Awareness of cholesterol levels in 46,309 Italian children and adolescents unveils the tip of the iceberg.

BACKGROUND AND AIMS: Cardiovascular diseases (CVD) risk factors include high cholesterol. Children with total cholesterol (TC) levels ≥ 170 mg/dL are usually considered hypercholesterolemic. This study aimed at investigating the awareness of TC levels in a large Italian paediatric population and at looking for a possible correlation between their TC and TC in their parents' blood. METHODS AND RESULTS: A survey was carried out in 46,309 subjects (mean age 9.7 ± 2.3 years; age range 6-14 years) to check the awareness of their own TC levels by using a personal and family medical history questionnaire. In 95.67% of the sample TC value was unknown. In 2.69% TC was < 170 mg/dL, whereas 1.64% were hypercholesterolemic (TC ≥ 170 mg/dL). A statistically significant correlation was found between children with normal TC values and physiological TC values in both parents (p < 0.0001). Again, a significant association between children with high TC and their parents with high TC was detected when parents were analysed separately (i.e. children with TC ≥ 170 mg/dl vs maternal TC ≥ 200 mg/dL: OR 2.01 (95% CI 1.61-2.49, p < 0.001); children with TC ≥ 200 mg/dl vs maternal TC ≥ 240 mg/dL: OR 3.14 (95% CI 2.14-4.6, p < 0.001); children with TC ≥ 170 mg/dl vs paternal TC ≥ 200 mg/dL: OR 2.39 (95% CI 1.91-2.98, p < 0.001); children with TC ≥ 200 mg/dl vs paternal TC ≥ 240 mg/dL: OR 3.85 (95% CI 2.70-5,.50, p < 0.001). CONCLUSION: Just a minority of the investigated young patients knew their TC. This is worrisome. Children with normal TC values are more likely to be born from healthy parents with physiological TC. In addition, high TC in the enrolled subjects is significantly associated with high TC in their parents. Overall, these findings seem to highlight the importance of health education and genetics in TC pathogenesis.

Nailfold capillaroscopy reveals early peripheral microcirculation abnormalities in children affected by heterozygous familial hypercholesterolemia.

BACKGROUND: nailfold capillaroscopy (NCF) is a non-invasive imaging technique to seek peripheral microcirculation abnormalities in children and adults. Familial hypercholesterolemia is a genetic disorder caused by mutations capable of increasing blood levels of low-density lipoproteins cholesterol (LDL-C), thus triggering early atherosclerosis. The study aims at evaluating peripheral microcirculation in children with heterozygous familial hypercholesterolemia (HeFH) by means of NFC in comparison with healthy peers and at searching for possible correlations between these abnormalities and patients' lipid panel. METHODS: thirty-six HeFH patients were enrolled (13 males and 23 females. Mean age 8 ± 3 years; age range 3-13 years). They had increased levels of total cholesterol (237.9 ± 34.2 mg/dl) and LDL-C (154.2 ± 37.6 mg/dl). Both values were ≥95th gender and age specific centile. All the subjects in the study underwent NFC. RESULTS: In 69.4 % of HeFH children nailfold capillaries were tortuous (p < 0.00001 compared to healthy controls). In 41.6 % the number of capillaries was markedly reduced (<7 capillaries/mm). The mean number of capillaries was 8.4 ± 2.6/mm in HeFH and 12.2 ± 1.4/mm in healthy controls (p < 0.00001). In 100 % of the sample size capillary blood flow was slowed down (p < 0.00001). In 50 % of the sample size a blood "sludge" phenomenon was seen (p < 0.00001). No gender differences were detected. Sludge phenomenon was seen only in those with LDL-C over 99th centile (p < 0.00001). CONCLUSION: NCF allows the identification of an early peripheral microvascular dysfunction in HeFH children which is similar to that already seen in atherosclerotic disease. Prompt identification of these capillary abnormalities may be crucial in implementing early prevention measures.

Neural binocular summation and the effect of defocus on the pattern electroretinogram and visual evoked potentials for different pupil sizes.

