Familial hypercholesterolemia is characterized by severely elevated low-density lipoprotein (LDL) cholesterol levels and premature cardiovascular disease. The short-term efficacy of statin therapy in ...children is well established, but longer follow-up studies evaluating changes in the risk of cardiovascular disease are scarce.
We report a 20-year follow-up study of statin therapy in children. A total of 214 patients with familial hypercholesterolemia (genetically confirmed in 98% of the patients), who were previously participants in a placebo-controlled trial evaluating the 2-year efficacy and safety of pravastatin, were invited for follow-up, together with their 95 unaffected siblings. Participants completed a questionnaire, provided blood samples, and underwent measurements of carotid intima-media thickness. The incidence of cardiovascular disease among the patients with familial hypercholesterolemia was compared with that among their 156 affected parents.
Of the original cohort, 184 of 214 patients with familial hypercholesterolemia (86%) and 77 of 95 siblings (81%) were seen in follow-up; among the 214 patients, data on cardiovascular events and on death from cardiovascular causes were available for 203 (95%) and 214 (100%), respectively. The mean LDL cholesterol level in the patients had decreased from 237.3 to 160.7 mg per deciliter (from 6.13 to 4.16 mmol per liter) - a decrease of 32% from the baseline level; treatment goals (LDL cholesterol <100 mg per deciliter 2.59 mmol per liter) were achieved in 37 patients (20%). Mean progression of carotid intima-media thickness over the entire follow-up period was 0.0056 mm per year in patients with familial hypercholesterolemia and 0.0057 mm per year in siblings (mean difference adjusted for sex, -0.0001 mm per year; 95% confidence interval, -0.0010 to 0.0008). The cumulative incidence of cardiovascular events and of death from cardiovascular causes at 39 years of age was lower among the patients with familial hypercholesterolemia than among their affected parents (1% vs. 26% and 0% vs. 7%, respectively).
In this study, initiation of statin therapy during childhood in patients with familial hypercholesterolemia slowed the progression of carotid intima-media thickness and reduced the risk of cardiovascular disease in adulthood. (Funded by the AMC Foundation.).
Aim
The prevalence of true therapy‐resistant asthma among children whose asthma remains uncontrolled, despite daily controller therapy, is unknown. The aim of this study was to investigate the ...underlying causes in children with uncontrolled asthma.
Methods
This was a retrospective chart review of 142 children aged from five to 17 years over a five‐year period. The patients had uncontrolled asthma and were referred by general practitioners to a hospital‐based paediatric asthma clinic.
Results
An underlying cause for uncontrolled asthma was found in 138 children (97.2%). The causes were poor adherence (n = 53, 37.3%), ongoing exposure to environmental triggers (n = 40, 28.2%), comorbidities (n = 28, 19.7%), incorrect inhaler technique (n = 11, 7.7%) and incorrect diagnosis (n = 6, 4.2%). After properly addressing these basics in asthma management, the asthma was well controlled in all 138 patients and lung function was normal. Only four children (2.8%) fulfilled the criteria for true therapy‐resistant asthma.
Conclusion
A remedial cause in the basics of asthma management could be found in 97% of children with uncontrolled asthma referred to a hospital‐based asthma clinic. True therapy‐resistant asthma was found to be very rare in children.
Asthma and allergic rhinitis are the two most common chronic disorders in childhood and adolescence. To date, no study has examined the impact of comorbid allergic rhinitis on asthma control in ...children.
To examine the prevalence of allergic rhinitis in children with asthma, and the impact of the disease and its treatment on asthma control.
A cross-sectional survey in 203 children with asthma (5-18 years) using validated questionnaires on rhinitis symptoms (stuffy or runny nose outside a cold) and its treatment, and the paediatric Asthma Control Questionnaire (ACQ). Fraction of nitric oxide in exhaled air (FeNO) was measured with a Niox Mino analyser; total and specific IgE levels were assessed by the Immunocap system.
157 children (76.2%) had symptoms of allergic rhinitis but only 88 of these (56.1%) had been diagnosed with the condition by a physician. ACQ scores were worse in children with allergic rhinitis than in those without the condition (p=0.012). An ACQ score ≥ 1.0 (incomplete asthma control) was significantly more likely in children with allergic rhinitis than in those without (OR 2.74, 95% CI 1.28 to 5.91, p=0.0081), also after adjustment for FeNO levels and total serum IgE. After adjustment for nasal corticosteroid therapy, allergic rhinitis was no longer associated with incomplete asthma control (OR 0.72, 95% CI 0.47 to 1.12, p=0.150).
Allergic rhinitis is common in children with asthma, and has a major impact on asthma control. The authors hypothesise that recognition and treatment of this condition with nasal corticosteroids may improve asthma control in children, but randomised clinical trials are needed to test this hypothesis.
