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Aims Stress echocardiography is widely used to identify obstructive coronary artery disease (CAD). High accuracy is reported in expert hands but is dependent on operator training and image quality. The EVAREST study provides UK-wide data to evaluate real-world performance and accuracy of stress echocardiography. Methods and results Participants undergoing stress echocardiography for CAD were recruited from 31 hospitals. Participants were followed up through health records which underwent expert adjudication. Cardiac outcome was defined as anatomically or functionally significant stenosis on angiography, revascularization, medical management of ischaemia, acute coronary syndrome, or cardiac-related death within 6 months. A total of 5131 patients (55% male) participated with a median age of 65 years (interquartile range 57–74). 72.9% of studies used dobutamine and 68.5% were contrast studies. Inducible ischaemia was present in 19.3% of scans. Sensitivity and specificity for prediction of a cardiac outcome were 95.4% and 96.0%, respectively, with an accuracy of 95.9%. Sub-group analysis revealed high levels of predictive accuracy across a wide range of patient and protocol sub-groups, with the presence of a resting regional wall motion abnormalitiy significantly reducing the performance of both dobutamine (P Conclusion Stress echocardiography has high accuracy across UK-based hospitals and thus indicates stress echocardiography is being delivered effectively in real-world practice, reinforcing its role as a first-line investigation in the assessment of patients with stable chest pain.

Supplemental Digital Content is available in the text., 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

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model), Treatment of hypertension and its complications remains a major ongoing health care challenge. Around 25% of heart attacks in Europe are already attributed to hypertension and by 2025 up to 60% of the population will have hypertension. Physical inactivity has contributed to the rising prevalence of hypertension, but patients who exercise or engage in physical activity reduce their risk of stroke, myocardial infarction, and cardiovascular mortality. Hence, current international guidelines on cardiovascular disease prevention provide generic advice to increase aerobic activity, but physiological responses differ with blood pressure (BP) level, and greater reductions in BP across a population may be achievable with more personalized advice. We performed a systematic review of meta-analyses to determine whether there was sufficient evidence for a scientific Consensus Document reporting how exercise prescription could be personalized for BP control. The document discusses the findings of 34 meta-analyses on BP-lowering effects of aerobic endurance training, dynamic resistance training as well as isometric resistance training in patients with hypertension, high-normal, and individuals with normal BP. As a main finding, there was sufficient evidence from the meta-review, based on the estimated range of exercise-induced BP reduction, the number of randomized controlled trials, and the quality score, to propose that type of exercise can be prescribed according to initial BP level, although considerable research gaps remain. Therefore, this evidence-based Consensus Document proposes further work to encourage and develop more frequent use of personalized exercise prescription to optimize lifestyle interventions for the prevention and treatment of hypertension.

