Association between serum ALT levels and incidence of new-onset diabetes in general population of Japanese: a longitudinal observational study (ISSA-CKD).

OBJECTIVE: We aimed to clarify the relationship between serum alanine transaminase (ALT) levels and incidence of new-onset diabetes in a Japanese general population. SETTING: Population-based retrospective cohort study using annual health check-up data for residents of Iki City, Nagasaki Prefecture, Japan. PARTICIPANTS: A total of 5330 Japanese individuals (≥30 years old) without diabetes at baseline were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Serum ALT levels were determined using an enzymatic method and were classified into gender-specific quartile groups as follows: group 1 (3-16 U/L in men and 3-13 U/L in women), group 2 (17-21 U/L in men and 14-16 U/L in women), group 3 (22-29 U/L in men and 17-22 U/L in women) and group 4 (30-428 U/L in men and 23-268 U/L in women). The study outcome was the incidence of diabetes (fasting glucose ≥7.0 mmol/L, non-fasting glucose ≥11.1 mmol/L, glycated haemoglobin ≥6.5% or use of glucose-lowering therapies). RESULTS: After an average follow-up period of 5.0 years, 279 individuals developed diabetes. The incidence rate of diabetes increased with elevation of serum ALT levels (0.7% per 100 person-years in group 1, 0.9% in group 2, 0.9% in group 3 and 1.7% in group 4) (p<0.001 for trend). This association was significant after adjustment for other risk factors including age, sex, obesity, hypertension, dyslipidaemia, smoking, current daily alcohol intake and regular exercise (p<0.001 for trend). Comparable associations were observed between men and women (p=0.459 for interaction). CONCLUSION: Serum ALT levels were associated with future development of diabetes in the general Japanese population.

Elevation in white blood cell count and development of hyper LDL cholesterolemia.

To investigate the relationship between white blood cell (WBC) count and incidence of hyper-low-density lipoprotein (LDL) cholesterolemia in a population-based longitudinal study. This is a retrospective study using data of annual health check-ups for residents of Iki City, Japan. A total of 3312 residents (≥ 30 years) without hyper-LDL cholesterolemia at baseline were included in this analysis. Primary outcome was incidence of hyper-LDL cholesterolemia (LDL cholesterol levels ≥ 3.62 mmol/L and/or use of lipid lowering drugs). During follow-up (average 4.6 years), 698 participants development of hyper-LDL cholesterolemia (incidence 46.8 per 1000 person-years). Higher incidence of hyper-LDL cholesterolemia was observed among participants with higher leukocyte count (1st quartile group: 38.5, 2nd quartile group: 47.7, 3rd quartile group: 47.3, and 4th quartile group: 52.4 per 1,000 person-years, P = 0.012 for trend). Statistically significant relation was observed even after adjustment for age, gender, smoking, alcohol intake, leisure-time exercise, obesity, hypertension and diabetes: hazard ratio 1.24 (95% confidence interval 0.99 to 1.54) for 2nd quartile group, 1.29 (1.03-1.62) for 3rd quartile group and 1.39 (1.10-1.75) for 4th quartile group, compared with 1st quartile group (P for trend = 0.006). Increased WBC count was related to incidence of hyper-LDL cholesterolemia in general Japanese population.

Association between pulse pressure and progression of chronic kidney disease.

The aim of this study was to investigate the association between pulse pressure (PP) and chronic kidney disease (CKD) progression among the general population in Japan. We conducted a population-based cohort study of the residents of Iki Island, Nagasaki, Japan, from 2008 to 2018. We identified 1042 participants who had CKD (estimated glomerular filtration rate(eGFR) < 60 mL/min/1.73 m2 or the presence of proteinuria) at baseline. Cox's proportional hazard model was used to evaluate the association between PP and progression of CKD. During a 4.66-year mean follow-up, there were 241 cases of CKD progression (incident rate: 49.8 per 1000 person-years). A significant increase existed in CKD progression per 10 mmHg of PP elevation, even when adjusted for confounding factors [adjusted hazard ratio 1.17 (1.06-1.29) p < 0.001]. Similar results were obtained even after dividing PP into quartiles [Q2: 1.14 (0.74-1.76), Q3: 1.35 (0.88-2.06), Q4: 1.87 (1.23-2.83) p = 0.003 for trend]. This trend did not change significantly irrespective of baseline systolic or diastolic blood pressures. PP remained a potential predictive marker, especially for eGFR decline. In conclusion, we found a significant association between PP and CKD progression. PP might be a potential predictive marker for CKD progression.