Polyphenols in grape and wine have been suggested to contribute to the cardiovascular health benefits of the Mediterranean lifestyle. The reported effects of grape products on blood pressure (BP) ...remain, however, equivocal. In a double-blind placebo controlled crossover study, the effect of two grape extracts on BP and vascular function was assessed in 60 untreated, mildly hypertensive subjects after four weeks intervention. Both extracts (grape-red wine and grape alone) had high concentrations of anthocyanins and flavonols, but the grape alone was relatively poor in catechins and procyanidins. Parameters measured included ambulatory and office BP, flow-mediated vasodilation, arterial distensibility, platelet function and plasma lipoproteins. Results showed that 24-hour ambulatory systolic/diastolic BPs were significantly lower in the grape-wine extract intervention (135.9 ± 1.3/84.7 ± 0.8 mmHg; mean ± SEM) compared to placebo (138.9 ± 1.3/86.6 ± 1.2 mmHg), predominantly during daytime. Plasma concentrations of the vasoconstrictor endothelin-1 decreased by 10%, but other measures of vascular function were not affected. Grape juice extract alone had no effect on BP or any measures of vascular function. Polyphenol-rich food products, and may be specifically catechins and procyanidins, may thus help sustain a healthy BP and contribute to the healthy Mediterranean lifestyle.
Cognitive decline is associated with lifestyle-related factors such as overweight, blood pressure, and dietary composition. Studies have reported beneficial effects of dietary anthocyanins on ...cognition in older adults and children. However, the effect of anthocyanin-rich
extract (AME) on cognition is unknown. Therefore, this study aimed to determine the effect of long-term supplementation with AME on cognitive performance, mood, and vascular function in healthy, middle-aged, overweight adults. In a randomized double-blind placebo-controlled parallel study, 101 participants either consumed 90 mg AME, 150 mg AME, or placebo for 24 weeks. The grooved pegboard test, number cross-out test, and Stroop test were performed as measures for psychomotor speed, attention, and cognitive flexibility. Mood was evaluated with a visual analogue scale, serum brain-derived neurotrophic factor (BDNF) was determined, and vascular function was assessed by carotid ultrasounds and blood pressure measurements. AME improved psychomotor speed compared to placebo (90 mg AME: change = -3.37;
= 0.009). Furthermore, 150 mg AME decreased brachial diastolic blood pressure compared to 90 mg AME (change = 2.44;
= 0.011), but not compared to placebo. Attention, cognitive flexibility, BDNF, and other vascular parameters were not affected. In conclusion, AME supplementation showed an indication of beneficial effects on cognitive performance and blood pressure in individuals at risk of cognitive decline.
Although asthma has been linked to psychological morbidity, this relationship may be confounded by poor asthma control. We aimed to compare the prevalence of anxiety, depression and low level of ...self-esteem in children with well-controlled asthma with that of healthy peers.
Dedicated asthma clinic in a general hospital.
70 patients with mostly well-controlled asthma and 70 matched healthy controls.
Comprehensive asthma education, management and follow-up for asthma patients.
Validated Dutch versions of the Childhood Depression inventory (CDI), Revised Fear Survey for Children (RFSC), Self Perception Profile for Children (SPC-C) and Adolescents (SPC-A) and State-Trait Anxiety Inventory for Children (STAIC). Asthma control assessed by asthma control questionnaire.
No significant differences were found in total scores between asthmatics and controls (95% CI for difference -0.2 to 2.9 for CDI, -5.9 to 11.2 for RFSC, -19.9 to 6.3 for SPC-C, -24.1 to 5.0 for SPC-A and -2.7 to 0.01 for STAIC). There were also no significant differences between asthmatics and controls in the prevalence of scores exceeding cut-off levels for clinically relevant anxiety (13.3 vs 13.0%, p=0.605), depression (12.9 vs 5.7%, p=0.243) or low self-esteem (21.4 vs 12.9%, p=0.175). A significant correlation was found between poorer asthma control and CDI (p=0.012) and anxiety trait symptoms (p<0.001).
Children with well-controlled asthma enrolled in a comprehensive asthma management programme do not have an increased risk of anxiety, depression and poor self-esteem. Earlier reports of psychological comorbidity in asthma may have been related to inadequately controlled asthma.
Inhaled corticosteroids (ICS) reduce growth during the first year of treatment, but this growth suppressing effect does not continue during further treatment. Decreasing adherence may play a role in ...explaining this. The aim of this study was to examine the relationship between cumulative real exposure (with objectively assessed adherence) to ICS and height growth in children with asthma.
We investigated 99 prepubertal children with asthma, 2-13 years of age, who had been using ICS in guideline-recommended dosages for ≥3 months, and continued to do so during 1-year follow-up. ICS adherence was assessed by electronic monitoring devices, allowing calculation of true cumulative exposure to ICS. We analysed the relationship between cumulative ICS dose and height growth velocity (assessed as change in height SD score) over 1 year.
