Is slower early growth beneficial for long-term cardiovascular health?

Background - Accelerated neonatal growth increases the later propensity to cardiovascular disease (CVD) in animals, whereas slower growth is thought to have a beneficial effect. To test this hypothesis in humans, we measured flow-mediated endothelium-dependent dilation (FMD) in a population subject to slower early growth and in healthy controls.Methods and Results - High-resolution vascular ultrasound was used to measure the change in brachial artery diameter in response to reactive hyperemia in adolescents age 13 to 16 years who were either part of a cohort born preterm and followed up prospectively (n = 216) or controls born at term ( n = 61). Greater weight gain or linear growth in the first 2 weeks postnatally was associated with lower FMD at adolescence ( regression coefficient, - 0.026-mm change in mean arterial diameter per 100-g increase in weight; 95% CI, - 0.040 to - 0.012 mm; P = 0.0003) independent of birthweight and potential confounding factors. Mean FMD in the half of the preterm population with the lowest rates of early growth was higher than in both the half with the greatest growth ( P = 0.001) and subjects born at term ( P = 0.03).Conclusions - FMD was 4% lower in adolescents with the highest compared with the lowest rate of weight gain in the first 2 weeks after birth, a substantial negative effect similar to that for insulin-dependent diabetes mellitus or smoking in adults. Our findings are consistent with the adverse effects of accelerated neonatal growth on long-term cardiovascular health and suggest that postnatal growth patterns could explain the previously reported association between birthweight and later CVD

The association of maternal prenatal psychosocial stress with vascular function in the child at age 10-11 years: findings from the Avon longitudinal study of parents and children

Objective To investigate whether (1) maternal psychosocial stress (depression/anxiety) during pregnancy is associated with offspring vascular function and (2) whether any association differs depending on the gestational timing of exposure to stress. We also investigated whether any association is likely to be due to intrauterine mechanisms by (3) comparing with the association of paternal stress with offspring vascular function and (4) examining whether any prenatal association is explained by maternal postnatal stress. Methods and results Associations were examined in a UK birth cohort, with offspring outcomes (systolic and diastolic blood pressure, SBP and DBP, endothelial function assessed by brachial artery flow-mediated dilatation (FMD); arterial stiffness assessed by carotid to radial pulse wave velocity (PWV), brachial artery distensibility (DC), and brachial artery diameter (BD) assessed at age 10–11 years (n = 4318). Maternal depressive symptoms and anxiety were assessed at 18 and 32 weeks gestation and 8 months postnatally. Paternal symptoms were assessed at week 19. With the exception of DBP and BD, there were no associations of maternal depressive symptoms with any of the vascular outcomes. Maternal depressive and anxiety symptoms were associated with lower offspring DBP and wider BD, though the latter attenuated to the null with adjustment for confounding factors. Paternal symptoms were not associated with offspring outcomes. Maternal postnatal depressive symptoms were associated with lower offspring SBP. Conclusions We found no evidence to support the hypothesis that maternal stress during pregnancy adversely affects offspring vascular function at age 10–12 years via intrauterine mechanisms

Influence of leptin on arterial distensibility - A novel link between obesity and cardiovascular disease?

Background-The mechanisms by which obesity increases the risk of atherosclerotic cardiovascular disease (CVD) are poorly understood. In experimental models, leptin, a hormone produced by adipose tissue, has been shown adversely to affect vascular health. Therefore, we tested the hypothesis that high leptin concentrations are associated with lower arterial distensibility, an index of circulatory function relevant to the atherosclerotic process.Methods and Results-Noninvasive, high-resolution, vascular ultrasound was used to measure brachial artery distensibility in 294 healthy adolescents (aged 13 to 16 years) who had a broad range of body mass indexes. Fat mass was measured by bioelectric impedance analysis; fasting serum leptin concentration by radioimmunoassay; and lipid profile, fasting insulin, glucose, and C-reactive protein concentrations by standard laboratory techniques. Higher leptin concentrations were associated with impaired arterial distensibility (regression coefficient, -1.3% change in arterial distension per 10% increase in leptin; 95% CI, -1.9% to -0.8%; P<0.001). This association was independent of fat mass, blood pressure, and C-reactive protein, fasting insulin, or LDL cholesterol concentrations.Conclusions-Elevation in leptin was associated with impaired vascular function, independent of the metabolic and inflammatory disturbances associated with obesity. Our observations are consistent with data from experimental models and suggest that high leptin concentration is an important mechanism for the adverse influence of body fatness on CVD

