Showing papers by "Josep Redon published in 2022"

Healthy lifestyle, metabolomics and incident type 2 diabetes in a population-based cohort from Spain

Abstract: The contribution of metabolomic factors to the association of healthy lifestyle with type 2 diabetes risk is unknown. We assessed the association of a composite measure of lifestyle with plasma metabolite profiles and incident type 2 diabetes, and whether relevant metabolites can explain the prospective association between healthy lifestyle and incident type 2 diabetes.A Healthy Lifestyle Score (HLS) (5-point scale including diet, physical activity, smoking status, alcohol consumption and BMI) was estimated in 1016 Hortega Study participants, who had targeted plasma metabolomic determinations at baseline examination in 2001-2003, and were followed-up to 2015 to ascertain incident type 2 diabetes.The HLS was cross-sectionally associated with 32 (out of 49) plasma metabolites (2.5% false discovery rate). In the subset of 830 participants without prevalent type 2 diabetes, the rate ratio (RR) and rate difference (RD) of incident type 2 diabetes (n cases = 51) per one-point increase in HLS was, respectively, 0.69 (95% CI, 0.51, 0.93), and - 8.23 (95% CI, - 16.34, - 0.13)/10,000 person-years. In single-metabolite models, most of the HLS-related metabolites were prospectively associated with incident type 2 diabetes. In probit Bayesian Kernel Machine Regression, these prospective associations were mostly driven by medium HDL particle concentration and phenylpropionate, followed by small LDL particle concentration, which jointly accounted for ~ 50% of the HLS-related decrease in incident type 2 diabetes.The HLS showed a strong inverse association with incident type 2 diabetes, which was largely explained by plasma metabolites measured years before the clinical diagnosis.

Gene-environment interaction analysis of redox-related metals and genetic variants with plasma metabolic patterns in a general population from Spain: The Hortega Study

Abstract: Limited studies have evaluated the joint influence of redox-related metals and genetic variation on metabolic pathways. We analyzed the association of 11 metals with metabolic patterns, and the interacting role of candidate genetic variants, in 1145 participants from the Hortega Study, a population-based sample from Spain. Urine antimony (Sb), arsenic, barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), molybdenum (Mo) and vanadium (V), and plasma copper (Cu), selenium (Se) and zinc (Zn) were measured by ICP-MS and AAS, respectively. We summarized 54 plasma metabolites, measured with targeted NMR, by estimating metabolic principal components (mPC). Redox-related SNPs (N = 291) were measured by oligo-ligation assay. In our study, the association with metabolic principal component (mPC) 1 (reflecting non-essential and essential amino acids, including branched chain, and bacterial co-metabolism versus fatty acids and VLDL subclasses) was positive for Se and Zn, but inverse for Cu, arsenobetaine-corrected arsenic (As) and Sb. The association with mPC2 (reflecting essential amino acids, including aromatic, and bacterial co-metabolism) was inverse for Se, Zn and Cd. The association with mPC3 (reflecting LDL subclasses) was positive for Cu, Se and Zn, but inverse for Co. The association for mPC4 (reflecting HDL subclasses) was positive for Sb, but inverse for plasma Zn. These associations were mainly driven by Cu and Sb for mPC1; Se, Zn and Cd for mPC2; Co, Se and Zn for mPC3; and Zn for mPC4. The most SNP-metal interacting genes were NOX1, GSR, GCLC, AGT and REN. Co and Zn showed the highest number of interactions with genetic variants associated to enriched endocrine, cardiovascular and neurological pathways. Exposures to Co, Cu, Se, Zn, As, Cd and Sb were associated with several metabolic patterns involved in chronic disease. Carriers of redox-related variants may have differential susceptibility to metabolic alterations associated to excessive exposure to metals.

Exosomal and Plasma Non-Coding RNA Signature Associated with Urinary Albumin Excretion in Hypertension

Abstract: Objective: Non-coding RNA (ncRNA), released into circulation or packaged into exosomes, play important roles in many biological processes in the kidney. The purpose of the present study is to identify a common ncRNA signature associated with early renal damage and its related molecular pathways by constructing a RNA-based transcriptional network. Design and method: This is an observational case-control study which included 43 hypertensives, twenty-one patients with essential hypertension and twenty-two without persistent elevated urinary albuminuria (UAE) (higher or equal to 30 mg/g urinary creatinine). Three individual libraries (plasma and urinary exosomes and total plasma) were prepared from each hypertensive patient for ncRNA sequencing analysis. Next, a RNA-based transcriptional regulatory network was constructed. Results: The three RNA biotypes with the greatest number of differentially expressed transcripts were long-ncRNA (lncRNA), microRNA (miRNA) and piwi-interacting RNA (piRNA). We identified a common 24 ncRNA molecular signature related to hypertension-associated albuminuria, of which lncRNA was the most representative. In addition, the transcriptional regulatory network analysis showed five lncRNA (LINC02614, BAALC-AS1, FAM230B, LOC100505824 and LINC01484), and the miR-301a-3p to play a significant role in network organization and to target critical pathways regulating filtration barrier integrity, tubule reabsorption and systemic endothelial dysfunction. Conclusions: Our study found a combined ncRNA signature associated with albuminuria, independently of biofluid origin (urine or plasma, circulating or in exosomes) that identifies a handful of potential targets involved in filtration barrier, tubule reabsorption and endothelial function that may be utilized to treating hypertension-associated albuminuria and cardiovascular damage progression.

