup>, MD, PhD; Geneviève Plu-Bureau <sup>1, ID</sup>, MD, PhD; Sandrine Kretz <sup>1, ID</sup>, MD, PhD; Jacques Blacher <sup>1, ID</sup>, MD, PhD; Valérie Olie <sup>1, ID</sup>, PhD

**BACKGROUND:** We aimed to evaluate the impact of hypertensive disorders of pregnancy occurrence, recurrence, onset time, and severity on mortality and on a wide range of cardiovascular outcomes in France.

**METHODS AND RESULTS:** CONCEPTION (Cohort of Cardiovascular Diseases in Pregnancy) is a French nationwide prospective cohort using data from the National Health Data System. We included all women in CONCEPTION with no history of a cardiovascular event who delivered in France for the first time between 2010 and 2018 (N=2819655). Hypertensive disorders of pregnancy and cardiovascular outcomes during the study follow-up were identified using algorithms combining *International Classification of Diseases, Tenth Revision (ICD-10)* coded diagnoses during hospitalization and purchases of medication between 2010 and 2021. We fitted Cox models with time-varying exposure to assess the associations of hypertensive disorders of pregnancy with mortality and cardiovascular events. Women with gestational hypertension had a 1.25- to 2-fold higher risk of stroke, acute coronary syndrome, peripheral arterial disease, pulmonary embolism, and chronic kidney disease, and a 2- to 4-fold higher risk of rhythm and conduction disorder and heart failure. Women with preeclampsia had a 1.35- to 2-fold higher risk of rhythm or conduction disorder and pulmonary embolism during follow-up; a 2- to 4-fold higher risk of stroke, acute coronary syndrome, and peripheral arterial disease; and a 7- to 9-fold higher risk of heart failure and chronic kidney disease. They were 1.8 times more likely to die and 4.4 times more likely to die of cardiovascular causes.

**CONCLUSIONS:** Hypertensive disorders of pregnancy drastically increase the risk of mortality, cardiovascular, and renal events early after pregnancy. Recurrent, severe, and early-onset preeclampsia further increases this risk.

**Key Words:** cardiovascular diseases ■ cardiovascular risk factors ■ epidemiology ■ gestational hypertension ■ hypertensive disorders of pregnancy ■ preeclampsia

Hypertensive disorders of pregnancy (HDP) are a group of diseases that include chronic hypertension predating pregnancy, gestational hypertension, and preeclampsia.¹ These conditions, which

affect approximately 1 pregnant woman in 10, are a
leading cause of mother and child morbidity, and are
considered major public health issues worldwide.²,³
Although they typically resolve after delivery, many

Correspondence to: Grégory Lailler, MD, PhD, Santé Publique France, 12 rue du Val d'Osne, 94415 Saint-Maurice, France. Email: gregory.lailler@santepubliquefrance.fr

This article was sent to Monik C. Jiménez, SM, ScD, Associate Editor, for review by expert referees, editorial decision, and final disposition.

Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.123.033252

For Sources of Funding and Disclosures, see page 9.

© 2024 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

JAHA is available at: www.ahajournals.org/journal/jaha
<figure><img src="image_2.png" /></figure>

ORIGINAL RESEARCH

Early Mortality, Cardiovascular, and Renal
Diseases in Women's Lives Following
Hypertensive Disorders of Pregnancy:
The Prospective Nationwide Study
CONCEPTION

Grégory Lailler <sup>1, ID</sup>, MD, PhD; Clémence Grave <sup>1, ID</sup>, MD; Amélie Gabet <sup>1, ID</sup>, PhD; Pierre Joly, PhD; Nolwenn Regnault <sup>1, ID</sup>, PhD; Catherine Deneux-Tharaux <sup>1, ID</sup>, MD, PhD; Vassilis Tstsaris <sup>1, ID</sup>, MD, PhD; Geneviève Plu-Bureau <sup>1, ID</sup>, MD, PhD; Sandrine Kretz <sup>1, ID</sup>, MD, PhD; Jacques Blacher <sup>1, ID</sup>, MD, PhD; Valérie Olie <sup>1, ID</sup>, PhD

**BACKGROUND:** We aimed to evaluate the impact of hypertensive disorders of pregnancy occurrence, recurrence, onset time, and severity on mortality and on a wide range of cardiovascular outcomes in France.

**METHODS AND RESULTS:** CONCEPTION (Cohort of Cardiovascular Diseases in Pregnancy) is a French nationwide prospective cohort using data from the National Health Data System. We included all women in CONCEPTION with no history of a cardiovascular event who delivered in France for the first time between 2010 and 2018 (N=2819655). Hypertensive disorders of pregnancy and cardiovascular outcomes during the study follow-up were identified using algorithms combining *International Classification of Diseases, Tenth Revision (ICD-10)* coded diagnoses during hospitalization and purchases of medication between 2010 and 2021. We fitted Cox models with time-varying exposure to assess the associations of hypertensive disorders of pregnancy with mortality and cardiovascular events. Women with gestational hypertension had a 1.25- to 2-fold higher risk of stroke, acute coronary syndrome, peripheral arterial disease, pulmonary embolism, and chronic kidney disease, and a 2- to 4-fold higher risk of rhythm and conduction disorder and heart failure. Women with preeclampsia had a 1.35- to 2-fold higher risk of rhythm or conduction disorder and pulmonary embolism during follow-up; a 2- to 4-fold higher risk of stroke, acute coronary syndrome, and peripheral arterial disease; and a 7- to 9-fold higher risk of heart failure and chronic kidney disease. They were 1.8 times more likely to die and 4.4 times more likely to die of cardiovascular causes.

**CONCLUSIONS:** Hypertensive disorders of pregnancy drastically increase the risk of mortality, cardiovascular, and renal events early after pregnancy. Recurrent, severe, and early-onset preeclampsia further increases this risk.

**Key Words:** cardiovascular diseases ■ cardiovascular risk factors ■ epidemiology ■ gestational hypertension ■ hypertensive disorders of pregnancy ■ preeclampsia

Hypertensive disorders of pregnancy (HDP) are a group of diseases that include chronic hypertension predating pregnancy, gestational hypertension, and preeclampsia.¹ These conditions, which

affect approximately 1 pregnant woman in 10, are a
leading cause of mother and child morbidity, and are
considered major public health issues worldwide.²,³
Although they typically resolve after delivery, many

Correspondence to: Grégory Lailler, MD, PhD, Santé Publique France, 12 rue du Val d'Osne, 94415 Saint-Maurice, France. Email: gregory.lailler@santepubliquefrance.fr

This article was sent to Monik C. Jiménez, SM, ScD, Associate Editor, for review by expert referees, editorial decision, and final disposition.

Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.123.033252

For Sources of Funding and Disclosures, see page 9.

© 2024 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

JAHA is available at: www.ahajournals.org/journal/jaha
# CLINICAL PERSPECTIVE

## What Is New?

* Hypertensive disorders of pregnancy drastically increase the risk of mortality, cardiovascular, and renal events early after pregnancy.

* This risk is further increased when preeclampsia is recurrent, severe, early-onset, or combined with hypertension or with small-for-gestational-age infants.

## What Are the Clinical Implications?

* Health care professionals should inform women with a history of hypertensive disorder of pregnancy of their increased cardiovascular risk.

* These women should visit their physician at least once a year for checks on blood pressure and metabolic factors and to encourage them adopt a healthier lifestyle.

## Nonstandard Abbreviations and Acronyms

**CONCEPTION** Cohort of Cardiovascular Diseases in Pregnancy

**HDP** hypertensive disorders of pregnancy

**SNDS** French National Health Insurance Information System database (Système National des Données de Santé)

studies have reported that women with a history of HDP are more likely to develop chronic hypertension,⁴⁻⁶ cardiovascular disease,⁷⁻¹⁰ kidney disease,¹¹ heart failure,⁹,¹⁰ and to die of cardiovascular causes¹² later in life. In 2011, the growing body of evidence on these risks prompted the American Heart Association to recognize that having a history of HDP constitutes a cardiovascular risk factor.¹³

Many of the findings from the above-mentioned studies were based on large population-based databases, which limit the risk of selection bias and provide sufficient statistical power to identify associations between HDP and rare events.¹⁴⁻²¹ Some of the studies also investigated the association between these outcomes and HDP recurrence,⁹,¹⁶ the severity and onset time of preeclampsia,⁴,¹²,²¹⁻²³ preeclampsia combined with small-for-gestational-age (SGA) infants,¹⁸,²¹ and preeclampsia combined with chronic hypertension.²¹,²⁴

However, the substantial differences in the study populations, investigation periods, and methods used

(study design, type of HDP and outcomes studied, definition and identification of HDP and outcomes, follow-up time, adjustment for confounders) in these studies translate into a high level of heterogeneity in meta-analyses compiling their results.⁸⁻¹² Moreover, the associations between HDP and cardiovascular events are mainly studied over the long term; few studies have looked at the first decade after pregnancy.

To the best of our knowledge, no study to date has made a comprehensive analysis of the association between HDP (type, severity, precocity, recurrence) and either mortality or cardiovascular, cerebrovascular, and renal events.

In this context, the present study aimed to evaluate the impact of HDP occurrence, as well as the impact of recurrent, early onset, and severe gestational hypertension and preeclampsia on both mortality and on a wide range of cardiovascular and renal outcomes in France, using data from the CONCEPTION (Cohort of Cardiovascular Diseases in Pregnancy) nationwide cohort study.

# METHODS

## Data Source

CONCEPTION is a prospective cohort study designed to investigate hypertensive disorder and cardiovascular event epidemiology in women who gave birth in France after 22 weeks of gestation between January 1, 2010 and December 31, 2018.²⁵ It is based on data from the French National Health Insurance Information System database (Système National des Données de Santé [SNDS]), and includes >4.5 million women and 7.1 million childbirths. The study's methodology and characteristics are described elsewhere.³,⁴ The SNDS database contains comprehensive information on all health care expenditures reimbursed by the national health insurance system for the entire French population (≈6600000 people). It comprises 2 information sources: the National Hospital Discharge Database, which records information on public and private hospital stays, including diagnoses, using *International Classification of Diseases, Tenth Revision (ICD-10)* codes, and the Interscheme Consumption Data Mart, which records information on out-of-hospital care (eg, medicines, imaging, outpatient medical care).

In line with the French national regulations and ethics committee, participant consent and institutional review board approval were not required for this study. Santé Publique France, the French public health agency, has full and permanent access to the Système National des Données de Santé (governmental deliberation number 2016-316, October 13, 2016). We cannot share national health data system data, because they are only available on a secure portal. Authorization to access this portal needs registration and clearance.
# CLINICAL PERSPECTIVE

## What Is New?

* Hypertensive disorders of pregnancy drastically increase the risk of mortality, cardiovascular, and renal events early after pregnancy.

* This risk is further increased when preeclampsia is recurrent, severe, early-onset, or combined with hypertension or with small-for-gestational-age infants.

## What Are the Clinical Implications?

* Health care professionals should inform women with a history of hypertensive disorder of pregnancy of their increased cardiovascular risk.

* These women should visit their physician at least once a year for checks on blood pressure and metabolic factors and to encourage them adopt a healthier lifestyle.

## Nonstandard Abbreviations and Acronyms

**CONCEPTION** Cohort of Cardiovascular Diseases in Pregnancy

**HDP** hypertensive disorders of pregnancy

**SNDS** French National Health Insurance Information System database (Système National des Données de Santé)

studies have reported that women with a history of HDP are more likely to develop chronic hypertension,⁴⁻⁶ cardiovascular disease,⁷⁻¹⁰ kidney disease,¹¹ heart failure,⁹,¹⁰ and to die of cardiovascular causes¹² later in life. In 2011, the growing body of evidence on these risks prompted the American Heart Association to recognize that having a history of HDP constitutes a cardiovascular risk factor.¹³

Many of the findings from the above-mentioned studies were based on large population-based databases, which limit the risk of selection bias and provide sufficient statistical power to identify associations between HDP and rare events.¹⁴⁻²¹ Some of the studies also investigated the association between these outcomes and HDP recurrence,⁹,¹⁶ the severity and onset time of preeclampsia,⁴,¹²,²¹⁻²³ preeclampsia combined with small-for-gestational-age (SGA) infants,¹⁸,²¹ and preeclampsia combined with chronic hypertension.²¹,²⁴

However, the substantial differences in the study populations, investigation periods, and methods used

(study design, type of HDP and outcomes studied, definition and identification of HDP and outcomes, follow-up time, adjustment for confounders) in these studies translate into a high level of heterogeneity in meta-analyses compiling their results.⁸⁻¹² Moreover, the associations between HDP and cardiovascular events are mainly studied over the long term; few studies have looked at the first decade after pregnancy.

