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Preeclampsia is associated with an increased risk of long-term cardiometabolic disease; however, little is known regarding metabolic factors in the early postpartum years potentially contributing to these health disparities. This study aimed to compare body composition, serum biochemical parameters, energy balance and diet 6 months and 2 years after normotensive pregnancy versus preeclampsia. This is the longitudinal metabolic sub-study of the Postpartum Physiology, Psychology and Paediatric cohort study. Women were assessed 6 months and 2 years after normotensive pregnancy (n = 118) and preeclampsia (n = 47). Metabolic measures included anthropometry, body composition via bioelectrical impedance analysis, serum biochemical parameters, diet via a food recall diary, and 24-h energy expenditure using SenseWear Armbands. Two years postpartum, women after preeclampsia continued to have significantly higher weight (median 67.1 kg vs. 63.1 kg, p = .04) compared to normotensive pregnancies, in addition to higher LDL cholesterol levels (2.7 ± 0.8 mmol/L vs. 2.4 ± 0.6 mmol/L, p = .03). These women were also more likely to have an elevated HOMA-IR score ≥2.08 (44% vs. 19%, p = .01). For all women in our study, waist-to-hip ratio, percent fat mass and activity-associated energy expenditure improved overtime. However, HDL cholesterol levels deteriorated, and excess saturated fat and sodium intake persisted from 6 months postpartum. Therefore, two years after preeclampsia, women remain at greater metabolic risk than their normotensive counterparts, with greater weight, LDL cholesterol and markers of insulin resistance, potentially contributing to long-term cardiovascular morbidity and requiring early intervention., (© 2024 The Author(s). Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Increased cardiovascular risk following preeclampsia is well established and there are signs of early cardiovascular aging 6 months postpartum. This study assessed whether blood pressure (BP) and other cardiovascular measures are abnormal 2 years postpartum in the same cohort to determine ongoing risk markers., Methods: Six months and 2 years postpartum, BP was measured using sphygmomanometry, 24-hour ambulatory BP monitoring, and noninvasive central BP. Anthropometric measures, blood, and urine biochemistry were performed. Cross-sectional comparisons between preeclampsia and normotensive pregnancy (NP) groups and longitudinal comparisons within each group were made at 6 months and 2 years., Results: Two years postpartum, 129 NP, and 52 preeclampsia women were studied who also had 6 months measures. At both time points, preeclampsia group had significantly higher BP (office BP 2 years, 112±12/72±8 versus 104±9/67±7 mm Hg NP; [ P <0.001]; mean ambulatory BP monitoring 116±9/73±8 versus 106±8/67±6 mm Hg NP; [ P <0.001]). No significant BP changes noted 6 months to 2 years within either group. Office BP thresholds of 140 mm Hg systolic and 90 mm Hg diastolic classified 2% preeclampsia and 0% NP at 2 years. American Heart Association 2017 criteria (above normal, >120/80 mm Hg) classified 25% versus 8% ( P <0.002), as did our reference range threshold of 122/79 mm Hg. American Heart Association criteria classified 60% post-preeclampsia versus 16% after NP with above-normal ambulatory BP monitoring ( P <0.001). Other cardiovascular risk markers more common 2 years post-preeclampsia included higher body mass index (median 26.6 versus 23.1, P =0.003) and insulin resistance., Conclusions: After preeclampsia, women have significantly higher BP 6 months and 2 years postpartum, and have higher body mass index and insulin-resistance scores, increasing their future cardiovascular risk. Regular cardiovascular risk screening should be implemented for all who have experienced preeclampsia., Competing Interests: None.

The microbiome has emerged as a key determinant of human health and reproduction, with recent evidence suggesting a dysbiotic microbiome is implicated in adverse perinatal health outcomes. The existing research has been limited by the sample collection and timing, cohort design, sample design, and lack of data on the preconception microbiome. This prospective, longitudinal cohort study will recruit 2000 Australian women, in order to fully explore the role of the microbiome in the development of adverse perinatal outcomes. Participants are enrolled for a maximum of 7 years, from 1 year preconception, through to 5 years postpartum. Assessment occurs every three months until pregnancy occurs, then during Trimester 1 (5 + 0-12 + 6 weeks gestation), Trimester 2 (20 + 0-24 + 6 weeks gestation), Trimester 3 (32 + 0-36 + 6 weeks gestation), and postpartum at 1 week, 2 months, 6 months, and then annually from 1 to 5 years. At each assessment, maternal participants self-collect oral, skin, vaginal, urine, and stool samples. Oral, skin, urine, and stool samples will be collected from children. Blood samples will be obtained from maternal participants who can access a study collection center. The measurements taken will include anthropometric, blood pressure, heart rate, and serum hormonal and metabolic parameters. Validated self-report questionnaires will be administered to assess diet, physical activity, mental health, and child developmental milestones. Medications, medical, surgical, obstetric history, the impact of COVID-19, living environments, and pregnancy and child health outcomes will be recorded. Multiomic bioinformatic and statistical analyses will assess the association between participants who developed high-risk and low-risk pregnancies, adverse postnatal conditions, and/or childhood disease, and their microbiome for the different sample types.

