Julian Ayer

Childhood risk factors for adult cardiovascular disease and primary prevention in childhood

Atherosclerosis has been demonstrated in autopsy studies to have its origins in childhood.1 In the young, there is a correlation between the intensity of exposure to risk factors such as cigarette smoking, hypertension, dyslipidaemia and diabetes mellitus and the extent and severity of arterial fatty streaks or raised plaques (fig 1). Figure 1  Fatty streaks and raised plaques are seen in childhood and correlate with the intensity of exposure to risk factors. An important current trend that may increase the future burden of coronary heart disease (CHD) is a significant increase in the prevalence of childhood obesity.2 In obesity, many of the risk factors for CHD are clustered together. Moreover, these risk factors usually persist or track into adulthood, so that their effect on the cardiovascular system may be present and influential for several decades. To reduce the future burden of CHD, we need to define prevention and intervention strategies that decrease the prevalence of cardiovascular risk factors in children and young adults and thereby hope to retard atherogenic processes. The purpose of this article is to review the evidence for the importance of the childhood risk factors for adult cardiovascular disease and to outline the evidence for the efficacy of primary prevention in young people. Studies on the impact of risk factors in childhood and on the effect of potentially beneficial interventions have been facilitated by the development of a number of non-invasive diagnostic techniques that can detect “atherosclerosis” at a preclinical stage (or at least the changes in arterial structure and/or function indicative of vascular damage). For example, the arterial endothelium plays a key role in atherogenesis, and clinical evaluation of the function of the endothelium is now possible through the assessment of nitric oxide-mediated vasodilatation produced by sheer stress (flow mediated dilatation (FMD)). FMD can be measured …

Levosimendan for low cardiac output: a pediatric experience.

This was a retrospective observational study in a pediatric intensive care unit, in which 19 patients received levosimendan. There were no adverse events attributable to levosimendan and no instances where the clinical condition worsened after administration. Arterial lactate levels decreased significantly following levosimendan administration during cardiopulmonary bypass for anticipated low cardiac output. In those with established low cardiac output, trends toward improved hemodynamics were seen, with heart rate reduction, an increase in mean blood pressure, a reduction in arterial lactate, and reduced conventional inotrope use. Levosimendan was safely used in a small number of pediatric patients with established low cardiac output state who demonstrated improved hemodynamics and tissue perfusion, with a tendency to reduced conventional inotrope usage, and this warrants its evaluation as an inotrope in the pediatric population.

Weight Gain in Infancy and Vascular Risk Factors in Later Childhood

OBJECTIVE: We hypothesized that early weight gain would be associated with incident obesity, higher blood pressure, systemic inflammation, and arterial wall thickening in later childhood. METHODS: A longitudinal birth cohort was recruited antenatally from 2 maternity hospitals in Sydney, Australia, between September 1997 and December 1999. Three hundred ninety-five nondiabetic children who were followed to age 8 years had complete data for early weight gain and arterial wall thickness. RESULTS: Independent predictors of excess early weight gain (age 0–18 months; adjusted for height gain) included male gender (0.411 kg [SE: 0.103], P < .001), fewer weeks’ gestation (−0.121 kg [SE: 0.044] per week, P = .006), birth length (0.156 kg [SE: 0.024] per cm, P < .001), and failure to breastfeed to 6 months of age (0.498 kg [SE: 0.108], P < .001). Early height-adjusted weight gain was significantly associated with later childhood overweight (odds ratio [OR]: 1.67 [95% confidence interval (CI): 1.26 to 2.20] per kg) and obesity (OR: 2.07 [95% CI: 1.53 to 2.79] per kg), excess central adiposity (OR: 1.54 [95% CI: 1.20 to 1.98] per kg), higher systolic blood pressure (1.24 mm Hg [SE: 0.33] per kg, P < .001), higher C-reactive protein (0.17 mg/dL [SE: 0.06] per 100% increase in weight gain, P = .006), and greater carotid intima-media thickness (0.012 mm [SE: 0.004] per kg, P = .002). CONCLUSIONS: Early postnatal weight gain from birth to age 18 months is significantly associated with later childhood overweight and obesity, excess central adiposity, and greater arterial wall thickness.