Association between exercise frequency with renal and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk

Abstract: Guidelines recommend physical activity to reduce cardiovascular (CV) events. The association between physical activity and progression of chronic kidney disease (CKD) with and without diabetes is unknown. We assessed the association of self-reported physical activity with renal and CV outcomes in high-risk patients aged ≥ 55 years over a median follow-up of 56 months in post-hoc analysis of a previously randomized trial program.Analyses were done with Cox regression analysis, mixed models for repeated measures, ANOVA and χ2-test. 31,312 patients, among them 19,664 with and 11,648 without diabetes were analyzed.Physical activity was inversely associated with renal outcomes (doubling of creatinine, end-stage kidney disease (ESRD)) and CV outcomes (CV death, myocardial infarction, stroke, heart failure hospitalization). Moderate activity (at least 2 times/week to every day) was associated with lower risk of renal outcomes and lower incidence of new albuminuria (p < 0.0001 for both) compared to lower exercise levels. Similar results were observed for those with and without diabetes without interaction for renal outcomes (p = 0.097-0.27). Physical activity was associated with reduced eGFR decline with a moderate association between activity and diabetes status (p = 0.05).Moderate physical activity was associated with improved kidney outcomes with a threshold at two sessions per week. The association of physical activity with renal outcomes did not meaningfully differ with or without diabetes but absolute benefit of activity was even greater in people with diabetes. Thus, risks were similar between those with diabetes undertaking high physical activity and those without diabetes but low physical activity.http://clinicaltrials.gov.uniqueidentifier :NCT00153101.

Real-World Data of Anticoagulant Treatment in Non-valvular Atrial Fibrillation

Abstract: Aims To assess the impact of anticoagulant treatment on risk for stroke and all-cause mortality of patients with atrial fibrillation using real-world data (RWD). Methods Patients with prevalent or incident atrial fibrillation were selected throughout a study period of 5 years. Stroke, transitory ischemic attack, hemorrhagic stroke, and all-cause mortality were identified in the claims of the electronic health records (EHRs). Subjects were classified according to the anticoagulant treatment in four groups: untreated, vitamin K antagonists (VKAs), New Oral Anticoagulants (NOACs), and antiplatelet (AP). Risk of events and protection with anticoagulant therapy were calculated by Cox proportional hazard models adjusted by potential confounders. Results From a total population of 3,799,884 patients older than 18,123,227 patients with incident or prevalent atrial fibrillation (AF) were identified (mean age 75.2 ± 11.5 years old; 51.9% women). In a follow-up average of 3.2 years, 17,113 patients suffered from an ischemic stroke and transitory ischemic attack (TIA), 780 hemorrhagic stroke, and 42,558 all-cause death (incidence of 46, 8, 2, and 120 per 1,000 patients/year, respectively). Among CHA2DS2, VASc Score equal or >2, 11.7% of patients did not receive any anticoagulant therapy, and a large proportion of patients, 47%, shifted from one treatment to another. Although all kinds of anticoagulant treatments were significantly protective against the events and mortality, NOAC treatment offered significantly better protection compared to the other groups. Conclusion In the real world, the use of anticoagulant treatments is far from guidelines recommendations and is characterized by variability in their use. NOACs offered better protection compared with VKAs.

A comprehensive urban programme to reduce energy poverty and its effects on health and wellbeing of citizens in six European countries: study protocol of a controlled trial

