Jamie Kitt

BACKGROUND: Women display retinal vessel caliber abnormalities after hypertensive pregnancy, but whether these predate or reflect vascular aging is unknown. METHODS: Retinal imaging was performed in 2 cohorts: 196 women at 6 to 12 months postpartum (167 hypertensive, 29 normotensive), and 105 women at 15 to 25 years postpartum (64 hypertensive, 41 normotensive), using identical imaging/analysis protocols (Imedos Health, GmbH). Central retinal arteriolar and venular equivalents were calculated, corrected for mean arterial pressure at the time of imaging, and compared across hypertensive and normotensive pregnancy groups using multivariable linear regression models adjusted for body mass index and time postpartum. Z tests were used to compare effect sizes across time points. RESULTS: At both time points, corrected central retinal arteriolar and venular equivalents were lower after hypertensive pregnancies compared with normotensive pregnancies ( P Z =−4.19; P Z =−3.83; P P P <0.001). CONCLUSIONS: Hypertensive pregnancy is associated with retinal vessel changes up to 25 years postpartum that predate age-related reductions and are associated with early pregnancy blood pressure. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04273854 and NCT05434195.

BACKGROUND: Hypertensive pregnancies are associated with increased risks of renal failure in pregnancy and later life. However, traditional markers of renal function normalize postpartum, making identification of those at future disease risk difficult. We studied whether the type and severity of hypertensive pregnancy associated with postpartum renal structure. METHODS: One hundred and twenty-five women from interventional trials (61 preeclamptic, 33 gestational hypertension, and 31 normotensive pregnancy), aged ≥18 years, were imaged using magnetic resonance imaging 6 to 12 months postpartum. Anthropometric, demographic, blood pressure, and blood sample data were collected during pregnancy and postpartum. Kidney volume indexed to body surface area and corticomedullary differentiation were compared between groups using a 1-way ANCOVA, whereas associations with other outcomes were assessed using correlation tests. RESULTS: Postpartum total kidney volume indexed to body surface area was smaller in women who had preeclampsia compared with those who had gestational hypertension or a normotensive pregnancy ( P =0.049). Total kidney volume postpartum correlated with estimated glomerular filtration rate at delivery ( P P =0.02) and normotensive women ( P =0.007). There were no associations between renal measures and blood pressure during or after pregnancy. CONCLUSIONS: At 6 to 12 months postpartum, preeclamptic women have smaller kidney volumes than women with gestational hypertension or normotensive pregnancies. These smaller volumes relate to lower renal function at delivery but not corticomedullary differentiation, which only differed in women with gestational hypertension. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT04273854 and NCT05434195.

BACKGROUND: Hypertensive pregnancy disorders are associated with long-term adverse cardiac and vascular remodeling postindex pregnancy. The POP-HT trial (Physician Optimised Postpartum Hypertension Treatment) demonstrated that improved puerperal blood pressure control leads to reduced blood pressure and beneficial cardiac remodeling during the first year postpartum. This study describes the impact on postpartum vascular remodeling. METHODS: A prospective, randomized, open-label, blinded end point trial in a single UK hospital where 220 women were assigned 1:1 to intervention (self-management via physician-guided antihypertensive titration) or control (usual postnatal care via primary care doctor±midwife). Eligible participants were ≥18 years, with preeclampsia or gestational hypertension and requiring antihypertensives on discharge. Prespecified secondary vascular outcomes included aortic blood pressure and pulse wave velocity measured by Vicorder at baseline and 9 months postpartum, and additional cardiovascular magnetic resonance measures of aortic distensibility were performed. RESULTS: There were no baseline differences in aortic blood pressure or pulse wave velocity but by 9 months postpartum, aortic diastolic blood pressure was −5.2 mm Hg lower ([95% CI, −8.0 to −2.2]; P P =0.048) in the intervention arm compared with the control arm, which corresponded with greater aortic distensibility by 0.78×10 ^{− 3} mm Hg ^{− 1} ([95% CI, −0.01 to 1.55]; P =0.046). CONCLUSIONS: Postpartum blood pressure self-monitoring combined with physician-guided medication titration is associated with reduced central arterial stiffness during the first year after a hypertensive pregnancy, in addition to the previously demonstrated effects on blood pressure and cardiac remodeling. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04273854.

