Pulse pressure, wide [keywords]
- A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways. [JOURNAL ARTICLE]
- Hum Mol Genet 2016 Aug 23.
More than a million childhood diarrhoeal episodes occur worldwide each year, and in developed countries a considerable part of them are caused by viral infections. In this study we aimed to search for genetic variants associated with diarrhoeal disease in young children by meta-analyzing genome-wide association studies, and to elucidate plausible biological mechanisms.The study was conducted in the context of the Early Genetics and Lifecourse Epidemiology (EAGLE) consortium. Data about diarrhoeal disease in two time windows (around one year of age and around two years of age) was obtained via parental questionnaires, doctor interviews or medical records. Standard quality control and statistical tests were applied to the 1000 Genomes imputed genotypic data.The meta-analysis (N=5,758) followed by replication (N=3,784) identified a genome-wide significant association between rs8111874 and diarrhoea at age one year. Conditional analysis suggested that the causal variant could be rs601338 (W154X) in the FUT2 gene. Children with the A allele, which results in a truncated FUT2 protein, had lower risk of diarrhoea. FUT2 participates in the production of histo-blood group antigens and has previously been implicated in the susceptibility to infections, including Rotavirus and Norovirus Gene-set enrichment analysis suggested pathways related to the histo-blood group antigen production, and the regulation of ion transport and blood pressure. Among others, the gastrointestinal tract, the immune and neuro-secretory systems were detected as relevant organs.In summary, this genome-wide association meta-analysis suggests the implication of the FUT2 gene in diarrhoeal disease in young children from the general population.
- How to estimate heart rate from pulse rate reported by oscillometric method in atrial fibrillation: The value of pulse rate variation. [JOURNAL ARTICLE]
- Int J Cardiol 2016 Aug 6.:1022-1026.
To evaluate whether the mean pulse rate (PR) from three oscillometric blood pressure (BP) measurements provides an accurate estimation of electrocardiogram ventricular rate (HR) in patients with permanent atrial fibrillation (AF).BP and PR were measured with an oscillometric BP device for three times with one-minute interval. Simultaneously, one-minute electrocardiogram was also recorded for three times. The first PR and HR values were recorded as PR1 and HR1, and the averages of three PR and HR values as mean PR (mPR) and mean HR (mHR). Meanwhile, the differences between the highest and lowest values among the three PR and HR were calculated as ΔPR and ΔHR. Furthermore, the patients were stratified on ΔPR into the 0-15 and >15 subgroups.A moderate positive correlation existed between PR1 and HR1 or mPR and mHR, and Bland-Altman plot also showed quite wide 95% limits between them. Meanwhile, ΔPR was significantly higher than ΔHR (12.1±8.6 vs 3.6±2.5bpm, P<0.001). However, in the 0-15 subgroup, the correlation between mPR and mHR was high (R2=0.800), and the 95% limits were only from -11.3 to 14.2bpm with a difference of 1.4bpm. The coincidence (mPR-mHR<10bpm) rate was 93.9% when PR≤80bpm, 96.3% when PR 81-100bpm, and 88.9% when PR over 100bpm.The average of three PR values reported by an oscillometric BP device could provide a clinically accepted estimation of mean HR of 3min in AF patients with ΔPR 0-15bpm and mean PR ≤100bpm.
- Multidisciplinary management of diabetic kidney disease: a systematic review and meta-analysis. [Journal Article]
- JBI Database System Rev Implement Rep 2016 Jul; 14(7):169-207.