Background Stress echocardiography has become established as the most widely applied non-invasive imaging test for diagnosis of coronary artery disease within the UK. However, stress echocardiography has been substantially qualitative, rather than quantitative, based on visual wall motion assessment. For the first time, we have identified and validated quantitative descriptors of cardiac geometry and motion, extracted from ultrasound images acquired using contrast agents in an automated way. Purpose To establish whether these novel imaging features can be generated in an automated, quantifiable and reproducible way from images acquired with perfluoropropane contrast, as well as investigating how these extracted measures compare to those extracted from sulphur hexafluoride contrast and non-contrast studies. Methods 100 patients who received perfluoropropane contrast during their stress echocardiogram were recruited. Their stress echocardiography images were processed through a deep learning algorithm. Novel feature values were recorded and a subset of 10 studies were repeated. The automated measures of global longitudinal strain (GLS) and ejection fraction (EF) extracted from these images were compared to values previously extracted from sulphur hexafluoride contrast and non-contrast images using the same software. Results A full set of 31 novel imaging features were successfully extracted from 79 studies acquired using the perfluoropropane contrast agent with a dropout rate of 14% (n=92, 8 incomplete image sets). Repeated analysis in a subset of 10 perfluoropropane cases demonstrated excellent reproducibility of the extracted feature values (R2=1). Automated values of GLS and EF, at both rest (GLS = −16.4±4.8%, EF = 63±13%) and stress stages (GLS = −17.7±5.8%, EF = 68±11%), were extracted from 83 perfluoropropane studies, with a dropout rate of 16% (n=99, fewer incomplete sets as short axis view not required). The ranges of GLS and EF measures extracted from the perfluoropropane images were comparable to the other contrast studies (n=222) (Rest GLS = −16.8±5.8%, Rest EF = 63±10%; Stress GLS = −19.1±6.7%, Stress EF = 71±9%) and non-contrast studies (n=86) (Rest GLS = −15.7±5.3%, Rest EF = 57±10%; Stress GLS = −17.3±6.4%, Stress EF = 61±14%). Conclusions Novel features and clinically relevant measures were extracted from images acquired using perfluoropropane contrast for the first time in a fully automated and reproducible way using a deep learning algorithm. The analysis failure rate and generated measures are comparable to those extracted from images using other commonly used sulphur hexafluoride contrast agents and non-contrast stress echocardiography studies. These findings demonstrate that deep learning algorithms can be used for automated quantitative analysis of stress echocardiograms acquired using various contrast agents and in non-contrast studies to improve stress echocardiography practice. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Lantheus Medical Imaging, Inc.

Background Pregnancy complications such as preterm birth and fetal growth restriction are associated with altered prenatal and postnatal cardiac development. We studied whether there were changes related specifically to pregnancy hypertension. Methods and Results Left and right ventricular volumes, mass, and function were assessed at birth and 3 months of age by echocardiography in 134 term‐born infants. Fifty‐four had been born to mothers who had normotensive pregnancy and 80 had a diagnosis of preeclampsia or pregnancy‐induced hypertension. Differences between groups were interpreted, taking into account severity of pregnancy disorder, sex, body size, and blood pressure. Left and right ventricular mass indexed to body surface area ( LVMI and RVMI ) were similar in both groups at birth ( LVMI 20.9±3.7 versus 20.6±4.0 g/m 2 , P =0.64, RVMI 17.5±3.7 versus 18.1±4.7 g/m 2 , P =0.57). However, right ventricular end diastolic volume index was significantly smaller in those born to hypertensive pregnancy (16.8±5.3 versus 12.7±4.7 mL/m 2 , P =0.001), persisting at 3 months of age (16.4±3.2 versus 14.4±4.8 mL/m 2 , P =0.04). By 3 months of age these infants also had significantly greater LVMI and RVMI ( LVMI 24.9±4.6 versus 26.8±4.9 g/m 2 , P =0.04; RVMI 17.1±4.2 versus 21.1±3.9 g/m 2 , P RVMI and right ventricular end diastolic volume index at 3 months, but not left ventricular measures, correlated with severity of the hypertensive disorder. No differences in systolic or diastolic function were evident. Conclusions Infants born at term to a hypertensive pregnancy have evidence of both prenatal and postnatal differences in cardiac development, with right ventricular changes proportional to the severity of the pregnancy disorder. Whether differences persist long term as well as their underlying cause and relationship to increased cardiovascular risk requires further study.