Abstract: Abstract Background Nearly 11% of the European population is affected by energy poverty. Energy poverty is defined by the European Commission (2016) as the inability to afford basic energy services to guarantee a decent standard of living. Energy poverty is considered a complex, multidimensional problem that affects environment, housing, urban development, and health. Living in energy poverty conditions is associated with poorer human health and wellbeing. Hence, the WELLBASED intervention programme aims to design, implement and evaluate a comprehensive urban programme, based on the social-ecological model, to reduce energy poverty and its effects on the citizens’ health and wellbeing in six European urban study sites: Valencia, Spain; Heerlen, The Netherlands; Leeds, United Kingdom; Edirne, Turkey; Obuda, Hungary, and; Jelgava, Latvia. Methods A controlled trial is performed. A total of 875 participants are recruited (125–177 per study site) to receive the WELLBASED intervention programme for 12 months (intervention condition) and 875 participants act as controls (control condition). Data will be collected with a baseline measurement at inclusion (T0), and follow-up measurements after 6 months (T1), 12 months (T2), and 18 months (T3). In both study arms, effects of the WELLBASED intervention programme are measured: health-related quality of life (HR-QoL), mental health, frailty in older adults, self-perceived health, chronic conditions, and care utilization. At the same time points, household expenditure on energy and energy consumption are obtained. In the intervention arm, health-monitoring data (i.e. peak flow, oxygen saturation, blood pressure, and heart rate) are obtained monthly and sleep quality with a three-month interval. Household data with regard to temperature, humidity and air quality are collected near real-time by home sensors. Qualitative interviews are conducted in each study site to evaluate the impacts of the WELLBASED intervention programme and to help explain findings. Discussion The WELLBASED intervention programme will provide new insights into the effectiveness of a comprehensive urban programme to tackle energy poverty and its effects on health and wellbeing across Europe. Hence, this study can contribute to European-wide replicable solutions for policy-makers and city practitioners to alleviate energy poverty. Trial registration ISRCTN registry number is ISRCTN14905838 . Date of registration is 15/02/2022.

Lipoprotein profiles of fat distribution and its association with insulin sensitivity

Abstract: Background Fat deposition is associated with adverse outcomes. Waist-to-hip (WHR) ratio is a simple feasible index to assess fat distribution. Lipoprotein particle composition in relation to WHR and to what extent their association is mediated by insulin sensitivity are less investigated. Methods In 504 randomly recruited Flemish (mean age: 48.9 years; women: 51.6%), we analyzed the lipoprotein particle constitutions using nuclear magnetic resonance spectroscopy. WHR obesity described a WHR of ≥ 0.85 for women or 0.9 for men. Insulin sensitivity was evaluated by the homeostasis model assessment-estimated insulin resistance (HOMA-IR). SCORE-2 risk algorithm was applied to estimate 10-year cardiovascular risk. Statistical methods included multivariable-adjusted linear regression analysis, logistic regression analysis, and mediation analysis. Results The prevalence of WHR obesity was 54.6%, approximately 3 times of BMI-determined obesity (19.1%). Individuals with WHR obesity had significantly higher metabolic complications, such as hypertension (57.1%), dyslipidemia (61.8%), and insulin resistance (14.2%). WHR and WHR obesity were positively associated with total very-low-density lipoprotein (VLDL) particle concentration, remnant cholesterol, and triglycerides, but were negatively associated with VLDL particle size (P ≤ 0.027), independent of body mass index and other covariates. WHR was inversely associated with total high-density lipoprotein (HDL) particle concentration, whereas WHR obesity was inversely associated with HDL cholesterol (P ≤ 0.039). Neither WHR nor WHR obesity was associated with the concentration of total low-density lipoprotein (LDL) particles, LDL particle size, and LDL cholesterol (P ≥ 0.089). In the mediation analysis, insulin sensitivity significantly mediated the effect of WHR on total VLDL particle concentration (mediation percentage: 37.0%), remnant cholesterol (47.7%), and HDL cholesterol (41.1%). Individuals with WHR obesity were at increased cardiovascular risk, regardless of LDL cholesterol (P ≤0.028). In WHR obesity, higher total VLDL particle concent36ration and remnant cholesterol, and lower HDL cholesterol were associated with an increased cardiovascular risk (P≤ 0.002). Conclusions Upper-body fat deposition was independently associated with an unfavorable lipoprotein profile, and insulin sensitivity significantly mediated this association. LDL cholesterol might underestimate lipid abnormality for people with upper-body obesity and lowering VLDL particles and remnant cholesterol might potentially reduce the residual cardiovascular risk.

Biofluid Specificity of Long Non-Coding RNA Profile in Hypertension: Relevance of Exosomal Fraction