To the best of our knowledge, no study to date has made a comprehensive analysis of the association between HDP (type, severity, precocity, recurrence) and either mortality or cardiovascular, cerebrovascular, and renal events.

In this context, the present study aimed to evaluate the impact of HDP occurrence, as well as the impact of recurrent, early onset, and severe gestational hypertension and preeclampsia on both mortality and on a wide range of cardiovascular and renal outcomes in France, using data from the CONCEPTION (Cohort of Cardiovascular Diseases in Pregnancy) nationwide cohort study.

# METHODS

## Data Source

CONCEPTION is a prospective cohort study designed to investigate hypertensive disorder and cardiovascular event epidemiology in women who gave birth in France after 22 weeks of gestation between January 1, 2010 and December 31, 2018.²⁵ It is based on data from the French National Health Insurance Information System database (Système National des Données de Santé [SNDS]), and includes >4.5 million women and 7.1 million childbirths. The study's methodology and characteristics are described elsewhere.³,⁴ The SNDS database contains comprehensive information on all health care expenditures reimbursed by the national health insurance system for the entire French population (≈66000000 people). It comprises 2 information sources: the National Hospital Discharge Database, which records information on public and private hospital stays, including diagnoses, using *International Classification of Diseases, Tenth Revision (ICD-10)* codes, and the Interscheme Consumption Data Mart, which records information on out-of-hospital care (eg, medicines, imaging, outpatient medical care).

In line with the French national regulations and ethics committee, participant consent and institutional review board approval were not required for this study. Santé Publique France, the French public health agency, has full and permanent access to the Système National des Données de Santé (governmental deliberation number 2016-316, October 13, 2016). We cannot share national health data system data, because they are only available on a secure portal. Authorization to access this portal needs registration and clearance.
## Study Population

For the present study, we included all women in CONCEPTION who gave birth for the first time in France after 22 weeks of gestation between January 1, 2010 and December 31, 2018. Before 22 weeks of gestation, miscarriages are not systematically documented in medical records in France, hence their exclusion from the present analyses. For women who gave birth by vaginal delivery, the parity was directly available in patients' medical records. Women who had a cesarean section were considered primiparous if no previous childbirth was identified since 2006. We excluded women aged <15 and >49 years, those with a medical history of cardiovascular disease since 2006, and those with an invalid date of pregnancy. Study follow-up spanned from the beginning of the first pregnancy to December 31, 2021 (ie, 3-year minimum follow-up for those who delivered for the first time at the end of 2018).

## Hypertensive Disorders of Pregnancy

For all women included in the final population, we identified all HDP during the first and subsequent pregnancies until December 31, 2021, with algorithms combining diagnoses coded during hospital stays (ICD-10) and reimbursements for specific drugs.

Chronic hypertension predating the first pregnancy was defined as receiving prescribed antihypertensive drugs on at least 3 different dates (2 different dates if at least 1 large package of 90 pills was dispensed) between 1 year preceding the first pregnancy and 20 weeks of gestation. The definition of new-onset chronic hypertension was the same throughout the study follow-up (including interpregnancy periods), but with the dispensing of antihypertensive drugs over a rolling period of 1 year. For each pregnancy, women were also defined as having preexisting chronic hypertension if they were hospitalized with a primary diagnosis of preexisting chronic hypertension (ICD-10 codes: O10, O11) during pregnancy or postpartum. We considered the date of the first dispensing of antihypertensive drugs as the date of diagnosis of chronic hypertension. Women diagnosed with this condition before or during the study were considered to have it for the rest of the follow-up period irrespective of where or not antihypertensive drugs were interrupted.

Gestational hypertension was defined as either receiving at least 1 antihypertensive drug between 20 weeks of gestation and 6 weeks postpartum, or hospitalization with a diagnosis of gestational hypertension (ICD-10 code O13) in the absence of previous chronic hypertension. To avoid potential misclassification, women reimbursed for antihypertensive drugs and hospitalized with preterm labor as a primary diagnosis (ICD-10 codes O47, O60.0–O60.2) were excluded from

the gestational hypertension group, because antihypertensive treatment may have been prescribed for this situation.

Preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelets syndrome were defined as hospitalization, with ICD-10 diagnosis codes O14, O15, and O14.2, respectively. We considered pre-eclampsia to be severe when recorded as such (code O14.1), or when it was complicated by eclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome. For all other situations, it was considered mild. Furthermore, preeclampsia was defined as early onset when it occurred before 34 weeks of gestation, and late onset otherwise. Finally, for singleton pregnancies with a delivery in or after 2013, preeclampsia combined with SGA infant was defined as a birth weight inferior to the 10th percentile for gestational age and sex.²⁶ This year was chosen because data on the fetus' weight and sex pre-2013 were not exhaustive.

## Outcomes

The study outcomes were mortality and the occurrence of the following cardiovascular, cerebrovascular, and renal events during follow-up: stroke (all types, ischemic, hemorrhagic), acute coronary syndrome, peripheral artery disease, heart failure, rhythm or conduction disorder, pulmonary embolism, and chronic kidney disease. These events (ie, except mortality) were identified by the primary diagnoses coded during hospitalization (Table S1). The date of hospitalization was considered to be the date of the event. With regard to mortality, the date of death was directly available in the SNDS. Causes of death coded with the ICD-10 classification were available only until 2017. Accordingly, for the 2010 to 2017 period, we identified cardiovascular deaths if the primary diagnosis of death belonged to Chapter IX of the ICD-10 classification (I00–I99: diseases of the circulatory system).

## Study Population Characteristics and Covariates

At baseline, preexisting diabetes was identified using an algorithm based on the dispensing of 3 antidiabetic drugs on 3 different dates in the year preceding the first pregnancy, or on 2 dates if at least 1 large package (ie, 90 pills) of antidiabetic drugs was dispensed. Obesity and tobacco smoking were identified by ICD-10 codes during hospitalization, and by the dispensing of prescribed nicotine replacement therapy before or during pregnancy for tobacco smoking. People who benefitted from Universal Medical Coverage, a social benefit in France for those whose income is below a certain ceiling, at baseline were defined as living in social deprivation.
## Study Population

For the present study, we included all women in CONCEPTION who gave birth for the first time in France after 22 weeks of gestation between January 1, 2010 and December 31, 2018. Before 22 weeks of gestation, miscarriages are not systematically documented in medical records in France, hence their exclusion from the present analyses. For women who gave birth by vaginal delivery, the parity was directly available in patients' medical records. Women who had a cesarean section were considered primiparous if no previous childbirth was identified since 2006. We excluded women aged <15 and >49 years, those with a medical history of cardiovascular disease since 2006, and those with an invalid date of pregnancy. Study follow-up spanned from the beginning of the first pregnancy to December 31, 2021 (ie, 3-year minimum follow-up for those who delivered for the first time at the end of 2018).

## Hypertensive Disorders of Pregnancy

For all women included in the final population, we identified all HDP during the first and subsequent pregnancies until December 31, 2021, with algorithms combining diagnoses coded during hospital stays (ICD-10) and reimbursements for specific drugs.

Chronic hypertension predating the first pregnancy was defined as receiving prescribed antihypertensive drugs on at least 3 different dates (2 different dates if at least 1 large package of 90 pills was dispensed) between 1 year preceding the first pregnancy and 20 weeks of gestation. The definition of new-onset chronic hypertension was the same throughout the study follow-up (including interpregnancy periods), but with the dispensing of antihypertensive drugs over a rolling period of 1 year. For each pregnancy, women were also defined as having preexisting chronic hypertension if they were hospitalized with a primary diagnosis of preexisting chronic hypertension (ICD-10 codes: O10, O11) during pregnancy or postpartum. We considered the date of the first dispensing of antihypertensive drugs as the date of diagnosis of chronic hypertension. Women diagnosed with this condition before or during the study were considered to have it for the rest of the follow-up period irrespective of where or not antihypertensive drugs were interrupted.

Gestational hypertension was defined as either receiving at least 1 antihypertensive drug between 20 weeks of gestation and 6 weeks postpartum, or hospitalization with a diagnosis of gestational hypertension (ICD-10 code O13) in the absence of previous chronic hypertension. To avoid potential misclassification, women reimbursed for antihypertensive drugs and hospitalized with preterm labor as a primary diagnosis (ICD-10 codes O47, O60.0–O60.2) were excluded from

the gestational hypertension group, because antihypertensive treatment may have been prescribed for this situation.

Preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelets syndrome were defined as hospitalization, with ICD-10 diagnosis codes O14, O15, and O14.2, respectively. We considered pre-eclampsia to be severe when recorded as such (code O14.1), or when it was complicated by eclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome. For all other situations, it was considered mild. Furthermore, preeclampsia was defined as early onset when it occurred before 34 weeks of gestation, and late onset otherwise. Finally, for singleton pregnancies with a delivery in or after 2013, preeclampsia combined with SGA infant was defined as a birth weight inferior to the 10th percentile for gestational age and sex.²⁶ This year was chosen because data on the fetus' weight and sex pre-2013 were not exhaustive.

## Outcomes

The study outcomes were mortality and the occurrence of the following cardiovascular, cerebrovascular, and renal events during follow-up: stroke (all types, ischemic, hemorrhagic), acute coronary syndrome, peripheral artery disease, heart failure, rhythm or conduction disorder, pulmonary embolism, and chronic kidney disease. These events (ie, except mortality) were identified by the primary diagnoses coded during hospitalization (Table S1). The date of hospitalization was considered to be the date of the event. With regard to mortality, the date of death was directly available in the SNDS. Causes of death coded with the ICD-10 classification were available only until 2017. Accordingly, for the 2010 to 2017 period, we identified cardiovascular deaths if the primary diagnosis of death belonged to Chapter IX of the ICD-10 classification (I00–I99: diseases of the circulatory system).

## Study Population Characteristics and Covariates

At baseline, preexisting diabetes was identified using an algorithm based on the dispensing of 3 antidiabetic drugs on 3 different dates in the year preceding the first pregnancy, or on 2 dates if at least 1 large package (ie, 90 pills) of antidiabetic drugs was dispensed. Obesity and tobacco smoking were identified by ICD-10 codes during hospitalization, and by the dispensing of prescribed nicotine replacement therapy before or during pregnancy for tobacco smoking. People who benefitted from Universal Medical Coverage, a social benefit in France for those whose income is below a certain ceiling, at baseline were defined as living in social deprivation.
## Statistical Analysis

We first described the characteristics (number and percentages for categorical variables, mean and standard deviation for continuous variables) of women at baseline, and the rates of HDP and cardiovascular events during follow-up. We then calculated the rates of each event during follow-up for all women combined, and then separately for women with gestational hypertension and those with preeclampsia. The associations between HDP and the different outcomes were assessed by hazard ratios (HRs) calculated using crude and adjusted Cox proportional regression models. In all models, occurrences of HDP were treated as time-varying variables. The follow-up started at the beginning of the first pregnancy and was censored at December 30, 2021 or death. In a first set of models, we considered the following HDP exposures (with relevant modalities): total gestational hypertension, total preeclampsia, gestational hypertension recurrence (no gestational hypertension, gestational hypertension only once, gestational hypertension at least twice), preeclampsia recurrence (no preeclampsia, preeclampsia only once, preeclampsia at least twice). In a second set of models, we focused on the following preeclampsia features: preeclampsia severity (no preeclampsia, mild preeclampsia, severe preeclampsia), early-onset preeclampsia (no preeclampsia, late preeclampsia, early preeclampsia), preeclampsia associated with SGA infant (no preeclampsia, preeclampsia with no SGA infant, preeclampsia with SGA infant; this analysis was restricted singleton pregnancies with a delivery in or after 2013), and preeclampsia combined with chronic hypertension (no preeclampsia, preeclampsia with no chronic hypertension, preeclampsia with chronic hypertension). The modality preeclampsia

with hypertension included both women with chronic hypertension predating pregnancy and women who developed chronic hypertension after preeclampsia occurred.

