Cardiac Remodeling After Hypertensive Pregnancy Following Physician-Optimized Blood Pressure Self-Management: The POP-HT Randomized Clinical Trial Imaging Substudy.

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<0.001) lower in the intervention group between baseline and follow-up, and cardiovascular magnetic resonance at follow-up demonstrated a lower left ventricular mass (-6.37 g/m2; 95% CI, -7.99 to -4.74; P<0.001), end-diastolic volume (-3.87 mL/m2; 95% CI, -6.77 to -0.98; P=0.009), and end-systolic volume (-3.25 mL/m2; 95% CI, 4.87 to -1.63; P<0.001) and higher left and right ventricular ejection fraction by 2.6% (95% CI, 1.3-3.9; P<0.001) and 2.8% (95% CI, 1.4-4.1; P<0.001), respectively. Echocardiography-assessed left ventricular diastolic function demonstrated a mean difference in average E/E' of 0.52 (95% CI, -0.97 to -0.07; P=0.024) and a reduction in left atrial volumes of -4.33 mL/m2 (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.

Long-Term Blood Pressure Control After Hypertensive Pregnancy Following Physician-Optimized Self-Management: The POP-HT Randomized Clinical Trial.

Importance: Pregnancy hypertension results in adverse cardiac remodeling and higher incidence of hypertension and cardiovascular diseases in later life. Objective: To evaluate whether an intervention designed to achieve better blood pressure control in the postnatal period is associated with lower blood pressure than usual outpatient care during the first 9 months postpartum. Design, Setting, and Participants: Randomized, open-label, blinded, end point trial set in a single hospital in the UK. Eligible participants were aged 18 years or older, following pregnancy complicated by preeclampsia or gestational hypertension, requiring antihypertensive medication postnatally when discharged. The first enrollment occurred on February 21, 2020, and the last follow-up, November 2, 2021. The follow-up period was approximately 9 months. Interventions: Participants were randomly assigned 1:1 to self-monitoring along with physician-optimized antihypertensive titration or usual postnatal care. Main Outcomes and Measures: The primary outcome was 24-hour mean diastolic blood pressure at 9 months postpartum, adjusted for baseline postnatal blood pressure. Results: Two hundred twenty participants were randomly assigned to either the intervention group (n = 112) or the control group (n = 108). The mean (SD) age of participants was 32.6 (5.0) years, 40% had gestational hypertension, and 60% had preeclampsia. Two hundred participants (91%) were included in the primary analysis. The 24-hour mean (SD) diastolic blood pressure, measured at 249 (16) days postpartum, was 5.8 mm Hg lower in the intervention group (71.2 [5.6] mm Hg) than in the control group (76.6 [5.7] mm Hg). The between-group difference was -5.80 mm Hg (95% CI, -7.40 to -4.20; P < .001). Similarly, the 24-hour mean (SD) systolic blood pressure was 6.5 mm Hg lower in the intervention group (114.0 [7.7] mm Hg) than in the control group (120.3 [9.1] mm Hg). The between-group difference was -6.51 mm Hg (95% CI, -8.80 to -4.22; P < .001). Conclusions and Relevance: In this single-center trial, self-monitoring and physician-guided titration of antihypertensive medications was associated with lower blood pressure during the first 9 months postpartum than usual postnatal outpatient care in the UK. Trial Registration: ClinicalTrials.gov Identifier: NCT04273854.

Postpartum blood pressure self-management following hypertensive pregnancy: protocol of the Physician Optimised Post-partum Hypertension Treatment (POP-HT) trial.

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.

Short-Term Postpartum Blood Pressure Self-Management and Long-Term Blood Pressure Control: A Randomized Controlled Trial.

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The Immediate and Long-Term Impact of Preeclampsia on Offspring Vascular and Cardiac Physiology in the Preterm Infant.

Hypertensive disorders of pregnancy, including preeclampsia, affect nearly 10% of all pregnancies and are associated with significant long-term detrimental effects on both maternal and offspring cardiovascular health. Current management of preeclampsia involves timely delivery with the more severe form of disease requiring iatrogenic preterm birth. The effects on the maternal cardiovascular system have been studied extensively; however, less is known about the short- and long-term impacts on offspring cardiovascular health. There is a growing body of evidence suggesting that the offspring of pre-eclamptic pregnancies have an altered cardiac structure and function, along with a unique vascular physiology driven by lower endothelial function. Many of these changes can also be seen in those born preterm even in the absence of pregnancy hypertension. It is difficult to determine the relative contribution of pre-maturity and preeclampsia to the cardiovascular phenotype of those exposed to these pregnancy complications as they are, in many cases, inextricably linked. This review, therefore, focuses specifically on the evidence from clinical studies showing a negative cardiovascular impact of preeclampsia in preterm-born offspring, investigating phenotypic similarities and differences between offspring born preterm to normotensive vs. pre-eclamptic pregnancies. We explore the unique cardiac and vascular alterations in pre-eclamptic offspring born preterm, highlighting knowledge gaps, and potential areas of further research in the field.

