Preterm heart in adult life: cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry, and function.

BACKGROUND: Preterm birth leads to an early switch from fetal to postnatal circulation before completion of left ventricular in utero development. In animal studies, this results in an adversely remodeled left ventricle. We determined whether preterm birth is associated with a distinct left ventricular structure and function in humans. METHODS AND RESULTS: A total of 234 individuals 20 to 39 years of age underwent cardiovascular magnetic resonance. One hundred two had been followed prospectively since preterm birth (gestational age=30.3±2.5 week; birth weight=1.3±0.3 kg), and 132 were born at term to uncomplicated pregnancies. Longitudinal and short-axis cine images were used to quantify left ventricular mass, 3-dimensional geometric variation by creation of a unique computational cardiac atlas, and myocardial function. We then determined whether perinatal factors modify these left ventricular parameters. Individuals born preterm had increased left ventricular mass (66.5±10.9 versus 55.4±11.4 g/m(2); P<0.001) with greater prematurity associated with greater mass (r = -0.22, P=0.03). Preterm-born individuals had short left ventricles with small internal diameters and a displaced apex. Ejection fraction was preserved (P>0.99), but both longitudinal systolic (peak strain, strain rate, and velocity, P<0.001) and diastolic (peak strain rate and velocity, P<0.001) function and rotational (apical and basal peak systolic rotation rate, P =0.05 and P =0.006; net twist angle, P=0.02) movement were significantly reduced. A diagnosis of preeclampsia during the pregnancy was associated with further reductions in longitudinal peak systolic strain in the offspring (P=0.02, n=29). CONCLUSIONS: Individuals born preterm have increased left ventricular mass in adult life. Furthermore, they exhibit a unique 3-dimensional left ventricular geometry and significant reductions in systolic and diastolic functional parameters. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01487824.

Global and regional left ventricular myocardial deformation measures by magnetic resonance feature tracking in healthy volunteers: comparison with tagging and relevance of gender.

BACKGROUND: Feature tracking software offers measurements of myocardial strain, velocities and displacement from cine cardiovascular magnetic resonance (CMR) images. We used it to record deformation parameters in healthy adults and compared values to those obtained by tagging. METHODS: We used TomTec 2D Cardiac Performance Analysis software to derive global, regional and segmental myocardial deformation parameters in 145 healthy volunteers who had steady state free precession (SSFP) cine left ventricular short (basal, mid and apical levels) and long axis views (horizontal long axis, vertical long axis and left ventricular out flow tract) obtained on a 1.5 T Siemens Sonata scanner. 20 subjects also had tagged acquisitions and we compared global and regional deformation values obtained from these with those from Feature Tracking. RESULTS: For globally averaged measurements of strain, only those measured circumferentially in short axis slices showed reasonably good levels of agreement between FT and tagging (limits of agreement -0.06 to 0.04). Longitudinal strain showed wide limits of agreement (-0.16 to 0.03) with evidence of overestimation of strain by FT relative to tagging as the mean of both measures increased. Radial strain was systematically overestimated by FT relative to tagging with very wide limits of agreement extending to as much as 100% of the mean value (-0.01 to 0.23). Reproducibility showed similar relative trends with acceptable global inter-observer variability for circumferential measures (coefficient of variation 4.9%) but poor reproducibility in the radial direction (coefficient of variation 32.3%). Ranges for deformation parameters varied between basal, mid and apical LV levels with higher levels at base compared to apex, and between genders by both FT and tagging. CONCLUSIONS: FT measurements of circumferential but not longitudinally or radially directed global strain showed reasonable agreement with tagging and acceptable inter-observer reproducibility. We record provisional ranges of FT deformation parameters at global, regional and segmental levels. They show evidence of variation with gender and myocardial region in the volunteers studied, but have yet to be compared with tagging measurements at the segmental level.

Normal variation of magnetic resonance T1 relaxation times in the human population at 1.5 T using ShMOLLI.