Associations of each HDP type with each outcome were modeled separately; women could have >1 incident outcome and be exposed to >1 HDP. If a woman had preeclampsia, we did not take into account gestational hypertension in subsequent pregnancies, for we considered that the risk associated with preeclampsia exposure outweighs that associated with gestational hypertension. Maternal age in years was used as the time scale instead of time on study in all models, because this method is better at reducing the risk of bias than subsequently adjusting or stratifying for maternal age.²⁷ The models were adjusted for social deprivation, obesity, tobacco smoking, and history of diabetes. HRs with their 95% CIs are presented in forest plots. The proportional hazard assumption was tested by assessing the correlation between Schoenfeld residuals and time. All statistical analyses were conducted using SAS software. Figures were created using the forest plot package in R.

## RESULTS

Among the 6302810 deliveries in France in 2010 to 2018 and included in the CONCEPTION cohort, we identified 2833376 first-time births (Figure 1). We excluded 99 women with discrepancies between the dates of subsequent pregnancies, 3578 women at extreme ages, and 10044 women with a history of cardiovascular, neurovascular, or renal disease after 2006. The final population included 2819655 women, accounting for 4913570 childbirths between 2010 and 2021.

<figure><img src="image_4.png" /><figcaption>**Figure 1.** Study flowchart.
CONCEPTION indicates Cohort of Cardiovascular Diseases in Pregnancy.</figcaption></figure>
## Statistical Analysis

We first described the characteristics (number and percentages for categorical variables, mean and standard deviation for continuous variables) of women at baseline, and the rates of HDP and cardiovascular events during follow-up. We then calculated the rates of each event during follow-up for all women combined, and then separately for women with gestational hypertension and those with preeclampsia. The associations between HDP and the different outcomes were assessed by hazard ratios (HRs) calculated using crude and adjusted Cox proportional regression models. In all models, occurrences of HDP were treated as time-varying variables. The follow-up started at the beginning of the first pregnancy and was censored at December 30, 2021 or death. In a first set of models, we considered the following HDP exposures (with relevant modalities): total gestational hypertension, total preeclampsia, gestational hypertension recurrence (no gestational hypertension, gestational hypertension only once, gestational hypertension at least twice), preeclampsia recurrence (no preeclampsia, preeclampsia only once, preeclampsia at least twice). In a second set of models, we focused on the following preeclampsia features: preeclampsia severity (no preeclampsia, mild preeclampsia, severe preeclampsia), early-onset preeclampsia (no preeclampsia, late preeclampsia, early preeclampsia), preeclampsia associated with SGA infant (no preeclampsia, preeclampsia with no SGA infant, preeclampsia with SGA infant; this analysis was restricted singleton pregnancies with a delivery in or after 2013), and preeclampsia combined with chronic hypertension (no preeclampsia, preeclampsia with no chronic hypertension, preeclampsia with chronic hypertension). The modality preeclampsia

with hypertension included both women with chronic hypertension predating pregnancy and women who developed chronic hypertension after preeclampsia occurred.

Associations of each HDP type with each outcome were modeled separately; women could have >1 incident outcome and be exposed to >1 HDP. If a woman had preeclampsia, we did not take into account gestational hypertension in subsequent pregnancies, for we considered that the risk associated with preeclampsia exposure outweighs that associated with gestational hypertension. Maternal age in years was used as the time scale instead of time on study in all models, because this method is better at reducing the risk of bias than subsequently adjusting or stratifying for maternal age.²⁷ The models were adjusted for social deprivation, obesity, tobacco smoking, and history of diabetes. HRs with their 95% CIs are presented in forest plots. The proportional hazard assumption was tested by assessing the correlation between Schoenfeld residuals and time. All statistical analyses were conducted using SAS software. Figures were created using the forest plot package in R.

## RESULTS

Among the 6302810 deliveries in France in 2010 to 2018 and included in the CONCEPTION cohort, we identified 2833376 first-time births (Figure 1). We excluded 99 women with discrepancies between the dates of subsequent pregnancies, 3578 women at extreme ages, and 10044 women with a history of cardiovascular, neurovascular, or renal disease after 2006. The final population included 2819655 women, accounting for 4913570 childbirths between 2010 and 2021.

<figure><img src="image_3.png" /><figcaption>**Figure 1.** Study flowchart.
CONCEPTION indicates Cohort of Cardiovascular Diseases in Pregnancy.</figcaption></figure>
**Table 1** presents the characteristics of the study population. At baseline (ie, start of the first pregnancy), the mean age was 28.3 years, 13.7% of women lived in social deprivation, 4.1% had obesity, 0.5% had diabetes, and 8.9% were smokers. The mean follow-up duration was 8.42 years (median, 8.53 years). During follow-up, 6.2% had gestational hypertension at least once, and 3.6% had preeclampsia at least once.

Crude numbers and rates of cardiovascular events across the follow-up according to HDP type are presented in Table 2. During follow-up, 21 708 women (0.77%) experienced at least 1 cardiovascular event, and 3658 died (all causes). Apart from rhythm and conduction disorder, all outcomes were more likely in women who had gestational hypertension at least once. This likelihood was even higher in women who had preeclampsia at least once. Specifically, 0.14% and 0.51% of those who had gestational hypertension

and preeclampsia, respectively, developed chronic kidney disease during follow-up. Similarly, 0.12% and 0.32%, respectively, developed heart failure. Moreover, the mean time-to-event was shorter (1 to 2 years) in women who had preeclampsia (Table S2).

After adjustment for confounders, and treating HDP as time-varying variables, the HRs (95% CIs) for cardiovascular disease in women who had gestational hypertension at least once during follow-up were 1.57 (1.42–1.74) for stroke (all types), 1.58 (1.39–1.78) for ischemic stroke, 1.62 (1.37–1.91) for hemorrhagic stroke, 1.85 (1.59–2.15) for acute coronary syndrome, 1.37 (1.02–1.83) for peripheral artery disease, 2.92 (2.53–3.38) for heart failure, 2.19 (2.04–2.36) for rhythm and conduction disorder, and finally 1.25 (1.12–1.39) for pulmonary embolism (Figure 2; Table S3). This same subgroup was also 1.98 (1.73–2.27) times more likely to develop chronic kidney disease, 1.33 (1.18–1.5) times more likely to die (all causes), and 2.09 (1.35–3.24) times more likely to die of cardiovascular death. HRs, except for chronic kidney disease, were higher in women who had gestational hypertension at least twice than in those who had it only once, but the difference was not statistically significant.

In women who had preeclampsia at least once, the HRs (95% CIs) were 2.67 (2.4–2.96) for stroke (all types), 2.33 (2.04–2.66) for ischemic stroke, 3.48 (2.97–4.07) for hemorrhagic stroke, 2.7 (2.31–3.16) for acute coronary syndrome, 3.3 (2.56–4.26) for peripheral artery disease, 7.75 (6.8–8.82) for heart failure, 1.35 (1.2–1.51) for rhythm and conduction disorder, and 1.92 (1.71–2.15) for pulmonary embolism.

This subgroup was 7.91 (7.11–8.80) times more likely to develop chronic kidney disease during follow-up, 1.78 (1.55–2.04) times more likely to die (all causes), and 4.37 (2.88–6.63) times more likely to die of cardiovascular death. HRs, except for all-cause death, were higher in women who had preeclampsia at least twice than in those who only had it once. The difference was only statistically significant for acute coronary syndrome and chronic kidney disease.

**Figure 3** shows the HRs for each outcome according to the severity and the onset time of preeclampsia, and according to preeclampsia combined with SGA infant and with hypertension. Women who had severe preeclampsia were significantly more likely to develop stroke (all types and hemorrhagic), heart failure, pulmonary embolism, and chronic kidney disease, and more likely to die (all cause) than women who had mild preeclampsia. Women who had early-onset preeclampsia were significantly more likely to develop stroke (all types and ischemic), acute coronary syndrome, peripheral artery disease, heart failure, pulmonary embolism, and chronic kidney disease than women who had late-onset preeclampsia. Women whose preeclampsia was combined with SGA infant were significantly

<table><caption>**Table 1.** Population Characteristics at Baseline and During Follow-Up (N=2819655)</caption><thead><tr><th></th><th>N or mean</th><th>% or SD</th></tr></thead><tbody><tr><td colspan="3"><strong>At baseline</strong></td></tr><tr><td>Age, y</td><td>28.30</td><td>5.36</td></tr><tr><td>Social deprivation</td><td>386661</td><td>13.7%</td></tr><tr><td>Chronic hypertension</td><td>41308</td><td>1.5%</td></tr><tr><td>Obesity</td><td>116450</td><td>4.1%</td></tr><tr><td>Diabetes</td><td>14250</td><td>0.5%</td></tr><tr><td>Smoking</td><td>250490</td><td>8.9%</td></tr><tr><td colspan="3"><strong>During follow-up</strong></td></tr><tr><td>Follow-up duration</td><td>8.42</td><td>2.60</td></tr><tr><td>No. of pregnancies</td><td>1.74</td><td>0.73</td></tr><tr><td>Only 1</td><td>1130537</td><td>40.1%</td></tr><tr><td>2</td><td>1344994</td><td>47.7%</td></tr><tr><td>≥3</td><td>344124</td><td>12.2%</td></tr><tr><td colspan="3"><strong>Hypertensive disorders of pregnancy (at least 1)</strong></td></tr><tr><td>Gestational hypertension</td><td>173460</td><td>6.2%</td></tr><tr><td>Preeclampsia</td><td>100348</td><td>3.6%</td></tr><tr><td>Mild and late preeclampsia</td><td>62006</td><td>2.2%</td></tr><tr><td>Severe or early preeclampsia</td><td>46855</td><td>1.7%</td></tr><tr><td colspan="3"><strong>Cardiovascular event during follow-up</strong></td></tr><tr><td>Stroke</td><td>4598</td><td>0.16%</td></tr><tr><td>Ischemic stroke</td><td>3131</td><td>0.11%</td></tr><tr><td>Hemorrhagic stroke</td><td>1642</td><td>0.06%</td></tr><tr><td>Acute coronary syndrome</td><td>1640</td><td>0.06%</td></tr><tr><td>Heart failure</td><td>1358</td><td>0.05</td></tr><tr><td>Pulmonary embolism</td><td>5168</td><td>0.18%</td></tr><tr><td>Peripheral arterial disease</td><td>544</td><td>0.02%</td></tr><tr><td>Kidney disease</td><td>1917</td><td>0.07%</td></tr><tr><td>Cardiac rhythm and conduction disorder</td><td>7219</td><td>0.26%</td></tr><tr><td>All-cause deaths</td><td>3658</td><td>0.13%</td></tr><tr><td>Cardiovascular deaths (until 2017)</td><td>193</td><td>0.01%</td></tr></tbody></table>
**Table 1** presents the characteristics of the study population. At baseline (ie, start of the first pregnancy), the mean age was 28.3 years, 13.7% of women lived in social deprivation, 4.1% had obesity, 0.5% had diabetes, and 8.9% were smokers. The mean follow-up duration was 8.42 years (median, 8.53 years). During follow-up, 6.2% had gestational hypertension at least once, and 3.6% had preeclampsia at least once.

