Henry Boardman

Clinical cardiovascular risk during young adulthood in offspring of hypertensive pregnancies: insights from a 20-year prospective follow-up birth cohort

Objectives Offspring of hypertensive pregnancies have increased cardiovascular risk factors during childhood. We hypothesised that offspring of hypertensive pregnancies would demonstrate increased clinical levels of hypertension by young adult life, which would be proportional to the severity of the pregnancy complication. Design Prospective birth cohort study Setting Tertiary obstetric hospital. Participants 2868 young adult offspring of women enrolled during pregnancy into the Western Australia Pregnancy Cohort (Raine) Study. Main outcome measures Cardiovascular risk, including incidence of hypertension and metabolic disease, in those born to hypertensive compared to normotensive pregnancies. Results Young adult offspring of hypertensive pregnancies were 2.5 times (95% CI 1.32 to 4.56, p=0.004) more likely to have global lifetime risk (QRISK) scores above the 75th centile. Thirty per cent of 20 year olds with hypertensive blood pressures were born following a hypertensive pregnancy. Pre-eclampsia or hypertension resulting in preterm birth associated with a threefold (95% CI 1.3 to 7.0, p=0.01) greater risk of being hypertensive by age 20 years, with no differences in body mass index. Whereas pregnancy-induced hypertension associated with a smaller 3±1 mm Hg blood pressure rise (p=0.001) and a twofold (95% CI 1.5 to 2.8, p=0.001) greater risk of being obese or overweight. Risk factor associations were consistent throughout early life and independent of other birth-factors. Conclusions Incidence of offspring hypertension was significantly increased in those whose mothers had a more complicated pregnancy history, including preterm birth and pre-eclampsia.

Breast milk consumption in preterm neonates and cardiac shape in adulthood

BACKGROUND AND OBJECTIVES: Preterm birth relates to long-term alterations in cardiac morphology and function. Understanding whether preterm postnatal life is a tractable period of cardiovascular development that can be positively altered by nutrition is relevant to long-term outcomes. We hypothesized that being fed human breast milk during early postnatal life is beneficial to long-term cardiac structure and function in preterm-born individuals compared with infant formulas. METHODS: A total of 926 preterm-born infants originally took part in a randomized controlled trial of postnatal milk-feeding regimens between 1982 and 1985 across 5 different UK centers. Preterm-born individuals were randomly assigned to either breast milk donated by unrelated lactating women or nutrient-enriched formulas. We followed 102 individuals from this cohort: 30 of whom had been randomized to being fed exclusively human milk and 16 to being fed exclusively formula. As a comparison group, we recruited an additional 102 individuals born term to uncomplicated pregnancies. Cardiac morphology and function were assessed by MRI. RESULTS: Preterm-born individuals fed exclusively human milk as infants had increased left and right ventricular end-diastolic volume index (+9.73%, P = .04 and +18.2%, P < .001) and stroke volume index (+9.79%, P = .05 and +22.1%, P = .01) compared with preterm-born individuals who were exclusively formula fed as infants. CONCLUSIONS: This study provides the first evidence of a beneficial association between breast milk and cardiac morphology and function in adult life in those born preterm and supports promotion of human milk for the care of preterm infants to reduce long-term cardiovascular risk.