Eating before bed and new-onset hypertension in a Japanese population: the Iki city epidemiological study of atherosclerosis and chronic kidney disease.

The aim of this study was to determine the relationship between eating before bed and the development of hypertension in a general Japanese population. We conducted a population-based retrospective cohort study using annual health check-up data collected from the residents of Iki City, Nagasaki Prefecture, Japan. In total, 2930 participants without hypertension at baseline (mean age 57.0 years, male 42.8%) were included in the present analysis. Eating before bed was defined as eating within 2 h of bedtime. The outcome of this study was incident hypertension (blood pressure ≥140/90 mmHg or initiation of blood pressure-lowering medications). Multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During an average follow-up of 4.5 years, 909 participants developed hypertension. The incidence (per 1000 person-years) of hypertension in the group of individuals who ate before bed was 82.8, whereas that in the group of individuals who did not eat before bed was 65.8. The association was significant even after adjusting for other risk factors, including age, sex, current smoking status, current alcohol intake, regular exercise, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia, with a hazard ratio of 1.23 (95% CI: 1.05-1.44) for the group of individuals who ate before bed compared with the group of individuals who did not eat before bed (P = 0.01 for trend). Eating before bed was correlated with a future risk of developing hypertension in the general Japanese population.

Effects of Weight Gain after 20 Years of Age and Incidence of Hyper-Low-Density Lipoprotein Cholesterolemia: The Iki Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD).

The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of Japanese people. METHODS: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. RESULTS: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of <10 kg (41.8/1000 person-years). This association remained statistically significant even after adjustment for age, sex, smoking, daily drinking, exercise, obesity, hypertension, and diabetes (multivariable hazard ratio 1.31, 95% confidence interval 1.08-1.58, p = 0.006). CONCLUSION: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese.

Eating Speed and Incidence of Diabetes in a Japanese General Population: ISSA-CKD.

BACKGROUND: We investigated whether eating speed was associated with the incidence of diabetes in a Japanese general population. METHODS: A total of 4853 Japanese individuals without diabetes at baseline were analyzed. Self-reported eating speed was categorized as slow, medium, and fast on the basis of questionnaire responses. The study outcome was the incidence of diabetes. RESULTS: After an average follow-up period of 5.1 years, 234 individuals developed diabetes. The incidence of diabetes per 1000 person-years was 4.9 in the slow eating speed group, 8.8 in the medium eating speed group, and 12.5 in the fast eating speed group, respectively (*** p < 0.001 for trend). The HRs were 1.69 (95%CI 0.94-3.06) for the medium eating speed and 2.08 (95%CI 1.13-3.84) for the fast eating speed, compared to the slow eating speed (* p = 0.014 for trend) after adjustment for age, gender, smoking status, drinking, exercise, obesity, hypertension, and dyslipidemia. CONCLUSION: Faster eating speed increased a risk for the incidence of diabetes in a general Japanese population.

White blood cell count and incidence of hypertension in the general Japanese population: ISSA-CKD study.

OBJECTIVES: This study aimed to clarify the relationship between the white blood cell (WBC) count and hypertension in the general Japanese population. METHODS: We conducted a population-based retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. A total of 2935 participants without hypertension at baseline were included in the present analysis. WBC counts were classified as tertile 1 (<4700/µL), tertile 2 (4700-5999/µL), and tertile 3 (≥6000/µL). The outcome was incident hypertension (blood pressure ≥140 mmHg). Multivariable-adjusted hazard ratios and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazards model. RESULT: During an average follow-up of 4.5 years, 908 participants developed hypertension. The incidence (per 100 person-years) of hypertension increased with an elevation in the WBC count (6.3 in tertile 1, 7.0 in tertile 2, and 7.4 in tertile 3). This association was significant, even after adjustment for other risk factors, including age, sex, current smoking habits, current alcohol intake, exercise habits, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia. The hazard ratios were 1.07 for tertile 2 (95% CI 0.90-1.26) and 1.27 for tertile 3 (95% CI 1.06-1.51) compared with the reference group of tertile 1 (p = 0.009). CONCLUSION: The WBC count was associated with future development of hypertension in the general Japanese population.