Background Cardiogenic shock (CS) is a state of critical end-organ hypoperfusion due to a primary cardiac disorder. For people with refractory CS despite maximal vasopressors, inotropic support and intra-aortic balloon pump, mortality approaches 100%. Mechanical assist devices provide mechanical circulatory support (MCS) which has the ability to maintain vital organ perfusion, to unload the failing ventricle thus reduce intracardiac filling pressures which reduces pulmonary congestion, myocardial wall stress and myocardial oxygen consumption. This has been hypothesised to allow time for myocardial recovery (bridge to recovery) or allow time to come to a decision as to whether the person is a candidate for a longer-term ventricular assist device (VAD) either as a bridge to heart transplantation or as a destination therapy with a long-term VAD. Objectives To assess whether mechanical assist devices improve survival in people with acute cardiogenic shock. Search methods We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and Web of Science Core Collection in November 2019. In addition, we searched three trials registers in August 2019. We scanned reference lists and contacted experts in the field to obtain further information. There were no language restrictions. Selection criteria Randomised controlled trials on people with acute CS comparing mechanical assist devices with best current intensive care management, including intra-aortic balloon pump and inotropic support. Data collection and analysis We performed data collection and analysis according to the published protocol. Primary outcomes were survival to discharge, 30 days, 1 year and secondary outcomes included, quality of life, major adverse cardiovascular events (30 days/end of follow-up), dialysis-dependent (30 days/end of follow-up), length of hospital stay and length of intensive care unit stay and major adverse events. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of a body of evidence as it relates to the studies which contribute data to the meta-analyses for the prespecified outcomes Summary statistics for the primary endpoints were risk ratios (RR), hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Main results The search identified five studies from 4534 original citations reviewed. Two studies included acute CS of all causes randomised to treatment using TandemHeart percutaneous VAD and three studies included people with CS secondary to acute myocardial infarction who were randomised to Impella CP or best medical management. Meta-analysis was performed only to assess the 30-day survival as there were insufficient data to perform any further meta-analyses. The results from the five studies with 162 participants showed mechanical assist devices may have little or no effect on 30-day survival (RR of 1.01 95% CI 0.76 to 1.35) but the evidence is very uncertain. Complications such as sepsis, thromboembolic phenomena, bleeding and major adverse cardiovascular events were not infrequent in both the MAD and control group across the studies, but these could not be pooled due to inconsistencies in adverse event definitions and reporting. We identified four randomised control trials assessing mechanical assist devices in acute CS that are currently ongoing. Authors' conclusions There is no evidence from this review of a benefit from MCS in improving survival for people with acute CS. Further use of the technology, risk stratification and optimising the use protocols have been highlighted as potential reasons for lack of benefit and are being addressed in the current ongoing clinical trials.

Importance: Risk of stroke and brain atrophy in later life relate to levels of cardiovascular risk in early adulthood. However, it is unknown whether cerebrovascular changes are present in young adults. Objective: To examine relationships between modifiable cardiovascular risk factors and cerebrovascular structure, function, and white matter integrity in young adults. Design, Setting, and Participants: A cross-sectional observational study of 125 young adults (aged 18-40 years) without clinical evidence of cerebrovascular disease. Data collection was completed between August 2014 and May 2016 at the University of Oxford, United Kingdom. Final data collection was completed on May 31, 2016. Exposures: The number of modifiable cardiovascular risk factors at recommended levels, based on the following criteria: body mass index (BMI) 6 months; blood pressure on awake ambulatory monitoring Main Outcomes and Measures: Cerebral vessel density, caliber and tortuosity, brain white matter hyperintensity lesion count. In a subgroup (n = 52), brain blood arrival time and cerebral blood flow assessed by brain magnetic resonance imaging (MRI). Results: A total of 125 participants, mean (SD) age 25 (5) years, 49% women, with a mean (SD) score of 6.0 (1.4) modifiable cardiovascular risk factors at recommended levels, completed the cardiovascular risk assessment and brain MRI protocol. Cardiovascular risk factors were correlated with cerebrovascular morphology and white matter hyperintensity count in multivariable models. For each additional modifiable risk factor categorized as healthy, vessel density was greater by 0.3 vessels/cm3 (95% CI, 0.1-0.5; P = .003), vessel caliber was greater by 8 μm (95% CI, 3-13; P = .01), and white matter hyperintensity lesions were fewer by 1.6 lesions (95% CI, −3.0 to −0.5; P = .006). Among the 52 participants with available data, cerebral blood flow varied with vessel density and was 2.5 mL/100 g/min higher for each healthier category of a modifiable risk factor (95% CI, 0.16-4.89; P = .03). Conclusions and Relevance: In this preliminary study involving young adults without clinical evidence of cerebrovascular disease, a greater number of modifiable cardiovascular risk factors at recommended levels was associated with higher cerebral vessel density and caliber, higher cerebral blood flow, and fewer white matter hyperintensities. Further research is needed to verify these findings and determine their clinical importance.