Objectives: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM)., Methods: We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days., Results: Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [ p  = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p  = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [ p  = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days ( p  = .04). OPM was associated with mean cost savings of £2658 (95% CR 460-4857) per patient., Conclusions: Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.

Background: Mental health is an integral part of overall health. Mental health disorders following childbirth are common and poor maternal mental health has consequences for both the mother and her infant. Preeclampsia is also relatively common in pregnancy but there is little known about the intersection between these two important conditions. Gaining a better understanding of the psychological consequences following preeclampsia is important, especially the link with depression, anxiety and posttraumatic stress disorder. If women who experience preeclampsia are recognised as being at increased risk of poor mental health, targeted screening in the postpartum period should be implemented., Aims: To describe the prevalence and symptom severity of depression, anxiety and posttraumatic stress disorder at six months postpartum in women, who had a diagnosis of preeclampsia, compared to those who had normal blood pressure in pregnancy., Methods: The mental health component of the prospective cohort study, the Postpartum, Physiology, Psychology and Paediatric follow-up study (P4 Study) was used. Women diagnosed with preeclampsia (n = 90) and those who were normotensive during pregnancy (n = 302) completed the Edinburgh Postnatal Depression Scale, General Anxiety Disorder Scale, and the Posttraumatic Stress Diagnostic Scale or Posttraumatic Stress Diagnostic Sclae-5 at six months postpartum., Results: At six months postpartum, depressive scores were similar in both groups but a higher proportion of women from the preeclampsia group scored above the threshold for depression (2% v 7% p = 0.04). There were no differences between the groups in the prevalence or severity of anxiety or PTSD. However, more women in the preeclampsia group reported their birth experience as a traumatic event (1% vs 7%, p = 0.01). On correlation testing and modelling, booking Edinburgh Postnatal Depression Scale score, any mental health history, experiencing birth as traumatic and the General Anxiety Disorder Scale score were independent predictors of postpartum Edinburgh Postnatal Depression Scale scores., Conclusion: The postpartum clinical care of women with preeclampsia often focusses on the immediate physical health issues, but these women may also benefit from mental health screening. Targeted screening of preeclamptic women in the postpartum period may lead to more timely referral and initiation of treatment., Trial Registration: Retrospectively registered on 18/11/2013 with the Australian and New Zealand Clinical Trials Registry. Registration Number: ACTRN12613001260718 ., (© 2022. The Author(s).)

Objective/hypothesis: To explore potential differences in faecal microbiome between women, and their infants, who had normotensive pregnancies (NP) and those who had a hypertensive pregnancy (HP), either gestational hypertension (GH) or preeclampsia (PE)., Methods: This is a sub study of P4 (Postpartum Physiology, Psychology, and Paediatrics Study) and includes 18 mother-infant pairs: 10 NP and 8 HP (HP as defined by blood pressure > 140/90mmHg; of which 6 had PE, and 2 GH), six months postpartum. The participating mothers collected stool samples from themselves and their infants. 16S rRNA V3-V4 amplicons were used to study the faecal microbiome., Results: The sample of women and their infants were mostly primiparous ( n =16) with vaginal birth ( n = 14). At the time of faecal sampling 8 women were using hormonal contraception, and one HP woman remained on an antihypertensive. All women had blood pressure < 130/80mmHg, and 10 had high BMI (> 30). All infants had started solids, 8 were exclusively breastfed, 1 exclusively formula fed and 9 both. Three infants had been exposed to a course of antibiotics. Six months postpartum, there were no significant differences in alpha or beta diversity between the gut microbiota of HP and NP women ( P  > 0.05). However, a statistically significant difference was detected in alpha diversity between infants following HP and NP, with lower diversity levels in HP infants ( P < 0.05). It was also found that at a genus and species level, the gut microbiota of HP women was enriched with Bifidobacterium and Bifididobacterium sp. and depleted in Barnisiella and Barnesiella intestinihominis when compared to NP women ( P < 0.05). Similarly, the gut microbiota of infants born from HP was enriched in Streptococcus infantis and depleted in Sutterella , Sutterella sp., Bacteroides sp. and Clostridium aldenense compared to infants born from NP ( P < 0.05)., Discussion: While our findings are at best preliminary, due to the very small sample size, they do suggest that the presence of hypertension in pregnancy may adversely affect the maternal microbiota postpartum, and that of their infants. Further analysis of postpartum microbiome data from future studies will be important to validate these early findings and provide further evidence about the changes in the microbiota in the offspring of women following hypertensive disorders of pregnancy (HDP), including possible links to the causes of long-term cardiovascular disease, the prevalence of which is increased in women who have experienced HDP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Susic, Wang, Roberts, Bai, Gia, McGovern, Jiang, Davis, El-Omar and Henry.)