Quality of life of adult congenital heart disease patients: a systematic review of the literature

Aims This review explores the quality of life of adult congenital heart disease patients and the relationship between disease severity and quality of life. METHODS: We searched seven electronic databases and the bibliography of articles. The 31 selected studies fulfilled the following criteria: adult population; quantitative; assessment of quality of life and/or impact of disease severity on quality of life using validated measures; English language. Data extraction forms were used to summarise the results. RESULTS: There are evident methodological limitations within the reviewed studies such as heterogeneous populations, designs, and quality of life conceptualisations and measurements. Despite these problems, findings suggest that the quality of life of adult congenital heart disease patients is compromised in the physical domain compared with their healthy counterparts, whereas no differences were found in relation to the psychosocial and environmental/occupational domain. Some severity variables appear to be significant correlates of quality of life and could be considered in a future standardised classification of disease severity. Conclusion The methodological limitations of past research in relation to the definition and measurement of quality of life, the study designs, and disease severity classifications need to be addressed in future studies in order to provide robust evidence and valid conclusions in this area of study. This will enable the development of targeted interventions for the improvement of quality of life in the adult population of congenital heart disease patients

Why democratize bioinformatics?

Network bioinformatics and web-based data collection instruments have the capacity to improve the efficiency of the UK’s appropriately high levels of investment into cardiovascular research. A very large proportion of scientific data falls into the long-tail of the cardiovascular research distribution curve, with numerous small independent research efforts yielding a rich variety of specialty data sets. The merging of such myriad datasets and the eradication of data silos, plus linkage with outcomes could be greatly facilitated through the provision of a national set of standardised data collection instruments—a shared-cardioinformatics library of tools designed by and for clinical academics active in the long-tail of biomedical research. Across the cardiovascular research domain, like the rest of medicine, the national aggregation and democratization of diverse long-tail data is the best way to convert numerous small but expensive cohort data sources into big data, expanding our knowledge-base, breaking down translational barriers, improving research efficiency and with time, improving patient outcomes

Birthweight, childhood growth and left ventricular structure at age 60-64 years in a British birth cohort study

BACKGROUND: High left ventricular mass (LVM) is an independent predictor of cardiovascular disease and mortality, but information relating LVM in older age to growth in early life is limited. We assessed the relationship of birthweight, height and body mass index (BMI) and overweight across childhood and adolescence with later life left ventricular (LV) structure. METHODS: We used data from the MRC National Survey of Health and Development (NSHD) on men and women born in 1946 in Britain and followed up ever since. We use regression models to relate prospective measures of birthweight and height and BMI from ages 2–20 years to LV structure at 60–64 years. RESULTS: Positive associations of birthweight with LVM and LV end diastolic volume (LVEDV) at 60–64 years were largely explained by adult height. Higher BMI, greater changes in BMI and greater accumulation of overweight across childhood and adolescence were associated with higher LVM and LVEDV and odds of concentric hypertrophy. Those who were overweight at two ages in early life had a mean LVM 11.5 g (95% confidence interval: -2.19,24.87) greater, and a mean LVEDV 10.0 ml (3.7,16.2) greater, than those who were not overweight. Associations were at least partially mediated through adult body mass index. Body size was less consistently associated with relative wall thickness (RWT), with the strongest association being observed with pubertal BMI change [0.007 (0.001,0.013) per standard deviation change in BMI 7–15 years]. The relationships between taller childhood height and LVM and LVEDV were explained by adult height. CONCLUSIONS: Given the increasing levels of overweight in contemporary cohorts of children, these findings further emphasize the need for effective interventions to prevent childhood overweight

Excess mortality in England and Wales during the first wave of the COVID-19 pandemic