Commentary on: Gartlehner G, Patel SV, Feltner C, et al . Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2017;318:2234–2249. There is a postmenopausal increase in the incidence of cognitive impairment, heart disease, osteoporosis, diabetes and some cancers. This has raised the question of whether hormone therapy can prevent chronic disease in asymptomatic postmenopausal women. Use of hormone therapy is associated with reduced cardiovascular and osteoporosis risk in observational studies.1 Subsequent large randomised controlled trials (RCT)2 3 cast doubt on these findings and raise concerns regarding an increased risk of harm in women randomised to receive hormone therapy. This systematic review and meta-analysis4 by the US Preventive Services Task Force (USPSTF) …

Objectives To study whether young adults with elevated blood pressure have an altered left ventricular stress response and whether this is determined by cardiac structure. Methods We recruited 148 young adults (mean age 27±5 years) with a range of blood pressures for cardiovascular phenotyping at rest with cardiac magnetic resonance. A subgroup (n=49) then underwent exercise stress echocardiography while exercising at 40%, 60%, and 80% of peak exercise capacity. Myocardial stress response was assessed from changes in ejection fraction and biochemistry (post-exercise copeptin release). Results were compared in participants with systolic or diastolic BP e 120/80 mm Hg (n=62, mean BP 129/77 mm Hg) vs. those with systolic and diastolic BP Results Resting left ventricular ejection fraction was similar between groups with higher or lower blood pressure. However, during physical exercise, despite similar achieved work load, higher blood pressure was associated with lower ejection fraction at 40% and 60% exercise load (73.9±3.25 vs. 80.0±4.54%, p Conclusions x0013_Young adults with modest blood pressure elevation have a significantly lower systolic response to exercise. The association between this altered stress response and daily functional limitations in young adulthood, as well as cardiovascular disease progression and event risk, requires further study.

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 cm(2), P0.001; 1.25 ± 0.36 vs. 1.94 ± 0.45 cm(2), P0.001, 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), P0.01, 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), P0.01) and carotid distensibility was decreased (4.75 ± 1.31 vs. 5.60 ± 1.48 mm Hg(-1)10(3), P0.001) 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(-1)10(3), 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.

Preterm-born individuals have elevated blood pressure. We tested the hypothesis that this associates with an enhanced antiangiogenic circulating profile and that this association is mediated by variations in capillary density. We studied 204 adults aged 25 years (range, 20–30 years), of which 102 had been followed up prospectively since very preterm birth (mean gestational age, 30.3±2.5 weeks) and 102 were born term to uncomplicated pregnancies. A panel of circulating biomarkers, including soluble endoglin and soluble fms-like tyrosine kinase-1, were compared between groups and related to perinatal history and adult cardiovascular risk. Associations with cardiovascular phenotype were studied in 90 individuals who had undergone detailed assessment of microvascular, macrovascular, and cardiac structure and function. Preterm-born individuals had elevations in soluble endoglin (5.64±1.03 versus 4.06±0.85 ng/mL; P P P P =0.002). Other circulating biomarkers, including those of inflammation and endothelial activation, were not related to blood pressure. There was a specific graded association between soluble endoglin and degree of functional and structural capillary rarefaction ( P =0.002 and P