PURPOSE: To evaluate the influence of defocus and pupil size on subjective (visual acuity [VA]) and objective (electrophysiology) descriptors of human vision and their effect on binocular visual performance by means of neural binocular summation (BS). METHODS: Fifteen healthy young subjects were recruited in this crossover study. Pattern electroretinogram (PERG) and visual evoked potentials (VEP) were measured under two levels of positive (+1.5 and +3.0 D) spherical and astigmatic defocus (axis 90°). Pupil size was controlled to reduce the inter-individual variability factor. RESULTS: Low- and high-contrast VA showed poorer visual performance in the monocular versus the binocular condition. Positive BS (for VA) was higher with greater pupil size and higher levels of defocus. In the visual electrophysiology tests (i.e., VEP and PERG), peak time and amplitude were affected by pupil size and defocus. The increase in peak time was larger and the reduction in amplitude was more significant with greater levels of defocus and smaller pupil sizes. For the VEP, positive BS was found in all conditions, being stronger with larger amounts of defocus and pupil size (for the P100 amplitude). Significant negative correlations were observed between the P100 amplitude and VA BSs. CONCLUSION: Smaller pupil size and levels of defocus produced greater changes in cortical activity as evidenced by both the PERG and VEP. Considering these changes and the obtained positive BS, the mechanism could be initiated as early as the retinal processing stage, then being modulated and enhanced along the visual pathway and within the visual cortex.

Parental awareness of the implications of myopia and strategies to control its progression: A survey-based study.

PURPOSE: Myopia has emerged as a significant public health concern. Effective methods have now been developed to delay its onset and progression. However, this information may not be reaching parents, and they are key players in terms of implementing the necessary preventive measures. This study investigated parental awareness of myopia, its implications and the strategies available for controlling it. METHODS: A self-administered online survey was distributed to parents of children 6-16 years of age. To be eligible to respond, their child had to be myopic or at risk of developing myopia due to family history. RESULTS: A total of 330 parents completed the survey, of which 321 were included for analysis. Sixty-seven percent of respondents had at least one myopic son/daughter, and most were between -1.00 and -1.75 D. Among parents of myopic children, 20.9% thought that their child's myopia progressed moderately. Sixty-seven percent of parents had a significant level of concern about the progression of the myopia and felt that it was caused mainly by the use of electronic devices and genetics. A generalised linear model showed that parental concern was significantly predicted by the perception of evolution (p < 0.001) and the number of known health-related consequences (p < 0.001). Almost 40% of parents were unaware of the existence of myopia control strategies. Relatives and eye care practitioners are the main sources of information. The most well-known myopia control strategy was myopia control soft contact lenses (29.2%), although the option that most parents would opt for was spectacles with peripheral defocus lenses (47.1%). The selection of a contact-lens-based myopia control method correlated significantly with the age of the children (p < 0.001). CONCLUSIONS: Society in general and parents in particular need more information about myopia, its consequences and the options available for its control. Eye care practitioners play an important role in this issue.

Pupil size effect on binocular summation for visual acuity and light disturbance.

PURPOSE: Smaller pupil size under binocular conditions could justify partially the improvement of visual performance when compared to monocular conditions. The purpose of this study was to assess the binocular summation for increasing levels of spherical and cylindrical defocus when the pupil size factor is ruled out as a confounding factor. METHODS: Fifteen young subjects were recruited in this crossover study. Light disturbance index (LDI) was evaluated with the light disturbance analyzer and low (LCDVA) and high (HCDVA) contrast visual acuity with the ETDRS test. Two positive spherical and cylindrical defocus levels (+ 1.5 and + 3.0 D) were used to induce a controlled degradation of the retinal image for two pupil sizes (3 and 5 mm). RESULTS: Our results showed poorer visual performance in monocular than the binocular condition. An increasing deterioration was observed with the level of spherical defocus. Positive binocular summation for visual acuity was found in all the parameters studied and was stronger under larger pupil size and for higher levels of spherical defocus. It was observed a positive binocular summation for the LDI under all the conditions studied. Strong and significant correlations were found between LDI and LCDVA and between LDI and HCDVA for all the conditions. Higher correlations were obtained between disturbance index and visual acuity for spherical defocus compared to cylindrical. CONCLUSION: Binocular summation was observed under different conditions of spherical and cylindrical optical degradation of the image quality when the pupil size was fully controlled. This suggests that a neural factor is involved.