Impaired Fetal Growth and Arterial Wall Thickening: A Randomized Trial of Omega-3 Supplementation

OBJECTIVES: Impaired fetal growth is an independent cardiovascular risk factor and is associated with arterial wall thickening in children. No preventive strategy has been identified. We sought to determine whether dietary omega-3 fatty acid supplementation during early childhood prevents the association between impaired fetal growth and carotid arterial wall thickening. METHODS: The Childhood Asthma Prevention Study was a randomized, controlled single-blind trial in 616 children born at term, recruited antenatally from maternity hospitals in Sydney. Participants were randomized to either a 500-mg-daily fish oil supplement and canola-based margarines and cooking oil (omega-3 group), or a 500-mg-daily sunflower oil supplement and omega-6 fatty acid–rich margarines and cooking oil (control group), from the start of bottle-feeding or 6 months of age until 5 years of age. Carotid intima-media thickness (IMT), a noninvasive measure of subclinical atherosclerosis, was the primary endpoint of a cardiovascular substudy (CardioCAPS) at age 8 years. We examined the association of fetal growth with carotid IMT in children with birth weight <90th percentile (omega-3 group [n = 187], control group [n = 176]). RESULTS: In the control group, fetal growth was inversely associated with carotid IMT, but this was prevented in the omega-3 group (difference between groups of 0.041 mm [95% confidence interval 0.006, 0.075] per kg birth weight, adjusted for gestational age and gender, Pheterogeneity = .02). CONCLUSIONS: The inverse association of fetal growth with arterial wall thickness in childhood can be prevented by dietary omega-3 fatty acid supplementation over the first 5 years of life.

Dietary supplementation with n−3 polyunsaturated fatty acids in early childhood: effects on blood pressure and arterial structure and function at age 8 y

BACKGROUND n-3 Fatty acid supplementation in adults results in cardiovascular benefits. However, the cardiovascular effects of n-3 supplementation in early childhood are unknown. OBJECTIVE The objective was to evaluate blood pressure (BP) and arterial structure and function in 8-y-old children who had participated in a randomized controlled trial of dietary n-3 and n-6 modification over the first 5 y of life. DESIGN The children (n = 616; 49% girls) were randomly assigned antenatally to active (n = 312; increase in n-3 intake and decrease in n-6 intake) or control (n = 304) diet interventions implemented from the time of weaning or introduction of solids until 5 y of age. At age 8.0 +/- 0.1 y, BP, carotid intima-media thickness, carotid artery distensibility, augmentation index, and brachial pulse wave velocity were measured in 405 of these children. Venous blood was collected for measurement of plasma fatty acids, lipoproteins, high-sensitivity C-reactive protein, and asymmetric dimethylarginine. Plasma fatty acid concentrations were also assessed during the intervention. RESULTS Plasma concentrations of n-3 fatty acids were higher and of n-6 were lower in the active than in the control diet group at 18 mo and 3 and 5 y (P < 0.0001). Concentrations of n-3 and n-6 fatty acids were similar at 8 y. At 8 y of age, no significant differences were found in BP, carotid intima-media thickness, carotid artery distensibility, augmentation index, asymmetric dimethylarginine, high-sensitivity C-reactive protein, or lipoproteins between diet groups. CONCLUSION A dietary supplement intervention to increase n-3 and decrease n-6 intakes from infancy until 5 y does not result in significant improvements in arterial structure and function at age 8 y. This trial was registered at the Australian Clinical Trials Registry as ACTRN012605000042640.

Lifetime risk: childhood obesity and cardiovascular risk

In a recent report, the worldwide prevalence of childhood obesity was estimated to have increased by 47% between 1980 and 2013. As a result, substantial concerns have been raised about the future burden of cardiovascular (CV) disease that could ensue. The purpose of this review is to summarize and interpret (i) the evidence linking early life obesity with adverse changes in CV structure and function in childhood, (ii) the lifetime risk for CV disease resulting from obesity in childhood, and (iii) the potential effects of lifestyle interventions in childhood to ameliorate these risks.