The increasing prevalence of diabetes poses significant challenges to healthcare systems around the world. Diabetes is the leading cause of end-stage renal disease. Diabetic kidney disease (DKD) is becoming a global health concern because it is a progressive disease associated with major health complications and increased health costs. The treatment goals for DKD are to slow the progression of the renal disease and prevent cardiovascular events. Accordingly, patients are expected to adhere to prescribed treatments and manage a wide range of daily self-care activities. Multidisciplinary management of chronic diseases, like diabetes and kidney disease, has been suggested as a means to improve patients' adherence to treatment and enhance health-related outcomes. This systematic review of multidisciplinary management of DKD is an important step in evaluating if such a management approach is effective in delaying disease progression.The goal of this systematic review was to identify the best available evidence regarding multidisciplinary management of DKD and to determine if a multidisciplinary management of DKD can improve patient outcomes. Specifically the review question was: What is the impact of multidisciplinary management of DKD on patient outcomes?The current review considered adults aged 18 years and older who had been diagnosed with type 1 or type 2 diabetes and chronic kidney disease.The current review examined studies that compared multidisciplinary interventions with usual standard care in ambulatory settings for patients with DKD.The current review considered studies with the following primary outcomes: kidney function, incidence of kidney failure, generic or specific health-related quality of life, patient self-care abilities, adherence to treatment recommendations or goals; and the following secondary clinical outcomes: mortality rates secondary to DKD, glycemic control, blood pressure (BP) control, lipid profile, incidence of cardiovascular disease/events, patient knowledge on diabetes or DKD, patient empowerment or self-efficacy, generic or specific patient satisfaction with care and patient healthcare utilization.The current review will consider randomized and quasi-experimental trials but included only randomized controlled trials (RCTs).A three-step search strategy was utilized starting with a search of MEDLINE and CINAHL for the identification of keywords, followed by a search using keywords and index terms across MEDLINE, CINAHL and Embase databases and clinical trials registry platforms, and finally a search of the reference list of all identified papers. Studies published from the time of the respective database inception to November 2014 in English, German and French were considered.Two independent reviewers assessed the methodological validity of the papers prior to inclusion in the review using the standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI).Data were extracted from papers included in the review using the standardized data extraction tool from JBI-MAStARI.Quantitative data were pooled using the RevMan 5 software for kidney function using estimated Glomerular Filtration Rate (eGFR), glycated hemoglobin, BP and total cholesterol (TC). Results were considered significant for P < 0.05.Three RCTs were included in this review. Meta-analysis showed that multidisciplinary management was associated with a statistically significant improvement of glycated hemoglobin as compared with standard usual care (Relative Risk [RR] -0.49, at 95% confidence interval [CI] -0.83, -0.16, P < 0.01). The meta-analysis for eGFR showed a tendency to favor standard care; however, this finding cannot be conclusive because the CI was too wide (RR -3.30, at 95% CI -6.55, -0.05, P = 0.05). Meta-analysis results for BP and TC failed to show a difference between the multidisciplinary management of DKD and the usual standard care. Only one study measured patient-oriented primary and secondary outcomes and showed an improvement in health-related quality of life, patient self-care abilities, patient level of knowledge on diabetes and exercise self-efficacy.Multidisciplinary management of DKD has the potential for improving glycemic control and thus preventing complications. Its effect on other clinical and patient-oriented outcomes, especially on delaying the progression of the disease through preserving and preventing the decline in kidney function, has yet to be determined. There is not enough evidence to recommend multidisciplinary management for preserving kidney function. Further studies are needed.
- Relationship Between Metabolic Syndrome and Cognitive Abilities in U.S. Adolescents. [JOURNAL ARTICLE]
- Metab Syndr Relat Disord 2016 Aug 16.
Metabolic syndrome is increasingly common in U.S. adolescents and has been linked to cognitive dysfunction. Purpose of this study is to explore associations between metabolic syndrome and cognitive impairment in U.S. adolescents using population-based data.Participants included adolescents aged 12-16 years who participated in the National Health and Nutrition Examination Survey (NHANES) III. The main outcome measures included assessments of cognitive function using Wide Range Achievement Test-Revised (WRAT-R) and Wechsler Intelligence Scale for Children-Revised (WISC-R) tools. The WRAT-R consisted of mathematics and reading tests. The WISC-R consisted of block design test, which measures spatial visualization and motor skills, and digit span test, which measures working memory and attention. Linear regression models were used to examine associations between metabolic syndrome and cognitive function. We used education levels of the family reference person, while controlling for education levels because of missing data.Presence or absence of metabolic syndrome was tested in 1170 of 2216 NHANES III participants aged 12-16 years. Regression models showed that participants with metabolic syndrome scored an average 1.25 [95% confidence interval (CI) = -2.14 to -0.36] points lower in reading examination and an average 0.89 (95% CI = -1.65 to -0.13) points lower in digit span examination, compared to those without metabolic syndrome. In addition, components of metabolic syndrome-elevated systolic blood pressure and increased waist circumference (WC)-were associated with impaired working memory/attention, and higher fasting glucose and increased WC were associated with poorer reading test scores.Metabolic syndrome was associated with impaired reading, working memory, and attention among adolescents.
- Understanding the Pathogenicity of Burkholderia contaminans, an Emerging Pathogen in Cystic Fibrosis. [Journal Article]
- PLoS One 2016; 11(8):e0160975.
Several bacterial species from the Burkholderia cepacia complex (Bcc) are feared opportunistic pathogens that lead to debilitating lung infections with a high risk of developing fatal septicemia in cystic fibrosis (CF) patients. However, the pathogenic potential of other Bcc species is yet unknown. To elucidate clinical relevance of Burkholderia contaminans, a species frequently isolated from CF respiratory samples in Ibero-American countries, we aimed to identify its key virulence factors possibly linked with an unfavorable clinical outcome. We performed a genome-wide comparative analysis of two isolates of B. contaminans ST872 from sputum and blood culture of a female CF patient in Argentina. RNA-seq data showed significant changes in expression for quorum sensing-regulated virulence factors and motility and chemotaxis. Furthermore, we detected expression changes in a recently described low-oxygen-activated (lxa) locus which encodes stress-related proteins, and for two clusters responsible for the biosynthesis of antifungal and hemolytic compounds pyrrolnitrin and occidiofungin. Based on phenotypic assays that confirmed changes in motility and in proteolytic, hemolytic and antifungal activities, we were able to distinguish two phenotypes of B. contaminans that coexisted in the host and entered her bloodstream. Whole genome sequencing revealed that the sputum and bloodstream isolates (each representing a distinct phenotype) differed by over 1,400 mutations as a result of a mismatch repair-deficient hypermutable state of the sputum isolate. The inferred lack of purifying selection against nonsynonymous mutations and the high rate of pseudogenization in the derived isolate indicated limited evolutionary pressure during evolution in the nutrient-rich, stable CF sputum environment. The present study is the first to examine the genomic and transcriptomic differences between longitudinal isolates of B. contaminans. Detected activity of a number of putative virulence factors implies a genuine pathogenic nature of this novel Bcc species.
- [OP.7C.08] BLOOD-PRESSURE ASSOCIATED VARIANTS IN NPR3 AFFECT HUMAN VASCULAR SMOOTH MUSCLE CELLS PROLIFERATION AND CALCIUM RESPONSE TO ANGIOTENSIN II. [Journal Article]
- J Hypertens 2016 Sep.:e92.
A recent genome-wide association study identified a locus within natriuretic peptide receptor C (NPR3) to be significantly associated with blood pressure (BP), To functionally characterise the effect of BP- associated SNPs (single nucleotide polymorphisms) at the NPR3 locus in the context of BP regulatory pathways(Figure is included in full-text article.): Primary human umbilical artery smooth muscle (HUASMCs) and vein endothelial (HUVECs) cells were genotyped for BP-associated NPR3 variants. Endogenous mRNA and protein expression levels were assessed by qRT-PCR, allelic expression imbalance assay and western blotting. Open chromatin regions were assayed using formaldehyde-assisted isolation of regulatory elements (FAIRE). Interaction between variants flanking region with nuclear protein was detected by electrophoretic mobility shift assay (EMSA). Cell proliferation and migration were determined by cell counting and scratch assays. Angiotensin II (Ang II)-induced calcium flux was evaluated using the intracellular fluorescent probe.The BP-elevating allele of the NPR3 variants in rs1173771 linkage disequilibrium (LD) block was associated with lower endogenous mRNA and protein levels in HUASMCs. This is consistent with the finding that BP-elevating allele is less located within open chromatin. The decreased NPR3 expression in HUASMCs carrying the BP-elevating allele is associated with increased cell proliferation and intracellular calcium flux in response to Ang II stimulation. No differences in migration rates were detected. No genotype-dependent characteristics were observed in HUVECs NPR3 expression and cell proliferation.This study has identified a potential mechanism for BP-associated SNPs at NPR3 locus to influence BP predominantly via an effect on vascular smooth muscle cell behaviors.
- [OP.1C.02] SPECTRAL ESTIMATION OF PETERSON'S MODULUS VARIABILITY FROM ARTERIAL BLOOD PRESSURE AND WAVELET ANALYSIS. [Journal Article]
- J Hypertens 2016 Sep.:e8.
Arterial stiffness is mainly characterized by its Peterson's Modulus (EP). Increased values of EP are associated with a reduced heart function and an increased arterial blood pressure. Assessment of EP requires simultaneous measurements of arterial diameter and pressure signals. However, instantaneous determination of arterial diameter signals implies optical and ultrasonic techniques and neither of them are portables.To evaluate a novel method for estimating the Ep spectral variability of arterial stiffness, without arterial diameter signals.Arterial pressure (Konigsberg micro-transducer) was measured in 10 sheeps (25-35 kg) during 24 hours. Instantaneous cardiac cycle of pressure signals were determined using five-level multi-resolution wavelet analysis and decomposition. A state machine processed and analysed different linear combinations of details d3, d4 and d5 of mother wavelet Symlet11. EP spectral estimation assessment involved the study of various temporal locations of the fiducial elasticity starting point within each beat. Moreover, discard criteria were added from the heart rate variability studio and coherence index between systolic pressure and beat to beat intervals around 0.1 Hz. Agreement between the actual direct measurement of EP and the proposed method of spectral stiffness estimation was analyzed according to the Bland-Altman approach.Results showed a high coherence (more than 70%) between the actual and proposed method for a wide frequency range (0 to 0.5 Hz). Bland & Altman test showed a standard deviation of the mean less of 10% between the proposed methodology and the direct assessment of EP.The methodology presented in this work evidenced high levels of spectral coherence in EP variability studios and no significantly difference between the actual and the proposed estimation method. So, this novel method is able to estimate the Peterson's modulus spectral variability by solely using the arterial blood pressure signal.
