https://orcid.org/0000-0001-7591-2045
Figures
Abstract
Background
Within the PAVA study, we investigated placenta-associated vascular aging in women 15 years after pregnancies complicated by preeclampsia and/or fetal growth restriction. During these pregnancies, blood pressure values >140/90 mmHg were considered to require treatment. Following evidence demonstrating improved pregnancy outcomes with tighter blood pressure control, updated German and international guidelines (International Society for the Study of Hypertension in Pregnancy, ISSHP) now recommend target values below 135/85 mmHg. To evaluate whether blood pressure levels during pregnancy are associated with long-term maternal cardiovascular health, we analyzed the impact of blood pressure control during pregnancy on cardiovascular risk profiles obtained in the PAVA follow-up study.
Methods
Between August 2019 and December 2022, 53 women were examined an average of 15 years after experiencing preeclampsia and/or fetal growth restriction. At the study visit, baseline data were collected, and a comprehensive clinical and functional assessment was performed. This analysis compared 35 women who were hypertensive at follow-up (blood pressure ≥140/90 mmHg and/or antihypertensive medication) with 18 normotensive participants (blood pressure <140/90 mmHg and no antihypertensive medication). Data on blood pressure levels during pregnancy were collected retrospectively from medical records.
Results
Blood pressure data during pregnancy were available for the second trimester in 15 women who later developed hypertension and 4 who remained normotensive, and for the third trimester in 19 and 14 participants, respectively. Data from the first trimester were not available. In group comparisons, systolic blood pressure in the second trimester and diastolic blood pressure in the third trimester were significantly higher in women who were hypertensive at follow-up (155 vs. 140 mmHg, p = 0.027; 96 vs. 87 mmHg, p = 0.026). In adjusted analyses, no statistically significant associations were observed; however, effect estimates suggested a potential association between blood pressure control during pregnancy and lower odds of later arterial hypertension (OR 0.22, 95% CI 0.03–1.53) and concentric remodeling (OR 0.37, 95% CI 0.03–4.29).
Conclusions
These findings suggest that blood pressure levels during pregnancy may be associated with long-term maternal cardiovascular health. However, given the limited sample size and exploratory nature of the analysis, these results should be interpreted with caution and require confirmation in larger prospective studies.
Citation: Lößner C, Loheit A, Multhaup A, Bäz L, Lehmann T, Heimann Y, et al. (2026) Impact of blood pressure control during pregnancy on long-term maternal cardiovascular health – secondary analysis of a follow-up study 15 years post preeclampsia (PAVA study). PLoS One 21(7): e0344378. https://doi.org/10.1371/journal.pone.0344378
Editor: Vincenzo Lionetti, Scuola Superiore Sant’Anna, ITALY
Received: February 16, 2026; Accepted: May 31, 2026; Published: July 15, 2026
Copyright: © 2026 Lößner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The data underlying the results presented in this study cannot be made publicly available because they contain potentially identifiable patient information and are subject to data protection and confidentiality regulations. Data are available upon reasonable request from the Department of Obstetrics, Jena University Hospital, Friedrich Schiller University Jena. Requests for access to the data should be directed to the institutional contact point at studien.geburtsmedizin@med.uni-jena.de. The Department of Obstetrics, Jena University Hospital, is the institution responsible for reviewing and processing data access requests.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Elevated blood pressure before, during and after pregnancy affects short-term maternal and fetal outcomes as well as long-term maternal health. Elevated blood pressure during pregnancy has been shown to be associated with an increased risk of pregnancy complications, such as preeclampsia (PE) [1]. Strict blood pressure control during pregnancy in women with chronic or gestational hypertension has been shown to improve pregnancy outcome and to prevent severe maternal hypertension [2]. Women with hypertensive pregnancy diseases have an increased long-term risk of cardiovascular disease such as hypertension, cerebrovascular stroke, coronary heart disease and even heart failure [3]. It has been shown, that after adjustment for confounding factors, the risk of chronic hypertension 1–5 years after pregnancy was 4–10 times higher in women with hypertensive disorders during pregnancy than in women with normotensive pregnancies [4]. The effect of blood pressure within the recommended targets during pregnancy on long-term cardiovascular health of affected women is so far understudied. We therefore analyzed the specific effects of blood pressure control during pregnancy on the cardiovascular risk profile 15 years after pregnancies complicated by placenta associated pregnancy diseases like PE and/or FGR, using the data retrieved during our PAVA-study.