Crude numbers and rates of cardiovascular events across the follow-up according to HDP type are presented in Table 2. During follow-up, 21 708 women (0.77%) experienced at least 1 cardiovascular event, and 3658 died (all causes). Apart from rhythm and conduction disorder, all outcomes were more likely in women who had gestational hypertension at least once. This likelihood was even higher in women who had preeclampsia at least once. Specifically, 0.14% and 0.51% of those who had gestational hypertension

<table><caption>**Table 1.** Population Characteristics at Baseline and During Follow-Up (N=2819655)</caption><thead><tr><th></th><th>N or mean</th><th>% or SD</th></tr></thead><tbody><tr><td colspan="3"><strong>At baseline</strong></td></tr><tr><td>Age, y</td><td>28.30</td><td>5.36</td></tr><tr><td>Social deprivation</td><td>386661</td><td>13.7%</td></tr><tr><td>Chronic hypertension</td><td>41308</td><td>1.5%</td></tr><tr><td>Obesity</td><td>116450</td><td>4.1%</td></tr><tr><td>Diabetes</td><td>14250</td><td>0.5%</td></tr><tr><td>Smoking</td><td>250490</td><td>8.9%</td></tr><tr><td colspan="3"><strong>During follow-up</strong></td></tr><tr><td>Follow-up duration</td><td>8.42</td><td>2.60</td></tr><tr><td>No. of pregnancies</td><td>1.74</td><td>0.73</td></tr><tr><td>Only 1</td><td>1130537</td><td>40.1%</td></tr><tr><td>2</td><td>1344994</td><td>47.7%</td></tr><tr><td>≥3</td><td>344124</td><td>12.2%</td></tr><tr><td colspan="3"><strong>Hypertensive disorders of pregnancy (at least 1)</strong></td></tr><tr><td>Gestational hypertension</td><td>173460</td><td>6.2%</td></tr><tr><td>Preeclampsia</td><td>100348</td><td>3.6%</td></tr><tr><td>Mild and late preeclampsia</td><td>62006</td><td>2.2%</td></tr><tr><td>Severe or early preeclampsia</td><td>46855</td><td>1.7%</td></tr><tr><td colspan="3"><strong>Cardiovascular event during follow-up</strong></td></tr><tr><td>Stroke</td><td>4598</td><td>0.16%</td></tr><tr><td>Ischemic stroke</td><td>3131</td><td>0.11%</td></tr><tr><td>Hemorrhagic stroke</td><td>1642</td><td>0.06%</td></tr><tr><td>Acute coronary syndrome</td><td>1640</td><td>0.06%</td></tr><tr><td>Heart failure</td><td>1358</td><td>0.05</td></tr><tr><td>Pulmonary embolism</td><td>5168</td><td>0.18%</td></tr><tr><td>Peripheral arterial disease</td><td>544</td><td>0.02%</td></tr><tr><td>Kidney disease</td><td>1917</td><td>0.07%</td></tr><tr><td>Cardiac rhythm and conduction disorder</td><td>7219</td><td>0.26%</td></tr><tr><td>All-cause deaths</td><td>3658</td><td>0.13%</td></tr><tr><td>Cardiovascular deaths (until 2017)</td><td>193</td><td>0.01%</td></tr></tbody></table>

and preeclampsia, respectively, developed chronic kidney disease during follow-up. Similarly, 0.12% and 0.32%, respectively, developed heart failure. Moreover, the mean time-to-event was shorter (1 to 2 years) in women who had preeclampsia (Table S2).

After adjustment for confounders, and treating HDP as time-varying variables, the HRs (95% CIs) for cardiovascular disease in women who had gestational hypertension at least once during follow-up were 1.57 (1.42–1.74) for stroke (all types), 1.58 (1.39–1.78) for ischemic stroke, 1.62 (1.37–1.91) for hemorrhagic stroke, 1.85 (1.59–2.15) for acute coronary syndrome, 1.37 (1.02–1.83) for peripheral artery disease, 2.92 (2.53–3.38) for heart failure, 2.19 (2.04–2.36) for rhythm and conduction disorder, and finally 1.25 (1.12–1.39) for pulmonary embolism (Figure 2; Table S3). This same subgroup was also 1.98 (1.73–2.27) times more likely to develop chronic kidney disease, 1.33 (1.18–1.5) times more likely to die (all causes), and 2.09 (1.35–3.24) times more likely to die of cardiovascular death. HRs, except for chronic kidney disease, were higher in women who had gestational hypertension at least twice than in those who had it only once, but the difference was not statistically significant.

In women who had preeclampsia at least once, the HRs (95% CIs) were 2.67 (2.4–2.96) for stroke (all types), 2.33 (2.04–2.66) for ischemic stroke, 3.48 (2.97–4.07) for hemorrhagic stroke, 2.7 (2.31–3.16) for acute coronary syndrome, 3.3 (2.56–4.26) for peripheral artery disease, 7.75 (6.8–8.82) for heart failure, 1.35 (1.2–1.51) for rhythm and conduction disorder, and 1.92 (1.71–2.15) for pulmonary embolism.

This subgroup was 7.91 (7.11–8.80) times more likely to develop chronic kidney disease during follow-up, 1.78 (1.55–2.04) times more likely to die (all causes), and 4.37 (2.88–6.63) times more likely to die of cardiovascular death. HRs, except for all-cause death, were higher in women who had preeclampsia at least twice than in those who only had it once. The difference was only statistically significant for acute coronary syndrome and chronic kidney disease.

**Figure 3** shows the HRs for each outcome according to the severity and the onset time of preeclampsia, and according to preeclampsia combined with SGA infant and with hypertension. Women who had severe preeclampsia were significantly more likely to develop stroke (all types and hemorrhagic), heart failure, pulmonary embolism, and chronic kidney disease, and more likely to die (all cause) than women who had mild preeclampsia. Women who had early-onset preeclampsia were significantly more likely to develop stroke (all types and ischemic), acute coronary syndrome, peripheral artery disease, heart failure, pulmonary embolism, and chronic kidney disease than women who had late-onset preeclampsia. Women whose preeclampsia was combined with SGA infant were significantly
<table><caption>**Table 2.** Crude Rates and Numbers of Cardiovascular Events During Follow-Up According to the HDP</caption><thead><tr><th rowspan="2">HDP</th><th colspan="2">Total</th><th colspan="2">Gestational hypertension</th><th colspan="2">Preeclampsia</th></tr><tr><th>N</th><th>%</th><th>N</th><th>%</th><th>N</th><th>%</th></tr></thead><tbody><tr><td>Stroke</td><td>4598</td><td>0.16%</td><td>415</td><td>0.24%</td><td>396</td><td>0.39%</td></tr><tr><td>Ischemic stroke</td><td>3131</td><td>0.11%</td><td>281</td><td>0.16%</td><td>237</td><td>0.24%</td></tr><tr><td>Hemorrhagic stroke</td><td>1642</td><td>0.06%</td><td>153</td><td>0.09%</td><td>180</td><td>0.18%</td></tr><tr><td>Acute coronary syndrome</td><td>1640</td><td>0.06%</td><td>196</td><td>0.11%</td><td>186</td><td>0.19%</td></tr><tr><td>Peripheral arterial disease</td><td>544</td><td>0.02%</td><td>49</td><td>0.03%</td><td>73</td><td>0.07%</td></tr><tr><td>Heart failure</td><td>1358</td><td>0.05%</td><td>214</td><td>0.12%</td><td>318</td><td>0.32%</td></tr><tr><td>Pulmonary embolism</td><td>5168</td><td>0.18%</td><td>362</td><td>0.21%</td><td>318</td><td>0.32%</td></tr><tr><td>Chronic kidney disease</td><td>1917</td><td>0.07%</td><td>236</td><td>0.14%</td><td>511</td><td>0.51%</td></tr><tr><td>Rhythm/conduction disorder</td><td>7219</td><td>0.26%</td><td>783</td><td>0.45%</td><td>307</td><td>0.31%</td></tr><tr><td>All-cause death</td><td>3658</td><td>0.13%</td><td>287</td><td>0.17%</td><td>223</td><td>0.22%</td></tr><tr><td>Cardiovascular death (until 2017)</td><td>193</td><td>0.01%</td><td>23</td><td>0.01%</td><td>27</td><td>0.03%</td></tr></tbody></table>

Women could contribute to >1 incident event and be exposed to both gestational hypertension and preeclampsia. Consequently, the numbers of events in each row and column may intersect, and no statistical test was performed. HDP indicates hypertensive disorders of pregnancy.

more likely to develop chronic kidney disease than women whose preeclampsia was not combined with SGA infant. Finally, women whose preeclampsia was combined with chronic hypertension were significantly more likely to have a stroke (all types), acute coronary syndrome, heart failure, and chronic kidney disease than women whose preeclampsia was not combined with chronic hypertension.

## DISCUSSION

In this large population-based study of >2.8 million women and 4.9 million childbirths, gestational

hypertension and preeclampsia were strongly associated with occurrence of cardiovascular, cerebrovascular, and renal events, and with all-cause and cardiovascular mortality early in the women's lives. Women who had preeclampsia at least twice were even more likely to have acute coronary syndrome or chronic kidney disease. Severe preeclampsia, early onset preeclampsia, preeclampsia in combination with SGA infant, and preeclampsia in combination with chronic hypertension all strengthened these associations, especially for chronic kidney disease.

Our findings are consistent with those reported in previous population-based and cohort studies. In their

<figure><img src="image_5.png" /><figcaption>**Figure 2.** Adjusted hazard ratios of cardiovascular events according to gestational hypertension or PE and its recurrence. All models were adjusted for diabetes history, social deprivation, obesity, and tobacco use. Maternal age was used as the time scale. Exposures were treated as time-varying variables. *The follow-up time was censored at December 31, 2017 in models analyzing cardiovascular death, because causes of death were available only for the 2010 to 2017 period. GH indicates gestational hypertension; and PE, preeclampsia.</figcaption></figure>
<table><caption>**Table 2.** Crude Rates and Numbers of Cardiovascular Events During Follow-Up According to the HDP</caption><thead><tr><th rowspan="2">HDP</th><th colspan="2">Total</th><th colspan="2">Gestational hypertension</th><th colspan="2">Preeclampsia</th></tr><tr><th>N</th><th>%</th><th>N</th><th>%</th><th>N</th><th>%</th></tr></thead><tbody><tr><td>Stroke</td><td>4598</td><td>0.16%</td><td>415</td><td>0.24%</td><td>396</td><td>0.39%</td></tr><tr><td>Ischemic stroke</td><td>3131</td><td>0.11%</td><td>281</td><td>0.16%</td><td>237</td><td>0.24%</td></tr><tr><td>Hemorrhagic stroke</td><td>1642</td><td>0.06%</td><td>153</td><td>0.09%</td><td>180</td><td>0.18%</td></tr><tr><td>Acute coronary syndrome</td><td>1640</td><td>0.06%</td><td>196</td><td>0.11%</td><td>186</td><td>0.19%</td></tr><tr><td>Peripheral arterial disease</td><td>544</td><td>0.02%</td><td>49</td><td>0.03%</td><td>73</td><td>0.07%</td></tr><tr><td>Heart failure</td><td>1358</td><td>0.05%</td><td>214</td><td>0.12%</td><td>318</td><td>0.32%</td></tr><tr><td>Pulmonary embolism</td><td>5168</td><td>0.18%</td><td>362</td><td>0.21%</td><td>318</td><td>0.32%</td></tr><tr><td>Chronic kidney disease</td><td>1917</td><td>0.07%</td><td>236</td><td>0.14%</td><td>511</td><td>0.51%</td></tr><tr><td>Rhythm/conduction disorder</td><td>7219</td><td>0.26%</td><td>783</td><td>0.45%</td><td>307</td><td>0.31%</td></tr><tr><td>All-cause death</td><td>3658</td><td>0.13%</td><td>287</td><td>0.17%</td><td>223</td><td>0.22%</td></tr><tr><td>Cardiovascular death (until 2017)</td><td>193</td><td>0.01%</td><td>23</td><td>0.01%</td><td>27</td><td>0.03%</td></tr></tbody></table>

Women could contribute to >1 incident event and be exposed to both gestational hypertension and preeclampsia. Consequently, the numbers of events in each row and column may intersect, and no statistical test was performed. HDP indicates hypertensive disorders of pregnancy.

more likely to develop chronic kidney disease than women whose preeclampsia was not combined with SGA infant. Finally, women whose preeclampsia was combined with chronic hypertension were significantly more likely to have a stroke (all types), acute coronary syndrome, heart failure, and chronic kidney disease than women whose preeclampsia was not combined with chronic hypertension.

## DISCUSSION

In this large population-based study of >2.8 million women and 4.9 million childbirths, gestational

hypertension and preeclampsia were strongly associated with occurrence of cardiovascular, cerebrovascular, and renal events, and with all-cause and cardiovascular mortality early in the women's lives. Women who had preeclampsia at least twice were even more likely to have acute coronary syndrome or chronic kidney disease. Severe preeclampsia, early onset preeclampsia, preeclampsia in combination with SGA infant, and preeclampsia in combination with chronic hypertension all strengthened these associations, especially for chronic kidney disease.