BACKGROUND: Quantitative T1-mapping is rapidly becoming a clinical tool in cardiovascular magnetic resonance (CMR) to objectively distinguish normal from diseased myocardium. The usefulness of any quantitative technique to identify disease lies in its ability to detect significant differences from an established range of normal values. We aimed to assess the variability of myocardial T1 relaxation times in the normal human population estimated with recently proposed Shortened Modified Look-Locker Inversion recovery (ShMOLLI) T1 mapping technique. METHODS: A large cohort of healthy volunteers (n = 342, 50% females, age 11-69 years) from 3 clinical centres across two countries underwent CMR at 1.5T. Each examination provided a single average myocardial ShMOLLI T1 estimate using manually drawn myocardial contours on typically 3 short axis slices (average 3.4 ± 1.4), taking care not to include any blood pool in the myocardial contours. We established the normal reference range of myocardial and blood T1 values, and assessed the effect of potential confounding factors, including artefacts, partial volume, repeated measurements, age, gender, body size, hematocrit and heart rate. RESULTS: Native myocardial ShMOLLI T1 was 962 ± 25 ms. We identify the partial volume as primary source of potential error in the analysis of respective T1 maps and use 1 pixel erosion to represent "midwall myocardial" T1, resulting in a 0.9% decrease to 953 ± 23 ms. Midwall myocardial ShMOLLI T1 was reproducible with an intra-individual, intra- and inter-scanner variability of ≤2%. The principle biological parameter influencing myocardial ShMOLLI T1 was the female gender, with female T1 longer by 24 ms up to the age of 45 years, after which there was no significant difference from males. After correction for age and gender dependencies, heart rate was the only other physiologic factor with a small effect on myocardial ShMOLLI T1 (6ms/10bpm). Left and right ventricular blood ShMOLLI T1 correlated strongly with each other and also with myocardial T1 with the slope of 0.1 that is justifiable by the resting partition of blood volume in myocardial tissue. Overall, the effect of all variables on myocardial ShMOLLI T1 was within 2% of relative changes from the average. CONCLUSION: Native T1-mapping using ShMOLLI generates reproducible and consistent results in normal individuals within 2% of relative changes from the average, well below the effects of most acute forms of myocardial disease. The main potential confounder is the partial volume effect arising from over-inclusion of neighbouring tissue at the manual stages of image analysis. In the study of cardiac conditions such as diffuse fibrosis or small focal changes, the use of "myocardial midwall" T1, age and gender matching, and compensation for heart rate differences may all help to improve the method sensitivity in detecting subtle changes. As the accuracy of current T1 measurement methods remains to be established, this study does not claim to report an accurate measure of T1, but that ShMOLLI is a stable and reproducible method for T1-mapping.

Digitally enabled acute care for atrial fibrillation: conception, feasibility and early outcomes of an AF virtual ward.

BACKGROUND: Atrial fibrillation (AF) represents a growing healthcare challenge, mainly driven by acute hospitalisations. Virtual wards could be the way forward to manage acute AF patients through remote monitoring, especially with the rise in global access to digital telecommunication and the growing acceptance of telemedicine post-COVID-19. METHODS: An AF virtual ward was implemented as a proof-of-concept care model. Patients presenting acutely with AF or atrial flutter and rapid ventricular response to the hospital were onboarded to the virtual ward and managed at home through remote ECG-monitoring and 'virtual' ward rounds, after being given access to a single-lead ECG device, a blood pressure monitor and pulse oximeter with instructions to record daily ECGs, blood pressure, oxygen saturations and to complete an online AF symptom questionnaire. Data were uploaded to a digital platform for daily review by the clinical team. Primary outcomes included admission avoidance, readmission avoidance and patient satisfaction. Safety outcomes included unplanned discharge from the virtual ward, cardiovascular mortality and all-cause mortality. RESULTS: There were 50 admissions to the virtual ward between January and August 2022. Twenty-four of them avoided initial hospital admission as patients were directly enrolled to the virtual ward from outpatient settings. A further 25 readmissions were appropriately prevented during virtual surveillance. Patient satisfaction questionnaires yielded 100% positive responses among participants. There were three unplanned discharges from the virtual ward requiring hospitalisation. Mean heart rate on admission to the virtual ward and discharge was 122±26 and 82±27 bpm respectively. A rhythm control strategy was pursued in 82% (n=41) and 20% (n=10) required 3 or more remote pharmacological interventions. CONCLUSION: This is a first real-world experience of an AF virtual ward that heralds a potential means for reducing AF hospitalisations and the associated financial burden, without compromising on patients' care or safety.

Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies.

Pre-eclampsia is increasingly recognized as more than an isolated disease of pregnancy. Women who have had a pregnancy complicated by pre-eclampsia have a 4-fold increased risk of later cardiovascular disease. Intriguingly, the offspring of affected pregnancies also have an increased risk of higher blood pressure and almost double the risk of stroke in later life. Experimental approaches to identify the key features of pre-eclampsia responsible for this programming of offspring cardiovascular health, or the key biological pathways modified in the offspring, have the potential to highlight novel targets for early primary prevention strategies. As pre-eclampsia occurs in 2-5% of all pregnancies, the findings are relevant to the current healthcare of up to 3 million people in the U.K. and 15 million people in the U.S.A. In the present paper, we review the current literature that concerns potential mechanisms for adverse cardiovascular programming in offspring exposed to pre-eclampsia, considering two major areas of investigation: first, experimental models that mimic features of the in utero environment characteristic of pre-eclampsia, and secondly, how, in humans, offspring cardiovascular phenotype is altered after exposure to pre-eclampsia. We compare and contrast the findings from these two bodies of work to develop insights into the likely key pathways of relevance. The present review and analysis highlights the pivotal role of long-term changes in vascular function and identifies areas of growing interest, specifically, response to hypoxia, immune modification, epigenetics and the anti-angiogenic in utero milieu.

Short-term exposure to exogenous lipids in premature infants and long-term changes in aortic and cardiac function.

OBJECTIVE: Intravenous lipid use is associated with an acute hyperlipidemia, but long-term consequences have not been studied. We investigated whether elevated lipids in humans during the critical period of preterm neonatal life have a long-term impact on aortic and myocardial function relevant to adult disease. METHODS AND RESULTS: We followed up 102 subjects born prematurely and now aged 23 to 28 years. Eighteen received intravenous lipids as neonates and were matched to controls with equivalent perinatal characteristics. Global and regional aortic stiffness and left ventricular function were assessed by cardiovascular magnetic resonance. Those who received intravenous lipids had greater aortic stiffness in early adulthood (P=0.0002), with greater stiffness in the abdominal aorta (P=0.012). The relationship was graded according to the elevation in neonatal cholesterol induced by intravenous lipids (P<0.0001) but not other metabolic parameters altered by the infusion. Peak systolic circumferential strain was also reduced in the lipid group (P=0.006), which, again, was proportional to neonatal cholesterol level (P<0.01). CONCLUSIONS: Aortic and myocardial function in young adulthood is associated with intralipid exposure during neonatal life for preterm infants, in a graded manner related to the rise in cholesterol. Circulating cholesterol during critical developmental periods may have long-term impacts on the human cardiovascular system.

Variations in Cardiovascular Structure, Function, and Geometry in Midlife Associated With a History of Hypertensive Pregnancy.

Hypertensive pregnancy is associated with increased maternal cardiovascular risk in later life. A range of cardiovascular adaptations after pregnancy have been reported to partly explain this risk. We used multimodality imaging to identify whether, by midlife, any pregnancy-associated phenotypes were still identifiable and to what extent they could be explained by blood pressure. Participants were identified by review of hospital maternity records 5 to 10 years after pregnancy and invited to a single visit for detailed cardiovascular imaging phenotyping. One hundred seventy-three women (age, 42±5 years, 70 after normotensive and 103 after hypertensive pregnancy) underwent magnetic resonance imaging of the heart and aorta, echocardiography, and vascular assessment, including capillaroscopy. Women with a history of hypertensive pregnancy had a distinct cardiac geometry with higher left ventricular mass index (49.9±7.1 versus 46.0±6.5 g/m2; P=0.001) and ejection fraction (65.6±5.4% versus 63.7±4.3%; P=0.03) but lower global longitudinal strain (-18.31±4.46% versus -19.94±3.59%; P=0.02). Left atrial volume index was also increased (40.4±9.2 versus 37.3±7.3 mL/m2; P=0.03) and E:A reduced (1.34±0.35 versus 1.52±0.45; P=0.003). Aortic compliance (0.240±0.053 versus 0.258±0.063; P=0.046) and functional capillary density (105.4±23.0 versus 115.2±20.9 capillaries/mm2; P=0.01) were reduced. Only differences in functional capillary density, left ventricular mass, and atrial volume indices remained after adjustment for blood pressure (P<0.01, P=0.01, and P=0.04, respectively). Differences in cardiac structure and geometry, as well as microvascular rarefaction, are evident in midlife after a hypertensive pregnancy, independent of blood pressure. To what extent these phenotypic patterns contribute to cardiovascular disease progression or provide additional measures to improve risk stratification requires further study.