Background: Deaths during the COVID-19 pandemic result directly from infection and exacerbation of other diseases and indirectly from deferment of care for other conditions, and are socially and geographically patterned. We quantified excess mortality in regions of England and Wales during the pandemic, for all causes and for non-COVID-19-associated deaths. Methods: Weekly mortality data for 1 January 2010 to 1 May 2020 for England and Wales were obtained from the Office of National Statistics. Mean-dispersion negative binomial regressions were used to model death counts based on pre-pandemic trends and exponentiated linear predictions were subtracted from: (i) all-cause deaths and (ii) all-cause deaths minus COVID-19 related deaths for the pandemic period (week starting 7 March, to week ending 8 May). Findings: Between 7 March and 8 May 2020, there were 47 243 (95% CI: 46 671 to 47 815) excess deaths in England and Wales, of which 9948 (95% CI: 9376 to 10 520) were not associated with COVID-19. Overall excess mortality rates varied from 49 per 100 000 (95% CI: 49 to 50) in the South West to 102 per 100 000 (95% CI: 102 to 103) in London. Non-COVID-19 associated excess mortality rates ranged from −1 per 100 000 (95% CI: −1 to 0) in Wales (ie, mortality rates were no higher than expected) to 26 per 100 000 (95% CI: 25 to 26) in the West Midlands. Interpretation: The COVID-19 pandemic has had markedly different impacts on the regions of England and Wales, both for deaths directly attributable to COVID-19 infection and for d

Birthweight, childhood growth and left ventricular structure at age 60-64 years in a British birth cohort study

Background: High left ventricular mass (LVM) is an independent predictor of cardiovascular disease and mortality, but information relating LVM in older age to growth in early life is limited. We assessed the relationship of birthweight, height and body mass index (BMI) and overweight across childhood and adolescence with later life left ventricular (LV) structure. Methods: We used data from the MRC National Survey of Health and Development (NSHD) on men and women born in 1946 in Britain and followed up ever since. We use regression models to relate prospective measures of birthweight and height and BMI from ages 2–20 years to LV structure at 60–64 years. Results: Positive associations of birthweight with LVM and LV end diastolic volume (LVEDV) at 60–64 years were largely explained by adult height. Higher BMI, greater changes in BMI and greater accumulation of overweight across childhood and adolescence were associated with higher LVM and LVEDV and odds of concentric hypertrophy. Those who were overweight at two ages in early life had a mean LVM 11.5 g (95% confidence interval: -2.19,24.87) greater, and a mean LVEDV 10.0 ml (3.7,16.2) greater, than those who were not overweight. Associations were at least partially mediated through adult body mass index. Body size was less consistently associated with relative wall thickness (RWT), with the strongest association being observed with pubertal BMI change [0.007 (0.001,0.013) per standard deviation change in BMI 7–15 years]. The relationships between taller childhood height and LVM and LVEDV were explained by adult height. Conclusions: Given the increasing levels of overweight in contemporary cohorts of children, these findings further emphasize the need for effective interventions to prevent childhood overweight

Percutaneous pulmonary valve implantation in humans - Results in 59 consecutive patients

Background - Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life.Methods and Results - Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n = 36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n = 8). The right ventricular (RV) pressure (64.4 +/- 17.2 to 50.4 +/- 14 mm Hg, P < 0.001), RVOT gradient (33 +/- 24.6 to 19.5 +/- 15.3, P < 0.001), and pulmonary regurgitation ( PR) (grade 2 of greater before, none greater than grade 2 after, P < 0.001) decreased significantly after PPVI. MRI showed significant reduction in PR fraction (21 +/- 13% versus 3 +/- 4%, P < 0.001) and in RV end-diastolic volume (EDV) (94 +/- 28 versus 82 +/- 24 mL (.) beat(-1) (.) m(-2), P < 0.001) and a significant increase in left ventricular EDV ( 64 +/- 12 versus 71 +/- 13 mL (.) beat(-1.) m(-2), P = 0.005) and effective RV stroke volume ( 37 +/- 7 versus 42 +/- 9 mL (.) beat(-1) (.) m(-2), P = 0.006) in 28 patients (age 19 +/- 8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in V(O2)max (26 +/- 7 versus 29 +/- 6 mL (.) kg(-1) (.) min(-1), P < 0.001). There was no mortality.Conclusions - PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity