Tochigi, Japan
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Roush G.C.,St Vincents Medical Center | Fagard R.H.,Catholic University of Leuven | Salles G.F.,University Hospital Clementino Fraga Filho | Pierdomenico S.D.,University of Chieti Pescara | And 9 more authors.
Journal of Hypertension | Year: 2015

Background: Whether ambulatory blood pressure (BP) among hypertensive patients better predicts cardiovascular events (CVEs) in women relative to men is unclear. Methods: We searched PUBMED and OVID databases. Cohorts were required to have hypertension, 1+ years of follow-up, with stroke and coronary artery disease as outcomes. Lead investigators for these cohorts provided ad hoc analyses. Random-effect meta-analyses gave hazard ratios for CVEs from a 1 standard deviation (SD) mmHg increase and a 10 mmHg increase in SBP. Subgroup and meta-regression analyses quantified the relative increase in risk in women versus men. Results: Patients were from Europe, Brazil, and Japan (10 cohorts, n = 17 312, CVEs = 1892). One cohort lacked sex-specific hazard ratios from 24 h and clinic SBP. Compared with men, women tended to have greater SDs and coefficients of variation of SBP. Subgroup analyses showed higher hazard ratios in women than in men from increases in ambulatory but not clinic SBPs. For women relative to men, a 1 SD increase in night-time, daytime, 24 h, and clinic SBP gave hazard ratios (95% confidence limits) of 1.17 (1.06-1.30), 1.24 (1.10-1.39), 1.21 (1.08-1.36), and 0.94 (0.84-1.05), respectively, whereas a 10 mmHg increase in SBP, gave hazard ratios of 1.06 (0.99-1.14), 1.13 (1.03-1.23), 1.10 (1.01-1.21), and 0.96 (0.89-1.03), respectively. Conclusion: In patients with hypertension, increases in ambulatory, but not clinic, SBP predict higher risks for CVEs in women than in men. Although women tended to have greater variability in SBP, this did not entirely explain the sex-ambulatory BP interactions. © 2015 Wolters Kluwer Health, Inc.


Palatini P.,University of Padua | Reboldi G.,University of Perugia | Beilin L.J.,University of Western Australia | Casiglia E.,University of Padua | And 10 more authors.
Journal of Clinical Hypertension | Year: 2016

The purpose of this study was to compare the predictive value of ambulatory blood pressure (BP) vs office BP for cardiovascular events during a 5.8-year follow-up period in the obese and nonobese participants of the Ambulatory Blood Pressure-International Study (n=10,817). Both ambulatory BP and office BP considered separately were predictive of cardiovascular events. However, in Cox models including both pressures, only ambulatory BP was associated with outcome. Among obese patients, the hazard ratios for a 10-mm Hg increase in 24-hour and office systolic BPs were 1.37 (95% confidence interval, 1.20-1.53) and 0.91 (95% confidence interval, 0.76-1.07), respectively. Among nonobese patients, the corresponding hazard ratios were 1.39 (95% confidence interval, 1.31-1.47) and 0.94 (95% confidence interval, 0.88-1.00) (P=not significant vs obese). Similar results were obtained for diastolic BP and for daytime and nighttime BPs. Ambulatory BP has similar predictive capacity in obese and nonobese patients, suggesting that ambulatory BP monitoring is a useful diagnostic tool for the assessment of obese individuals. © 2016 Wiley Periodicals, Inc.


Palatini P.,University of Padua | Reboldi G.,University of Perugia | Beilin L.J.,University of Western Australia | Eguchi K.,Jichi University | And 10 more authors.
International Journal of Cardiology | Year: 2013