Aortic stiffness and blood pressure variability in young people: a multimodality investigation of central and peripheral vasculature.

INTRODUCTION: Increased blood pressure (BP) variability is a cardiovascular risk marker for young individuals and may relate to the ability of their aorta to buffer cardiac output. We used a multimodality approach to determine relations between central and peripheral arterial stiffness and BP variability. METHODS: We studied 152 adults (mean age of 31 years) who had BP variability measures based on SD of awake ambulatory BPs, 24-h weighted SD and average real variability (ARV). Global and regional aortic distensibility was measured by cardiovascular magnetic resonance, arterial stiffness by cardio-ankle vascular index (CAVI) and pulse wave velocity (PWV) by SphygmoCor (carotid-femoral) and Vicorder (brachial-femoral). RESULTS: In young people, free from overt cardiovascular disease, all indices of SBP and DBP variability correlated with aortic distensibility (global aortic distensibility versus awake SBP SD: r = -0.39, P < 0.001; SBP ARV: r = -0.34, P < 0.001; weighted 24-h SBP SD: r = -0.42, P < 0.001). CAVI, which closely associated with aortic distensibility, also related to DBP variability, as well as awake SBP SD (r = 0.19, P < 0.05) and weighted 24-h SBP SD (r = 0.24, P < 0.01), with a trend for SBP ARV (r = 0.17, P = 0.06). In contrast, associations with PWV were only between carotid-femoral PWV and weighted SD of SBP (r = 0.20, P = 0.03) as well as weighted and ARV of DBP. CONCLUSION: Greater BP variability in young people relates to increases in central aortic stiffness, strategies to measure and protect aortic function from a young age may be important to reduce cardiovascular risk.

Chronic Activation of γ2 AMPK Induces Obesity and Reduces ß Cell Function.

Despite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK γ2 subunit, exhibit ghrelin signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation throughout all tissues can have adverse metabolic consequences, with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease.

From gene to epigene-based therapies targeting the vascular endothelium.

Vascular endothelial dysfunction is a key biological process underlying the development of cardiovascular disease and therefore of potential importance as a target for gene-based therapy. Modification of nitric oxide bioavailability through gene therapy is possible in animal studies and of clinical relevance because of the central role for nitric oxide in vascular homeostasis. However, most clinical trials have so far focused on endothelial-related pathways, in particular, vascular endothelial growth factor, to induce angiogenesis, with variable results. The slow progress of the development of gene-therapy targeted at the endothelium relates to a range of complexities of design of therapy including mode of gene delivery. This is usually achieved through the use of viral or non-viral vectors but the best physical and vector methods for delivery of complimentary DNA to the vascular endothelium remains under investigation. More recently there has been emerging interest into other genome-based methods to alter vascular phenotype, in particular, gene-based modification of endothelial progenitor cell function and whether gene function might be modifiable through induced epigenetic changes.

Prevention of vascular dysfunction after preeclampsia: a potential long-term outcome measure and an emerging goal for treatment.

Preeclampsia is increasingly being recognised as more than an isolated disease of pregnancy. In particular, preeclampsia has emerged as an independent risk factor for maternal cardiovascular disease and has recently been recognised as a risk factor for cardiovascular disease in children exposed in utero. Preeclampsia and cardiovascular disease may share important pathophysiological and molecular mechanisms and further investigation into these is likely to offer insight into the origins of both conditions. This paper considers the links between cardiovascular disease and preeclampsia and the implication of these findings for refinement of the management of patients whose care is complicated by preeclampsia.

