Editorial

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Open AccessEditorial

Cardiovascular Risk in Children: Focus on Pathophysiological Aspects

by Simonetta Genovesi and Gianfranco Parati

Int. J. Mol. Sci. 2020, 21(18), 6612; https://doi.org/10.3390/ijms21186612 - 10 Sep 2020

Cited by 11 | Viewed by 2117

Cardiovascular diseases are the leading cause of death, disability, and health care costs in industrialized countries. In general, cardiovascular diseases occur in adulthood, but cardiovascular damage, including stiffening of the arteries, begins very early. Already in the first decade of life, alterations that [...] Read more.

Cardiovascular diseases are the leading cause of death, disability, and health care costs in industrialized countries. In general, cardiovascular diseases occur in adulthood, but cardiovascular damage, including stiffening of the arteries, begins very early. Already in the first decade of life, alterations that will favor the formation of atherosclerotic plaques may be present. Cardiovascular risk factors, associated with genetic predisposition, may trigger a sequence of pathophysiological changes which are associated with the progression of the atherosclerosis process. In this frame, the role of obesity has been increasingly emphasized. Different mechanisms linking obesity to cardiovascular disease have been postulated. Endothelial dysfunction and subclinical inflammation seem to be related to the worsening of cardiovascular risk factors in obese subjects and might have an essential role in the development of insulin resistance and the initiation and progression of atherosclerotic lesions. Excess weight, and in particular visceral adiposity, are associated with hypertrophy and hyperplasia of the adipocytes, increased secretion of adipokines and inflammatory cytokines and increase in serum uric acid levels. The list of obesity-related biomarkers associated with cardiovascular damage is rapidly expanding and their importance has already been described in children as well. Pathophysiological changes involved in determining early cardiovascular damage starting from childhood are discussed in this Special Issue. Full article

(This article belongs to the Special Issue Cardiovascular Risk in Children and Adolescents: Focus on Methodological and Pathophysiological Aspects)

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Research

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14 pages, 259 KiB

Open AccessArticle

Evaluation of Different Adiposity Indices and Association with Metabolic Syndrome Risk in Obese Children: Is there a Winner?

by Alessandro Leone, Sara Vizzuso, Paolo Brambilla, Chiara Mameli, Simone Ravella, Ramona De Amicis, Alberto Battezzati, Gianvincenzo Zuccotti, Simona Bertoli and Elvira Verduci

Int. J. Mol. Sci. 2020, 21(11), 4083; https://doi.org/10.3390/ijms21114083 - 08 Jun 2020

Cited by 31 | Viewed by 3096

Abstract

Body shape index (ABSI) and triponderal mass index (TMI) have been recently associated with cardiovascular risk in adults. A cross-sectional study was conducted to evaluate the relationship between different anthropometric adiposity indexes and metabolic syndrome (MetS) in Caucasian obese children and adolescents. Consecutive [...] Read more.

Body shape index (ABSI) and triponderal mass index (TMI) have been recently associated with cardiovascular risk in adults. A cross-sectional study was conducted to evaluate the relationship between different anthropometric adiposity indexes and metabolic syndrome (MetS) in Caucasian obese children and adolescents. Consecutive obese children aged ≥7 years have been enrolled. Anthropometric parameters, body composition (by bioelectrical impedance), and systolic and diastolic blood pressure have been measured. Fasting blood samples have been analyzed for lipids, insulin, glucose. A multivariate logistic regression analyses, with body mass index z-score, waist to height ratio, ABSI z-score, TMI, conicity index as predictors for MetS (IDEFICS and IDF criteria according to age) has been performed. Four hundred and three (179 boys and 224 girls) obese children, aged 7–20 years, have been evaluated. When we explored the joint contribution of each anthropometric and adiposity index of interest and BMIz on the risk of MetS, we found that the inclusion of ABSIz improved the prediction of MetS compared to BMIz alone. ABSI-BMI can be a useful index for evaluating the relative contribution of central obesity to cardiometabolic risk in clinical management of obese children and adolescents. Full article

(This article belongs to the Special Issue Cardiovascular Risk in Children and Adolescents: Focus on Methodological and Pathophysiological Aspects)