Abstract: Objective: Non-coding RNA (ncRNA)-mediated targeting of various genes regulates the molecular mechanisms of the pathogenesis of hypertension (HTN). However, very few circulating long ncRNAs (lncRNAs) have been reported to be altered in essential HTN. The aim of this study was to identify simultaneously the lncRNA profiles in circulating plasma and packaged them into exosomes associated with UAE in HTN using deep sequencing technology. We also assessed the effect of the biofluid origin on lncRNA signature and regulated pathways. Design and method: In a cohort of hypertensive patients with (n = 22) or without urinary albumin excretion (UAE) (n = 26), we analyzed by next generation sequencing the lncRNA profile associated to UAE. Then, long Non-Coding RNA target predictions and molecular pathways analyses were performed through GO terms and KEGG pathways. Results: Plasma exosomes showed higher diversity and fold change of lncRNAs than plasma, and low transcript overlapping was found between the two biofluids. The majority of unique differentially expressed lncRNA in the exosome fraction were downregulated (71%) in albuminuric patients and 61% in plasma samples. In addition, in plasma samples only 40% of statistically significant transcripts had a log2 fod change higher or equal to 2 or lower or equal to -2, compared with 100% top lncRNAs in exosomal fraction. Enrichment analysis identified different biological pathways regulated in plasma or exosome fraction, which were implicated in fatty acid metabolism, extracellular matrix, and mechanisms of sorting ncRNAs into exosomes, while plasma pathways were implicated in genome reorganization, interference with RNA polymerase, and as scaffolds for assembling transcriptional regulators. Conclusions: Our study found a biofluid specific lncRNA profile associated with albuminuria, with higher diversity in exosomal fraction, which identifies several potential targets that may be utilized to study mechanisms of albuminuria and cardiovascular damage.

Insights From Matched Office and Ambulatory Blood Pressure in Youth: Clinical Relevance

Abstract: Background: Information on the relationship between ambulatory blood pressure (ABP) and concurrently office blood pressure (BP) values in youth still suffers from limitations. We provide information on the differences between office BP and ABP, the factors related, and the clinical implications. Methods: Three thousand six hundred ninety matched measurements of office BP and ABP on the same day, from 2390 children, aged 5 to 15 years, of both sexes were eligible. Office BP was measured using an oscillometric device (Omron 705 IT) and 24-hour ABP using oscillometric SpaceLabs 90207. Average of office, 24-hour, daytime, nighttime, systolic, and diastolic BP and heart rate was calculated. BP categories according to the European guidelines and phenotype of mismatch office BP versus ABP were defined. Results: Both daytime systolic and diastolic BP were higher than office BP with a progressive reduction of the differences from 5 to 15 years. The office minus daytime BP differences were the largest in normotensive subjects, less at high-normal, and reversed in hypertensive ones, independently of age and weight status. White coat and masked hypertension covered no more than 13.6% at all ages. Conclusions: In youth, it is inaccurate to obtain reference values for ABP by extrapolating from office BP values. The differences between office BP and ABP are minimal in children with office BP values in the range of hypertension, reinforcing the recommendation to use ABP measurement at the time to confirm hypertension.

Incidence and impact of atrial fibrillation in heart failure patients: real‐world data in a large community

Abstract: The objective of the present study is to assess the bidirectional association between heart failure (HF) and atrial fibrillation (AF) using real‐world data.

High sensitivity troponins: A potential biomarkers of cardiovascular risk for primary prevention

Abstract: There have been several approaches to building charts for CV risk, all of which have both strengths and limitations. Identifying early organ damage provides relevant information and should be included in risk charts, although the direct relationship with risk is imprecise, variability between operators at the time to assess, and low availability in some healthcare systems, limits its use. Biomarkers, like troponin (cTns) isoforms cTnI and cTnT, a cardiac specific myocyte injury marker, have the great advantage of being relatively reproducible, more readily accessible, and applicable to different populations. New and improved troponin assays have good analytical performance, can measure very low levels of circulating troponin, and have low intra individual variation, below 10 %. Several studies have analyzed the blood levels in healthy subjects and their predictive value for cardiovascular events in observational, prospective and post-hoc studies. All of them offered relevant information and shown that high sensitivity hs-cTnI has a place as an additional clinical marker to add to current charts, and it also reflects sex- and age-dependent differences. Although few more questions need to be answered before recommend cTnI for assessing CV risk in primary prevention, seems to be a potential strong marker to complement CV risk charts.

Real world data of anticoagulant treatment in non-valvular atrial fibrillation across renal function status

Abstract: The objective is to assess the impact of anticoagulant treatment in non-valvular atrial fibrillation (AF) and different categories of renal dysfunction in real world. Electronic Health recordings of patients with diagnosis of AF and renal function collected throughout 5 years and classified according to KDIGO categories. Stroke, transitory ischemic attack (TIA), intracranial hemorrhage and all-cause mortality were identified. Anticoagulant treatments during the study period were classified in untreated (never received therapy), VKA, NOAC and Aspirin. The risk of events was calculated by Cox-proportional hazard models adjusted by confounders. A total of 65,734 patients with AF, mean age 73.3 ± 10.49 years old and 47% females and follow-up of 3.2 years were included. KDIGO classification were: G1 33,903 (51.6%), G2 17,456 (26.6%), G3 8024 (12.2%) and G4 6351 (9.7%). There were 8592 cases of stroke and TIA, 437 intracranial hemorrhage, and 9603 all-cause deaths (incidence 36, 2 and 38 per 103 person/year, respectively). 4.1% of patients with CHA2DS2-VASc Score 2 or higher did not receive anticoagulant therapy. Risk of stroke, TIA, and all-cause mortality increased from G1 to G4 groups. Anticoagulant treatments reduced the risk of events in the four categories, but NOAC seemed to offer significantly better protection. Renal dysfunction increases the risk of events in AF and anticoagulant treatments reduced the risk of stroke and all-cause mortality, although NOAC were better than VKA. Efforts should be done to reduce the variability in the use of anticoagulants even in this high risk group.

