Our findings provide evidence that a high prevalence of hyperuricemia occurs in hypertensive patients from central and east Europe. The data also show that gender-related differences in the association between SUA and cardionephrometabolic variables exist. This is also the case for the relationships between SUA and CKD.

The present study found a positive association between uric acid and blood pressure, insulin and triglycerides. As uric acid levels increase there is a relevant clustering of metabolic risk factors, whereas elevated blood pressure is the risk factor less frequently present. Further studies need to assess the mechanistic link between uric acid and the cardiometabolic risk factors.

BackgroundEarly life is a period of drastic epigenetic remodeling in which the epigenome is especially sensitive to extrinsic and intrinsic influence. However, the epigenome-wide dynamics of the DNA methylation changes that occur during this period have not been sufficiently characterized in longitudinal studies.MethodsTo this end, we studied the DNA methylation status of more than 750,000 CpG sites using Illumina MethylationEPIC arrays on 33 paired blood samples from 11 subjects at birth and at 5 and 10 years of age, then characterized the chromatin context associated with these loci by integrating our data with histone, chromatin-state and enhancer-element external datasets, and, finally, validated our results through bisulfite pyrosequencing in two independent longitudinal cohorts of 18 additional subjects.ResultsWe found abundant DNA methylation changes (110,726 CpG sites) during the first lustrum of life, while far fewer alterations were observed in the subsequent 5 years (460 CpG sites). However, our analysis revealed persistent DNA methylation changes at 240 CpG sites, indicating that there are genomic locations of considerable epigenetic change beyond immediate birth. The chromatin context of hypermethylation changes was associated with repressive genomic locations and genes with developmental and cell signaling functions, while hypomethylation changes were linked to enhancer regions and genes with immunological and mRNA and protein metabolism functions. Significantly, our results show that genes that suffer simultaneous hyper- and hypomethylation are functionally distinct from exclusively hyper- or hypomethylated genes, and that enhancer-associated methylation is different in hyper- and hypomethylation scenarios, with hypomethylation being more associated to epigenetic changes at blood tissue-specific enhancer elements.ConclusionsThese data show that epigenetic remodeling is dramatically reduced after the first 5 years of life. However, there are certain loci which continue to manifest DNA methylation changes, pointing towards a possible functionality beyond early development. Furthermore, our results deepen the understanding of the genomic context associated to hyper- or hypomethylation alterations during time, suggesting that hypomethylation of blood tissue-specific enhancer elements could be of importance in the establishment of functional states in blood tissue during early-life.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1751-9) contains supplementary material, which is available to authorized users.

BackgroundEarly life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life.MethodsThe study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects.ResultsDNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function.ConclusionsOur results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention.

The present prospective study assessed the association of birth weight (BW) and growth pattern on cardiometabolic risk factors in a cohort followed from birth to 10 years of age. One hundred and forty-five subjects (73 girls) who fulfilled the inclusion criteria and had all their data recorded at birth and at 5 years were enrolled. Of these, 100 (52 girls) also recorded data at 10 years. Anthropometric measurements, office and 24-hour blood pressure, and metabolic parameters were obtained. At 5 years, both BW and current weight were determinants of blood pressure and metabolic parameters; however, as the subjects got older, the impact of body size increased. Higher BW and maternal obesity increased the risk of becoming obese at 5 years while this was reduced if breastfeeding. Maternal obesity was the only factor associated with becoming obese at 10 years. Twenty-two children at 10 years had insulin values ≥15 U/L, some of whom were persistent from 5 years while in others it increased afterward. Subjects with insulin values ≥15 U/L showed significant higher values of office systolic blood pressure, triglycerides, and uric acid and lower values of high-density lipoprotein than did those with normal insulin values. Highest weight gain from 5 to 10 years and lowest BW were the main determinants of high insulin levels. In conclusion, although BW was a proxy of the events during fetal life and projected its influence later, the influence of gaining weight was a key determinant in the risk to develop obesity and metabolic abnormalities.

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In overweight and obese hypertensive patients, ISH is prevalent, posing a challenge for the clinician of whether these may therefore be diagnosed and managed as hypertensive patients. Until prospective studies can give more knowledge, 24-h ABPM can offer information for making clinical decisions.

Obstructive sleep apnea syndrome is a reduction of the airflow during sleep which not only produces a reduction in sleep quality but also has major health consequences. The prevalence in the obese pediatric population can surpass 50%, and polysomnography is the current gold standard method for its diagnosis. Unfortunately, it is expensive, disturbing and time-consuming for experienced professionals. The objective is to develop a patient-friendly screening tool for the obese pediatric population to identify those children at higher risk of suffering from this syndrome. Three supervised learning classifier algorithms (i.e., logistic regression, support vector machine and AdaBoost) common in the field of machine learning were trained and tested on two very different datasets where oxygen saturation raw signal was recorded. The first dataset was the Childhood Adenotonsillectomy Trial (CHAT) consisting of 453 individuals, with ages between 5 and 9 years old and one-third of the patients being obese. Cross-validation was performed on the second dataset from an obesity assessment consult at the Pediatric Department of the Hospital General Universitario of Valencia. A total of 27 patients were recruited between 5 and 17 years old; 42% were girls and 63% were obese. The performance of each algorithm was evaluated based on key performance indicators (e.g., area under the curve, accuracy, recall, specificity and positive predicted value). The logistic regression algorithm outperformed (accuracy = 0.79, specificity = 0.96, area under the curve = 0.9, recall = 0.62 and positive predictive value = 0.94) the support vector machine and the AdaBoost algorithm when trained with the CHAT datasets. Cross-validation tests, using the Hospital General de Valencia (HG) dataset, confirmed the higher performance of the logistic regression algorithm in comparison with the others. In addition, only a minor loss of performance (accuracy = 0.75, specificity = 0.88, area under the curve = 0.85, recall = 0.62 and positive predictive value = 0.83) was observed despite the differences between the datasets. The proposed minimally invasive screening tool has shown promising performance when it comes to identifying children at risk of suffering obstructive sleep apnea syndrome. Moreover, it is ideal to be implemented in an outpatient consult in primary and secondary care.