Assessing the influence of cannabis and alcohol use on different visual functions: A comparative study.

This study aimed to assess and compare the influence of alcohol intake and cannabis smoking on different visual functions. A total of 64 young and healthy volunteers took part in the study. All undertook several randomised experimental sessions in which different visual functions, namely distance stereopsis, retinal straylight, visual discrimination capacity, and contrast sensitivity, were tested. Cannabis smokers (N = 30) took a baseline session and a session after smoking a cannabis cigarette, whereas alcohol users (N = 34) underwent a baseline session, a session after a low alcohol intake (Alcohol 1), and a session after a moderate to high alcohol intake (Alcohol 2). All visual functions were impaired by cannabis and alcohol use, particularly for the Cannabis and Alcohol 2 groups. The deterioration of all visual variables was higher for the Alcohol 2 than for the Alcohol 1 and Cannabis groups, except for retinal straylight, the deterioration of which was equal for the Cannabis group, and distant stereopsis, which was more impaired for the Cannabis group. The Alcohol 2 group experienced the most impairing conditions, although very similar to the cannabis group, and that factors other than the experimental conditions, such as sex and age, also influenced these visual changes. Alcohol and cannabis use clearly impair vision. The deterioration caused by cannabis is similar to, but slightly lower than, that produced by a moderate to high alcohol intake, with the experimental conditions, sex and age all having an impact on the variability of visual deterioration.

Effect of interocular differences on binocular visual performance after inducing forward scattering.

PURPOSE: To assess binocular visual performance by means of binocular summation on visual function after inducing monocular forward scattering, and to study the influence of interocular differences on ocular parameters. METHODS: Seven young healthy subjects were recruited. Four Bangerter foils and five fog filters were used to induce monocular forward scattering. To analyse the impact of the scatter, visual acuity, contrast sensitivity, visual discrimination capacity and distance stereoacuity were measured binocularly with the filter placed over the dominant eye. Additionally, interocular differences were calculated for four ocular parameters: the Objective Scatter Index (OSI), Strehl ratio (SR), modulation transfer function cut-off (MTF cut off) and straylight (log[s]). Binocular summation was determined for these visual functions. RESULTS: A statistically significant deterioration in visual acuity, contrast sensitivity and stereoacuity was seen for all of the filter conditions with respect to the natural state (baseline), with the largest change being recorded for the Bangerter foils. Similarly, the interocular difference for the three retinal image quality parameters (OSI, SR and MTF cut-off) and log(s) increased significantly for the Bangerter foil condition, but not for the fog filters (except log(s)). Binocular summation declined gradually with the Bangerter foils, but not for the fog filters. Statistically significant correlations were found, that is, the greater the interocular differences, the lower the binocular summation of the visual functions and the greater the distance stereoacuity. CONCLUSION: Increased forward scattering in the dominant eye resulted in interocular differences, which reduced the overall binocular visual performance, including the binocular summation of several visual functions and distance stereoacuity. The results suggest that marked interocular differences in ocular parameters should be avoided in cases of ocular pathology, amblyopia and emmetropisation procedures (such as refractive surgery) or a monovision correction for presbyopia.

Salvianolic Acid B Strikes Back: New Evidence in the Modulation of Expression and Activity of Matrix Metalloproteinase 9 in MDA-MB-231 Human Breast Cancer Cells.