Impaired endothelial responses in apparently healthy young people associated with subclinical variation in blood pressure and cardiovascular phenotype.

BACKGROUND: A phenomenon of endothelial impairment, independent of classical cardiovascular risk factors, has been observed in young people. We identified subjects with persistently reduced, or declining, endothelial function during adolescence and early adulthood, without apparent cardiovascular risk, and investigated the clinical relevance of this finding. METHODS: Endothelial vasomotor responses were assessed by brachial artery flow-mediated dilatation (FMD) at age 15 years in 47 subjects (22 males) who returned for a repeated measurement at age 25. Subjects underwent quantification of left ventricular mass (LVM) and function by cardiovascular magnetic resonance, central arterial stiffness by applanation tonometry, and common carotid artery intima-media thickness using ultrasound on their visit at age 25. RESULTS: Individuals with low average FMD over 10-year period, although normotensive, had 5 mm Hg higher systolic blood pressure and, significantly greater LVM (73.48 ± 7.73 vs. 56.25 ± 9.54 g/m(2), P = 0.0001), carotid intima-media thickness (cIMT) (0.53 ± 0.06 vs. 0.47 ± 0.04 mm, P = 0.03), and pulse wave velocity (5.97 ± 0.63 vs. 5.29 ± 0.59 m/s, P = 0.02) than those with higher endothelial responses. Subjects with the greatest decline in FMD over 10 years had a significant increase in mean arterial pressure but similar cardiovascular phenotype. CONCLUSION: Persistently reduced, or declining, endothelial function during adolescence, in the absence of overt cardiovascular disease, is a sensitive early marker associated with subclinical changes in blood pressure (BP) and an adverse cardiovascular phenotype. The findings highlight the potential importance of endothelial responses during adolescence in primary prevention strategies for hypertension.

Cardiovascular risk factors in children and young adults born to preeclamptic pregnancies: a systematic review.

BACKGROUND AND OBJECTIVE: Preeclampsia is an independent cardiovascular risk factor for the mother, and recent studies reveal that offspring of affected pregnancies also may have an increased cardiovascular risk. Our objective was to examine evidence for increased cardiovascular risk factors in children exposed to preeclampsia in utero. METHODS: We performed a systematic review and meta-analysis on studies reporting traditional cardiovascular risk factors in those exposed to preeclampsia compared to controls. Information was extracted on the classic cardiovascular risk factors, including blood pressure, lipid profile, glucose metabolism, and BMI from articles published between 1948 and August 2011 in Medline and Embase. RESULTS: Eighteen studies provided cumulated data on 45,249 individuals. In utero exposure to preeclampsia was associated with a 2.39 mm Hg (95% confidence interval: 1.74-3.05; P < .0001) higher systolic and a 1.35 mm Hg (95% confidence interval: 0.90-1.80; P < .00001) higher diastolic blood pressure during childhood and young adulthood. BMI was increased by 0.62 kg/m2 (P < .00001). Associations were similar in children and adolescents, for different genders, and with variation in birth weight. There was insufficient evidence to identify consistent variation in lipid profile or glucose metabolism. CONCLUSIONS: Young offspring of pregnancies complicated by preeclampsia already have increased blood pressure and BMI, a finding that may need to be considered in future primary prevention strategies for cardiovascular disease.

Antenatal glucocorticoid exposure and long-term alterations in aortic function and glucose metabolism.

OBJECTIVE: Animal studies have demonstrated long-term effects of in utero glucocortcoid exposure on vascular development and glucose metabolism. We hypothesized that there would be a similar impact in humans. METHODS: One hundred and two young adults born preterm aged 23 to 28 years, with prospective data collection from birth, and 95 adults born term after uncomplicated pregnancies underwent cardiovascular MRI. We compared cardiac and aortic structure and function, as well as cardiovascular risk profile, in a nested case-control study of 16 participants exposed to antenatal steroids and 32 who were not, but with otherwise similar perinatal care. Outcomes were compared with normal ranges in those born term. RESULTS: Adults whose mothers had received antenatal steroids had decreased ascending aortic distensibility (9.88 ± 3.21 vs 13.62 ± 3.88 mm Hg(-1) × 10(3), P = .002) and increased aortic arch pulse wave velocity (5.45 ± 1.41 vs 4.47 ± 0.91 m/s, P = .006). The increase in stiffness was equivalent to that of term adults a decade older. Those who had in utero exposure to antenatal steroids also had significant differences in homeostatic model assessments for ß-cell function (P = .010), but in multiple regression analysis this did not explain the impact of steroids on aortic function. CONCLUSIONS: Antenatal glucocorticoid exposure in preterm infants is associated with increased aortic arch stiffness and altered glucose metabolism in early adulthood.