Background Heart rate variability (HRV) has emerged as a predictor of later cardiac risk. This study tested whether pregnancy complications that may have long-term offspring cardiac sequelae are associated with differences in HRV at birth, and whether these HRV differences identify abnormal cardiovascular development in the postnatal period. Methods Ninety-eight sleeping neonates had 5-min electrocardiogram recordings at birth. Standard time and frequency domain parameters were calculated and related to cardiovascular measures at birth and 3 months of age. Results Increasing prematurity, but not maternal hypertension or growth restriction, was associated with decreased HRV at birth, as demonstrated by a lower root mean square of the difference between adjacent NN intervals (rMSSD) and low (LF) and high-frequency power (HF), with decreasing gestational age (p Conclusions Altered cardiac autonomic function at birth relates to prematurity rather than other pregnancy complications and does not predict cardiovascular developmental patterns during the first 3 months post birth. Long-term studies will be needed to understand the relevance to cardiovascular risk.

Concomitant acute myocardial infarction (MI) and pulmonary embolism (PE) is exceedingly rare. However, establishing the diagnosis early is essential, since delay in treating the patient may lead to a potential fatal outcome. Right ventricular (RV) infarction in the setting of inferior ST-segment elevation MI (STEMI), coupled with acute massive PE confers particular risk due acute RV failure and low cardiac output, threatening survival. We report a rare case of concomitant PE and inferior STEMI in a 43-year-old woman with a history of acute chest pain. She was haemodynamically compromised, with Type I respiratory failure but lack of signs of heart failure. Early recognition of dual pathologies prompted administration of thrombolytic therapy and simultaneous right coronary artery thrombectomy to treat PE and STEMI. Prompt clinical diagnosis and delivery of targeted therapies adapted for the specific clinical presentation may have averted fatal outcome.

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.The authors performed echocardiographic imaging at prescribed exercise intensities to determine whether preterm-born adults have impaired LV functional response to physical exercise.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.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/mPreterm-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).

[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 Women's 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 Women's 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

Introduction: Women with a history of preeclampsia have a two-fold higher risk of acute ischemic stroke even after controlling for classic cardiovascular risk factors. We determined whether specific patterns in cerebral damage are present after preeclampsia that may explain this risk. Methods: We performed brain magnetic resonance imaging in women between 5 and 15 years after either a preeclamptic or normotensive pregnancy. 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 grey matter volumes was performed in T1 weighted sequences with adjustment for skull size. Cardiovascular, obstetric profiles were assessed. Results: Thirty-four previously preeclamptic women (aged 42.8 ± 5.1 years, mean ± SD) and 49 controls were included. Previously preeclamptic women had reduced cortical grey matter volume (523.2 ± 30.1 vs 544.4 ± 44.7 ml, p-6 mm 2 /sec, p Conclusions: A history of preeclampsia is associated with temporal lobe white matter damage and cortical atrophy in young women, which is out of proportion to their classic cardiovascular risk profile and increases with time from pregnancy, consistent with ongoing susceptibility and cumulative brain damage.

Background Adults 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. Methods Cardiac 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. Results At 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

To determine whether changes in cerebral structure are present after preeclampsia that may explain increased cerebrovascular risk in these women.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.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,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.

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

© 2016 American Heart Association, Inc. 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.

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.

Cardiovascular deaths remain the most common cause of pregnancy-related deaths.1 Pregnancy is a time of unique cardiovascular adaptation with maternal physiology altering through gestation to support the demands of the growing fetus. Several organs have particularly increased blood requirements during pregnancy, beside the uterus, including skin, kidneys and breasts. However, reports of the magnitude and timing of increases in cardiac output during normal pregnancy have been inconsistent. A clear understanding of how cardiac output and other haemodynamic parameters change in normal pregnancy might allow earlier and more accurate identification of maladapted cardiovascular physiology that characterises some complications in pregnancy and possibly allow attenuation of future sequelae. In particular, there has been interest in the impact of hypertensive disorders of pregnancy on cardiac function because they occur in up to 20% of pregnancies and are specifically associated with both changes in cardiac output during pregnancy, cardiac dysfunction2 and increased risks of cardiovascular diseases in later life for both mother and child.3 In their Heart publication, Meah et al 4 have adopted a new methodological approach to describe changes in cardiac output during pregnancy, which has allowed them to report findings from a substantially larger dataset than previously possible. They have performed a systematic review of the literature and undertaken a series of meta-analyses on the accumulated findings of cardiac output and other haemodynamic data in healthy singleton pregnancies, from non-pregnancy through to post partum. To ensure an adequate sample size, they have had to draw on a heterogeneous source of data and include studies that report a range of modalities including echocardiography, impedance cardiography, suprasternal Doppler and inert gas rebreathing. Nevertheless, they found that this …