Salvianolic acid B (SalB) is a bioactive compound from Salviae miltiorrhizae, one of the most important traditional herbal medicines widely used in several countries for the treatment of cardiovascular diseases. The aim of this study was to evaluate the in vitro effect of SalB on the expression and the activity of matrix metalloproteinase 9 (MMP-9), a zinc-dependent proteolytic enzyme, in human MDA-MB-231 breast cancer cells. This cellular model is characterized by a marked invasive phenotype, supported by a high constitutive expression of MMPs, especially gelatinases. SalB was first of all evaluated by in silico approaches primarily aimed at predicting the main pharmacokinetic parameters. The most favorable interaction between the natural compound and MMP-9 was instead tested by molecular docking analysis that was subsequently verified by an enzymatic inhibition assay. MDA-MB-231 cells were treated with SalB 5 µM and 50 µM for 24 h and 48 h. The conditioned media obtained from treated cells were then analyzed by gelatin zymography and reverse zymography to, respectively, evaluate the MMP-9 activity and the presence of TIMP-1. The expression of the enzyme was then evaluated by Western blot on conditioned media and by analysis of transcripts through reverse transcriptase-polymerase chain reaction (RT-PCR). The in silico approach showed the ability of SalB to interact with the catalytic zinc ion of the enzyme, with a plausible competitive mode of action. The analysis of conditioned culture media showed a reduction in MMP-9 activity and the concomitant decrease in the enzyme concentration, partially confirmed by analysis of transcripts. SalB showed the ability to modulate the function of MMP-9 in MDA-MB-231 cells. To our knowledge, this is the first time in which the role of SalB on MMP-9 in a highly invasive cellular model is investigated. The obtained results impose further and more specific evaluations in order to obtain a better understanding of the biochemical mechanisms that regulate the interaction between this natural compound and the MMP-9.

Machine Learning in Hypertension Detection: A Study on World Hypertension Day Data.

Many modifiable and non-modifiable risk factors have been associated with hypertension. However, current screening programs are still failing in identifying individuals at higher risk of hypertension. Given the major impact of high blood pressure on cardiovascular events and mortality, there is an urgent need to find new strategies to improve hypertension detection. We aimed to explore whether a machine learning (ML) algorithm can help identifying individuals predictors of hypertension. We analysed the data set generated by the questionnaires administered during the World Hypertension Day from 2015 to 2019. A total of 20206 individuals have been included for analysis. We tested five ML algorithms, exploiting different balancing techniques. Moreover, we computed the performance of the medical protocol currently adopted in the screening programs. Results show that a gain of sensitivity reflects in a loss of specificity, bringing to a scenario where there is not an algorithm and a configuration which properly outperforms against the others. However, Random Forest provides interesting performances (0.818 sensitivity - 0.629 specificity) compared with medical protocols (0.906 sensitivity - 0.230 specificity). Detection of hypertension at a population level still remains challenging and a machine learning approach could help in making screening programs more precise and cost effective, when based on accurate data collection. More studies are needed to identify new features to be acquired and to further improve the performances of ML models.

Obstructive Sleep Apnea and Hypertension: Why Treatment Does Not Consistently Improve Blood Pressure.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) and hypertension are two phenomena deeply linked together and, although a causal relationship has been suggested, a recent meta-analysis showed only a very modest effect of OSA treatment on blood pressure (BP). However, a vast number of randomized controlled trials published so far share some limitations, mainly of methodological nature: neither OSA nor BP is always assessed in a standardized way. Moreover, compliance with OSA treatment is often sub-optimal making the results of these trials difficult to interpret. RECENT FINDINGS: Recent studies have shown that antihypertensive drugs can reduce BP more than OSA treatment, showing a better compliance profile and very few side effects. Considering the importance of reducing the overall cardiovascular risk of OSA patients, a more careful management of patient's antihypertensive medication could allow a better BP control also in this condition. In addition, greater efforts should be made to improve patient's acceptance of OSA treatment with the aim of improving their compliance.

Lifestyle and awareness of cholesterol blood levels among 29159 community school children in Italy.

BACKGROUND AND AIM: Lifestyle habits including indoor and outdoor activities among community school children, adherence to the Mediterranean diet and awareness about total cholesterol blood levels represent determinant factors in cardiovascular disease (CVD) prevention. The aim of this study was to analyze the relationship between adherence to the Mediterranean diet, total cholesterol blood levels, body composition and hours per day spent in in-house or outdoor among 29,159 Italian 6-14 years-old community school children (50% boys). The KidMed questionnaire, modified to handle missing information on olive oil consumption, was used to assess the adherence to the Mediterranean diet among participants. METHODS AND RESULTS: Associations between variables were tested according to 3 classes of the Mediterranean diet adherence score using analysis of variance. Participants with high adherence to Mediterranean diet were few (1%). Overall awareness of total cholesterol blood levels was low among children (4.5%), slightly higher among parents (26.2 and 24.1% in mothers and fathers, respectively). Among Mediterranean diet adherent children, BMI was significantly (p < 0.001) smaller than among the non-Mediterranean or intermediate adherent children as were the total hours spent per day watching television or playing with videogames (p < 0.001) whereas the hours/day in sport or outdoor activities were more (p < 0.001). These results were confirmed by multiple linear regression with KidMed scored 0 to 8 as dependent variable. CONCLUSION: Although awareness of total cholesterol blood levels and adherence to the Mediterranean diet are rare among community school children, only among these a healthier lifestyle was practiced with a tendency to lower CVD risks. These results are important as the first sized experience of this type in Italy.