Background: Hypertensive disorders of pregnancy (HDP) are associated with significant cardiac remodeling during pregnancy and are important contributors to maternal morbidity and mortality. Whether acute adverse outcomes during HDP are associated with additional clinically relevant cardiac impairment has not been widely studied. Methods: A prospective observational study was conducted on 255 women with HDP who underwent transthoracic echocardiography during the peripartum period. Maternal echocardiographic parameters, including left ventricular morphology and function, were analyzed to determine their association with adverse maternal outcomes by univariate and multivariate analyses. The composite adverse maternal outcome was defined as at least one of the following: admission to a high dependence unit, acute renal injury, adverse cardio-pulmonary events, stroke and disseminated intravascular coagulation. Results: Adverse maternal outcomes occurred in 68 (26.7%) participants. Women with adverse outcomes had significantly higher left atrial volume index (LAVI) (28.8 [23.4-32.3] ml/m ² vs 26.6 [22.2-30.9] ml/m ² , p=0.045) and E/e′ ratio (7.8 [6.6-9.2] vs 7.0 [5.9-8.1], p=0.002) compared to those without complications. In multivariable analysis, both LAVI (adjusted OR 1.09 [1.02-1.16], p=0.009) and E/e′ ratio (adjusted OR 1.25 [1.04-1.49], p=0.018) remained independently associated with adverse maternal outcomes after adjusting for maternal factors and clinical variables. Conclusions: Cardiac abnormalities, particularly in diastolic function, are more common in women with adverse maternal outcomes in HDP. Whether enhanced cardiovascular monitoring and management of these women in the peripartum period could have immediate and long-term health benefits requires further evaluation. GRAPHIC

BACKGROUND: Hypertensive pregnancy disorders are associated with adverse cardiac remodeling, which can fail to reverse in the postpartum period in some women. The Physician-Optimized Postpartum Hypertension Treatment trial demonstrated that improved blood pressure control while the cardiovascular system recovers postpartum associates with persistently reduced blood pressure. We now report the effect on cardiac remodeling. METHODS: In this prospective, randomized, open-label, blinded end point trial, in a single UK hospital, 220 women were randomly assigned 1:1 to self-monitoring with research physician-optimized antihypertensive titration or usual postnatal care from a primary care physician and midwife. Participants were 18 years of age or older, with preeclampsia or gestational hypertension, requiring antihypertensives on hospital discharge postnatally. Prespecified secondary cardiac imaging outcomes were recorded by echocardiography around delivery, and again at blood pressure primary outcome assessment, around 9 months postpartum, when cardiovascular magnetic resonance was also performed. RESULTS: A total of 187 women (101 intervention; 86 usual care) underwent echocardiography at baseline and follow-up, at a mean 258±14.6 days postpartum, of which 174 (93 intervention; 81 usual care) also had cardiovascular magnetic resonance at follow-up. Relative wall thickness by echocardiography was 0.06 (95% CI, 0.07–0.05; P 2 ; 95% CI, –7.99 to –4.74; P 2 ; 95% CI, –6.77 to –0.98; P =0.009), and end-systolic volume (–3.25 mL/m ² ; 95% CI, 4.87 to –1.63; P P P P =0.024) and a reduction in left atrial volumes of –4.33 mL/m ² (95% CI, –5.52 to –3.21; P <0.001) between baseline and follow-up when adjusted for baseline differences in measures. CONCLUSIONS: Short-term postnatal optimization of blood pressure control after hypertensive pregnancy, through self-monitoring and physician-guided antihypertensive titration, associates with long-term changes in cardiovascular structure and function, in a pattern associated with more favorable cardiovascular outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04273854.

Accurate staging of hypertension-related cardiac changes, before the development of significant left ventricular hypertrophy, could help guide early prevention advice. We evaluated whether a novel semi-supervised machine learning approach could generate a clinically meaningful summary score of cardiac remodelling in hypertension. A contrastive trajectories inference approach was applied to data collected from three UK studies of young adults. Low-dimensional variance was identified in 66 echocardiography variables from participants with hypertension (systolic ≥160 mmHg) relative to a normotensive group (systolic < 120 mmHg) using a contrasted principal component analysis. A minimum spanning tree was constructed to derive a normalized score for each individual reflecting extent of cardiac remodelling between zero (health) and one (disease). Model stability and clinical interpretability were evaluated as well as modifiability in response to a 16-week exercise intervention. A total of 411 young adults (29 ± 6 years) were included in the analysis, and, after contrastive dimensionality reduction, 21 variables characterized >80% of data variance. Repeated scores for an individual in cross-validation were stable (root mean squared deviation = 0.1 ± 0.002) with good differentiation of normotensive and hypertensive individuals (area under the receiver operating characteristics 0.98). The derived score followed expected hypertension-related patterns in individual cardiac parameters at baseline and reduced after exercise, proportional to intervention compliance (P = 0.04) and improvement in ventilatory threshold (P = 0.01). A quantitative score that summarizes hypertension-related cardiac remodelling in young adults can be generated from a computational model. This score might allow more personalized early prevention advice, but further evaluation of clinical applicability is required.