Background: Preeclampsia is a major pregnancy complication associated with long-term maternal cardiometabolic disease. Research generally is focused on metabolic and pathophysiological changes during pregnancy; however, there is much less focus on the early postpartum period in subjects who suffered preeclampsia. The aim of this study was to (1) characterize energy intake and expenditure 6 months following normotensive and preeclamptic pregnancies and (2) examine associations between energy balance, body composition, insulin resistance measures (HOMA-IR), and clinical characteristics., Design: A cross-sectional study 6 months following normotensive (n = 75) and preeclamptic (n = 22) pregnancies was performed. Metabolic measurements included anthropometrics measures, body composition via bioelectrical impedance analysis, 24-h energy expenditure via SenseWear Armbands, energy intake via a 3-day food diary, and serum metabolic parameters., Results: Six months following preeclampsia, women had a significantly higher weight (77.3 ± 20.9 kg vs 64.5 ± 11.4 kg, P = 0.01), fat mass percentage (FM%; 40.7 ± 7.4% vs 34.9 ± 8.1%, P = 0.004), and insulin resistance (HOMA-IR 2.2 ± 1.5 vs 1.0 ± 0.7, P = 0.003), as well as reduced HDL levels (1.5 ± 0.4 mmol/L vs 1.8 ± 0.4 mmol/L, P = 0.01) compared to normotensive women. Women post-preeclampsia had lower activity-related energy expenditure (P = 0.02) but a decreased total energy intake (P = 0.02), leading to a more negative energy balance compared to their normotensive counterparts (-1942 kJ/24 h vs -480 kJ/24 h, P = 0.02)., Conclusion: Increases in insulin resistance and FM%, reduced high-density lipoprotein, and more sedentary lifestyles characterize the postpartum period following preeclamptic compared with normotensive pregnancies. Early post-preeclampsia interventions, such as lifestyle behavior change, should be implemented and assessed to determine whether they reduce long-term cardiometabolic risk in women who experienced preeclampsia during pregnancy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Women who have had hypertension in pregnancy, both pre-eclampsia and gestational hypertension, have a two- to three-fold increased risk of cardiovascular disease later in life. It is unclear whether this is an unmasking of latent risk, the result of damage to the vascular tree during pregnancy, or both. Irrespective of the underlying pathophysiology, these women are uniquely identified sufficiently early in their lives for lifestyle interventions, if adopted, to improve their long-term health. Currently, follow-up of these women is inadequate and implementation of a coordinated follow-up program, and further research into how best to provide it, is urgently needed., (© 2021 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Aims: Elevated serum immunoglobulins have been associated with experimental and human hypertension for decades but whether immunoglobulins and B cells play a causal role in hypertension pathology is unclear. In this study, we sought to determine the role of B cells and high-affinity class-switched immunoglobulins on hypertension and hypertensive end-organ damage to determine if they might represent viable therapeutic targets for this disease., Methods and Results: We purified serum immunoglobulin G (IgG) from mice exposed to vehicle or angiotensin (Ang) II to induce hypertension and adoptively transferred these to wild type (WT) recipient mice receiving a subpressor dose of Ang II. We found that transfer of IgG from hypertensive animals does not affect blood pressure, endothelial function, renal inflammation, albuminuria, or T cell-derived cytokine production compared with transfer of IgG from vehicle infused animals. As an alternative approach to investigate the role of high-affinity, class-switched immunoglobulins, we studied mice with genetic deletion of activation-induced deaminase (Aicda-/-). These mice have elevated levels of IgM but virtual absence of class-switched immunoglobulins such as IgG subclasses and IgA. Neither male nor female Aicda-/- mice were protected from Ang II-induced hypertension and renal/vascular damage. To determine if IgM or non-immunoglobulin-dependent innate functions of B cells play a role in hypertension, we studied mice with severe global B-cell deficiency due to deletion of the membrane exon of the IgM heavy chain (µMT-/-). µMT-/- mice were also not protected from hypertension or end-organ damage induced by Ang II infusion or deoxycorticosterone acetate-salt treatment., Conclusions: These results suggest that B cells and serum immunoglobulins do not play a causal role in hypertension pathology., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: To summarize key advances in our understanding of the role of interleukin 17A (IL-17A) in the pathogenesis of hypertension and highlight important areas for future research and clinical translation., Recent Findings: While T helper 17 (Th17) cells are major producers of IL-17A, there are several additional innate and adaptive immune cell sources including gamma-delta T cells, innate lymphoid cells, and natural killer cells. IL-17A promotes an increase in blood pressure through multiple mechanisms including inhibiting endothelial nitric oxide production, increasing reactive oxygen species formation, promoting vascular fibrosis, and enhancing renal sodium retention and glomerular injury. IL-17A production from Th17 cells is increased by high salt conditions in vitro and in vivo. There is also emerging data linking salt, the gut microbiome, and intestinal T cell IL-17A production. Novel therapeutics targeting IL-17A signaling are approved for the treatment of autoimmune diseases and show promise in both animal models of hypertension and human studies. Hypertensive stimuli enhance IL-17A production. IL-17A is a key mediator of renal and vascular dysfunction in hypertensive mouse models and correlates with hypertension in humans. Large randomized clinical trials are needed to determine whether targeting IL-17A might be an effective adjunct treatment for hypertension and its associated end-organ dysfunction.