Role of NADPH oxidase-2 and oxidative stress in children exposed to passive smoking.

This study explored oxidative stress, nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox2) activity and endothelial function in children exposed or not to passive smoking. Compared with controls (n=57), Nox2 activity and isoprostanes were higher in children exposed to passive smoking (n=57); conversely, nitric oxide (NO) bioavailability and flow-mediated dilation were lower in children exposed to passive smoking. A bivariate analysis showed that Nox2 activity correlated with flow-mediated dilation, NO bioavailability and isoprostanes. A multivariate analysis showed that Nox2 activity was significantly associated with serum isoprostanes and cotinine levels; flow-mediated dilation was associated with isoprostanes and carotid intima-media thickness.In children exposed to passive smoking, Nox2-derived oxidative stress is upregulated and inversely associated with impaired artery dilation.

Passive Smoking Exacerbates Nicotinamide-Adenine Dinucleotide Phosphate Oxidase Isoform 2-Induced Oxidative Stress and Arterial Dysfunction in Children with Persistent Allergic Rhinitis.

OBJECTIVE: To characterize nicotinamide-adenine dinucleotide phosphate oxidase isoform 2 (NOX2), oxidative stress, and endothelial function in children with and without allergic rhinitis and to ascertain the effect of passive smoke exposure on these factors, because there is an established association between allergic rhinitis and increased cardiovascular risk in adults. METHODS: We recruited 130 children-65 with persistent allergic rhinitis and 65 healthy controls. A cross-sectional study was performed to compare endothelial function by flow-mediated dilation, blood levels of isoprostanes, serum activity of soluble NOX2-dp (sNOX2-dp), and nitric oxide bioavailability, in these 2 groups of children. Serum cotinine levels were assessed to measure exposure to passive smoking. RESULTS: Compared with healthy controls, children with persistent allergic rhinitis had significantly higher sNOX2-dp and isoprostanes levels, lower flow-mediated dilation, and reduced nitric oxide bioavailability. Multivariable linear regression analysis showed that flow-mediated dilation, isoprostanes, and cotinine were independently associated with sNOX2-dp levels. Of note, sNOX2-dp serum levels were significantly higher in children with allergic rhinitis exposed to smoke, as compared with unexposed children with allergic rhinitis. CONCLUSION: NOX2 is activated in children with persistent allergic rhinitis and passive smoke exposure exacerbates this effect. We further demonstrate an association between higher sNOX2-dp and oxidative stress and endothelial dysfunction.

HPV Virus Transcriptional Status Assessment in a Case of Sinonasal Carcinoma.

Human Papilloma Virus (HPV) can play a causative role in the development of sinonasal tract malignancies. In fact, HPV may be the most significant causative agent implicated in sinonasal tumorigenesis and is implicated in as many as 21% of sinonasal carcinomas. To date, there are no definitive, reliable and cost-effective, diagnostic tests approved by the FDA for the unequivocal determination of HPV status in head and neck cancers. We followed an exhaustive algorithm to correctly test HPV infection, including a sequential approach with p16INK4a IHC, viral DNA genotyping and in situ hybridization for E6/E7 mRNA. Here, we report a case of sinonasal carcinoma with discordant results using HPV test assays. The tumor we describe showed an irregular immunoreactivity for p16INK4a, and it tested positive for HPV DNA; nevertheless, it was negative for HR-HPV mRNA. We discuss the possible meaning of this discrepancy. It would be advisable to test HPV transcriptional status of sinonasal carcinoma on a diagnostic routine basis, not only by p16INK4a IHC assay, but also by HPV DNA genotyping and HR-HPV mRNA assessment.