15 pages, 724 KiB

Open AccessArticle

Fatty Acid Profile and Desaturase Activities in 7–10-Year-Old Children Attending Primary School in Verona South District: Association between Palmitoleic Acid, SCD-16, Indices of Adiposity, and Blood Pressure

by Sara Bonafini, Alice Giontella, Angela Tagetti, Irene Bresadola, Rossella Gaudino, Paolo Cavarzere, Diego Alberto Ramaroli, Lorella Branz, Denise Marcon, Angelo Pietrobelli, Pietro Minuz, Franco Antoniazzi, Claudio Maffeis and Cristiano Fava

Int. J. Mol. Sci. 2020, 21(11), 3899; https://doi.org/10.3390/ijms21113899 - 30 May 2020

Cited by 9 | Viewed by 2419

Abstract

In previous studies, dietary and circulating fatty acids (FA) and desaturases activity (delta-5 desaturase [D5D], delta-6 desaturase [D6D], and stearoyl-CoA desaturase [SCD-16]) involved in their metabolism were associated with metabolic and cardiovascular disorders. The aim of the study was to assess the association [...] Read more.

In previous studies, dietary and circulating fatty acids (FA) and desaturases activity (delta-5 desaturase [D5D], delta-6 desaturase [D6D], and stearoyl-CoA desaturase [SCD-16]) involved in their metabolism were associated with metabolic and cardiovascular disorders. The aim of the study was to assess the association between different FAs and desaturases activity (estimated as product:precursor ratios) with individual cardiovascular risk factors (in particular, anthropometric measurements and blood pressure [BP]) in children. The FA profile was determined on a whole-blood drop in 243 children (age: 8.6 ± 0.72 years) participating in a school-based cross-sectional study. Docosahexaenoic acid (DHA) inversely correlated with indices of adiposity, glucose, and triglycerides. Palmitoleic acid and SCD-16 were directly associated with markers of adiposity and BP, even after adjustment for main confounders. D6D correlated directly with the waist/height ratio. Children with excess weight (>85th percentile; that is overweight plus obese ones) showed higher palmitic acid, palmitoleic acid, and higher SCD-16 activity as compared to normal-weight children. Most of the associations were confirmed in the excess-weight group. Omega-3 FAs, particularly DHA, but not omega-6 FA, showed a potentially beneficial association with metabolic parameters, whereas palmitoleic acid and SCD-16 showed a potentially harmful association with indices of adiposity and BP, especially in obese children. Full article

(This article belongs to the Special Issue Cardiovascular Risk in Children and Adolescents: Focus on Methodological and Pathophysiological Aspects)

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12 pages, 2938 KiB

Open AccessArticle

Endothelial Hyper-Permeability Induced by T1D Sera Can be Reversed by iNOS Inactivation

by Alessandra Cazzaniga, Roberta Scrimieri, Elisa Giani, Gian Vincenzo Zuccotti and Jeanette A. M. Maier

Int. J. Mol. Sci. 2020, 21(8), 2798; https://doi.org/10.3390/ijms21082798 - 17 Apr 2020

Cited by 3 | Viewed by 1870

Abstract

Type 1 Diabetes Mellitus (T1D) is associated with accelerated atherosclerosis that is responsible for high morbidity and mortality. Endothelial hyperpermeability, a feature of endothelial dysfunction, is an early step of atherogenesis since it favours intimal lipid uptake. Therefore, we tested endothelial leakage by [...] Read more.

Type 1 Diabetes Mellitus (T1D) is associated with accelerated atherosclerosis that is responsible for high morbidity and mortality. Endothelial hyperpermeability, a feature of endothelial dysfunction, is an early step of atherogenesis since it favours intimal lipid uptake. Therefore, we tested endothelial leakage by loading the sera from T1D patients onto cultured human endothelial cells and found it increased by hyperglycaemic sera. These results were phenocopied in endothelial cells cultured in a medium containing high concentrations of glucose, which activates inducible nitric oxide synthase with a consequent increase of nitric oxide. Inhibition of the enzyme prevented high glucose-induced hyperpermeability, thus pointing to nitric oxide as the mediator involved in altering the endothelial barrier function. Since nitric oxide is much higher in sera from hyperglycaemic than normoglycaemic T1D patients, and the inhibition of inducible nitric oxide synthase prevents sera-dependent increased endothelial permeability, this enzyme might represent a promising biochemical marker to be monitored in T1D patients to predict alterations of the vascular wall, eventually promoting intimal lipid accumulation. Full article