Central arterial pulse wave augmentation is greater in girls than boys, independent of height.

Objectives Central arterial pulse wave augmentation, quantified by the augmentation index (AIx), is a key marker of arterial health, an important contributor to cardiac afterload and is significantly greater in older women than men. We measured carotid AIx in 8-year-old children to examine the influences of sex, height and arterial stiffness on central arterial pulse wave augmentation Methods Four hundred and five children (age 8.0 ± 0.1 years, 49% girls) had anthropometry, brachial systolic and diastolic blood pressure, heart rate and carotid artery pressure waveforms (by applanation tonometry), diastolic diameter and distensibility assessed. Results Carotid AIx was significantly higher in girls than boys (−11.7 ± 8.1 versus −16.5 ± 9.3%, respectively, P < 0.001). Boys and girls had similar height (129 ± 6 versus 128 ± 6 cm), systolic blood pressure (100 ± 7 versus 101 ± 7 mmHg), diastolic blood pressure (59 ± 6 versus 60 ± 5 mmHg) and heart rate (80 ± 10 versus 82 ± 10 bpm). Carotid diastolic diameter was smaller in girls than boys (0.45 ± 0.03 versus 0.47 ± 0.04 cm, P < 0.001). The sex difference in AIx remained significant after adjustment for height, heart rate, blood pressure, diastolic diameter and birth weight. The time to the onset of the reflected wave was shorter in girls (155 ± 19 versus 163 ± 18 ms, P < 0.001). Girls had greater carotid artery distensibility (6.2 ± 1.8 versus 5.8 ± 1.5% per 10 mmHg, P = 0.016), suggesting lower regional carotid artery stiffness. Conclusion Greater pulse wave augmentation in prepubertal girls results from earlier wave reflection and is independent of height, carotid artery diameter and stiffness. When combined with age-related changes in arterial compliance, this may contribute to adverse cardiovascular outcomes in older women.

Maternal cigarette smoking is associated with reduced high-density lipoprotein cholesterol in healthy 8-year-old children

AIMS Smoking in pregnancy is common. Its effects on lipoprotein levels and arterial structure in childhood are not well characterized. We aimed to determine the effects of maternal smoking in pregnancy on lipoprotein levels and arterial wall thickness in healthy pre-pubertal children. METHODS AND RESULTS A community-based longitudinal study with prospective ascertainment of exposure to smoking in pregnancy and environmental tobacco smoke (ETS) since birth and then lipoprotein and arterial measurements at age 8 years. In 616 newborn infants (gestation >36 weeks and birth weight >2.5 kg) data were collected prospectively by questionnaire on smoking in pregnancy and ETS exposure in childhood. At age 8-years, 405 of the children had measurements of lipoproteins, blood pressure (BP) and carotid intima-media thickness. Children born to mothers who smoked in pregnancy had lower HDL cholesterol [1.32 vs. 1.50 mmol/L, 95% confidence interval (CI) for difference -0.28 to -0.08, P = 0.0005], higher triglycerides (1.36 vs. 1.20 mmol/L, 95% CI for ratio 1.01-1.30, P = 0.04) and higher systolic BP (102.1 vs. 99.9 mmHg, 95% CI for difference 0.6-3.8, P = 0.006). After adjustment for maternal passive smoking, post-natal ETS exposure, gender, breast feeding duration, physical inactivity, and adiposity, smoking in pregnancy remained significantly associated with lower HDL cholesterol (difference = -0.22 mmol/L, 95% CI -0.36 to -0.08, P = 0.003) but not with higher systolic BP. Neither smoking in pregnancy nor post-natal ETS exposure was associated with alterations of carotid artery wall thickness. CONCLUSION Smoking in pregnancy is independently associated with significantly lower HDL cholesterol in healthy 8-year-old children.