Background: Data from prospective cohort studies regarding the association between ambulatory heart rate (HR) and cardiovascular events (CVE) are conflicting. Methods: To investigate whether ambulatory HR predicts CVE in hypertension, we performed 24-hour ambulatory blood pressure and HR monitoring in 7600 hypertensive patients aged 52±16 years from Italy, U.S.A., Japan, and Australia, included in the 'ABP-International' registry. All were untreated at baseline examination. Standardized hazard ratios for ambulatory HRs were computed, stratifying for cohort, and adjusting for age, gender, blood pressure, smoking, diabetes, serum total cholesterol and serum creatinine. Results: During a median follow-up of 5.0 years there were 639 fatal and nonfatal CVE. In a multivariable Cox model, night-time HR predicted fatal combined with nonfatal CVE more closely than 24 h HR (p=0.007 and =0.03, respectively). Daytime HR and the night:day HR ratio were not associated with CVE (p=0.07 and=0.18, respectively). The hazard ratio of the fatal combinedwith nonfatal CVE for a 10-beats/min increment of the night-time HR was 1.13 (95% CI, 1.04-1.22). This relationship remained significant when subjects taking beta-blockers during the follow-up (hazard ratio, 1.15; 95% CI, 1.05-1.25) or subjects who had an event within 5 years after enrollment (hazard ratio, 1.23; 95% CI, 1.05-1.45) were excluded from analysis. Conclusions: At variance with previous data obtained from general populations, ambulatory HR added to the risk stratification for fatal combined with nonfatal CVE in the hypertensive patients from the ABP-International study. Night-time HR was a better predictor of CVE than daytime HR. © 2013 Elsevier Ireland Ltd. All rights reserved.


Palatini P.,University of Padua | Reboldi G.,University of Perugia | Beilin L.J.,University of Western Australia | Casiglia E.,University of Padua | And 10 more authors.
Hypertension | Year: 2014

The association of ambulatory blood pressure (BP) variability with mortality and cardiovascular events is controversial. To investigate whether BP variability predicts cardiovascular events and mortality in hypertension, we analyzed 7112 untreated hypertensive participants (3996 men) aged 52±15 years enrolled in 6 prospective studies. Median followup was 5.5 years. SD of night-time BP was positively associated with age, body mass index, smoking, diabetes mellitus, and average night-time BP (all P<0.001). In a multivariable Cox model, night-time BP variability was an independent predictor of all-cause mortality (systolic, P<0.001/diastolic, P<0.0001), cardiovascular mortality (P=0.008/<0.0001), and cardiovascular events (P<0.001/<0.0001). In contrast, daytime BP variability was not an independent predictor of outcomes in any model. In fully adjusted models, a night-time systolic BP SD of ≥12.2 mm Hg was associated with a 41% greater risk of cardiovascular events, a 55% greater risk of cardiovascular death, and a 59% increased risk of all-cause mortality compared with an SD of <12.2 mm Hg. The corresponding values for a diastolic BP SD of ≥7.9 mm Hg were 48%, 132%, and 77%. The addition of night-time BP variability to fully adjusted models had a significant impact on risk reclassification and integrated discrimination for all outcomes (relative integrated discrimination improvement for systolic BP variability: 9% cardiovascular events, 14.5% all-cause death, 8.5% cardiovascular death, and for diastolic BP variability: 10% cardiovascular events, 19.1% all-cause death, 23% cardiovascular death, all P<0.01). Thus, addition of BP variability to models of long-term outcomes improved the ability to stratify appropriately patients with hypertension among risk categories defined by standard clinical and laboratory variables. © 2014 American Heart Association, Inc.


PubMed | University of Padua, Hospital of Assisi, Tohoku University, University of Western Australia and 5 more.
Type: Journal Article | Journal: Journal of clinical hypertension (Greenwich, Conn.) | Year: 2016

The purpose of this study was to compare the predictive value of ambulatory blood pressure (BP) vs office BP for cardiovascular events during a 5.8-year follow-up period in the obese and nonobese participants of the Ambulatory Blood Pressure-International Study (n=10,817). Both ambulatory BP and office BP considered separately were predictive of cardiovascular events. However, in Cox models including both pressures, only ambulatory BP was associated with outcome. Among obese patients, the hazard ratios for a 10-mm Hg increase in 24-hour and office systolic BPs were 1.37 (95% confidence interval, 1.20-1.53) and 0.91 (95% confidence interval, 0.76-1.07), respectively. Among nonobese patients, the corresponding hazard ratios were 1.39 (95% confidence interval, 1.31-1.47) and 0.94 (95% confidence interval, 0.88-1.00) (P=not significant vs obese). Similar results were obtained for diastolic BP and for daytime and nighttime BPs. Ambulatory BP has similar predictive capacity in obese and nonobese patients, suggesting that ambulatory BP monitoring is a useful diagnostic tool for the assessment of obese individuals.