Methods
Design and study population
This study constitutes a subgroup analysis of the PAVA study, a prospective, cross-sectional, single-center trial conducted by our group and published in 2024 [5]. In the original PAVA cohort, 53 women with a history of PE and/or FGR and 51 women with previously uncomplicated pregnancies were assessed on average 15 years postpartum. In order to investigate the effect of blood pressure control during pregnancy affected by PE and/or FGR, we further analysed the retrieved long term follow up data of the subgroup of 53 women with a history of PE and/or FGR. Within this cohort we compared clinical characteristics and date of cardiovascular function analysis in women presenting with hypertension at the follow-up study visit and the cohort of normotensive women. (Fig 1) Hypertension was defined as presenting with systolic blood pressure values ≥ 140 mmHg and/or a diastolic blood pressure ≥ 90 mmHg and/or currently taking antihypertensive medication, whereas normotension was defined as having a systolic blood pressure below 140 mmHg and a diastolic blood pressure below 90 mmHg in the absence of antihypertensive medication. Written informed consent was obtained for each enrolled patient during the PAVA study. Data were processed in accordance with the European data safety regulations. Clinical data from the index pregnancies were retrospectively collected from hospital database and patient records where available. To ensure pseudonymized analysis of data, each patient record was given a unique patient identification number when it was entered into the study database. Ethical approval was obtained from the Ethics Committee of the Friedrich Schiller University, Jena, Germany (no. 2019–1498_BO). The PAVA trial is registered with the US National Library of Medicine Clinical- Trials.gov (No: NCT04484766).
Clinical characteristics
Clinical characteristics and results of transthoracic echocardiography and VICORDER measurement (Skidmore Medical Ltd, Bristol, United Kingdom), were retrieved as described in detail in the original article [5]. Based on available echocardiological data, we calculated left ventricular mass (LVM), left ventricular mass index (LVMI) and relative wall thickness (RWT) analogous to the algorithm published by Hashem et al.[6] and subsequently categorized results in physiological cardiac values (RWT ≤ 0.42, LVMI < 95 g/m2), concentric cardiac remodelling (RWT > 0.42, LVMI < 95 g/m2), concentric cardiac hypertrophy (RWT > 0.42, LVMI ≥ 95 g/m2) or eccentric cardiac hypertrophy (RWT ≤ 0.42, LVMI ≥ 95 g/m2).
To improve comparability, blood pressure values retrieved from obstetric records were documented as the minimum and maximum as well as the mean value for each trimester of pregnancy. During pregnancy, blood pressure was measured by medical staff according to standard criteria.
Statistical analysis
Categorical variables were compared between groups and are reported as absolute and relative frequencies. Continuous variables were analyzed using the non-parametric Mann–Whitney U test, as appropriate due to the distributional characteristics of the data and the relatively small sample size. Accordingly, medians as well as 25th and 75th percentiles are reported for continuous variables. All tests were two-sided.
Group characteristics such as maternal BMI prior to pregnancy, gestational age at delivery, and blood pressure within target range during pregnancy (≤135/85 mmHg) were used as independent variables in binary logistic regression analysis. Binary logistic regression with the Wald backward elimination method was applied. Results were considered statistically significant at p < 0.05. Statistical analyses were performed using IBM SPSS Statistics version 28.0 (IBM Corp., Armonk, NY, USA).
Results
We examined 53 women with a history of pregnancies complicated by PE and/or FGR. At the time of the study visit, 35 women (66%) were hypertensive, while 18 women (34%) were normotensive. Both systolic and diastolic mean oscillometric blood pressure were significantly higher in the group of hypertensive women than in the normotensive group (systolic 146 mmHg vs. 123 mmHg, p < 0.001; diastolic 94.5 mmHg vs. 80 mmHg, p < 0.001). A summary of selected group characteristics at the PAVA follow-up study visit is presented in Table 1.
Blood pressure measurements retrieved during the second trimester of pregnancy were available for 15 women who subsequently developed hypertension and for 4 women who remained normotensive. Data from the third trimester were available for 19 and 14 women, respectively. In group comparisons, women who later developed hypertension exhibited higher mean blood pressure values during pregnancy. This difference reached statistical significance for systolic blood pressure in the second trimester (155 mmHg vs. 140 mmHg, p = 0.027) and for diastolic blood pressure in the third trimester (96 mmHg vs. 87 mmHg, p = 0.026). Overall, a significantly smaller proportion of women in the group that later developed hypertension had gestational blood pressure values within the target range of ≤135/85 mmHg (6.7% vs. 35.3%, p = 0.013). A summary of blood pressure values and additional characteristics before and during the index pregnancy is provided in Table 2.