Postprandial Vascular Reactivity in Obese and Normal Weight Young Adults

As humans spend a significant amount of time in the postprandial state, we examined whether vascular reactivity (a key indicator of cardiovascular health) was different after a high‐fat meal in 11 obese (median BMI 46.4, age 32.1 ± 6.3 years, 7 men) and 11 normal weight (median BMI 22.6) age‐ and sex‐matched controls. At baseline and 1 and 3 h postmeal, blood pressure (BP), heart rate (HR), reactive hyperemia peripheral artery tonometry (RH‐PAT) index, radial augmentation index adjusted for HR (AIx75), brachial pulse wave velocity (PWVb), glucose, insulin, total and high‐density lipoprotein (HDL) cholesterol, and triglycerides were measured. Brachial flow‐mediated dilatation (FMD) and, by venous plethysmography, resting and hyperemic forearm blood flows (FBFs) were measured at baseline and 3 h. At baseline, obese subjects had higher systolic BP, HR, resting FBF, insulin and equivalent FMD, RH‐PAT, hyperemic FBF, AIx75, PWVb, glucose, total cholesterol, triglycerides, and lower HDL cholesterol. In obese and lean subjects, FMD at baseline and 3 h was not significantly different (6.2 ± 1.7 to 5.8 ± 4.3% for obese and 4.7 ± 4.1 to 4.3 ± 3.9% for normal weight, P = 0.975 for group × time). The meal did not produce significant changes in RH‐PAT, hyperemic FBF, and PWVb in either group (P > 0.1 for the effect of time and for group × time interactions). In conclusion, the vascular responses to a high‐fat meal are similar in obese and normal weight young adults. An exaggerated alteration in postprandial vascular reactivity is thus unlikely to contribute importantly to the increased cardiovascular risk of obesity.

Severe Obesity Is Associated With Impaired Arterial Smooth Muscle Function in Young Adults

The degree of arterial dilatation induced by exogenous nitrates (nitrate‐mediated dilatation, NMD) has been similar in obese and normal‐weight adults after single high‐dose glyceryl trinitrate (GTN). We examined whether NMD is impaired in obesity by performing a GTN dose‐response study, as this is a potentially more sensitive measure of arterial smooth muscle function. In this cross‐sectional study, subjects were 19 obese (age 31.0 ± 1.2 years, 10 male, BMI 44.1 ± 2.1) and 19 age‐ and sex‐matched normal‐weight (BMI 22.4 ± 0.4) young adults. Blood pressure (BP), triglycerides, high‐density lipoprotein (HDL), and low‐density lipoprotein (LDL)‐cholesterol, glucose, insulin, high‐sensitivity C‐reactive protein (hs‐CRP), carotid intima‐media thickness (CIMT), and flow‐mediated dilatation (FMD) were measured. After incremental doses of GTN, brachial artery maximal percent dilatation (maximal NMD) and the area under the dose‐response curve (NMD AUC) were calculated. Maximal NMD (13.4 ± 0.9% vs. 18.3 ± 1.1%, P = 0.002) and NMD AUC (54,316 ± 362 vs. 55,613 ± 375, P = 0.018) were lower in obese subjects. The obese had significantly higher hs‐CRP, insulin, and CIMT and lower HDL‐cholesterol. Significant bivariate associations existed between maximal NMD or NMD AUC and BMI‐group (r = −0.492, P = 0.001 or r = −0.383, P = 0.009), hs‐CRP (r = −0.419, P = 0.004 or r = −0.351, P = 0.015), and HDL‐cholesterol (r = 0.374, P = 0.01 or r = 0.270, P = 0.05). On multivariate analysis, higher BMI‐group remained as the only significant determinant of maximal NMD (r2 = 0.242, β = −0.492, P = 0.002) and NMD AUC (r2 = 0.147, β = −0.383, P = 0.023). In conclusion, arterial smooth muscle function is significantly impaired in the obese. This may be important in their increased cardiovascular risk.