Background Evidence from systematic reviews of observational studies suggests that hormone therapy may have beneficial effects in reducing the incidence of cardiovascular disease events in post-menopausal women, however the results of randomised controlled trials (RCTs) have had mixed results. This is an updated version of a Cochrane review published in 2013. Objectives To assess the effects of hormone therapy for the prevention of cardiovascular disease in post-menopausal women, and whether there are differential effects between use in primary or secondary prevention. Secondary aims were to undertake exploratory analyses to (i) assess the impact of time since menopause that treatment was commenced (≥ 10 years versus < 10 years), and where these data were not available, use age of trial participants at baseline as a proxy (≥ 60 years of age versus < 60 years of age); and (ii) assess the effects of length of time on treatment. Search methods We searched the following databases on 25 February 2014: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE and LILACS. We also searched research and trials registers, and conducted reference checking of relevant studies and related systematic reviews to identify additional studies. Selection criteria RCTs of women comparing orally administered hormone therapy with placebo or a no treatment control, with a minimum of six months follow-up. Data collection and analysis Two authors independently assessed study quality and extracted data. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for each outcome. We combined results using random effects meta-analyses, and undertook further analyses to assess the effects of treatment as primary or secondary prevention, and whether treatment was commenced more than or less than 10 years after menopause. Main results We identified six new trials through this update. Therefore the review includes 19 trials with a total of 40,410 post-menopausal women. On the whole, study quality was good and generally at low risk of bias; the findings are dominated by the three largest trials. We found high quality evidence that hormone therapy in both primary and secondary prevention conferred no protective effects for all-cause mortality, cardiovascular death, non-fatal myocardial infarction, angina, or revascularisation. However, there was an increased risk of stroke in those in the hormone therapy arm for combined primary and secondary prevention (RR 1.24, 95% CI 1.10 to 1.41). Venous thromboembolic events were increased (RR 1.92, 95% CI 1.36 to 2.69), as were pulmonary emboli (RR 1.81, 95% CI 1.32 to 2.48) on hormone therapy relative to placebo. The absolute risk increase for stroke was 6 per 1000 women (number needed to treat for an additional harmful outcome (NNTH) = 165; mean length of follow-up: 4.21 years (range: 2.0 to 7.1)); for venous thromboembolism 8 per 1000 women (NNTH = 118; mean length of follow-up: 5.95 years (range: 1.0 to 7.1)); and for pulmonary embolism 4 per 1000 (NNTH = 242; mean length of follow-up: 3.13 years (range: 1.0 to 7.1)). We performed subgroup analyses according to when treatment was started in relation to the menopause. Those who started hormone therapy less than 10 years after the menopause had lower mortality (RR 0.70, 95% CI 0.52 to 0.95, moderate quality evidence) and coronary heart disease (composite of death from cardiovascular causes and non-fatal myocardial infarction) (RR 0.52, 95% CI 0.29 to 0.96; moderate quality evidence), though they were still at increased risk of venous thromboembolism (RR 1.74, 95% CI 1.11 to 2.73, high quality evidence) compared to placebo or no treatment. There was no strong evidence of effect on risk of stroke in this group. In those who started treatment more than 10 years after the menopause there was high quality evidence that it had little effect on death or coronary heart disease between groups but there was an increased risk of stroke (RR 1.21, 95% CI 1.06 to 1.38, high quality evidence) and venous thromboembolism (RR 1.96, 95% CI 1.37 to 2.80, high quality evidence). Authors' conclusions Our review findings provide strong evidence that treatment with hormone therapy in post-menopausal women overall, for either primary or secondary prevention of cardiovascular disease events has little if any benefit and causes an increase in the risk of stroke and venous thromboembolic events.