(This article belongs to the Special Issue Cardiovascular Risk in Children and Adolescents: Focus on Methodological and Pathophysiological Aspects)

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12 pages, 261 KiB

Open AccessArticle

The Association between Nitric Oxide Pathway, Blood Pressure Abnormalities, and Cardiovascular Risk Profile in Pediatric Chronic Kidney Disease

by Chien-Ning Hsu, Pei-Chen Lu, Mao-Hung Lo, I-Chun Lin and You-Lin Tain

Int. J. Mol. Sci. 2019, 20(21), 5301; https://doi.org/10.3390/ijms20215301 - 24 Oct 2019

Cited by 28 | Viewed by 2693

Abstract

Cardiovascular disease (CVD) is common in chronic kidney disease (CKD), while major CV events are rare in young CKD patients. In addition to nitric oxide (NO)-related biomarkers, several surrogate markers have been assessed to stratify CV risk in youth with CKD, including 24-h [...] Read more.

Cardiovascular disease (CVD) is common in chronic kidney disease (CKD), while major CV events are rare in young CKD patients. In addition to nitric oxide (NO)-related biomarkers, several surrogate markers have been assessed to stratify CV risk in youth with CKD, including 24-h ambulatory blood pressure monitoring (ABPM), carotid artery intima-media thickness (cIMT), pulse wave velocity (PWV), ABPM-derived arterial stiffness index (AASI), flow-mediated dilatation (FMD), and left ventricular mass index (LVMI). The aim of this study was to identify subclinical CVD through the analysis of indices of CV risk in children and adolescents with CKD. Between 2016 and 2018, the prospective observational study enrolled 125 patients aged 3 to 18 years with G1–G4 CKD stages. Close to two-thirds of young patients with CKD exhibited blood pressure (BP) abnormalities on ABPM. CKD children with abnormal office BP showed lower plasma arginine levels and arginine-to-asymmetric dimethylarginine (ADMA) ratio, but higher ratios of ADMA-to-symmetric dimethylarginine (SDMA) and citrulline-to-arginine. High PWV and AASI, indices of arterial stiffness, both strongly correlated with high BP load. Additionally, LV mass and LVMI exhibited strong correlations with high BP load. Using an adjusted regression model, we observed the citrulline-to-arginine ratio was associated with 24-h systolic and diastolic BP, systolic blood pressure (SBP) load, and diastolic blood pressure (DBP) load. Early assessments of NO-related parameters, BP load abnormalities, arterial stiffness indices, and LV mass will aid in early preventative care toward decreasing CV risk later in life for children and adolescents with CKD. Full article

(This article belongs to the Special Issue Cardiovascular Risk in Children and Adolescents: Focus on Methodological and Pathophysiological Aspects)

Review

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17 pages, 336 KiB

Open AccessReview

The Impact of Diabetes Mellitus on Cardiovascular Risk Onset in Children and Adolescents

by Ida Pastore, Andrea Mario Bolla, Laura Montefusco, Maria Elena Lunati, Antonio Rossi, Emma Assi, Gian Vincenzo Zuccotti and Paolo Fiorina

Int. J. Mol. Sci. 2020, 21(14), 4928; https://doi.org/10.3390/ijms21144928 - 12 Jul 2020

Cited by 24 | Viewed by 4335

Abstract

The prevalence of diabetes mellitus is rising among children and adolescents worldwide. Cardiovascular diseases are the main cause of morbidity and mortality in diabetic patients. We review the impact of diabetes on establishing, during childhood and adolescence, the premises for cardiovascular diseases later [...] Read more.