Our findings are consistent with those reported in previous population-based and cohort studies. In their

<figure><img src="image_4.png" /><figcaption>**Figure 2.** Adjusted hazard ratios of cardiovascular events according to gestational hypertension or PE and its recurrence. All models were adjusted for diabetes history, social deprivation, obesity, and tobacco use. Maternal age was used as the time scale. Exposures were treated as time-varying variables. *The follow-up time was censored at December 31, 2017 in models analyzing cardiovascular death, because causes of death were available only for the 2010 to 2017 period. GH indicates gestational hypertension; and PE, preeclampsia.</figcaption></figure>
<figure><img src="image_6.png" /><figcaption>**Figure 3.** Adjusted hazard ratios of cardiovascular events according to the severity and earliness of PE and its association with SGA infant and chronic hypertension.</figcaption></figure>

All models were adjusted for diabetes history, social deprivation, obesity, and tobacco use. Maternal age was used as the time scale. Exposures were treated as time-varying variables. Models explain PE with/without SGA infant. Birth weight was available only for singleton births between 2013 and 2018. The follow-up time was censored at December 31, 2017 in models explaining cardiovascular death, because causes of death were available only for the 2010 to 2017 period. HT indicates hypertension; PE, preeclampsia; and SGA, small for gestational age.

systematic review and meta-analysis, Wu et al found that women with a history of preeclampsia had a 2-fold higher risk of coronary heart disease, stroke, and cardiovascular disease death, and a 4-fold higher risk of heart failure.¹⁰ Lo et al found that women with a history of gestational hypertension were 1.8 times more likely to have cardiovascular diseases, coronary heart disease, and heart failure (but not stroke).⁹ Barrett et al found that the risk of chronic kidney disease was 2.1 times higher in women who had preeclampsia, and 1.5 times higher in women who had gestational hypertension.¹¹

Many studies have focused on the excess risk induced by severe and early-onset preeclampsia,¹²,¹⁶,²²,²⁸ preeclampsia combined with SGA infant,¹⁸,²⁸ preeclampsia combined hypertension,²⁴ and by HDP recurrence¹⁶,²⁹⁻³¹ on a wide variety of outcomes. Nonetheless, these studies are heterogeneous in terms of their populations, designs, HDP studied, and outcomes, making it difficult to compare and compile their results. This is reflected in Pittara et al's systematic review, where 73% of the 90 associations collected for long-term outcomes after preeclampsia had a high or very high degree of heterogeneity.⁸ Our study provides a comprehensive overview of the different impacts of all types of HDP, their recurrence, onset time, severity, combination with SGA infant, and combination with hypertension, on the occurrence of 11 cardiovascular, cerebrovascular, and renal events, including all-cause and cardiovascular death. Many of these associations have never been previously assessed.

The question as to whether HDP have a causal relationship with cardiovascular disease onset or only reveal an underlying higher cardiovascular risk is a controversial one. Many authors consider pregnancy as a stress test for life, unmasking physiological susceptibility to cardiovascular disease,³²,³³ whereas others highlight that cardiac and hemodynamic impairment caused by preeclampsia can persist long after the end of pregnancy.³⁴,³⁵ Interestingly, we found that having gestational hypertension at least twice was not associated with a higher risk of cardiovascular events than once-off gestational hypertension occurrence, whereas women who had preeclampsia at least twice had a significantly higher risk of acute coronary syndrome and chronic kidney disease than women who had it only once. Similarly, severe and early-onset preeclampsia was associated with an even higher risk of cardiovascular events. These results support the hypothesis of a direct and persistent effect of preeclampsia on the cardiovascular system. Recently, another study based on data from the CONCEPTION cohort reported that preeclampsia duration increased the risk of developing hypertension in the first years following childbirth.⁴ This association was only partly explained by the difference of gestational age. Moreover, echocardiographic studies found that hemodynamic alterations are correlated with severe and early-onset preeclampsia.³⁶ Together, these findings suggest that, in women with a history of preeclampsia, the longer and more severe the exposure to antiangiogenic factors, the higher is the long-term cardiovascular risk.
<figure><img src="image_5.png" /><figcaption>**Figure 3.** Adjusted hazard ratios of cardiovascular events according to the severity and earliness of PE and its association with SGA infant and chronic hypertension.</figcaption></figure>

All models were adjusted for diabetes history, social deprivation, obesity, and tobacco use. Maternal age was used as the time scale. Exposures were treated as time-varying variables. Models explain PE with/without SGA infant. Birth weight was available only for singleton births between 2013 and 2018. The follow-up time was censored at December 31, 2017 in models explaining cardiovascular death, because causes of death were available only for the 2010 to 2017 period. HT indicates hypertension; PE, preeclampsia; and SGA, small for gestational age.

systematic review and meta-analysis, Wu et al found that women with a history of preeclampsia had a 2-fold higher risk of coronary heart disease, stroke, and cardiovascular disease death, and a 4-fold higher risk of heart failure.¹⁰ Lo et al found that women with a history of gestational hypertension were 1.8 times more likely to have cardiovascular diseases, coronary heart disease, and heart failure (but not stroke).⁹ Barrett et al found that the risk of chronic kidney disease was 2.1 times higher in women who had preeclampsia, and 1.5 times higher in women who had gestational hypertension.¹¹

Many studies have focused on the excess risk induced by severe and early-onset preeclampsia,¹²,¹⁶,²²,²⁸ preeclampsia combined with SGA infant,¹⁸,²⁸ preeclampsia combined hypertension,²⁴ and by HDP recurrence¹⁶,²⁹⁻³¹ on a wide variety of outcomes. Nonetheless, these studies are heterogeneous in terms of their populations, designs, HDP studied, and outcomes, making it difficult to compare and compile their results. This is reflected in Pittara et al's systematic review, where 73% of the 90 associations collected for long-term outcomes after preeclampsia had a high or very high degree of heterogeneity.⁸ Our study provides a comprehensive overview of the different impacts of all types of HDP, their recurrence, onset time, severity, combination with SGA infant, and combination with hypertension, on the occurrence of 11 cardiovascular, cerebrovascular, and renal events, including all-cause and cardiovascular death. Many of these associations have never been previously assessed.

The question as to whether HDP have a causal relationship with cardiovascular disease onset or only reveal an underlying higher cardiovascular risk is a controversial one. Many authors consider pregnancy as a stress test for life, unmasking physiological susceptibility to cardiovascular disease,³²,³³ whereas others highlight that cardiac and hemodynamic impairment caused by preeclampsia can persist long after the end of pregnancy.³⁴,³⁵ Interestingly, we found that having gestational hypertension at least twice was not associated with a higher risk of cardiovascular events than once-off gestational hypertension occurrence, whereas women who had preeclampsia at least twice had a significantly higher risk of acute coronary syndrome and chronic kidney disease than women who had it only once. Similarly, severe and early-onset preeclampsia was associated with an even higher risk of cardiovascular events. These results support the hypothesis of a direct and persistent effect of preeclampsia on the cardiovascular system. Recently, another study based on data from the CONCEPTION cohort reported that preeclampsia duration increased the risk of developing hypertension in the first years following childbirth.⁴ This association was only partly explained by the difference of gestational age. Moreover, echocardiographic studies found that hemodynamic alterations are correlated with severe and early-onset preeclampsia.³⁶ Together, these findings suggest that, in women with a history of preeclampsia, the longer and more severe the exposure to antiangiogenic factors, the higher is the long-term cardiovascular risk.
In view of the above evidence, the postpartum period should be regarded as a window of opportunity to implement interventions aimed at assessing and reducing cardiovascular risk in women who had an HDP. Most national and international guidelines recommend that these women be provided counseling on this excess risk and on the importance of the medical follow-up throughout their lives.37-39 Specifically, they should visit a physician at least once a year to check their blood pressure and metabolic factors. Recent studies showed that home self-monitoring by mothers could be a promising alternative to improve blood pressure control.40 The International Federation of Gynecology and Obstetrics recently promoted tailored lifestyle modifications in women with a history of HDP, such as a heart-healthy diet (consumption of fruits and vegetables, Dietary Approaches to Stop Hypertension diet), physical activity, and body mass index control.41 Breastfeeding is also effective in reducing future cardiovascular risk.42 Unfortunately, the implementation of these educational measures is still largely insufficient. Qualitative studies and surveys have reported that many women are not given information about their increased cardiovascular risk after an HDP.43,44 Even more worrying is the lack of awareness of physicians themselves about the association between HDP and cardiovascular events reported in other studies.45,46 Moreover, information on a history of HDP is not always transmitted to primary care providers (general practitioners, obstetricians/gynecologists) who offer postpartum follow-up.47 This communication gap translates into a lost opportunity for women and should be tackled.

The present study has several strengths. First, thanks to its prospective population-based design, made possible by the use of France's national medico-administrative database (SNDS), we were able to comprehensively include all hospital deliveries in France over a period of 10 years. Accordingly, the risk of inclusion bias was limited, because out-of-hospital deliveries represent only 0.6% of all deliveries in France.48 Second, thanks to the large number of women included, we had excellent statistical power to be able to estimate, in a holistic manner, the independent associations between HDP types, their recurrence, onset time, and severity on a wide range of cardiovascular outcomes, including estimating the association between rare exposure (eg, preeclampsia recurrence) and rare events (eg, peripheral artery disease). To the best of our knowledge, these associations have never previously been assessed in a single population using only 1 method. Moreover, many of the associations we explored have never been reported in previous studies. Finally, the use of a method with time-varying exposures provided us with a comprehensive overview of the occurrence of these events from the beginning of the first pregnancy to the end of follow-up.

The study also has limitations. First, the SNDS database was initially designed for medico-administrative purposes and therefore lacks clinical data; we identified chronic hypertension and gestational hypertension through the dispensing of antihypertensive drugs and diagnosis codes. Accordingly, we probably missed some cases of untreated gestational hypertension and hypertension not coded during hospital stays, most probably mild forms of these diseases, which might have diluted the risk of the events. Similarly, we were not able to identify cardiovascular events that did not lead to hospitalization. This is particularly true for diseases commonly treated in ambulatory care, such as rhythm disorder or kidney disease. Having said that, insufficient identification of events was likely to be of the same order in HDP-exposed and nonexposed women; consequently, the lack of these data should not skew the associations between HDP and the various events considered. For the same reason, covariates such as obesity and tobacco use were insufficiently identified, and we had no data on ethnicity, alcohol consumption, or weight gain/loss during follow-up. These missing data may have led to residual confounding. Finally, we did not have information on other causes of missing follow-up such as emigration. Nonetheless, we believe that these causes are rare, evenly distributed in the exposed and nonexposed groups, and unlikely to cause a significant bias in the association between HDP and outcomes.

## CONCLUSIONS

This population-based prospective study showed that all HDP were associated with the occurrence of cardiovascular, cerebrovascular, and renal events and with all-cause and cardiovascular mortality in the early years after the first pregnancy. Severe, early-onset, and recurrent preeclampsia were associated with an even higher cardiovascular risk in these women. In light of these results, and with the aim of improving women's health and life expectancy, it would appear crucial for policymakers to improve awareness about the increased risk of cardiovascular and renal events in women with a history of HDP, to encourage them to visit their physician at least once a year for checks on blood pressure and metabolic factors, and to urge them to follow healthier lifestyles.

## ARTICLE INFORMATION

Received December 6, 2023; accepted February 27, 2024.