Aims: Hypertensive pregnancy is associated with increased risks of developing a range of vascular disorders in later life. Understanding when hypertensive target organ damage first emerges could guide optimal timing of preventive interventions. This review identifies evidence of hypertensive target organ damage across cardiac, vascular, cerebral, and renal systems at different time points from pregnancy to postpartum. Methods and results: Systematic review of Ovid/MEDLINE, EMBASE, and ClinicalTrials.gov up to and including February 2023 including review of reference lists. Identified articles underwent evaluation via a synthesis without meta-analysis using a vote-counting approach based on direction of effect, regardless of statistical significance. Risk of bias was assessed for each outcome domain, and only higher quality studies were used for final analysis. From 7644 articles, 76 studies, including data from 1 742 698 pregnancies, were identified of high quality that reported either blood pressure trajectories or target organ damage during or after a hypertensive pregnancy. Left ventricular hypertrophy, white matter lesions, proteinuria, and retinal microvasculature changes were first evident in women during a hypertensive pregnancy. Cardiac, cerebral, and retinal changes were also reported in studies performed during the early and late post-partum period despite reduction in blood pressure early postpartum. Cognitive dysfunction was first reported late postpartum. Conclusion: The majority of target organ damage reported during a hypertensive pregnancy remains evident throughout the early and late post-partum period despite variation in blood pressure. Early peri-partum strategies may be required to prevent or reverse target organ damage in women who have had a hypertensive pregnancy.

There is widespread acceptance of the increased prevalence of cardiovascular diseases occurring within 1 to 2 decades in women following a preeclamptic pregnancy. More recent evidence suggests that the deranged biochemical and echocardiographic findings in women do not resolve in the majority of preeclamptic women following giving birth. Many women continue to be hypertensive in the immediate postnatal period with some exhibiting occult signs of cardiac dysfunction. There is now promising evidence that with close monitoring and effective control of blood pressure control in the immediate postnatal period, women may have persistently lower blood pressures many years after stopping their medication. This review highlights the evidence that delivering effective medical care in the fourth trimester of pregnancy can improve the long-term cardiovascular health after a preeclamptic birth.

Introduction New-onset hypertension affects approximately 10% of pregnancies and is associated with a significant increase in risk of cardiovascular disease in later life, with blood pressure measured 6 weeks postpartum predictive of blood pressure 5–10 years later. A pilot trial has demonstrated that improved blood pressure control, achevied via self-management during the puerperium, was associated with lower blood pressure 3-4 years postpartum. Physician Optimised Post-partum Hypertension Treatment (POP-HT) will formally evaluate whether improved blood pressure control in the puerperium results in lower blood pressure at 6 months post partum, and improvements in cardiovascular and cerebrovascular phenotypes. Methods and analysis POP-HT is an open-label, parallel arm, randomised controlled trial involving 200 women aged 18 years or over, with a diagnosis of pre-eclampsia or gestational hypertension, and requiring antihypertensive medication at discharge. Women are recruited by open recruitment and direct invitation around time of delivery and randomised 1:1 to, either an intervention comprising physician-optimised self-management of postpartum blood pressure or, usual care. Women in the intervention group upload blood pressure readings to a ‘smartphone’ app that provides algorithm-driven individualised medication-titration. Medication changes are approved by physicians, who review blood pressure readings remotely. Women in the control arm follow assessment and medication adjustment by their usual healthcare team. The primary outcome is 24-hour average ambulatory diastolic blood pressure at 6–9 months post partum. Secondary outcomes include: additional blood pressure parameters at baseline, week 1 and week 6; multimodal cardiovascular assessments (CMR and echocardiography); parameters derived from multiorgan MRI including brain and kidneys; peripheral macrovascular and microvascular measures; angiogenic profile measures taken from blood samples and levels of endothelial circulating and cellular biomarkers; and objective physical activity monitoring and exercise assessment. An additional 20 women will be recruited after a normotensive pregnancy as a comparator group for endothelial cellular biomarkers. Ethics and dissemination IRAS PROJECT ID 273353. This trial has received a favourable opinion from the London—Surrey Research Ethics Committee and HRA (REC Reference 19/LO/1901). The investigator will ensure that this trial is conducted in accordance with the principles of the Declaration of Helsinki and follow good clinical practice guidelines. The investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study. Authors will acknowledge that the study was funded by the British Heart Foundation Clinical Research Training Fellowship (BHF Grant number FS/19/7/34148). Authorship will be determined in accordance with the ICMJE guidelines and other contributors will be acknowledged. Trial registration number NCT04273854.