The prevalence of diabetes mellitus is rising among children and adolescents worldwide. Cardiovascular diseases are the main cause of morbidity and mortality in diabetic patients. We review the impact of diabetes on establishing, during childhood and adolescence, the premises for cardiovascular diseases later in life. Interestingly, it seems that hyperglycemia is not the only factor that establishes an increased cardiovascular risk in adolescence. Other factors have been recognized to play a role in triggering the onset of latent cardiovascular diseases in the pediatric population. Among these cardiovascular risk factors, some are modifiable: glucose variability, hypoglycemia, obesity, insulin resistance, waist circumference, hypertension, dyslipidemia, smoking alcohol, microalbuminuria and smoking. Others are unmodifiable, such as diabetes duration and family history. Among the etiological factors, subclinical endothelial dysfunction represents one of the earliest key players of atherosclerosis and it can be detected during early ages in patients with diabetes. A better assessment of cardiovascular risk in pediatric population still represents a challenge for clinicians, and thus further efforts are required to properly identify and treat pediatric patients who may suffer from cardiovascular disease later in early adulthood. Full article

(This article belongs to the Special Issue Cardiovascular Risk in Children and Adolescents: Focus on Methodological and Pathophysiological Aspects)

13 pages, 759 KiB

Open AccessReview

Fructose and Uric Acid: Major Mediators of Cardiovascular Disease Risk Starting at Pediatric Age

by Elisa Russo, Giovanna Leoncini, Pasquale Esposito, Giacomo Garibotto, Roberto Pontremoli and Francesca Viazzi

Int. J. Mol. Sci. 2020, 21(12), 4479; https://doi.org/10.3390/ijms21124479 - 24 Jun 2020

Cited by 34 | Viewed by 8381

Abstract

Recently, there has been a growing interest in epidemiological and clinical studies supporting a pathogenetic role of fructose in cardio-metabolic diseases, especially in children and adolescents. In the present review, we summarize experimental data on the potential biological mechanisms linking fructose and uric [...] Read more.

Recently, there has been a growing interest in epidemiological and clinical studies supporting a pathogenetic role of fructose in cardio-metabolic diseases, especially in children and adolescents. In the present review, we summarize experimental data on the potential biological mechanisms linking fructose and uric acid in the development of insulin resistance, metabolic syndrome, obesity, diabetes, hypertension, non-alcoholic fatty liver disease and chronic renal disease, thereby contributing to an increase in cardiovascular risk at pediatric age. Full article

(This article belongs to the Special Issue Cardiovascular Risk in Children and Adolescents: Focus on Methodological and Pathophysiological Aspects)

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16 pages, 956 KiB

Open AccessReview

Vitamin D and Cardiovascular Risk: Which Implications in Children?

by Silvia Savastio, Erica Pozzi, Francesco Tagliaferri, Roberta Degrandi, Roberta Cinquatti, Ivana Rabbone and Gianni Bona

Int. J. Mol. Sci. 2020, 21(10), 3536; https://doi.org/10.3390/ijms21103536 - 16 May 2020

Cited by 15 | Viewed by 3686

Abstract

Vitamin D (25OHD) pleiotropic effects are widely recognized and studied. Recently, vitamin D cardiovascular effects are gaining interest, especially in children, although the studies present conflicting data. Some randomized controlled trials (RCTs) have demonstrated that cardiovascular risk markers, such as lipid parameters, inflammation [...] Read more.

Vitamin D (25OHD) pleiotropic effects are widely recognized and studied. Recently, vitamin D cardiovascular effects are gaining interest, especially in children, although the studies present conflicting data. Some randomized controlled trials (RCTs) have demonstrated that cardiovascular risk markers, such as lipid parameters, inflammation markers, blood pressure, and arterial stiffness, are unaffected by vitamin D supplementation. By contrast, other studies show that low vitamin D levels are associated with higher risk of cardiovascular disease (CVD) and mortality, and support that increased risk of these diseases occurs primarily in people with vitamin D deficiency. An update on these points in pediatric patients is certainly of interest to focus on possible benefits of its supplementation. Full article

(This article belongs to the Special Issue Cardiovascular Risk in Children and Adolescents: Focus on Methodological and Pathophysiological Aspects)

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