## Affiliations

Santé Publique France, Saint-Maurice, France (G.L., C.G., A.G., N.R., V.O.); Université Paris Est, Créteil, France (G.L.); Centre Inserm U1219—Bordeaux Population Health, Université de Bordeaux—ISPED, Bordeaux, France (P.J.); Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé,
In view of the above evidence, the postpartum period should be regarded as a window of opportunity to implement interventions aimed at assessing and reducing cardiovascular risk in women who had an HDP. Most national and international guidelines recommend that these women be provided counseling on this excess risk and on the importance of the medical follow-up throughout their lives.37-39 Specifically, they should visit a physician at least once a year to check their blood pressure and metabolic factors. Recent studies showed that home self-monitoring by mothers could be a promising alternative to improve blood pressure control.40 The International Federation of Gynecology and Obstetrics recently promoted tailored lifestyle modifications in women with a history of HDP, such as a heart-healthy diet (consumption of fruits and vegetables, Dietary Approaches to Stop Hypertension diet), physical activity, and body mass index control.41 Breastfeeding is also effective in reducing future cardiovascular risk.42 Unfortunately, the implementation of these educational measures is still largely insufficient. Qualitative studies and surveys have reported that many women are not given information about their increased cardiovascular risk after an HDP.43,44 Even more worrying is the lack of awareness of physicians themselves about the association between HDP and cardiovascular events reported in other studies.45,46 Moreover, information on a history of HDP is not always transmitted to primary care providers (general practitioners, obstetricians/gynecologists) who offer postpartum follow-up.47 This communication gap translates into a lost opportunity for women and should be tackled.

The present study has several strengths. First, thanks to its prospective population-based design, made possible by the use of France's national medico-administrative database (SNDS), we were able to comprehensively include all hospital deliveries in France over a period of 10 years. Accordingly, the risk of inclusion bias was limited, because out-of-hospital deliveries represent only 0.6% of all deliveries in France.48 Second, thanks to the large number of women included, we had excellent statistical power to be able to estimate, in a holistic manner, the independent associations between HDP types, their recurrence, onset time, and severity on a wide range of cardiovascular outcomes, including estimating the association between rare exposure (eg, preeclampsia recurrence) and rare events (eg, peripheral artery disease). To the best of our knowledge, these associations have never previously been assessed in a single population using only 1 method. Moreover, many of the associations we explored have never been reported in previous studies. Finally, the use of a method with time-varying exposures provided us with a comprehensive overview of the occurrence of these events from the beginning of the first pregnancy to the end of follow-up.

The study also has limitations. First, the SNDS database was initially designed for medico-administrative purposes and therefore lacks clinical data; we identified chronic hypertension and gestational hypertension through the dispensing of antihypertensive drugs and diagnosis codes. Accordingly, we probably missed some cases of untreated gestational hypertension and hypertension not coded during hospital stays, most probably mild forms of these diseases, which might have diluted the risk of the events. Similarly, we were not able to identify cardiovascular events that did not lead to hospitalization. This is particularly true for diseases commonly treated in ambulatory care, such as rhythm disorder or kidney disease. Having said that, insufficient identification of events was likely to be of the same order in HDP-exposed and nonexposed women; consequently, the lack of these data should not skew the associations between HDP and the various events considered. For the same reason, covariates such as obesity and tobacco use were insufficiently identified, and we had no data on ethnicity, alcohol consumption, or weight gain/loss during follow-up. These missing data may have led to residual confounding. Finally, we did not have information on other causes of missing follow-up such as emigration. Nonetheless, we believe that these causes are rare, evenly distributed in the exposed and nonexposed groups, and unlikely to cause a significant bias in the association between HDP and outcomes.

## CONCLUSIONS

This population-based prospective study showed that all HDP were associated with the occurrence of cardiovascular, cerebrovascular, and renal events and with all-cause and cardiovascular mortality in the early years after the first pregnancy. Severe, early-onset, and recurrent preeclampsia were associated with an even higher cardiovascular risk in these women. In light of these results, and with the aim of improving women's health and life expectancy, it would appear crucial for policymakers to improve awareness about the increased risk of cardiovascular and renal events in women with a history of HDP, to encourage them to visit their physician at least once a year for checks on blood pressure and metabolic factors, and to urge them to follow healthier lifestyles.

## ARTICLE INFORMATION

Received December 6, 2023; accepted February 27, 2024.

## Affiliations

Santé Publique France, Saint-Maurice, France (G.L., C.G., A.G., N.R., V.O.); Université Paris Est, Créteil, France (G.L.); Centre Inserm U1219—Bordeaux Population Health, Université de Bordeaux—ISPED, Bordeaux, France (P.J.); Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé,
Centre for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), INSERM, Paris, France (C.D.-T., V.T., G.P.-B.); Université Paris Cité, Paris, France (C.D.-T., G.P.-B., J.B.); Maternité Port-Royal, FHU PREMA, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France (V.T.); Unité de Gynécologie Médicale, APHP, Hôpital Port-Royal Cochin, Paris, France (G.P.-B.); and Centre de Diagnostic et de Thérapeutique, Hôtel Dieu, AP-HP, Paris, France (S.K., J.B).

## Sources of Funding

This study was funded by the Société Française d'Hypertension Artérielle, Fondation de Recherche sur l'Hypertension Artérielle, and the Fédération Française de Cardiologie through the call for scientific projects Thematic Grant 2019: Cardiovascular Diseases in Women. The funders had no role in the study design, data collection, data analysis, decision to publish, or drafting of the article.

## Disclosures

S.K. reports, outside the submitted work, nonfinancial support from Lilly France, Novonordisk, Novartis Pharma, Roche Diabetes Care, Lifescan, Abbott France, Sanofi, ViiV Healthcare, Servier, and Becton Dickinson, and personal fees from Icomed, Pascaleo, BT3SI, and M3global Research. J.B. has received, outside the submitted work, compensation as speaker/chairman/consultant/educational activities from Astra-Zeneca, Bayer, Elkendi, Hikma, Leurquin, Omron, Organon, Sanofi Aventis, Vivactis, and Vivoptim. The remaining authors have no disclosures to report.

## Ethical Approval

In accordance with French national regulations and the ethics committee, participant consent was not required for this study. Santé Publique France, the French public health agency, has full and permanent access to the SNDS (governmental deliberation number 2016-316, October 13, 2016).

## Supplemental Material

Tables S1-S3

## REFERENCES

1. Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, Hall DR, Warren CE, Adoyi G, Ishaku S, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. *Hypertension*. 2018;72:43–doi: 10.1161/HYPERTENSIONAHA.117.10803

2. Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. *Best Pract Res Clin Obstet Gynaecol*. 2011;25:391–403. doi: 10.1016/j.bpobgyn.2011.01.006

3. Olie V, Moutengou E, Grave C, Deneux-Tharaux C, Regnault N, Kretz S, Gabet A, Mounier-Vehier C, Tsatsaris V, Plu-Bureau G, et al. Prevalence of hypertensive disorders during pregnancy in France (2010–2018): the nationwide CONCEPTION study. *J Clin Hypertens (Greenwich)*. 2021;23:1344–1353. doi: 10.1111/jch.14254

4. Boucheron P, Lailler G, Moutengou E, Regnault N, Gabet A, Deneux-Tharaux C, Kretz S, Grave C, Mounier-Vehier C, Tsatsaris V, et al. Hypertensive disorders of pregnancy and onset of chronic hypertension in France: the nationwide CONCEPTION study. *Eur Heart J*. 2021;43:3352–3361. doi: 10.1093/eurheartj/ehab686

5. Behrens I, Basit S, Melbye M, Lykke JA, Wohlfahrt J, Bundgaard H, Thilaganathan B, Boyd HA. Risk of post-pregnancy hypertension in women with a history of hypertensive disorders of pregnancy: nationwide cohort study. *BMJ*. 2017;358:j3078. doi: 10.1136/bmj.j3078

6. Black MH, Zhou H, Sacks DA, Dublin S, Lawrence JM, Harrison TN, Reynolds K. Hypertensive disorders first identified in pregnancy increase risk for incident prehypertension and hypertension in the year after delivery. *J Hypertens*. 2016;34:728–735. doi: 10.1097/HJH.0000000000000855

7. Okoth K, Chandan JS, Marshall T, Thangaratinam S, Thomas GN, Nirantharakumar K, Adderley NJ. Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review. *BMJ*. 2020;371:m3502. doi: 10.1136/bmj.m3502

8. Pittara T, Vyrides A, Lamnisos D, Giannakou K. Pre-eclampsia and long-term health outcomes for mother and infant: an umbrella review. *BJOG*. 2021;128:1421–1430. doi: 10.1111/1471-0528.16683

9. Lo CCW, Lo ACQ, Leow SH, Fisher G, Corker B, Batho O, Morris B, Chowaniec M, Vladutiu CJ, Fraser A, et al. Future cardiovascular disease risk for women with gestational hypertension: a systematic review and meta-analysis. *J Am Heart Assoc*. 2020;9:e013991. doi: 10.1161/JAHA.119.013991

10. Wu P, Haththotuwa R, Kwok CS, Babu A, Kotronias RA, Rushton C, Zaman A, Fryer AA, Kadam U, Chew-Graham CA, et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. *Circ Cardiovasc Qual Outcomes*. 2017;10:e003497. doi: 10.1161/CIRCOUTCOMES.116.003497

11. Barrett PM, McCarthy FP, Kublickiene K, Cormican S, Judge C, Evans M, Kublickas M, Perry LJ, Stenvinkel P, Khashan AS. Adverse pregnancy outcomes and long-term maternal kidney disease: a systematic review and meta-analysis. *JAMA Netw Open*. 2020;3:e1920964. doi: 10.1001/jamanetworkopen.2019.20964

12. Grandi SM, Filion KB, Yoon S, Ayele HT, Doyle CM, Hutcheon JA, Smith GN, Gore GC, Ray JG, Nerenberg K, et al. Cardiovascular disease-related morbidity and mortality in women with a history of pregnancy complications. *Circulation*. 2019;139:1069–1079. doi: 10.1161/CIRCULATIONAHA.118.036748

13. Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK, Pina IL, Roger VL, Shaw LJ, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the American Heart Association. *J Am Coll Cardiol*. 2011;57:1404–1423. doi: 10.1016/j.jacc.2011.02.005

14. Honigberg MC, Zekavat SM, Aragam K, Klarin D, Bhatt DL, Scott NS, Peloso GM, Natarajan P. Long-term cardiovascular risk in women with hypertension during pregnancy. *J Am Coll Cardiol*. 2019;74:2743–2754. doi: 10.1016/j.jacc.2019.09.052

15. Leon LJ, McCarthy FP, Direk K, Gonzalez-Izquierdo A, Prieto-Merino D, Casas JP, Chappell L. Preeclampsia and cardiovascular disease in a large UK pregnancy cohort of linked electronic health records: a CALIBER study. *Circulation*. 2019;140:1050–1060. doi: 10.1161/CIRCULATIONAHA.118.038080

16. Venetkoski M, Joensuu J, Gissler M, Ylikorkala O, Mikkola TS, Savolainen-Peltonen H. Pre-eclampsia and cardiovascular risk: a long-term nationwide cohort study on over 120 000 Finnish women. *BMJ Open*. 2022;12:e064736. doi: 10.1136/bmjopen-2022-064736

17. Crump C, Sundquist J, McLaughlin MA, Dolan SM, Govindarajulu U, Sieh W, Sundquist K. Adverse pregnancy outcomes and long term risk of ischemic heart disease in mothers: national cohort and co-sibling study. *BMJ*. 2023;380:e072112. doi: 10.1136/bmj-2022-072112

18. Welters SM, de Boer M, Teunissen PW, Hermes W, Ravelli ACJ, Mol BW, de Groot CJM. Cardiovascular mortality in women in their futures after hypertensive disorders of pregnancy in The Netherlands: a national cohort study. *Lancet Healthy Longev*. 2023;4:e34–e42. doi: 10.1016/S2666-7568(22)00292-6

19. Yeh JS, Cheng HM, Hsu PF, Sung SH, Liu WL, Fang HL, Chuang SY. Synergistic effect of gestational hypertension and postpartum incident hypertension on cardiovascular health: a nationwide population study. *J Am Heart Assoc*. 2014;3:e001008. doi: 10.1161/JAHA.114.001008

20. Oliver-Williams C, Stevens D, Payne RA, Wilkinson IB, Smith GCS, Wood A. Association between hypertensive disorders of pregnancy and later risk of cardiovascular outcomes. *BMC Med*. 2022;20:19. doi: 10.1186/s12916-021-02218-8

21. Yang F, Janszky I, Gissler M, Roos N, Wikstrom AK, Yu Y, Chen H, Bonamy AE, Li J, Laszlo KD. Association of maternal preeclampsia with offspring risks of ischemic heart disease and stroke in Nordic countries. *JAMA Netw Open*. 2022;5:e2242064. doi: 10.1001/jamanetworkopen.2022.42064

22. Kestenbaum B, Seliger SL, Easterling TR, Gillen DL, Critchlow CW, Stehman-Breen CO, Schwartz SM. Cardiovascular and thromboembolic events following hypertensive pregnancy. *Am J Kidney Dis*. 2003;42:982–989. doi: 10.1016/j.ajkd.2003.07.001

23. Wikstrom AK, Haglund B, Olovsson M, Lindeberg SN. The risk of maternal ischaemic heart disease after gestational hypertensive disease. *BJOG*. 2005;112:1486–1491. doi: 10.1111/j.1471-0528.2005.00733.x

24. Hung SK, Lee MS, Lin HY, Chen LC, Chuang CJ, Chew CH, Yu BH, Yang HJ, Hsu FC, Chiou WY. Impact of hypertensive disorders of pregnancy on the risk of stroke stratified by subtypes and follow-up time. *Stroke*. 2022;53:338–344. doi: 10.1161/STROKEAHA.121.034109

25. Tuppin P, de Roquefeuil L, Weill A, Ricordeau P, Merliere Y. French national health insurance information system and the permanent beneficiary sample. *Rev Epidemiol Santé Publique*. 2010;58:286–290. doi: 10.1016/j.respe.2010.04.005
Centre for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), INSERM, Paris, France (C.D.-T., V.T., G.P.-B.); Université Paris Cité, Paris, France (C.D.-T., G.P.-B., J.B.); Maternité Port-Royal, FHU PREMA, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France (V.T.); Unité de Gynécologie Médicale, APHP, Hôpital Port-Royal Cochin, Paris, France (G.P.-B.); and Centre de Diagnostic et de Thérapeutique, Hôtel Dieu, AP-HP, Paris, France (S.K., J.B).