PubMed | Tokyo Women's Medical University, University of Tsukuba, Jichi University, Osaka University and 2 more.
Type: Journal Article | Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | Year: 2014

Antineutrophil cytoplasmic autoantibody (ANCA) directed against myeloperoxidase (MPO), a diagnostic criterion in MPO-ANCA-associated vasculitis (MPO-AAV), does not always correlate with disease activity. Here, we detected autoantibodies against moesin, which was located on the surface of stimulated endothelial cells, in the serum of patients.The anti-moesin autoantibody titer was evaluated by ELISA. Seventeen kinds of cytokines/chemokines were measured by a Bio-Plex system.Serum creatinine in the anti-moesin autoantibody-positive group was higher than that in the negative group. Additionally, interferon (IFN)-, macrophage chemotactic peptide-1 (MCP-1), interleukin (IL)-2, IL-7, IL-12p70, IL-13, granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor were significantly higher in the positive group. Furthermore, IL-7 and IL-12p70 levels correlated with the anti-moesin autoantibody titer. Based on these findings and the binding of anti-moesin IgG to neutrophils and monocytes, we detected the secretion of cytokines/chemokines such as IFN-, MCP-1 and GM-CSF from these cells.The anti-moesin autoantibody existed in the serum of patients with MPO-AAV and was associated with the production of inflammatory cytokines/chemokines targeting neutrophils with a cytoplasmic profile, which suggests that the anti-moesin autoantibody has the possibility to be a novel autoantibody developing vasculitis via neutrophil and endothelial cell activation.


Suzuki K.,Chiba University | Suzuki K.,Asia International Institute of Infectious Disease Control | Suzuki K.,University of Tsukuba | Suzuki K.,Osaka University | And 9 more authors.
Nephrology Dialysis Transplantation | Year: 2014

Background. Antineutrophil cytoplasmic autoantibody (ANCA) directed against myeloperoxidase (MPO), a diagnostic criterion in MPO-ANCA-associated vasculitis (MPO-AAV), does not always correlate with disease activity. Here, we detected autoantibodies against moesin, which was located on the surface of stimulated endothelial cells, in the serum of patients. Methods. The anti-moesin autoantibody titer was evaluated by ELISA. Seventeen kinds of cytokines/chemokines were measured by a Bio-Plex system. Results. Serum creatinine in the anti-moesin autoantibodypositive group was higher than that in the negative group. Additionally, interferon (IFN)-γ, macrophage chemotactic peptide-1 (MCP-1), interleukin (IL)-2, IL-7, IL-12p70, IL-13, granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor were significantly higher in the positive group. Furthermore, IL-7 and IL-12p70 levels correlated with the anti-moesin autoantibody titer. Based on these findings and the binding of anti-moesin IgG to neutrophils and monocytes, we detected the secretion of cytokines/ chemokines such as IFN-γ, MCP-1 and GM-CSF from these cells. Conclusions. The anti-moesin autoantibody existed in the serum of patients with MPO-AAV and was associated with the production of inflammatory cytokines/chemokines targeting neutrophils with a cytoplasmic profile, which suggests that the anti-moesin autoantibody has the possibility to be a novel autoantibody developing vasculitis via neutrophil and endothelial cell activation. © 2013 The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.