Narrative update of clinical trials with antihypertensive drugs in children and adolescents

Abstract: Introduction To date, our knowledge on antihypertensive pharmacological treatment in children and adolescents is still limited because there are few randomized clinical trials (CTs), hampering appropriate management. The objective was to perform a narrative review of the most relevant aspects of clinical trials carried out in primary and secondary hypertension. Methods Studies published in PubMed with the following descriptors: clinical trial, antihypertensive drug, children, adolescents were selected. A previous Cochrane review of 21 randomized CTs pointed out the difficulty that statistical analysis could not assess heterogeneity because there were not enough data. A more recent meta-analysis, that applied more stringent inclusion criteria and selected 13 CTs, also concluded that heterogeneity, small sample size, and short follow-up time, as well as the absence of studies comparing drugs of different classes, limit the utility. Results In the presented narrative review, including 30 studies, there is a paucity of CTs focusing only on children with primary or secondary, mainly renoparenchymal, hypertension. In trials on angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics, a significant reduction of both SBP and DBP in mixed cohorts of children with primary and secondary hypertension was achieved. However, few studies assessed the effect of antihypertensive drugs on hypertensive organ damage. Conclusions Given the increasing prevalence and undertreatment of hypertension in this age group, innovative solutions including new design, such as ‘n-of-1', and optimizing the use of digital health technologies could provide more precise and faster information about the efficacy of each antihypertensive drug class and the potential benefits according to patient characteristics.

Decreased urinary levels of sirt1 as non-invasive biomarker of early renal damage in hypertension.

Abstract: OBJECTIVE Hypertension and diabetes mellitus (DM) produce renal injury. Sirtuins have become important players in renal damage, but their value as biomarkers is poorly assessed. The aims of the study were to evaluate the sirtuin1 levels (SIRT1), and miRNAs miR-34a and miR-200, that regulate SIRT1 expression in urinary cell pellet from hypertensive patients with incipient renal damage with and without diabetes. In addition, to mimic disease conditions and deepen into the implications of SIRT1 in podocyte injury, employed cultured podocytes subjected to high glucose (HG) and angiotensin II (Ang II) concentrations. DESIGN AND METHOD We quantified urinary SIRT1 and claudin 1 (CLDN1) mRNA and miR-34a and miR-200a levels by quantitative real-time polymerase chain reaction (RT-qPCR) from urinary cell free pellet from patients and in cultured human immortalized podocytes treated with HG and ANG II. Protein levels and subcellular localization were analyzed by Western blot and fluorescence analyses by confocal microscopy. RESULTS We found decreased SIRT1 levels in patients with increased urinary albumin excretion (UAE), the lowest with diabetes presence, and a strong association with UAE, discriminating incipient renal damage. In vitro experiments also showed SIRT1 overall decreases in podocyte cultures under treatment conditions. In urine samples, miR-34a was reduced and miR-200a increased, both related to UAE levels. However, both miRNAs were generally increased in podocyte cultures under high glucose and angiotensin-II treatment. CONCLUSIONS Results evidenced reduction of urinary SIRT1 from hypertensives with or without DM. The decrease of SIRT1 and increase of CLDN1 in patients and podocytes subjected to stress support the implication of both in renal injury and evidence a reflection in urinary levels. The alterations found in miR-34a and miR-200a both in patients' urine and podocyte cultures reveal novel points to further address their implication in renal injury through SIRT1 regulation. Interestingly, SIRT1 mRNA levels and miR-200a are related to increases in UAE and discriminate the presence of UAE in patients. In summary, SIRT1 mRNA measurements is an easily accessible and non-invasive method to early characterize renal damage in patients.