## Sources of Funding

This study was funded by the Société Française d'Hypertension Artérielle, Fondation de Recherche sur l'Hypertension Artérielle, and the Fédération Française de Cardiologie through the call for scientific projects Thematic Grant 2019: Cardiovascular Diseases in Women. The funders had no role in the study design, data collection, data analysis, decision to publish, or drafting of the article.

## Disclosures

S.K. reports, outside the submitted work, nonfinancial support from Lilly France, Novonordisk, Novartis Pharma, Roche Diabetes Care, Lifescan, Abbott France, Sanofi, ViiV Healthcare, Servier, and Becton Dickinson, and personal fees from Icomed, Pascaleo, BT3SI, and M3global Research. J.B. has received, outside the submitted work, compensation as speaker/chairman/consultant/educational activities from Astra-Zeneca, Bayer, ElKendi, Hikma, Leurquin, Omron, Organon, Sanofi Aventis, Vivactis, and Vivoptim. The remaining authors have no disclosures to report.

## Ethical Approval

In accordance with French national regulations and the ethics committee, participant consent was not required for this study. Santé Publique France, the French public health agency, has full and permanent access to the SNDS (governmental deliberation number 2016-316, October 13, 2016).

## Supplemental Material

Tables S1-S3

## REFERENCES

1. Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, Hall DR, Warren CE, Adoyi G, Ishaku S, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. *Hypertension*. 2018;72:24–43. doi: 10.1161/HYPERTENSIONAHA.117.10803

2. Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. *Best Pract Res Clin Obstet Gynaecol*. 2011;25:391–403. doi: 10.1016/j.bpobgyn.2011.01.006

3. Olie V, Moutengou E, Grave C, Deneux-Tharaux C, Regnault N, Kretz S, Gabet A, Mounier-Vehier C, Tsatsaris V, Plu-Bureau G, et al. Prevalence of hypertensive disorders during pregnancy in France (2010–2018): the nationwide CONCEPTION study. *J Clin Hypertens (Greenwich)*. 2021;23:1344–1353. doi: 10.1111/jch.14254

4. Boucheron P, Lailler G, Moutengou E, Regnault N, Gabet A, Deneux-Tharaux C, Kretz S, Grave C, Mounier-Vehier C, Tsatsaris V, et al. Hypertensive disorders of pregnancy and onset of chronic hypertension in France: the nationwide CONCEPTION study. *Eur Heart J*. 2021;43:3352–3361. doi: 10.1093/eurheartj/ehab686

5. Behrens I, Basit S, Melbye M, Lykke JA, Wohlfahrt J, Bundgaard H, Thilaganathan B, Boyd HA. Risk of post-pregnancy hypertension in women with a history of hypertensive disorders of pregnancy: nationwide cohort study. *BMJ*. 2017;358:j3078. doi: 10.1136/bmj.j3078

6. Black MH, Zhou H, Sacks DA, Dublin S, Lawrence JM, Harrison TN, Reynolds K. Hypertensive disorders first identified in pregnancy increase risk for incident prehypertension and hypertension in the year after delivery. *J Hypertens*. 2016;34:728–735. doi: 10.1097/HJH.0000000000000855

7. Okoth K, Chandan JS, Marshall T, Thangaratinam S, Thomas GN, Nirantharakumar K, Adderley NJ. Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review. *BMJ*. 2020;371:m3502. doi: 10.1136/bmj.m3502

8. Pittara T, Vyrides A, Lamnisos D, Giannakou K. Pre-eclampsia and long-term health outcomes for mother and infant: an umbrella review. *BJOG*. 2021;128:1421–1430. doi: 10.1111/1471-0528.16683

9. Lo CCW, Lo ACQ, Leow SH, Fisher G, Corker B, Batho O, Morris B, Chowaniec M, Vladutiu CJ, Fraser A, et al. Future cardiovascular disease risk for women with gestational hypertension: a systematic review and meta-analysis. *J Am Heart Assoc*. 2020;9:e013991. doi: 10.1161/JAHA.119.013991

10. Wu P, Haththotuwa R, Kwok CS, Babu A, Kotronias RA, Rushton C, Zaman A, Fryer AA, Kadam U, Chew-Graham CA, et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. *Circ Cardiovasc Qual Outcomes*. 2017;10:e003497. doi: 10.1161/CIRCOUTCOMES.116.003497

11. Barrett PM, McCarthy FP, Kublickiene K, Cormican S, Judge C, Evans M, Kublickas M, Perry LJ, Stenvinkel P, Khashan AS. Adverse pregnancy outcomes and long-term maternal kidney disease: a systematic review and meta-analysis. *JAMA Netw Open*. 2020;3:e1920964. doi: 10.1001/jamanetworkopen.2019.20964

12. Grandi SM, Filion KB, Yoon S, Ayele HT, Doyle CM, Hutcheon JA, Smith GN, Gore GC, Ray JG, Nerenberg K, et al. Cardiovascular disease-related morbidity and mortality in women with a history of pregnancy complications. *Circulation*. 2019;139:1069–1079. doi: 10.1161/CIRCULATIONAHA.118.036748

13. Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK, Pina IL, Roger VL, Shaw LJ, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the American Heart Association. *J Am Coll Cardiol*. 2011;57:1404–1423. doi: 10.1016/j.jacc.2011.02.005

14. Honigberg MC, Zekavat SM, Aragam K, Klarin D, Bhatt DL, Scott NS, Peloso GM, Natarajan P. Long-term cardiovascular risk in women with hypertension during pregnancy. *J Am Coll Cardiol*. 2019;74:2743–2754. doi: 10.1016/j.jacc.2019.09.052

15. Leon LJ, McCarthy FP, Direk K, Gonzalez-Izquierdo A, Prieto-Merino D, Casas JP, Chappell L. Preeclampsia and cardiovascular disease in a large UK pregnancy cohort of linked electronic health records: a CALIBER study. *Circulation*. 2019;140:1050–1060. doi: 10.1161/CIRCULATIONAHA.118.038080

16. Venetkoski M, Joensuu J, Gissler M, Ylikorkala O, Mikkola TS, Savolainen-Peltonen H. Pre-eclampsia and cardiovascular risk: a long-term nationwide cohort study on over 120 000 Finnish women. *BMJ Open*. 2022;12:e064736. doi: 10.1136/bmjopen-2022-064736

17. Crump C, Sundquist J, McLaughlin MA, Dolan SM, Govindarajulu U, Sieh W, Sundquist K. Adverse pregnancy outcomes and long term risk of ischemic heart disease in mothers: national cohort and co-sibling study. *BMJ*. 2023;380:e072112. doi: 10.1136/bmj-2022-072112

18. Welters SM, de Boer M, Teunissen PW, Hermes W, Ravelli ACJ, Mol BW, de Groot CJM. Cardiovascular mortality in women in their futures after hypertensive disorders of pregnancy in The Netherlands: a national cohort study. *Lancet Healthy Longev*. 2023;4:e34–e42. doi: 10.1016/S2666-7568(22)00292-6

19. Yeh JS, Cheng HM, Hsu PF, Sung SH, Liu WL, Fang HL, Chuang SY. Synergistic effect of gestational hypertension and postpartum incident hypertension on cardiovascular health: a nationwide population study. *J Am Heart Assoc*. 2014;3:e001008. doi: 10.1161/JAHA.114.001008

20. Oliver-Williams C, Stevens D, Payne RA, Wilkinson IB, Smith GCS, Wood A. Association between hypertensive disorders of pregnancy and later risk of cardiovascular outcomes. *BMC Med*. 2022;20:19. doi: 10.1186/s12916-021-02218-8

21. Yang F, Janszky I, Gissler M, Roos N, Wikstrom AK, Yu Y, Chen H, Bonamy AE, Li J, Laszlo KD. Association of maternal preeclampsia with offspring risks of ischemic heart disease and stroke in Nordic countries. *JAMA Netw Open*. 2022;5:e2242064. doi: 10.1001/jamanetworkopen.2022.42064

22. Kestenbaum B, Seliger SL, Easterling TR, Gillen DL, Critchlow CW, Stehman-Breen CO, Schwartz SM. Cardiovascular and thromboembolic events following hypertensive pregnancy. *Am J Kidney Dis*. 2003;42:982–989. doi: 10.1016/j.ajkd.2003.07.001

23. Wikstrom AK, Haglund B, Olovsson M, Lindeberg SN. The risk of maternal ischaemic heart disease after gestational hypertensive disease. *BJOG*. 2005;112:1486–1491. doi: 10.1111/j.1471-0528.2005.00733.x

24. Hung SK, Lee MS, Lin HY, Chen LC, Chuang CJ, Chew CH, Yu BH, Yang HJ, Hsu FC, Chiou WY. Impact of hypertensive disorders of pregnancy on the risk of stroke stratified by subtypes and follow-up time. *Stroke*. 2022;53:338–344. doi: 10.1161/STROKEAHA.121.034109

25. Tuppin P, de Roquefeuil L, Weill A, Ricordeau P, Merliere Y. French national health insurance information system and the permanent beneficiary sample. *Rev Epidemiol Santé Publique*. 2010;58:286–290. doi: 10.1016/j.respe.2010.04.005
26. Ego A, Prunet C, Lebreton E, Blondel B, Kaminski M, Goffinet F, Zeitlin J. Customized and non-customized French intrauterine growth curves. *I—Methodology*. Article in French. *J Gynecol Obstet Biol Reprod (Paris)*. 2016;45:155–164. doi: 10.1016/j.jgyn.2015.08.009

27. Thiebaut AC, Benichou J. Choice of time-scale in Cox's model analysis of epidemiologic cohort data: a simulation study. *Stat Med*. 2004;23:3803–3820. doi: 10.1002/sim.2098

28. Cirillo PM, Cohn BA. Pregnancy complications and cardiovascular disease death: 50-year follow-up of the Child Health and Development Studies pregnancy cohort. *Circulation*. 2015;132:1234–1242. doi: 10.1161/CIRCULATIONAHA.113.003901

29. Brouwers L, van der Meiden-van Roest AJ, Savelkoul C, Vogelvang TE, Lely AT, Franx A, van Rijn BB. Recurrence of pre-eclampsia and the risk of future hypertension and cardiovascular disease: a systematic review and meta-analysis. *BJOG*. 2018;125:1642–1654. doi: 10.1111/1471-0528.15394

30. Auger N, Fraser WD, Schnitzer M, Leduc L, Healy-Profitos J, Paradis G. Recurrent pre-eclampsia and subsequent cardiovascular risk. *Heart*. 2017;103:235–243. doi: 10.1136/heartjnl-2016-309671