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm

BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

Long-term cerebral white and gray matter changes after preeclampsia

Objective: To determine whether changes in cerebral structure are present after preeclampsia that may explain increased cerebrovascular risk in these women. Methods: We conducted a case control study in women between 5 and 15 years after either a preeclamptic or normotensive pregnancy. Brain MRI was performed. Analysis of white matter structure was undertaken using voxel-based segmentation of fluid-attenuation inversion recovery sequences to assess white matter lesion volume and diffusion tensor imaging to measure microstructural integrity. Voxel-based analysis of gray matter volumes was performed with adjustment for skull size. Results: Thirty-four previously preeclamptic women (aged 42.8 ± 5.1 years) and 49 controls were included. Previously preeclamptic women had reduced cortical gray matter volume (523.2 ± 30.1 vs 544.4 ± 44.7 mL, p < 0.05) and, although both groups displayed white matter lesions, changes were more extensive in previously preeclamptic women. They displayed increased temporal lobe white matter disease (lesion volume: 23.2 ± 24.9 vs 10.9 ± 15.0 μL, p < 0.05) and altered microstructural integrity (radial diffusivity: 538 ± 19 vs 526 ± 18 × 10−6 mm2/s, p < 0.01), which also extended to occipital and parietal lobes. The degree of temporal lobe white matter change in previously preeclamptic women was independent of their current cardiovascular risk profile (p < 0.05) and increased with time from index pregnancy (p < 0.05). Conclusion: A history of preeclampsia is associated with temporal lobe white matter changes and reduced cortical volume in young women, which is out of proportion to their classic cardiovascular risk profile. The severity of changes is proportional to time since pregnancy, which would be consistent with continued accumulation of damage after pregnancy.

Will Exercise Advice Be Sufficient for Treatment of Young Adults With Prehypertension and Hypertension? A Systematic Review and Meta-Analysis.

Previous studies report benefits of exercise for blood pressure control in middle age and older adults, but longer-term effectiveness in younger adults is not well established. We performed a systematic review and meta-analysis of published randomized control trials with meta-regression of potential effect modifiers. An information specialist completed a comprehensive search of available data sources, including studies published up to June 2015. Authors applied strict inclusion and exclusion criteria to screen 9524 titles. Eligible studies recruited younger adults with a cardiovascular risk factor (with at least 25% of cohort aged 18–40 years); the intervention had a defined physical activity strategy and reported blood pressure as primary or secondary outcome. Meta-analysis included 14 studies randomizing 3614 participants, mean age 42.2±6.3 (SD) years. At 3 to 6 months, exercise was associated with a reduction in systolic blood pressure of −4.40 mm Hg (95% confidence interval, −5.78 to −3.01) and in diastolic blood pressure of −4.17 mm Hg (95% confidence interval, −5.42 to −2.93). Intervention effect was not significantly influenced by baseline blood pressure, body weight, or subsequent weight loss. Observed intervention effect was lost after 12 months of follow-up with no reported benefit over control, mean difference in systolic blood pressure −1.02 mm Hg (95% confidence interval, −2.34 to 0.29), and in diastolic blood pressure −0.91 mm Hg (95% confidence interval, −1.85 to 0.02). Current exercise guidance provided to reduce blood pressure in younger adults is unlikely to benefit long-term cardiovascular risk. There is need for continued research to improve age-specific strategies and recommendations for hypertension prevention and management in young adults.

Comprehensive multi-modality assessment of regional and global arterial structure and function in adults born preterm

Preterm birth is associated with higher blood pressure, which could be because preterm birth alters early aortic elastin and collagen development to cause increased arterial stiffness. We measured central and conduit artery size and multiple indices of arterial stiffness to define the extent and severity of macrovascular changes in individuals born preterm. A total of 102 young adults born preterm and 102 controls who were born after an uncomplicated pregnancy underwent cardiovascular magnetic resonance on a Siemens 1.5 T scanner to measure the aortic cross-sectional area in multiple locations. Ultrasound imaging with a Philips CX50 and linear array probe was used to measure carotid and brachial artery diameters. Carotid-femoral pulse wave velocity and the augmentation index were measured by SphygmoCor, brachial-femoral pulse wave velocity by Vicorder and aortic pulse wave velocity by cardiovascular magnetic resonance. The cardio-ankle vascular index (CAVI) was used as a measurement of global stiffness, and ultrasound was used to assess peripheral vessel distensibility. Adults born preterm had 20% smaller thoracic and abdominal aortic lumens (2.19±0.44 vs. 2.69±0.60 cm2, P<0.001; 1.25±0.36 vs. 1.94±0.45 cm2, P<0.001, respectively) but similar carotid and brachial diameters to adults born at term. Pulse wave velocity was increased (5.82±0.80 vs. 5.47±0.59 m s−1, P<0.01, 9.06±1.25 vs. 8.33±1.28 m s−1, P=0.01, 5.23±1.19 vs. 4.75±0.91 m s−1, P<0.01) and carotid distensibility was decreased (4.75±1.31 vs. 5.60±1.48 mm Hg−1103, P<0.001) in this group compared with the group born at term. However, the global and peripheral arterial stiffness measured by CAVI and brachial ultrasound did not differ (5.95±0.72 vs. 5.98±0.60, P=0.80 and 1.07±0.48 vs. 1.19±0.54 mm Hg−1103, P=0.12, respectively). Adults who are born preterm have significant differences in their aortic structure from adults born at term, but they have relatively small differences in central arterial stiffness that may be partially explained by blood pressure variations.