- [OP.6D.04] ASSOCIATION STUDY OF ANGIOTENSINASE A (ENPEP) GENOTYPE WITH DIABETIC NEPHROPATHY. [Journal Article]
- J Hypertens 2016 Sep.:e75-6.
It is well known that the renin angiotensin system (RAS) plays a pivotal role in the development of diabetic nephropathy (DMN). Recent genome-wide association studies have identified a number of common genetic variants associated with blood pressure variation in east Asians. One of such loci is angiotensinase A (ENPEP), which converts the angiotensin II to angiotensin III in the RAS. We therefore tested the hypothesis that genetic variants of ENPEP could show significant association with prevalence of DMN.We enrolled consecutive 345 subjects who had consulted our hospitals for type 2 diabetes. They consisted of cases with nephropathy (57.1 %) and controls (42.9%). Genomic DNA was isolated from human leukocytes by QIAamp kit. Genotypes were assayed with genomic DNA for a C/T variant of ENPEP (rs6825911) using the StepOnePlus real-time PCR system by TaqMan method. Association between the genetic variant and the prevalence of DMN was tested.The numbers of individuals with each genotype of ENPEP were as follows (CC, CT and TT): 64, 93 and 40 for cases and 29, 84 and 35 for controls. Accordingly, the risk for DMN was 1.39 (95% confidence interval; 1.02-1.88), p = 0.03 for allelic comparison and also p = 0.03 for Armitage's trend test. Thus, a significant association with DMN was observed for the ENPEP variant with 1.4 times risk.Thus, it is found that a genetic variant of ENPEP may have a significant impact on the onset of DMN.
- [OP.5C.03] HIGHER PREVALENCE OF HYPERTENSION IN MIGRANTS IN ITALY: A SNAPSHOT OF THE 2012 AND 2013C WORLD KIDNEY DAY. [Journal Article]
- J Hypertens 2016 Sep.:e60-1.
Among the many health-related challenges posed by the increased number of Migrants, cardiovascular risk evaluation has been less extensively evaluated than communicable disease prevention and treatment. Ethnic background is one of the many non-modifiable determinants of cardiovascular disease, whereas stress and modifiable factors such as dietary habits and smoking are very likely to be profoundly altered in the migrant population.To compare the prevalence of hypertension in Italian residents as compared with Migrants, a total of 6027 voluntary subjects underwent medical interview, body weight, height and blood pressure (BP) measurement, risk factor evaluation and urine analysis during the National Kidney Day survey held in 2012 and 2013 by the Federazione Italiana del Rene (FIR).Migrants were 445/6027 (7.38%), with a rate remarkably similar to the percentage of non-Italian residents (8.09%). A wide heterogeneity was evident, with 53 different nationalities, subdivided in Eastern Europe (38.2%), Northern Africa (17.6%), Center and Southern Africa (12.9%), Latin America (12.8%), Indian subcontinent (9.6%), Far East (5.5%), Middle East (3.4%) macro-areas. Gender distribution and body mass index were comparable in the Italian and in the Migrant groups. Despite a 10-year age difference (50 ± 12 vs. 41 ± 15 years; p <0.001), the overall prevalence of hypertension was similar in the two groups (44.7% in Italians vs. 43.4% in Migrants), as defined by BP>140/90 mmHg and/or current antyhypertensive treatment. When stratified by age, Migrants presented significantly higher BP values, the prevalence of hypertension being at least 10% higher than in Italian residents in any decade group. A similar trend was observed for awareness, active treatment and satisfactory BP control rates. Also the rate of proteinuria and glycosuria was higher in the spot urine sample analysis.In Migrants, hypertension prevalence, treatment rate and control rate are significantly higher than in the Italian resident population. In the future years this will inevitably increase the burden of cardiovascular disease on society and health system. These data underscore the urgent need of prevention and intervention in this special population, trying to take into proper account all the involved social, cultural, economic and health-related factors.