We thank Dr. Culebras for the comment on our article.1 Sleep apnea might be among the pathophysiologic pathways linking preeclampsia with increased risk of cerebrovascular disease in previously preeclamptic women. In fact, research recently focused on the role of sleep apnea in the etiopathogenesis of cerebrovascular and cardiovascular disease and demonstrated an increased stroke risk in patients with obstructive sleep apnea (OSA).2,3 Intermittent hypoxia with consecutive vascular dysregulation has been identified as a possible mechanism whereby OSA increases risk of stroke. This might be relevant to previously preeclamptic mothers in whom autonomic neurovascular dysfunction, inter alia mediated by functional changes to the sympathetic nervous system, was also demonstrated.4 It remains to be answered whether this similarity among pathologies indeed points to a causative link between preeclampsia and cerebrovascular disease.

Pregnancy complications, such as hypertensive disorders or preterm delivery, identify families predisposed to cardiovascular problems at other times in life. Whether the pregnancy complication induces cardiac disease or whether the pregnancy stress unmasks an underlying predisposition remains unclear. However, improved survival following severe pregnancy complications for both the mother and, in particular, the offspring – who is often born preterm – has resulted in a growing cohort of individuals who carry this increased cardiovascular risk. Research to understand the underlying pathological mechanisms that link these conditions might ultimately lead to novel therapeutic or prevention strategies for both cardiovascular and pregnancy disease.

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 cm(2), P

According to the World Health Organization (2009), an estimated 17.1 million people died from cardiovascular disease in 2005 (29% of global deaths), 7.2 million from coronary heart disease. It is the number one killer globally and with new and more complex ways of investigating the heart non-invasively, it is important to understand what is available and when to use each modality. This article explains how the different forms of non-invasive cardiac imaging work, their advantages and disadvantages (Table 1), when to use each one and finally what developments are likely in the future. Some may not be available in all hospitals, but access and availability to cardiac imaging is likely to change significantly in the future.

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 woman9s constitution prior to pregnancy rather than pregnancy itself triggering changes in a woman9s 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.

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.

Objectives Cardiopulmonary exercise testing (CPET) is a well-established investigation used to stratify operative and anaesthetic risk as well as being predictive of cardiovascular morbidity and mortality. Pregnancy is a biological stress test and we hypothesised that CPET could risk stratify women with cardio-respiratory or metabolic disease during pregnancy. However, normal values in normal pregnancy are required before the predictive value of this test can be assessed in women with cardio-respiratory disease. This pilot study was designed to test the feasibility and tolerability of performing combined CPET and exercise echocardiography during pregnancy. Methods We prospectively recruited 10 women with a singleton pregnancy; all were healthy with no known medical conditions. Each participant attended at mean 14+1 (±2 days) (visit 1) and 24+5 (±3 days) (visit 2) weeks of gestation. At each visit participants had a resting echocardiogram, fetal ultrasound scan and baseline blood sample collected. A stepwise incrementing CPET was then performed with a maternal echocardiogram at maximal exertion. A blood sample was collected at maximal exertion. Results The participants had a mean age at visit 1 of 35 years (±4), 6 were nulliparous, BMI was 24.3 (±3.3). Combined CPET and exercise echo was successfully completed in all participants. There was no significant difference between visits for resting mean arterial pressure: 86.7 mmHg (±9.6) at visit 1 and 86.5 mmHg (±8.1) at visit 2 (p = 0.95), but resting left ventricular (LV) end diastolic volume increased from 77.3 ml (±15.1) in visit 1 to 83.8 ml (±17.2) in visit 2 (p = 0.008). Systolic function did not significantly change between visits, ejection fraction: 63.8% (±5.9) compared to 61.4% (±4.6) at visit 2 (p = 0.36). Diastolic function was not significantly altered. During the CPET test the peak workload achieved was similar at both visits: 165 Watts (±35.7) in visit 1 and 170 Watts (±36.9) in visit 2 (p = 0.51) as was VO 2 max ml/Kg/min: 28.5 (±6.3) compared to 26.6 (±2.9) (p = 0.34). Respiratory exchange ratio (RER) increased significantly between visits: 1.05 (±0.05) compared to 1.11 (±0.05) at visit 2 (p = 0.01). Lactates collected increased from 1.1 mmol/L (range 0.9–1.7) before maximal exercise to 6.4 mmol/L (range 4.5–8.8) after in visit 1 (p All participants delivered healthy live neonates at term gestation, however 1 participant developed pregnancy induced hypertension and 2 developed preeclampsia. Conclusions We successfully demonstrated combined exercise echo and CPET studies is well tolerated in pregnant women at 14 and 24 weeks gestation. We also demonstrated this combined test as a successful technique for capturing a wealth of metabolic and cardiac structural and functional data. Cardiac volumes increased between visits. RER increased which might suggest test familiarity.