Physiological Stress Elicits Impaired Left Ventricular Function in Preterm-Born Adults.

Background Experimental and clinical studies show that prematurity leads to altered left ventricular (LV) structure and function with preserved resting LV ejection fraction (EF). Large-scale epidemiological data now links prematurity to increased early heart failure risk. Objectives The authors performed echocardiographic imaging at prescribed exercise intensities to determine whether preterm-born adults have impaired LV functional response to physical exercise. Methods We recruited 101 normotensive young adults born preterm (n = 47; mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) for detailed cardiovascular phenotyping. Full clinical resting and exercise stress echocardiograms were performed, with apical 4-chamber views collected while exercising at 40%, 60%, and 80% of peak exercise capacity, determined by maximal cardiopulmonary exercise testing. Results Preterm-born individuals had greater LV mass (p = 0.015) with lower peak systolic longitudinal strain (p = 0.038) and similar EF to term-born control subjects at rest (p = 0.62). However, by 60% exercise intensity, EF was 6.7% lower in preterm subjects (71.9 ± 8.7% vs 78.6 ± 5.4%; p = 0.004) and further declined to 7.3% below the term-born group at 80% exercise intensity (69.8 ± 6.4% vs 77.1 ± 6.3%; p = 0.004). Submaximal cardiac output reserve was 56% lower in preterm-born subjects versus term-born control subjects at 40% of peak exercise capacity (729 ± 1,162 ml/min/m2 vs. 1,669 ± 937 ml/min/m2; p = 0.021). LV length and resting peak systolic longitudinal strain predicted EF increase from rest to 60% exercise intensity in the preterm group (r = 0.68, p = 0.009 and r = 0.56, p = 0.031, respectively). Conclusions Preterm-born young adults had impaired LV response to physiological stress when subjected to physical exercise, which suggested a reduced myocardial functional reserve that might help explain their increased risk of early heart failure. (Young Adult Cardiovascular Health sTudy [YACHT]; NCT02103231)

Time to rethink physical activity advice and blood pressure: A role for occupation-based interventions?

Cardiovascular death is the leading cause of mortality in women. Low physical fitness and sedentary behaviour are recognized as major risk factors and increased physical activity is therefore promoted as a strategy to reduce cardiovascular risk. Recommendations advise at least 150 minutes of moderate to vigorous activity per week and, when possible, reduced sitting time, with cardiovascular benefits gained from as little as 15 minutes of exercise per day. The same recommendations apply to patients with a history of cardiovascular disease, such as myocardial infarction or chronic heart failure, and systematic review evidence supports the use of aerobic exercise and resistance training in other chronic disease management settings, including blood pressure control. A major challenge for the health care community is the delivery of affordable interventions, which maintain increased physical activity behaviour in the long term, to sustain the health benefits. Environmental and lifestyle modifications across a range of domains – including transport, leisure, home and education – provide an important opportunity to increase activity within a population. Workplacebased physical activity interventions in particular have been identified as a way to provide effective risk reduction and, reassuringly, the reported incidence of serious adverse events in randomized control trials and within disease populations undergoing cardiac rehabilitation programmes is low. However, despite this volume of evidence that physical activity is good, it is possible that cardiovascular risk is increased in some people during certain types of exercise. Physical activity increases blood pressure, with heavy resistance exercise being associated with the most extreme transient changes in systolic levels. This type of static exercise reduces venous return and increases the cardiac afterload as well as strain. The presence of disease may further exacerbate these increases in blood pressure as people at risk of hypertension are known to have an exaggerated blood pressure response to exercise. People who exhibit this response are at increased risk of stroke and cardiovascular death. Similar transient physiological stresses to those observed in resistance exercise programmes may occur in occupational settings where people lift or manoeuvre heavy loads. Allesoe et al. have reported a prospective cohort study that explores the association between questionnaire-reported workplace physical activity and incident ischaemic heart disease retrieved from a national register of hospital discharges. They found that, in an occupational setting, self-reported high physical activity levels in women with hypertension were associated with a three-fold greater risk of future ischaemic heart disease than that seen in normotensive women who reported moderate physical activity at work. This is a novel finding in a population of over 12,000 women monitored prospectively for nearly 15 years. Previous occupation-based studies have tended to focus on male employees and therefore the authors should be commended for addressing this relevant question in a female population. There are distinct features of cardiovascular disease specific to women, such as the development of early hypertension related to pregnancy, as well as unique patterns of aortic and cardiac remodelling that may be relevant to their blood pressure response and warrant tailored primary prevention advice. The type of occupation may need to be part of this advice, but, equally, occupation may be important because it offers a setting and