Table 3 summarizes parameters of cardiovascular function. Physiological cardiac values were present in 51.6% of hypertensive and 66.7% of normotensive women (p = 0.340). Echocardiographic assessment revealed no significant differences in left heart structure, except for a reduced left ventricular ejection fraction in hypertensive women (2CH: 63.5% vs. 67.5%, p = 0.02; 4CH: 62% vs. 66.5%, p = 0.036) and a thicker interventricular septum (11 mm vs. 10 mm, p = 0.05). The E/med E ratio was significantly elevated in hypertensive subjects (9.8 vs. 7.9, p = 0.006). Regarding right heart morphology, hypertensive women exhibited a larger right atrial area (13 cm² vs. 11 cm², p = 0.036), with no further differences observed. Rates of concentric remodelling (38.7% vs. 20%, p = 0.209), concentric hypertrophy (6.5% vs. 6.7%, p = 0.978), and eccentric hypertrophy (3.2% vs. 6.7%, p = 0.596) did not differ significantly between groups, although a non-significant trend toward higher prevalence of concentric remodelling was noted among hypertensive women.
VICORDER analysis demonstrated significantly higher aortic systolic (144 vs. 123 mmHg, p < 0.001) and diastolic blood pressure (76 vs. 62 mmHg, p < 0.001), increased pulse pressure (peripheral: 69 vs. 64 mmHg, p = 0.005; aortic: 66 vs. 61 mmHg, p < 0.001), and elevated mean arterial pressure (106 vs. 91 mmHg, p < 0.001) in hypertensive women. At comparable pulse wave velocity, the augmentation index was significantly higher in the hypertensive group (26 vs. 21, p = 0.014). Cardiac output was also increased, averaging 8 l/min compared with 7 l/min in normotensive women (p = 0.003).
Table 4 presents adjusted odds ratios (ORs) and corresponding confidence intervals (CIs) for selected long-term maternal cardiovascular outcomes, including arterial hypertension, diastolic dysfunction, abnormal relative wall thickness (RWT), and concentric remodelling. The models were adjusted for maternal pre-pregnancy body mass index (BMI), gestational age at delivery, and blood pressure control during pregnancy.
Discussion
This study examines the impact of blood pressure control during pregnancy on cardiovascular risk profiles 15 years following pregnancies complicated by PE and/or FGR. While our findings suggest a potential association between lower blood pressure values during pregnancy and more favorable long-term cardiovascular outcomes, these results should be interpreted with caution given the exploratory nature of the study and the limited sample size. Previous studies have demonstrated that adequate blood pressure control improves short-term maternal and fetal outcomes [2,7], and our data may indicate that this effect could extend to long-term maternal health.
Women with lower blood pressure values in the second and third trimesters tended to show a lower risk of arterial hypertension 15 years after a complicated pregnancy. The data obtained during the study visit — indicating a higher educational level, greater habitual physical activity, and more favorable BIA parameters in the group of normotensive women — suggest the presence of an additive lifestyle effect following pregnancy (Table 1). However, these baseline differences between groups, including body mass index, smoking behavior, education level, and physical activity, represent important cardiovascular risk factors and may have influenced the observed associations. Although adjustments were performed, residual confounding cannot be excluded.
The relatively small sample size and limited number of events reduce statistical power, which is reflected in the wide confidence intervals observed in binary logistic regression analyses. Accordingly, none of the investigated variables emerged as statistically significant predictors of long-term cardiovascular complications in adjusted models. Although maintenance of blood pressure within the target range (≤ 135/85 mmHg) was associated with a trend toward reduced odds of postpartum arterial hypertension and concentric remodelling (Table 4), these findings cannot be considered conclusive and should be regarded as hypothesis-generating.
In addition, the assessment of blood pressure control during pregnancy was limited by incomplete data. Blood pressure measurements from the first trimester were not available, and documentation in later trimesters was variable. The definition of “blood pressure within the target range” required all recorded values to remain below a predefined threshold, representing a relatively strict criterion. In the context of incomplete or infrequent measurements, this approach may have led to misclassification and may have influenced the observed associations.
Concentric remodeling refers to a structural adaptation of the left ventricle characterized by increased wall thickness without a concomitant increase in overall left ventricular mass. This pattern typically arises as a compensatory response to chronic pressure overload, such as that induced by hypertension, and is linked to an elevated risk of cardiovascular morbidity and mortality, even in the absence of overt left ventricular hypertrophy. Our results suggest an association between lower blood pressure values during pregnancy and a reduced risk of later concentric remodeling, which is consistent with findings from similar studies [3,8]. However, these studies primarily focused on hypertensive pregnancy complications as a whole rather than on blood pressure control during pregnancy itself.