Nishimura W.,Joslin Diabetes Center | Nishimura W.,Harvard University | Nishimura W.,National Health Research Institute | Nishimura W.,Jichi University | And 12 more authors.
PLoS ONE | Year: 2015

Early in pancreatic development, epithelial cells of pancreatic buds function as primary multipotent progenitor cells (1°MPC) that specify all three pancreatic cell lineages, i.e., endocrine, acinar and duct. Bipotent "Trunk" progenitors derived from 1°MPC are implicated in directly regulating the specification of endocrine progenitors. It is unclear if this specification process is initiated in the 1°MPC where some 1°MPC become competent for later specification of endocrine progenitors. Previously we reported that in Pdx1tTA/+;tetOMafA (bigenic) mice inducing expression of transcription factor MafA in Pdx1-expressing (Pdx1+) cells throughout embryonic development inhibited the proliferation and differentiation of 1°MPC cells, resulting in reduced pancreatic mass and endocrine cells by embryonic day (E) 17.5. Induction of the transgene only until E12.5 in Pdx1+ 1°MPC was sufficient for this inhibition of endocrine cells and pancreatic mass at E17.5. However, by birth (P0), as we now report, such bigenic pups had significantly increased pancreatic and endocrine volumes with endocrine clusters containing all pancreatic endocrine cell types. The increase in endocrine cells resulted from a higher proliferation of tubular epithelial cells expressing the progenitor marker Glut2 in E17.5 bigenic embryos and increased number of Neurog3-expressing cells at E19.5. A BrdU-labeling study demonstrated that inhibiting proliferation of 1°MPC by forced MafA-expression did not lead to retention of those progenitors in E17.5 tubular epithelium. Our data suggest that the forced MafA expression in the 1°MPC inhibits their competency to specify endocrine progenitors only until E17.5, and after that compensatory proliferation of tubular epithelium gives rise to a distinct pool of endocrine progenitors. Thus, these bigenic mice provide a novel way to characterize the competency of 1°MPC for their ability to specify endocrine progenitors, a critical limitation in our understanding of endocrine differentiation. © 2015 Nishimura et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Hozumi J.,University of Tokyo | Sumitani M.,University of Tokyo | Matsubayashi Y.,University of Tokyo | Abe H.,University of Tokyo | And 4 more authors.
Pain Research and Management | Year: 2016

Objectives: Overweight negatively affects musculoskeletal health; hence obesity is considered a risk factor for osteoarthritis and chronic low back pain. This was conducted to determine if obesity affects neuropathic pain, usually considered unrelated to the weight-load on the musculoskeletal system. Methods: Using a cut-off body mass index value of 25,44 patients with neuropathic pain were grouped into a "high-BMI" group and a "normal-BMI" group. Results: The numeric rating scale of the high-BMI group was significantly higher than that of the normal-weight group (P < 0.05). The total NPSI scores were significantly higher (P < 0.01), and the paroxysmal pain and the negative symptoms were more serious in the high-BMI group than in the normal-BMI group. The high-BMI subjects also had significantly higher SF-MPQ scores (P < 0.05). However, both physical and mental health status on the SF-36 were comparable between the groups. Discussion: Neuropathic pain that did not arise from musculoskeletal damage was higher in the high-BMI patients. Paroxysmal pain was more severe, suggesting that neural damage might be aggravated by obesity-associated inflammation. These findings should have needed to be confirmed in future studies. Copyright © 2016 Jun Hozumi et al.


PubMed | Jichi University and University of Tokyo
Type: | Journal: Pain research & management | Year: 2016

Objectives. Overweight negatively affects musculoskeletal health; hence obesity is considered a risk factor for osteoarthritis and chronic low back pain. This was conducted to determine if obesity affects neuropathic pain, usually considered unrelated to the weight-load on the musculoskeletal system. Methods. Using a cut-off body mass index value of 25, 44 patients with neuropathic pain were grouped into a high-BMI group and a normal-BMI group. Results. The numeric rating scale of the high-BMI group was significantly higher than that of the normal-weight group (P < 0.05). The total NPSI scores were significantly higher (P < 0.01), and the paroxysmal pain and the negative symptoms were more serious in the high-BMI group than in the normal-BMI group. The high-BMI subjects also had significantly higher SF-MPQ scores (P < 0.05). However, both physical and mental health status on the SF-36 were comparable between the groups. Discussion. Neuropathic pain that did not arise from musculoskeletal damage was higher in the high-BMI patients. Paroxysmal pain was more severe, suggesting that neural damage might be aggravated by obesity-associated inflammation. These findings should have needed to be confirmed in future studies.

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