Analysis of Children and Adolescents with Familial Hypercholesterolemia.

OBJECTIVE: To evaluate the effectiveness of criteria based on child-parent assessment in predicting familial hypercholesterolemia (FH)-causative mutations in unselected children with hypercholesterolemia. STUDY DESIGN: LDLR, APOB, and PCSK9 genes were sequenced in 78 children and adolescents (mean age 8.4 ± 3.7 years) with clinically diagnosed FH. The presence of polygenic hypercholesterolemia was further evaluated by genotyping 6 low-density lipoprotein cholesterol (LDL-C)-raising single-nucleotide polymorphisms. RESULTS: Thirty-nine children (50.0%) were found to carry LDLR mutant alleles but none with APOB or PCSK9 mutant alleles. Overall, 27 different LDLR mutations were identified, and 2 were novel. Children carrying mutations showed higher LDL-C (215.2 ± 52.7 mg/dL vs 181.0 ± 44.6 mg/dL, P <.001) and apolipoprotein B levels (131.6 ± 38.3 mg/dL vs 100.3 ± 30.0 mg/dL, P <.004), compared with noncarriers. A LDL-C of ~190 mg/dL was the optimal value to discriminate children with and without LDLR mutations. When different diagnostic criteria were compared, those proposed by the European Atherosclerosis Society showed a reasonable balance between sensitivity and specificity in the identification of LDLR mutations. In children without mutation, the FH phenotype was not caused by the aggregation of LDL-C raising single-nucleotide polymorphisms. CONCLUSIONS: In unselected children with hypercholesterolemia, LDL-C levels >190 mg/dL and a positive family history of hypercholesterolemia appeared to be the most reliable criteria for detecting FH. As 50% of children with suspected FH did not carry FH-causing mutations, genetic testing should be considered.

Circulating miR-200c is up-regulated in paediatric patients with familial hypercholesterolaemia and correlates with miR-33a/b levels: implication of a ZEB1-dependent mechanism.

Hypercholesterolaemia provokes reactive oxygen species (ROS) increase and is a major risk factor for cardiovascular disease (CVD) development. We previously showed that circulating miR-33a/b expression levels were up-regulated in children with familial hypercholesterolaemia (FH). miR-33a/b control cholesterol homoeostasis and recently miR-33b has been demonstrated to directly target the transcription factor zinc finger E-box-binding homeobox 1 (ZEB1). The latter acts in a negative feedback loop with the miR-200 family. Our previous studies showed that the ROS-dependent miR-200c up-regulation induces endothelial dysfunction and provokes a ZEB1-dependent apoptosis and senescence. In the present study, we aimed to verify whether circulating miR-200c was induced in FH children, and whether a correlation existed with miR-33a/b Total RNA was extracted from plasma of 28 FH children and 25 age-matched healthy subjects (HS) and miR-200c levels were measured. We found that miR-200c was up-regulated in FH compared with HS (4.00 ± 0.48-fold increase, P<0.05) and exhibited a positive correlation with miR-33a/b. miR-200c did not correlate with plasma lipids, but correlated with C-reactive protein (CRP) plasma levels and glycaemia (GLI). Ordinary least squares (OLS) regression analysis revealed that miR-200c was significantly affected by GLI and by miR-33a (P<0.01; P<0.001 respectively). Moreover, we found that miR-33 overexpression, in different cell lines, decreased ZEB1 expression and up-regulated both the intracellular and the extracellular miR-200c expression levels. In conclusion, circulating miR-200c is up-regulated in FH, probably due to oxidative stress and inflammation and via a miR-33a/b-ZEB1-dependent mechanism. The present study could provide the first evidence to point to the use of miR-33a/b and miR-200c, as early biomarkers of CVD, in paediatric FH.

Circulating miR-33a and miR-33b are up-regulated in familial hypercholesterolaemia in paediatric age.