31. Honigberg MC, Riise HKR, Daltveit AK, Tell GS, Sulo G, Igland J, Klungsoyr K, Scott NS, Wood MJ, Natarajan P, et al. Heart failure in women with hypertensive disorders of pregnancy: insights from the Cardiovascular Disease in Norway Project. *Hypertension*. 2020;76:1506–1513. doi: 10.1161/HYPERTENSIONAHA.120.15654

32. Williams D. Pregnancy: a stress test for life. *Curr Opin Obstet Gynecol*. 2003;15:465–471. doi: 10.1097/00001703-200312000-00002

33. Facca TA, Mastroianni-Kirsztajn G, Sabino ARP, Passos MT, Dos Santos LF, Fama EAB, Nishida SK, Sass N. Pregnancy as an early stress test for cardiovascular and kidney disease diagnosis. *Pregnancy Hypertens*. 2018;12:169–173. doi: 10.1016/j.preghy.2017.11.008

34. Reddy M, Wright L, Rolnik DL, Li W, Mol BW, La Gerche A, da Silva Costa F, Wallace EM, Palmer K. Evaluation of cardiac function in women with a history of preeclampsia: a systematic review and meta-analysis. *J Am Heart Assoc*. 2019;8:e013545. doi: 10.1161/JAHA.119.013545

35. Dennis AT, Castro J, Carr C, Simmons S, Permezel M, Royse C. Haemodynamics in women with untreated pre-eclampsia. *Anaesthesia*. 2012;67:1105–1118. doi: 10.1111/j.1365-2044.2012.07193.x

36. Castleman JS, Ganapathy R, Taki F, Lip GY, Steeds RP, Kotecha D. Echocardiographic structure and function in hypertensive disorders of pregnancy: a systematic review. *Circ Cardiovasc Imaging*. 2016;9:9. doi: 10.1161/CIRCIMAGING.116.004888

37. Scott G, Gillon TE, Pels A, von Dadelszen P, Magee LA. Guidelines-similarities and dissimilarities: a systematic review of international clinical practice guidelines for pregnancy hypertension. *Am J Obstet Gynecol*. 2022;226:S1222–S1236. doi: 10.1016/j.ajog.2020.08.018

38. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomstrom-Lundqvist C, Cifkova R, De Bonis M, Iung B, Johnson MR, Kintscher U, Kranke P, et al. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. *Eur Heart J*. 2018;39:3165–3241. doi: 10.1093/eurheartj/ehy340

39. Mounier-Vehier C, Amar J, Boivin J-M, Denolle T, Fauvel J-P, Plu-Bureau G, Tsatsaris V, Blacher J. Hypertension and pregnancy. Expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology. Article in French. *Presse Medicale*. 2016;45:682–699. doi: 10.1016/j.lpm.2016.05.012

40. Giorgione V, Jansen G, Kitt J, Ghossein-Doha C, Leeson P, Thilaganathan B. Peripartum and long-term maternal cardiovascular health after preeclampsia. *Hypertension*. 2023;80:231–241. doi: 10.1161/HYPERTENSIONAHA.122.18730

41. Poon LC, Nguyen-Hoang L, Smith GN, Bergman L, O'Brien P, Hod M, Okong P, Kapur A, Maxwell CV, McIntyre HD, et al. Hypertensive disorders of pregnancy and long-term cardiovascular health: FIGO best practice advice. *Int J Gynaecol Obstet*. 2023;160(suppl 1):22–34. doi: 10.1002/ijo.14540

42. Tschiderer L, Seekircher L, Kunutsor SK, Peters SAE, O'Keeffe LM, Willeit P. Breastfeeding is associated with a reduced maternal cardiovascular risk: systematic review and meta-analysis involving data from 8 studies and 1 192 700 parous women. *J Am Heart Assoc*. 2022;11:e022746. doi: 10.1161/JAHA.121.022746

43. Nielsen LM, Hauge MG, Ersbøll AS, Johansen M, Linde JJ, Damm P, Nielsen KK. Women's perceptions of cardiovascular risk after preeclampsia: a qualitative study. *BMC Pregnancy Childbirth*. 2022;22:832. doi: 10.1186/s12884-022-05179-9

44. Korb D, Tsatsaris V, Camilleri C, Deneux-Tharaux C. According to patients who have an history of preeclampsia, the information they receive in the postpartum period needs to be optimized to initiate appropriate follow up. *J Gynecol Obstet Hum Reprod*. 2023;52:102582. doi: 10.1016/j.jogoh.2023.102582

45. Young B, Hacker MR, Rana S. Physicians' knowledge of future vascular disease in women with preeclampsia. *Hypertens Pregnancy*. 2012;31:50–58. doi: 10.3109/10641955.2010.544955

46. Gogineni VSM, Manfrini D, Aroda SH, Zhang Y, Nelson DS, Egerman R, Park K. Variations in awareness of association between adverse pregnancy outcomes and cardiovascular risk by specialty. *Cardiol Ther*. 2021;10:577–592. doi: 10.1007/s40119-021-00220-y

47. Bick D, Silverio SA, Bye A, Chang YS. Postnatal care following hypertensive disorders of pregnancy: a qualitative study of views and experiences of primary and secondary care clinicians. *BMJ Open*. 2020;10:e034382. doi: 10.1136/bmjopen-2019-034382

48. Bellamy V. Les Naissances en 2016. Insee Première. 2017. Accessed November 15, 2023. https://www.insee.fr/fr/statistiques/3047024?sommaire=2898646
26. Ego A, Prunet C, Lebreton E, Blondel B, Kaminski M, Goffinet F, Zeitlin J. Customized and non-customized French intrauterine growth curves. *I—Methodology*. Article in French. *J Gynecol Obstet Biol Reprod (Paris)*. 2016;45:155–164. doi: 10.1016/j.jgyn.2015.08.009

27. Thiebaut AC, Benichou J. Choice of time-scale in Cox's model analysis of epidemiologic cohort data: a simulation study. *Stat Med*. 2004;23:3803–3820. doi: 10.1002/sim.2098

28. Cirillo PM, Cohn BA. Pregnancy complications and cardiovascular disease death: 50-year follow-up of the Child Health and Development Studies pregnancy cohort. *Circulation*. 2015;132:1234–1242. doi: 10.1161/CIRCULATIONAHA.113.003901

29. Brouwers L, van der Meiden-van Roest AJ, Savelkoul C, Vogelvang TE, Lely AT, Franx A, van Rijn BB. Recurrence of pre-eclampsia and the risk of future hypertension and cardiovascular disease: a systematic review and meta-analysis. *BJOG*. 2018;125:1642–1654. doi: 10.1111/1471-0528.15394

30. Auger N, Fraser WD, Schnitzer M, Leduc L, Healy-Profitos J, Paradis G. Recurrent pre-eclampsia and subsequent cardiovascular risk. *Heart*. 2017;103:235–243. doi: 10.1136/heartjnl-2016-309671

31. Honigberg MC, Riise HKR, Daltveit AK, Tell GS, Sulo G, Igland J, Klungsoyr K, Scott NS, Wood MJ, Natarajan P, et al. Heart failure in women with hypertensive disorders of pregnancy: insights from the Cardiovascular Disease in Norway Project. *Hypertension*. 2020;76:1506–1513. doi: 10.1161/HYPERTENSIONAHA.120.15654

32. Williams D. Pregnancy: a stress test for life. *Curr Opin Obstet Gynecol*. 2003;15:465–471. doi: 10.1097/00001703-200312000-00002

33. Facca TA, Mastroianni-Kirsztajn G, Sabino ARP, Passos MT, Dos Santos LF, Fama EAB, Nishida SK, Sass N. Pregnancy as an early stress test for cardiovascular and kidney disease diagnosis. *Pregnancy Hypertens*. 2018;12:169–173. doi: 10.1016/j.preghy.2017.11.008

34. Reddy M, Wright L, Rolnik DL, Li W, Mol BW, La Gerche A, da Silva Costa F, Wallace EM, Palmer K. Evaluation of cardiac function in women with a history of preeclampsia: a systematic review and meta-analysis. *J Am Heart Assoc*. 2019;8:e013545. doi: 10.1161/JAHA.119.013545

35. Dennis AT, Castro J, Carr C, Simmons S, Permezel M, Royse C. Haemodynamics in women with untreated pre-eclampsia. *Anaesthesia*. 2012;67:1105–1118. doi: 10.1111/j.1365-2044.2012.07193.x

36. Castleman JS, Ganapathy R, Taki F, Lip GY, Steeds RP, Kotecha D. Echocardiographic structure and function in hypertensive disorders of pregnancy: a systematic review. *Circ Cardiovasc Imaging*. 2016;9:9. doi: 10.1161/CIRCIMAGING.116.004888

37. Scott G, Gillon TE, Pels A, von Dadelszen P, Magee LA. Guidelines-similarities and dissimilarities: a systematic review of international clinical practice guidelines for pregnancy hypertension. *Am J Obstet Gynecol*. 2022;226:S1222–S1236. doi: 10.1016/j.ajog.2020.08.018

38. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomstrom-Lundqvist C, Cifkova R, De Bonis M, Iung B, Johnson MR, Kintscher U, Kranke P, et al. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. *Eur Heart J*. 2018;39:3165–3241. doi: 10.1093/eurheartj/ehy340

39. Mounier-Vehier C, Amar J, Boivin J-M, Denolle T, Fauvel J-P, Plu-Bureau G, Tsatsaris V, Blacher J. Hypertension and pregnancy. Expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology. Article in French. *Presse Medicale*. 2016;45:682–699. doi: 10.1016/j.lpm.2016.05.012

40. Giorgione V, Jansen G, Kitt J, Ghossein-Doha C, Leeson P, Thilaganathan B. Peripartum and long-term maternal cardiovascular health after preeclampsia. *Hypertension*. 2023;80:231–241. doi: 10.1161/HYPERTENSIONAHA.122.18730

41. Poon LC, Nguyen-Hoang L, Smith GN, Bergman L, O'Brien P, Hod M, Okong P, Kapur A, Maxwell CV, McIntyre HD, et al. Hypertensive disorders of pregnancy and long-term cardiovascular health: FIGO best practice advice. *Int J Gynaecol Obstet*. 2023;160(suppl 1):22–34. doi: 10.1002/ijo.14540

42. Tschiderer L, Seekircher L, Kunutsor SK, Peters SAE, O'Keeffe LM, Willeit P. Breastfeeding is associated with a reduced maternal cardiovascular risk: systematic review and meta-analysis involving data from 8 studies and 1 192 700 parous women. *J Am Heart Assoc*. 2022;11:e022746. doi: 10.1161/JAHA.121.022746

43. Nielsen LM, Hauge MG, Ersbøll AS, Johansen M, Linde JJ, Damm P, Nielsen KK. Women's perceptions of cardiovascular risk after preeclampsia: a qualitative study. *BMC Pregnancy Childbirth*. 2022;22:832. doi: 10.1186/s12884-022-05179-9

44. Korb D, Tsatsaris V, Camilleri C, Deneux-Tharaux C. According to patients who have an history of preeclampsia, the information they receive in the postpartum period needs to be optimized to initiate appropriate follow up. *J Gynecol Obstet Hum Reprod*. 2023;52:102582. doi: 10.1016/j.jogoh.2023.102582

45. Young B, Hacker MR, Rana S. Physicians' knowledge of future vascular disease in women with preeclampsia. *Hypertens Pregnancy*. 2012;31:50–58. doi: 10.3109/10641955.2010.544955

46. Gogineni VSM, Manfrini D, Aroda SH, Zhang Y, Nelson DS, Egerman R, Park K. Variations in awareness of association between adverse pregnancy outcomes and cardiovascular risk by specialty. *Cardiol Ther*. 2021;10:577–592. doi: 10.1007/s40119-021-00220-y

47. Bick D, Silverio SA, Bye A, Chang YS. Postnatal care following hypertensive disorders of pregnancy: a qualitative study of views and experiences of primary and secondary care clinicians. *BMJ Open*. 2020;10:e034382. doi: 10.1136/bmjopen-2019-034382

48. Bellamy V. Les Naissances en 2016. Insee Première. 2017. Accessed November 15, 2023. https://www.insee.fr/fr/statistiques/3047024?sommaire=2898646