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Cardiovascular risk assessment of dyslipidemic children: analysis of biomarkers to identify monogenic dyslipidemia.

ABSTRACT: The distinction between a monogenic dyslipidemia and a polygenic/environmental dyslipidemia is important for the cardiovascular risk assessment, counseling, and treatment of these patients. The present work aims to perform the cardiovascular risk assessment of dyslipidemic children to identify useful biomarkers for clinical criteria improvement in clinical settings. Main cardiovascular risk factors were analyzed in a cohort of 237 unrelated children with clinical diagnosis of familial hypercholesterolemia (FH). About 40% carried at least two cardiovascular risk factors and 37.6% had FH, presenting mutations in LDLR and APOB. FH children showed significant elevated atherogenic markers and lower concentration of antiatherogenic particles. Children without a molecular diagnosis of FH had higher levels of TGs, apoC2, apoC3, and higher frequency of BMI and overweight/obesity, suggesting that environmental factors can be the underlying cause of their hypercholesterolem?ia. An apoB/apoA1 ratio ?0.68 was identified as the best biomarker (area under the curve = 0.835) to differentiate FH from other dyslipidemias. The inclusion in clinical criteria of a higher cut-off point for LDL cholesterol or an apoB/apoA1 ratio ?0.68 optimized the criteria sensitivity and specificity. The correct identification, at an early age, of all children at-risk is of great importance so that specific interventions can be implemented. apoB/apoA1 can improve the identification of FH patients.

SUBMITTER: Medeiros AM

PROVIDER: S-EPMC3995472 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Cardiovascular risk assessment of dyslipidemic children: analysis of biomarkers to identify monogenic dyslipidemia.

Medeiros Ana Margarida AM Alves Ana Catarina AC Aguiar Pedro P Bourbon Mafalda M

Journal of lipid research 20140313 5

The distinction between a monogenic dyslipidemia and a polygenic/environmental dyslipidemia is important for the cardiovascular risk assessment, counseling, and treatment of these patients. The present work aims to perform the cardiovascular risk assessment of dyslipidemic children to identify useful biomarkers for clinical criteria improvement in clinical settings. Main cardiovascular risk factors were analyzed in a cohort of 237 unrelated children with clinical diagnosis of familial hyperchole ...[more]

PMID: 24627126

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Project description:Importance:Higher Mediterranean diet (MED) intake has been associated with lower risk of cardiovascular disease (CVD), but limited data are available about the underlying molecular mechanisms of this inverse disease association in human populations. Objective:To better characterize the relative contribution of traditional and novel factors to the MED-related risk reduction in CVD events in a US population. Design, Setting, and Participants:Using a prospective cohort design, baseline MED intake was assessed in 25?994 initially healthy US women in the Women's Health Study who were followed up to 12 years. Potential mediating effects of a panel of 40 biomarkers were evaluated, including lipids, lipoproteins, apolipoproteins, inflammation, glucose metabolism and insulin resistance, branched-chain amino acids, small-molecule metabolites, and clinical factors. Baseline study information and samples were collected between April 30, 1993, and January 24, 1996. Analyses were conducted between August 1, 2017, and October 30, 2018. Exposures:Intake of MED is a 9-category measure of adherence to a Mediterranean dietary pattern. Participants were categorized into 3 levels based on their adherence to the MED. Main Outcomes and Measures:Incident CVD confirmed through medical records and the proportion of CVD risk reduction explained by mediators. Results:Among 25?994 women (mean [SD] age, 54.7 [7.1] years), those with low, middle, and upper MED intakes composed 39.0%, 36.2%, and 24.8% of the study population and experienced 428 (4.2%), 356 (3.8%), and 246 (3.8%) incident CVD events, respectively. Compared with the reference group who had low MED intake, CVD risk reductions were observed for the middle and upper groups, with respective HRs of 0.77 (95% CI, 0.67-0.90) and 0.72 (95% CI, 0.61-0.86) (P for trend?<?.001). The largest mediators of the CVD risk reduction of MED intake were biomarkers of inflammation (accounting for 29.2% of the MED-CVD association), glucose metabolism and insulin resistance (27.9%), and body mass index (27.3%), followed by blood pressure (26.6%), traditional lipids (26.0%), high-density lipoprotein measures (24.0%) or very low-density lipoprotein measures (20.8%), with lesser contributions from low-density lipoproteins (13.0%), branched-chain amino acids (13.6%), apolipoproteins (6.5%), or other small-molecule metabolites (5.8%). Conclusions and Relevance:In this study, higher MED intake was associated with approximately one-fourth relative risk reduction in CVD events, which could be explained in part by known risk factors, both traditional and novel.

Project description:BackgroundAutopsy studies reveal that atherosclerosis lesions can be found as early as two years of age. To slow the development of this early pathology, obesity and dyslipidemia prevention should start from childhood making it urgent to explore new ways to evaluate dyslipidemia risk in children that can be applied widely, such as the non-invasive anthropometric evaluation.ObjectiveAssess the metabolic profile of a pediatric population at a specific age to describe the association between anthropometric and biochemical cardiovascular disease risk factors; and evaluate selected anthropometric variables as potential predictors for dyslipidemic cardiovascular risk.Design and methodsAnthropometric features, bioimpedance parameters and fasting clinical profile were assessed in Lisbon and the Tagus Valley region pre-pubertal nine-year-old children (n = 1.496) from 2009-2013 in a descriptive, cross-sectional study. Anthropometric variables predictive power was evaluated through regression analysis.ResultsAt least one abnormal lipid parameter was found in 65% of "normal weight", 73% of "overweight" and 81% of "obese" children according to the International Obesity Task Force (IOTF) standards. Dyslipidemia was present in 67.8% of children. Waist-hip ratio (WHR) explained 0.4% of total cholesterol (TC) variance. Waist circumference (WC) explained 2.8% of apolipoprotein (APO) A1 variance. Waist-circumference-to-height-ratio (WHtR) explained 2.7%, 2.8% and 1.9% of low-density lipoprotein cholesterol (LDL-c), APO B, and N_HDL-c variance, respectively. Children with abnormally high WHR levels had an increase in risk of 4.49, 3.40 and 5.30 times, respectively, for developing cardiovascular disease risk factors measured as high-risk levels of TC, LDL-c and non-HDL-c (N_HDL-c) (p<0.05). Only 29.9% of "normal weight" children had no anthropometric, bioimpedance or biochemical parameters associated with CV risk.ConclusionA large proportion of school age children have at least one lipid profile abnormality. BMI, zBMI, calf circumference (CC), hip circumference (HC), WC, and WHR are directly associated with dyslipidemia, whereas HC and calf circumference (CC) adjusted to WC, and mid-upper arm circumference (MUAC), are all inversely associated with dyslipidemia. Selected anthropometric variables are likely to help predict increased odds of having CV risk factors.

Dataset Information

Cardiovascular risk assessment of dyslipidemic children: analysis of biomarkers to identify monogenic dyslipidemia.

Publications

Cardiovascular risk assessment of dyslipidemic children: analysis of biomarkers to identify monogenic dyslipidemia.

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