Cochrane corner: oral hormone therapy and cardiovascular outcomes in post-menopausal women

![Graphic][1] Hormone therapy (HT) is commonly prescribed for the relief of climacteric symptoms in post-menopausal women; 54% (620490) of women enrolled in the Million Women Study1 in the UK (mean age 56 years) have tried it and 31% (358252) use it. Observational studies have shown oral HT is associated with lower rates of cardiovascular disease in post-menopausal women2; however randomised controlled trials (RCTs) have presented mixed results. The 2002 publication of the Womens Health Initiative I (WHI I) reported an association between combined oestrogen and progestin use and increased rates of both coronary heart disease and stroke. Subsequent publication of the Womens Health Initiative II (WHI II) reported an association between oestrogen and increased rates of stroke. These publications, and the significant publicity that they received, led to a reduction in prescriptions of oral HT. It also led to several RCTs assessing HT and cardiovascular outcomes stopping before their planned end date. However, post hoc analysis of the WHI data has suggested that associations between oral HT and cardiovascular outcomes are not uniform across all age groups. The mean ages at recruitment in WHI I and WHI II were early to mid-60s; more than a decade after the mean age of initiation of menopause, when post-menopausal women most commonly suffer from climacteric symptoms. This subgroup analysis demonstrated there was a trend to reduced likelihood of cardiovascular outcomes in women who started HT before the age of 60.3 In 2012, the Danish Osteoporosis Prevention Study (DOPS) was published. It was designed to assess the effect of oral HT on osteoporosis and cardiovascular outcomes and … [1]: /embed/inline-graphic-1.gif

Oxfordshire Women and Their Children's Health (OxWATCH): protocol for a prospective cohort feasibility study.

Introduction Some specific pregnancy disorders are known to be associated with increased incidence of long-term maternal ill health (eg, gestational diabetes with late onset type 2 diabetes; pre-eclampsia with arterial disease). To what degree these later health conditions are a consequence of the womans constitution prior to pregnancy rather than pregnancy itself triggering changes in a womans health is unknown. Additionally, there is little prospective evidence for the impact of pre-pregnancy risk factors on the outcome of pregnancy. To understand the importance of pre-pregnancy health requires the recruitment of women into a long-term cohort study before their first successful pregnancy. The aim of this feasibility study is to test recruitment procedures and acceptability of participation to inform the planning of a future large-scale cohort study. Methods The prospective cohort feasibility study will recruit nulliparous women aged 18–40 years. Women will be asked to complete a questionnaire to assess the acceptability of our recruitment and data collection procedures. Baseline biophysical, genetic, socioeconomic, behavioural and psychological assessments will be conducted and samples of blood, urine, saliva and DNA will be collected. Recruitment feasibility and retention rates will be assessed. Women who become pregnant will be recalled for pregnancy and postpregnancy assessments. Ethics and dissemination The study protocol was approved by South Central Portsmouth REC (Ref: 12/SC/0492). The findings from the study will be disseminated through peer reviewed journals, national and international conference presentations and public events. Trial registration number http://www.clinicaltrials.gov; NCT02419898.