Atherogenic lipoprotein profile associated with anthropometric indices of obesity and their association with cardiometabolic risk markers: a cross-sectional study in community

Abstract: Obesity, especially abdominal fat accumulation, is strongly associated with various metabolic comorbidities. Whether simple anthropometric measures are independently associated with atherogenic lipoproteins is not completely clear. We randomly recruited 505 participants (51.5% women; mean age: 48.8 years) from the Flemish community, who had undergone lipoprotein particle measurements by nuclear magnetic resonance spectroscopy and conventional lipid measurements. Each lipoprotein fraction was subgrouped into large, medium, and small subclass. Anthropometric measures included body mass index (BMI) and waist-to-hip ratio (WHR), and defined BMI obesity as BMI ≥30 kg/m2, and WHR obesity as WHR ≥0.85 (women) or 0.9 (men). In the multivariable logistic regression analysis, total very-low-density lipoprotein (VLDL) particle and its subclasses were positively associated with BMI obesity (adjusted odds ratio [OR] for total VLDL: 2.37; 95% confidence interval [CI]: 1.70–3.31) and WHR obesity (OR for total VLDL: 2.06 [95% CI: 1.55–2.73]). The level of total high-density lipoprotein (HDL) particle and its subclass was negatively associated with BMI (OR for total HDL: 0.63 [95% CI: 0.45–0.90), but not with WHR (P≥0.11). None of the low-density lipoprotein (LDL) particles was associated with the two types of obesity (P≥0.092). BMI was inversely associated with the size of LDL and HDL particles, whereas high WHR was significantly associated with smaller VLDL and HDL sizes. For conventional lipid measures, both BMI and WHR were independently associated with high triglyceride and remnant cholesterol, both mainly driven from VLDL particles, and low HDL cholesterol (P≤0.008). These associations were confirmed in multivariable linear regression analysis, except the association of BMI with HDL number and the association of WHR with HDL size. With partial least squares analysis, the lipoprotein profiles of BMI and WHR were significantly associated with a high 10-year cardiovascular disease risk score, the homeostasis model assessment-estimated insulin resistance (HOMA-IR), and C-reactive protein. BMI and WHR were independently associated with high triglyceride-rich lipoproteins, decreased HDL cholesterol. The size of LDL and HDL was more consistently associated with BMI than WHR. The lipoprotein alterations may link obesity with high cardiometabolic risk. Type of funding sources: Public grant(s) – EU funding. Main funding source(s): The European Research Council; the European Research Area Net for Cardiovascular Diseases

Persistence of blood pressure phenotypes according to office and 24 hour ambulatory blood pressure in children

Abstract: Objective: To assess the persistence of BP phenotypes according to office and 24-h ABPM in youth over time. Design and method: Retrospective study including 582 children who underwent measurement of both office BP (OBP) and ABPM on the same day. The second office BP and ABPM was performed within 1 year apart. OBP was measured using an oscillometric device validated in children. ABPM was performed using oscillometric SpaceLabs 90207 monitors. OBP and ABPM were classified according to the criteria of the ESH (Lurbe et al J Hypertens 2016). Four phenotypes based on OBP and ABPM were defined: true normotensives, sustained hypertensives, white-coat hypertensives, and masked hypertensives. Persistence and Kappa statistic were used to evaluate the concordance of BP phenotypes. Factors related with persistence on BP phenotypes were evaluated using logistic regression models. Results: At the initial assessment, the majority of children fell within the category of true normotension (77%), followed by masked hypertension (13%), sustained hypertension (5%) and white coat hypertension (5%). The prevalence of true normotensive increased significantly in the follow-up. The flow through phenotypes is shown in the Figure. Only 38 initial true normotensive patients changed to other categories, mainly masked (12); 63 of initial masked hypertension changed, mainly to normotensive (58); 24 of white coat changed predominantly to normotension (16); finally, 25 of sustained changed, largely to normotension (14), but 9 children migrated to masked. The overall agreement was 74.2% (kappa 0.20). The grade of agreement was slightly higher for boys than for girls. In the multivariable model, higher age showed to be a protective factor, whereas increased office SBP and waist circumference were significant risk factors. The masked hypertensive phenotype carried the highest risk for lack of persistence. Conclusions: Children with hypertensive BP phenotypes should be re-evaluated because a large percentage of them will become normotensive. High BP levels and high BMI z-score or waist circumference were significant risk predictors for the lack of persistence on BP phenotypes.

Combined exosomal and plasma non-coding rna signature associated with urinary albumin excretion in hypertension.

Abstract: OBJECTIVE Non-coding RNA (ncRNA), released into circulation or packaged into exosomes, play important roles in many biological processes in the kidney. The purpose of the present study is to identify a common ncRNA signature associated with early renal damage and its related molecular pathways by constructing a RNA-based transcriptional network. DESIGN AND METHOD This is an observational case-control study which included 43 hypertensives, twenty-one patients with essential hypertension and twenty-two without persistent elevated urinary albuminuria (UAE) (higher or equal to 30 mg/g urinary creatinine). Three individual libraries (plasma and urinary exosomes and total plasma) were prepared from each hypertensive patient for ncRNA sequencing analysis. Next, a RNA-based transcriptional regulatory network was constructed. RESULTS The three RNA biotypes with the greatest number of differentially expressed transcripts were long-ncRNA (lncRNA), microRNA (miRNA) and piwi-interacting RNA (piRNA). We identified a common 24 ncRNA molecular signature related to hypertension-associated albuminuria, of which lncRNA was the most representative. In addition, the transcriptional regulatory network analysis showed five lncRNA (LINC02614, BAALC-AS1, FAM230B, LOC100505824 and LINC01484), and the miR-301a-3p to play a significant role in network organization and to target critical pathways regulating filtration barrier integrity, tubule reabsorption and systemic endothelial dysfunction. CONCLUSIONS Our study found a combined ncRNA signature associated with albuminuria, independently of biofluid origin (urine or plasma, circulating or in exosomes) that identifies a handful of potential targets involved in filtration barrier, tubule reabsorption and endothelial function that may be utilized to treating hypertension-associated albuminuria and cardiovascular damage progression.