Unique blood pressure characteristics in mother and offspring after early onset preeclampsia.

Risk of hypertension in mother and offspring after preeclampsia is greater if preeclampsia develops early in pregnancy. We investigated whether those who develop early onset disease have unique adverse blood pressure characteristics. One hundred forty women were studied 6 to 13 years either after a pregnancy complicated by preeclampsia (45 women with early onset preeclampsia before 34 weeks gestation and 45 women with late-onset preeclampsia) or after a normotensive pregnancy (50 women). Forty-seven offspring from these pregnancies also participated. Data on maternal antenatal and postnatal blood pressures were extracted from maternity records and related to peripheral, central, and ambulatory blood pressure measurements in later life. Compared with late-onset preeclampsia, early onset preeclampsia was associated with higher diastolic blood pressure 6 weeks postnatally (86.25 ± 13.46 versus 75.00 ± 5.00 mm Hg, P<0.05), a greater increase in blood pressure relative to booking blood pressure over the subsequent 6 to 13 years, and higher nocturnal systolic and diastolic blood pressures in later life (111.07 ± 13.18 versus 101.13 ± 11.50 mm Hg, P=0.04, and 67.00 ± 7.25 versus 58.60 ± 5.79 mm Hg, P=0.002). Furthermore, at age 6 to 13 years their offspring had higher systolic blood pressure compared with those born to late-onset preeclampsia (96.27 ± 7.30 versus 88.39 ± 7.57 mm Hg, P=0.005). Mothers who developed early onset preeclampsia, and the offspring of that pregnancy display specific adverse blood pressure characteristics later in life. These are not evident in mothers and offspring after late-onset preeclampsia or normotensive pregnancy.

Elevated blood pressure in offspring born premature to hypertensive pregnancy: is endothelial dysfunction the underlying vascular mechanism?

Offspring born to mothers with hypertensive pregnancy have higher childhood blood pressure. We hypothesized this relates to prenatally programmed differences in the underlying vascular pathophysiology of the offspring and that these would be most apparent in those born preterm because of severe hypertension. We carried out a 20-year follow-up study of 71 subjects born preterm, 19 to a hypertensive pregnancy and 52 to a normotensive pregnancy. Findings were compared with 38 subjects born at term to uncomplicated pregnancies. Peripheral and central blood pressures were measured, and then central arterial stiffness was assessed by carotid-femoral pulse wave velocity using applanation tonometry. Ultrasound was used to assess flow-mediated endothelial-dependent and independent brachial artery responses and common carotid artery intima-media thickness. Offspring born preterm to either hypertensive or normotensive pregnancy had higher peripheral and central blood pressure compared with full-term born offspring (central mean arterial pressure after preterm hypertensive pregnancy: 84.92+/-7.0 mm Hg; preterm normotensive pregnancy: 84.13+/-8.9 mm Hg; full-term pregnancy: 76.24+/-7.96 mm Hg; P=0.0009). However, underlying vascular phenotype differed. Preterm offspring of normotensive pregnancy had greater arterial stiffness than offspring of hypertensive pregnancy (5.92+/-0.84 versus 5.42+/-0.73 m/s; P=0.039), whereas offspring of hypertensive pregnancy had greater carotid intima-media thickness (0.52+/-0.04 versus 0.48+/-0.06 mm; P=0.013) and 30% lower flow-mediated dilatation (4.25+/-4.02% versus 6.79+/-4.38%; P=0.05). Prematurity is associated with elevated blood pressure in later life. However, predominant underlying vascular phenotype depends on maternal pathology. Targeting endothelial function may be particularly important for primary prevention after hypertension in pregnancy.