Introduction Young adults with cardiovascular risk factors, such as hypertension, may gain long-term risk benefits from effective targeted lifestyle interventions. We compared the effectiveness of lifestyle interventions with defined physical activity components targeting change in blood pressure, in young adults (aged 20 to 40) with established cardiovascular risk factors. Methods We searched databases including CENTRAL, MEDLINE, EMBASE, CINAHL (from earliest dates available to May 2014) and assessed reference lists of relevant articles for potential titles. Study selection criteria including: randomised control trials with at least 12 weeks follow-up; reporting blood pressure as the primary outcome; targeting participants aged between 20 to 40 years or within one standard deviation of this age range. Four authors (WW, PK, AL, HR), independently screened the eligibility of trials. Titles selected for full review were discussed and disagreement settled with an independent pair of authors (CF and PL). Meta-analysis was completed using Review Manager (RevMan) Version 5.2 using a random effects model imputing post intervention blood pressures. Study protocol available on PROSPERO 2014:CRD42014009604. Results 13 studies satisfied all inclusion criteria, baseline mean age of participants was 42.7 years (SD 6.4) (n = 3338). 11 trials targeted increased moderate to vigorous physical activity (MVPA) either via supervised exercise (n = 8) or via behavioural counselling (n = 3). One trial investigated effects of resistance exercise and 1 study implemented a yoga trial. Meta-analysis was restricted to the trials targeting increased MVPA with analysis performed according to duration of follow-up. In total 10 studies (n = 2716) reported 3 to 6 months outcomes, mean reduction in systolic BP was –4.4 mmHg (95% CI -5.8 to -3) and mean reduction in diastolic BP was –4.3 mmHg (95% CI -5.6 to -3.0). The effects of intervention on blood pressure at 3 to 5 year follow-up (3 studies, n = 2553) was positive but with significant heterogeneity. Mean reduction in systolic BP was -1.3 mmHg (95% CI -2.9 to 0.3, I 2 80%) and mean reduction in diastolic BP was –1.2 mmHg (95% CI -2.3 to -0.2, I 2 74%). Conclusions Our review found that interventions targeting an increased dose of MVPA through supervised and self-directed programmes achieved significant short-term improvements in blood pressure. However, studies targeting blood pressure reduction in participants below the age of 40 years with cardiovascular risk factors are limited in number. The clinical and statistical heterogeneity of the studies limits conclusions on the effectiveness of individual components of the interventions. It remains unclear how to translate short-term intervention effects into sustained reduction in blood pressure and cardiovascular risk. As understanding increases of young adult populations predisposed to early cardiovascular disease more research is needed on primary and secondary prevention in these groups.