Also, VICORDER analysis revealed group differences. The group of hypertensive women exhibited increased systolic aortic blood pressure in combination with increased peripheral and aortic pulse pressure, exceeding clinically accepted reference limits (Table 3). An elevated pulse pressure indicates increased vascular stiffness and is associated with cardiovascular risk. A meta-analysis showed that, for every 10 mmHg increase in pulse pressure, the relative risk of cardiovascular mortality increases by 13%, while the relative risk of all-cause mortality increases by 9% [9]. In this context, our findings suggest a potentially unfavorable vascular profile in women who remain hypertensive 15 years after pregnancy; however, causal inferences cannot be drawn.
Strengths and limitations
This study has several limitations. Its retrospective design and the relatively small sample size limit statistical power and generalizability of the findings. In addition, incomplete blood pressure data, particularly from the first trimester, restrict the assessment of blood pressure control throughout pregnancy and may have introduced misclassification. The number of statistical comparisons performed in relation to the sample size also raises the possibility of type I error, and no formal adjustment for multiple testing was applied. Therefore, the results, particularly those approaching statistical significance, should be interpreted with caution.
Despite these limitations, the study has important strengths. It is based on a well-characterized cohort of women who underwent comprehensive cardiovascular assessment approximately 15 years after preeclampsia. The parallel use of transthoracic echocardiography and VICORDER measurements enabled an in-depth evaluation of both cardiovascular structure and function as well as vascular properties. This comprehensive phenotyping provides a robust dataset for the analysis of long-term cardiovascular sequelae following preeclampsia.
Conclusions
Collectively, our findings suggest that blood pressure control during pregnancy may be associated with long-term maternal cardiovascular health. They highlight the importance of close blood pressure monitoring and management during pregnancy to reduce perinatal complications and potentially influence long-term risk. However, given the exploratory nature of the study and its methodological limitations, these findings should be interpreted cautiously. Future research should focus on larger, prospective studies investigating optimal strategies and timing of blood pressure management during pregnancy, with the aim of improving both short- and long-term maternal outcomes.
References
- 1. Jung YM, Oh GC, Noh E, Lee H-Y, Oh M-J, Park JS, et al. Pre-pregnancy blood pressure and pregnancy outcomes: a nationwide population-based study. BMC Pregnancy Childbirth. 2022;22(1):226. pmid:35305601
- 2. Magee LA, von Dadelszen P, Singer J, Lee T, Rey E, Ross S, et al. The CHIPS Randomized Controlled Trial (Control of Hypertension in Pregnancy Study): Is Severe Hypertension Just an Elevated Blood Pressure?. Hypertension. 2016;68(5):1153–9. pmid:27620393
- 3. Honigberg MC, Zekavat SM, Aragam K, Klarin D, Bhatt DL, Scott NS, et al. Long-Term Cardiovascular Risk in Women With Hypertension During Pregnancy. J Am Coll Cardiol. 2019;74(22):2743–54.
- 4. Benschop L, Duvekot JJ, Roeters van Lennep JE. Future risk of cardiovascular disease risk factors and events in women after a hypertensive disorder of pregnancy. Heart. 2019;105(16):1273–8.
- 5. Lößner C, Multhaup A, Bäz L, Lehmann T, Heimann Y, Schleußner E, et al. Cardiovascular health of women 10 to 20 years after placenta-related pregnancy diseases considering the possible effect of pentaerythrityl tetranitrate treatment during pregnancy on long-term maternal cardiovascular health (PAVA study). PLoS One. 2024;19(10):e0309177. pmid:39405308
- 6. Hashem M-S, Kalashyan H, Choy J, Chiew SK, Shawki A-H, Dawood AH, et al. Left ventricular relative wall thickness versus left ventricular mass index in non-cardioembolic stroke patients. Medicine (Baltimore). 2015;94(20):e872. pmid:25997067
- 7. Tita AT, Szychowski JM, Boggess K, Dugoff L, Sibai B, Lawrence K, et al. Treatment for Mild Chronic Hypertension during Pregnancy. N Engl J Med. 2022;386(19):1781–92. pmid:35363951
- 8. Melchiorre K, Sutherland GR, Liberati M, Thilaganathan B. Preeclampsia is associated with persistent postpartum cardiovascular impairment. Hypertension. 2011;58(4):709–15. pmid:21844489
- 9. Zhao L, Song Y, Dong P, Li Z, Yang X, Wang S. Brachial pulse pressure and cardiovascular or all-cause mortality in the general population: a meta-analysis of prospective observational studies. J Clin Hypertens (Greenwich). 2014;16(9):678–85. pmid:25052820