3D Human Big Data Exchange Between the Healthcare and Garment Sectors

Abstract: Abstract 3D personal data is a type of data that contains useful information for product design, online sale services, medical research and patient follow-up. Currently, hospitals store and grow massive collections of 3D data that are not accessible by researchers, professionals or companies. About 2.7 petabytes a year are stored in the EU26. In parallel to the advances made in the healthcare sector, a new, low-cost 3D body-surface scanning technology has been developed for the goods consumer sector, namely, apparel, animation and art. It is estimated that currently one person is scanned every 15 min in the USA and Europe. And increasing. The 3D data of the healthcare sector can be used by designers and manufacturers of the consumer goods sector. At the same time, although 3D body-surface scanners have been developed primarily for the garment industry, 3D scanners’ low cost, non-invasive character and ease of use make them appealing for widespread clinical applications and large-scale epidemiological surveys. However, companies and professionals of the consumer goods sector cannot easily access the 3D data of the healthcare sector. And vice versa. Even exchanging information between data owners in the same sector is a big problem today. It is necessary to overcome problems related to data privacy and the processing of huge 3D datasets. To break these silos and foster the exchange of data between the two sectors, the BodyPass project has developed: (1) processes to harmonize 3D databases; (2) tools able to aggregate 3D data from different huge datasets; (3) tools for exchanging data and to assure anonymization and data protection (based on blockchain technology and distributed query engines); (4) services and visualization tools adapted to the necessities of the healthcare sector and the garment sector. These developments have been applied in practical cases by hospitals and companies of in the garment sector.

Real world impact of blood pressure changes on morbidity and mortality in type 2 diabetes

Abstract: Objective: To assess the impact of BP changes on the risk of cardiovascular events and mortality in type 2 diabetes. Design and method: The sample was selected using the HER of the Valencian Community. Type 2 diabetics were selected through ICD codes and retrospectively evaluated from January 2012 to December 2016. To evaluate BP changes, the follow-up time was divided in six-month blocks and the average of BP for each interval was considered. SBP was categorized: < 120 mmHg; 120–129 mmHg (reference); 130–139 mmHg; 140–149 mmHg; > 150 mmHg. To evaluate the influence of DBP, the population was stratified according to categories of average DBP: < 60 mmHg; 60–69 mmHg; 70–79 mmHg; > 80 mmHg. Information about cardiovascular events, including Stroke and Acute Coronary Syndrome (ACS) was extracted from the ICD codes. Total mortality was determined by matching records and death certificates. Time-varying Cox regression for SBP stratified by DBP categories was used to assess the risk associated with changes of SBP. The models were adjusted by age, sex, HBA1c, KDIGO, previous cardiovascular events and use of cardiovascular drugs. Results: 156 363 type 2 diabetics patients were included (mean age 69.5(11.5), 48.7% females, mean glycated Hb 7.05 (1.35%) 21% in secondary prevention, 21.4% under insulin treatment). The average number of BP measurements was 14. During an average follow-up of 4.18 y, there were 13399 deaths, 15100 strokes and 6295 ACS. In the fully adjusted time-varying Cox regression, having a SBP< 120 mmHg was a significant risk factor for death across all categories of DBP, whereas SBP> 130 mmHg conferred protection. For the case of ACS and stroke, a J-curve phenomenon was observed with significantly higher risk for those with SBP> 150 mmHg or < 120 mmHg across categories with DBP> 60 mmHg. This J-curve phenomenon was also observed graphically using restricted cubic splines (Figure). Conclusions: Although difficult to achieve in clinical practice, lower boundaries for BP goals in diabetics have to be taking into account.