Objectives: To test the accuracy of clinical pre-test probability (PTP) for prediction of obstructive coronary artery disease (CAD) in a pan-European setting., Methods: Patients with suspected CAD and stable chest pain who were clinically referred for invasive coronary angiography (ICA) or computed tomography (CT) were included by clinical sites participating in the pilot study of the European multi-centre DISCHARGE trial. PTP of CAD was determined using the Diamond-Forrester (D+F) prediction model initially introduced in 1979 and the updated D+F model from 2011. Obstructive coronary artery disease (CAD) was defined by one at least 50% diameter coronary stenosis by both CT and ICA., Results: In total, 1440 patients (654 female, 786 male) were included at 25 clinical sites from May 2014 until July 2017. Of these patients, 725 underwent CT, while 715 underwent ICA. Both prediction models overestimated the prevalence of obstructive CAD (31.7%, 456 of 1440 patients, PTP: initial D+F 58.9% (28.1-90.6%), updated D+F 47.3% (34.2-59.9%), both p < 0.001), but overestimation of disease prevalence was higher for the initial D+F (p < 0.001). The discriminative ability was higher for the updated D+F 2011 (AUC of 0.73 95% confidence interval [CI] 0.70-0.76 versus AUC of 0.70 CI 0.67-0.73 for the initial D+F; p < 0.001; odds ratio (or) 1.55 CI 1.29-1.86, net reclassification index 0.11 CI 0.05-0.16, p < 0.001)., Conclusions: Clinical PTP calculation using the initial and updated D+F prediction models relevantly overestimates the actual prevalence of obstructive CAD in patients with stable chest pain clinically referred for ICA and CT suggesting that further refinements to improve clinical decision-making are needed., Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT02400229 KEY POINTS: • Clinical pre-test probability calculation using the initial and updated D+F model overestimates the prevalence of obstructive CAD identified by ICA and CT. • Overestimation of disease prevalence is higher for the initial D+F compared with the updated D+F. • Diagnostic accuracy of PTP assessment varies strongly between different clinical sites throughout Europe.

Background There is increased risk of hypertension, early cardiovascular disease, and premature mortality in women who have had preeclampsia. This study was undertaken to determine the upper limit of normal blood pressure (BP) 6 months postpartum and the frequency of women with prior preeclampsia who had BP above these limits, as part of the P4 (Post-Partum Physiology, Psychology and Pediatric) follow-up study. Methods and Results BP was measured by sphygmomanometer, 24-hour ambulatory BP monitoring, and non-invasive central BP at 6 months postpartum in 302 women who had normotensive pregnancy and 90 who had preeclampsia. The upper limit of normal BP (mean+2 SD) for women with normotensive pregnancy was 122/79 mm Hg for routine BP, 115/81 mm Hg for central BP, and 121/78 mm Hg for 24-hour ambulatory BP monitoring. Traditional normal values detected only 3% of women who had preeclampsia as having high BP 6 months postpartum whereas these new values detected between 13% and 19%. Women with preeclampsia had greater body mass index (27.8 versus 25.0, P <0.001) and left ventricular wall thickness but similar augmentation index. They also had lower high-density lipoprotein (59±15 versus 65±16 mg/dL, P =0.002), higher triglycerides (77±51 versus 61±35 mg/dL, P =0.005), and higher homeostatic model assessment score (2.1±1.8 versus 1.3±1.9, P <0.001). Conclusions Clinicians wishing to detect high BP in these women should be aware of the lower than usual upper limit of normal for this young cohort and where possible should use 24-hour ambulatory BP monitoring to detect these changes. This may define a subgroup of women who had preeclampsia for whom targeted BP lowering therapy would be successful. Registration URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365295&isReview=true; Unique identifier: ACTRN12613001260718.