Hypercholesterolaemia is one of the major causes of CVD (cardiovascular disease). It is associated with enhanced oxidative stress, leading to increased lipid peroxidation which in turn determines endothelial dysfunction and susceptibility to coronary vasoconstriction and atherosclerosis. Different miRNAs are involved in the pathogenesis of CVD and play an important role in inflammatory process control, therefore, together with atherogenic factors, they can stimulate atherosclerotic degeneration of the vessel walls of arteries. miR-33a and miR-33b play a pivotal role in a variety of biological processes including cholesterol homoeostasis, HDL (high-density lipoprotein)-cholesterol formation, fatty acid oxidation and insulin signalling. Our study aimed to determine whether circulating miR-33a and miR-33b expression was altered in familial hypercholesterolaemic children. Total RNA was extracted from plasma, and miR-33a and miR-33b were measured by quantitative real-time PCR. We found that miR-33a and miR-33b were significantly up-regulated in the plasma of 28 hypercholesterolaemic children compared with 25 healthy subjects (4.49±0.27-fold increase, P<0.001, and 3.21±0.39-fold increase, P<0.05 respectively), and for both miRNAs, a positive correlation with total cholesterol, LDL (low-density lipoprotein)-cholesterol, LDL-cholesterol/HDL-cholesterol ratio, apolipoprotein B, CRP (C-reactive protein) and glycaemia was found. OLS (ordinary least squares) regression analysis revealed that miR-33a was significantly affected by the presence of FH (familial hypercholesterolaemia), glycaemia and CRP (P<0.001, P<0.05 and P<0.05 respectively). The same analysis showed that miR-33b was significantly related to FH and CRP (P<0.05 and P<0.05 respectively). Although it is only explorative, the present study could be the first to point to the use of miR-33a and miR-33b as early biomarkers for cholesterol levels in childhood, once validated in independent larger cohorts.

Anthropometric indices are not satisfactory predictors of metabolic comorbidities in obese children and adolescents.

OBJECTIVE: To assess the accuracy of body mass index (BMI), Z score of the BMI, waist circumference, and waist-to-height ratio in selecting obese children with fasting metabolic impairments or impaired glucose tolerance. STUDY DESIGN: In a cohort of 883 obese children and adolescents (age 8-18 years), we assessed the associations of anthropometric indices with traditional metabolic complications of obesity (impaired fasting glucose, impaired glucose tolerance, hypertension, high triglycerides, low high-density lipoprotein-cholesterol). The accuracy of anthropometric indices as markers of metabolic impairment was assessed by receiver operating characteristic analysis and the areas under the receiver operating characteristics curves (AUROCs) of anthropometric indices were compared with each other by the DeLong test. RESULTS: BMI, Z score of the BMI, waist circumference, and waist-to-height ratio were associated with metabolic impairments but showed low to moderate accuracy in discriminating both single and clustered metabolic impairments. The AUROCs ranged from 0.55-0.70. The 4 anthropometric indices did not show significantly different AUROCs as predictors of clustered metabolic risk factors (all P values of DeLong tests: >.05). CONCLUSIONS: Commonly used anthropometric indices are not satisfactory markers of metabolic comorbidity among obese children and adolescents and should not be adopted as screening tools for the metabolic assessment of this category of patients.

The Association between Mid-Upper Arm Circumference and Blood Pressure in an Italian Population of School-Aged Children and Adolescents with Lipid Disorders.

Background: Many anthropometric measurements have been investigated concerning their association with blood pressure (BP) in paediatric age groups. This study aims to find a relationship between mid-upper arm circumference (MUAC) and BP in a population of children and adolescents aged 1-18 years. Methods: 5853 subjects (2977 females and 2876 males) were studied. MUAC, body mass index (BMI), and BP were measured. The individuals in the study were subdivided and grouped by gender and type of school attended in Italy: 1-5 years (pre-school), 6-10 years (primary school), 11-13 years (secondary school), 14-18 years (high school). Results: In the age range of 6-13 years, all the subjects with MUAC > 50th percentile had systolic and diastolic BP significantly higher than children with MUAC below 50th percentile (p < 0.0001). In the age range 14-18 years, the relationship persisted only in females (p < 0.001 and p < 0.05 for diastolic and systolic BP, respectively). A linear relationship was found between MUAC and BMI. Conclusions: In Italian children of both genders aged 6-13, arm distribution of body fat is strongly associated with increased systolic and diastolic BP. As such, a simple anthropometric measurement like MUAC might represent a tool to identify young subjects who are at risk for HTN.