Traffic density exposure and metabolomics in a population-based sample: The HORTEGA Study

Abstract: BACKGROUND AND AIM Metabolites participate in biological responses to exposure to various external factors such as disease, or environmental pollution, among others. Although the literature in humans is still scarce, several studies have shown that exposure to air pollution causes changes in various metabolic pathways. The aim of this study is was to evaluate the association between traffic density at the street of residence with plasma metabolomic profiles of a population-based sample. METHODS The subjects of this study belong to the Hortega Study cohort, which is a representative sample of the population of Valladolid, Spains. To assess the effect of traffic exposure and metabolite levels the Annual average daily traffic of the roads in the studied region was used, calculated as the total volume of transportation traffic of a road or highway for a year divided by 365 day. Metabolomic profile was determined by Nuclear Magnetic Resonance Spectroscopy in non-fasting plasma. RESULTS Traffic density was positively associated with lipoprotein profile and fatty acids levels and inversely associated with amino acid levels, the metabolites associated with fluid balance and the products derived from bacterial co-metabolism. As for oxidative stress markers, MDA levels show a decrease of one tenth in the most exposed subjects. In relation to energy metabolism, the association is positive for lactate and acetone. CONCLUSIONS We observed a strong association of high traffic density exposure with changes in certain metabolic patterns. KEYWORDS Metabolomics; Traffic-density; Air pollution.

Differential association of metabolomic patterns with bone mineral density and fractures by metal exposure biomarker levels in The Hortega Study

Abstract: Background and aim: The bone remodeling process may be influenced by metabolic factors. We evaluated the cross-sectional association of metabolic patterns with reduced bone mineral density (BMD) and the prospective association of metabolic patterns with incident osteoporosis-related bone fractures. Since copper, selenium, zinc, arsenic, antimony, cadmium and cobalt have been related to metabolic patterns and oxidative stress biomarkers in our study population, and redox balance play a key role in bone metabolism, we also assessed potential differential associations in subgroups defined by metals above and below median (p50) biomarker levels. Methods: In 507 participants older than 50 years from the Hortega Study, a representative sample from a region in Spain, we estimated metabolic principal components (mPC) from 54 plasma metabolites with NMR-spectrometry. BMD was calculated in the right calcaneus using Peripheral Instantaneous X-ray Imaging system. Copper, selenium and zinc were measured in plasma by AAS, arsenic, antimony, cadmium and cobalt were measured in urine by ICPMS, and arsenobetaine was measured by HPLC-ICPMS. Results: In reduced BMD models, the association was inverse mPC1 (reflecting non-essential and essential amino acids, including branched chain, and bacterial co-metabolism versus fatty acids and VLDL subclasses) and positive for mPC2 (reflecting essential amino acids, including aromatic, and bacterial co-metabolism), and mPC3 (reflecting LDL subclasses). In incident bone fracture models, the association was inverse for mPC2, but positive for mPC1 and mPC4 (reflecting HDL subclasses). The association between mPC2 and bone fractures showed statistically significant interactions by antimony (p50=0.07 &#x3bc;g/g) and arsenobetaine-corrected arsenic (p50=6.81 &#x3bc;g/g), and selenium (p50=85.3 &#x3bc;g/L) (P interaction = 0.02, 0.001 and 0.03 respectively). Conclusions: Our results support the hypothesis that bone remodeling is influenced by metabolic factors, including amino acids, lipids and microbiota co-metabolism. Ageing individuals may benefit from intensified preventive interventions to reduce bone disease based on their metal exposure levels.

Angiotensin Receptor Blockers Evaluated by Office and Home Blood Pressure Measurements. TeleHBPM Study.

Abstract: BACKGROUND Adequate treatment of arterial hypertension and achieving arterial hypertension goals in are important in reducing cardiovascular outcomes. OBJECTIVES To describe angiotensin receptor blockers in monotherapy or double combination therapy and the rate of arterial hypertension control. METHODS This cross-sectional study evaluated patients who were using angiotensin receptor blockers between 2017 and 2020. Those using three or more antihypertensive drugs were excluded. The analyzed variables included sex, age, body mass index, valid home blood pressure monitoring (HBPM) measurements, casual and HBPM systolic and diastolic blood pressure measurements, blood pressure variability, and antihypertensive and angiotensin receptor blocker class. Paired t, chi-square, and Fisher's exact tests were used, as well as overlapping 95% confidence intervals and a significance level of 5% (p < 0.05). RESULTS Of 17,013 patients, 12,813 met the inclusion criteria, 62.1% of whom were female. The mean number of valid measurements was 23.3 (SD, 2.0). The mean HBPM and casual measurements for systolic blood pressure were 126.8 (SD, 15.8) mmHg and 133.5 (SD, 20.1) mmHg (p <0.001), respectively, while those for diastolic blood pressure were 79.1 (SD, 9.7 mmHg) and 83.6 (SD, 11.9) mmHg (p <0.001), respectively. Losartan was the most common angiotensin receptor blocker and resulted in the highest blood pressure values. Combinations of angiotensin receptor blockers with diuretics or calcium channel antagonists resulted in lower blood pressure values. CONCLUSIONS More than half of the patients used losartan, although it was the least efficient drug for reducing and controlling blood pressure.