Median (IQR) adherence over 1 year was 84 (68-92) %. Mean cumulative fluticasone dose was 64.6 (SD, 27.8) mg, reflecting a daily dose of 167 (SD, 7) µg. The negative correlation between cumulative ICS dose and height growth velocity (r=-0.266; p=0.008) became non-significant after adjustment for age and sex in a multiple regression model (adjusted r=-0.188; p=0.066).
One year of ICS treatment in guideline-recommended dosages with high adherence did not result in significant or relevant growth suppression. Unaffected growth can be maintained for at least 1 year in children with asthma during ICS treatment with high adherence.
Hyperventilation and other clinical manifestations of dysfunctional breathing have been reported in childhood, but the prevalence is unknown. In adults, dysfunctional breathing may be a relevant ...comorbidity in asthma. We aimed to determine the prevalence of dysfunctional breathing in children with asthma and its impact on asthma control. We performed a cross-sectional survey in 203 asthmatic children (aged 5-18 years), using the Nijmegen Questionnaire and the paediatric Asthma Control Questionnaire. Dysfunctional breathing was found in 11 (5.3%) children; more females (eight (12.9%) out of 62) than males (three (2.1%) out 144, p=0.002). There was a dose-dependent relationship between increasing Nijmegen Questionnaire scores (increased risk of dysfunctional breathing) and poorer asthma control. Poor asthma control was more common in patients with dysfunctional breathing (10 (90.9%) out of 11 children) than in children without (65 (32.3%) out of 192 children; OR 19.3, 95% CI 3.14-430.70; p<0.0001). The median Asthma Control Questionnaire in children with dysfunctional breathing was higher (median (range) 2.00 (1.50-3.17)) than in children without (0.50 (0.17-1.17); p<0.001). The prevalence of dysfunctional breathing in children and adolescents referred to a hospital-based paediatric asthma clinic for severe or difficult-to-control asthma is 5%. The association between dysfunctional breathing and asthma control suggests that this may be a clinically relevant comorbidity in paediatric asthma.
Background:Kawasaki disease (KD) is an acute pediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. Concerns have been raised regarding the possibility of a ...predisposition of KD to premature cardiovascular disease (CVD) risk later in life. Our aim was to assess carotid intima-media thickness (cIMT), as a surrogate marker of CVD risk, in patients with a history of KD compared with unaffected controls.Methods and Results:B-mode ultrasound cIMT measurements were performed in 168 patients with a history of KD, and 82 controls; 7 patients were excluded because of incomplete cIMT assessments. Mean cIMT (±SD) was increased in patients with KD compared with controls (0.378±0.030 mm vs. 0.360±0.027 mm, respectively; P adjusted <0.0001). If the cIMTs of CAA-negative patients and controls were plotted against age, increased cIMT was only apparent at young age. In patients with CAA, increased cIMT was observed over the entire age range.Conclusions:Our findings show that arterial wall thickening is more apparent in patients with a history of KD as compared with controls. In CAA-negative patients, cIMT is indistinguishable from controls at older age, whereas an increased cIMT is observed at any age in patients with CAA, suggesting a more general and severe effect of KD on the arterial wall. (Circ J 2015; 79: 2682–2687)
Epidemiological evidence of the effects of long-term exposure to air pollution on the chronic processes of atherogenesis is limited.
We investigated the association of long-term exposure to ...traffic-related air pollution with subclinical atherosclerosis, measured by carotid intima media thickness (IMT) and ankle-brachial index (ABI).
We performed a cross-sectional analysis using data collected during the reexamination (2007-2010) of 2,780 participants in the REGICOR (Registre Gironí del Cor: the Gerona Heart Register) study, a population-based prospective cohort in Girona, Spain. Long-term exposure across residences was calculated as the last 10 years' time-weighted average of residential nitrogen dioxide (NO2) estimates (based on a local-scale land-use regression model), traffic intensity in the nearest street, and traffic intensity in a 100 m buffer. Associations with IMT and ABI were estimated using linear regression and multinomial logistic regression, respectively, controlling for sex, age, smoking status, education, marital status, and several other potential confounders or intermediates.
Exposure contrasts between the 5th and 95th percentiles for NO2 (25 µg/m3), traffic intensity in the nearest street (15,000 vehicles/day), and traffic load within 100 m (7,200,000 vehicle-m/day) were associated with differences of 0.56% (95% CI: -1.5, 2.6%), 2.32% (95% CI: 0.48, 4.17%), and 1.91% (95% CI: -0.24, 4.06) percent difference in IMT, respectively. Exposures were positively associated with an ABI of > 1.3, but not an ABI of < 0.9. Stronger associations were observed among those with a high level of education and in men ≥ 60 years of age.
Long-term traffic-related exposures were associated with subclinical markers of atherosclerosis. Prospective studies are needed to confirm associations and further examine differences among population subgroups.
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