High incidence of obesity co-morbidities in young children: a cross-sectional study.

AIM: The prevalence of overweight and obesity in children is a public health problem because of future morbidity. However, the prevalence of medical complications in overweight and obese primary school children in Australia is not well documented. As part of the larger, prospective cohort Growth and Development Study, this report aimed to identify the medical complications of obesity in a population-based community sample of primary school-aged children. METHODS: Two groups of primary school children were studied: a random community sample of overweight/obese children (not seeking treatment) and a matched community sample of normal weight children. Demographics, medical history, family history and symptoms of complications of overweight were collected. Children had a physical examination, oral glucose tolerance tests with insulins, fasting lipid profiles and liver function tests. RESULTS: Data from 283 children are presented (6.1-13.4 years, mean 9.8 years). There were no differences in birth data, family composition, parental age or socio-economic status between groups. Overweight and obese children were more likely to complain of musculoskeletal pain, depression, anxiety and bullying, and had more adverse examination findings than control children. They also had more abnormal investigations: overweight children: impaired glucose tolerance (IGT) 1.3%, hyperinsulinism 19.5%, dyslipidaemia 63.8%, raised alanine transaminase (ALT) 9.0%; obese children: IGT 5.3%, hyperinsulinism 38.9%, dyslipidaemia 73.7%, raised ALT 31.6%. CONCLUSION: Overweight and obese primary school-aged children have significant medical complications of their weight status. Overweight children, in addition to obese children, should be screened for complications. A secondary finding is a high proportion of normal weight children with lipid levels outside desirable healthy ranges.

Endothelial function and carotid intima-medial thickness in adolescents with type 2 diabetes mellitus.

OBJECTIVE: We assessed the effect of type 2 diabetes mellitus and obesity on flow-mediated dilation (FMD) and endothelial-dependent vasodilation and carotid intima-medial thickness (cIMT) in young people. STUDY DESIGN: Adolescents were recruited in 3 groups: subjects with type 2 diabetes mellitus (n = 15), subjects who were obese and non-insulin resistant (n = 13), and lean control subjects (n = 13). Body mass index was similar in subjects with obesity and subjects with type 2 diabetes mellitus, but higher compared with that of lean control subjects (both P < .001). Brachial artery FMD and cIMT were assessed by using Duplex ultrasound scanning imaging. RESULTS: There were no significant differences in brachial or common carotid arterial diameters in the groups. cIMT was significantly greater in the group with type 2 diabetes mellitus (0.54 ± 0.01mm) compared with both the lean control (0.46 ± 0.02 mm, P < .001) and obese control (0.46 ± 0.02 mm, P < .01) groups. FMD was significantly decreased in the group with type 2 diabetes mellitus (7.98% ± 0.54%) compared with the lean group (10.40% ± 1.00%, P < .05). CONCLUSIONS: Measures of vascular health were impaired in adolescents with type 2 diabetes mellitus compared with lean and obese adolescents who were not insulin resistant. Measures of arterial function and structure may provide pre-clinical measures of cardiovascular disease in young people at elevated risk.

Fatness, fitness, and increased cardiovascular risk in young children.

OBJECTIVES: To investigate the relationships between cardiorespiratory fitness and adiposity among young children, and their influence on a comprehensive cardiovascular risk profile. STUDY DESIGN: The sample included 95 healthy weight, 54 overweight, and 31 obese children (n=180, 10.9+/-2.1 years). All children had a medical assessment that included a physical examination and fasting investigations including glycated hemoglobin, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, insulin and glucose levels. Body mass index and waist circumference z-scores were calculated. Children's fitness level was measured with the Queens College step test. RESULTS: Although low fitness was independently associated with cardiovascular risk, multi-level analysis demonstrated that waist circumference z-score was the only significant predictor of cardiovascular risk factors including SBP (beta=3.29, P<.001), DBP (beta=1.88, P<.005), high-density lipoprotein (beta=-0.12, P<.001), and triglyceride levels (beta=0.14, p<.001), fasting insulin (beta=2.83, P<.001), C-peptide (beta=0.11, P<.001), and HOMA-IR (beta=0.34, P<.001), with increasing waist circumference z-score associated with increasing cardiovascular risk. Within the healthy weight children, high fitness was associated with significantly reduced triglyceride levels, and lower fasting glucose, insulin and HOMA-IR. CONCLUSIONS: Young children's health may be influenced more by body fatness, and in particular, the distribution of body fat than by cardiorespiratory fitness. However, within the healthy weight children, high fitness was associated with a favorable metabolic profile, suggesting that cardiorespiratory fitness may exert a protective effect on metabolic risk in children whose risk is not confounded by fatness.