Differences between home blood pressure and strictly measured office blood pressure and their determinants in Japanese men.

Conventional office blood pressure (OBP) and home blood pressure (HBP) measurements are often inconsistent. The purpose of this research was (1) to test whether strictly measured OBP values with sufficient rest time before measurement (st-OBP) is comparable to HBP at the population level and (2) to ascertain whether there are particular determinants for the difference between HBP and st-OBP at the individual level. Data from a population-based group of 1056 men aged 40-79 years were analyzed. After a five-min rest, st-OBP was measured twice. HBP was measured after a 2-min rest every morning for seven consecutive days. To determine factors related to ΔSBP (HBP minus st-OBP measurements), multiple linear regression analyses and analyses of covariance were performed. While st-OBP and HBP were comparable (136.5 vs. 137.2 mmHg) at the population level, ΔSBP varied with a standard deviation of 13.5 mmHg. Smoking was associated with a larger ΔSBP regardless of antihypertensive usage, and BMI was associated with a larger ΔSBP in participants using antihypertensive drugs. The adjusted mean ΔSBP in the highest BMI tertile category was 4.6 mmHg in participants taking antihypertensive drugs. st-OBP and HBP measurements were comparable at the population level, although the distribution of ΔSBP was considerably broad. Smokers and obese men taking antihypertensive drugs had higher HBP than st-OBP, indicating that their blood pressure levels are at risk of being underestimated. Therefore, this group would benefit from the addition of HBP measurements.

Uric Acid and Prevalence of Hypertension in a General Population of Japanese: ISSA-CKD Study.

BACKGROUND: There is uncertainty surrounding the causal relationship between serum uric acid and hypertension. The aim was to investigate the association between serum uric acid and prevalence of hypertension in a general population of Japanese. METHODS: This was a population-based cross-sectional study using health check-up data of the residents of the Iki City, Nagasaki Prefecture, Japan. A total of 7,484 participants aged 30 years or older were included in this study. Serum uric acid was classified into four groups: group 1 (< 357 µmol/L (< 6 mg/dL)), group 2 (357 - 415 µmol/L (6 - 6.9 mg/dL)), group 3 (416 - 475 µmol/L (7 - 7.9 mg/dL)) and group 4 (≥ 476 µmol/L (≥ 8 mg/dL)). Hypertension was defined as blood pressure (BP) levels of ≥ 140/90 mm Hg or use of BP lowering medications. RESULTS: Hypertension was observed among 3,467 participants (prevalence 46.3%). The prevalence of hypertension increased with elevation of serum uric acid levels: 42.8% in group 1, 55.0% in group 2, 57.6% in group 3 and 59.8% in group 4 (P < 0.001 for trend). This association was significant even after adjustment for other risk factors including age, sex, current smoking, current alcohol intake, obesity, diabetes, dyslipidemia, estimated glomerular filtration rate and proteinuria: odds ratios (95% confidence intervals) were 1.50 (1.28 - 1.77) for group 2, 1.58 (1.25 - 1.99) for group 3 and 1.89 (1.36 - 2.64) for group 4 compared with the reference group of group 1 (P < 0.001 for trend). CONCLUSIONS: Serum uric acid was clearly associated with prevalence of hypertension in a general population of Japanese.

Socioeconomic and lifestyle factors associated with depressive tendencies in general Japanese men and women: NIPPON DATA2010.

BACKGROUND: The gender-specific characteristics of individuals at an increased risk of developing depression currently remain unclear despite a higher prevalence of depression in women than in men. This study clarified socioeconomic and lifestyle factors associated with an increased risk of subclinical depression in general Japanese men and women. METHODS: Study participants were residents not receiving psychiatric treatments in 300 sites throughout Japan in 2010 (1152 men, 1529 women). Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95%CIs) for socioeconomic factors and lifestyle factors were calculated using a logistic regression analysis. RESULTS: Risk of depressive tendencies was significantly higher in men who were single and living alone (OR, 3.27; 95% CI, 1.56-6.88) than those married. The risk was significantly lower in women who were not working and aged ≥ 60 years (OR, 0.39; 95% CI, 0.22-0.68) and higher in men who were not working and aged < 60 years (OR, 3.57; 95%CI, 1.31-9.72) compared with those who were working. Current smoking was also associated with a significantly increased risk of depressive tendencies in women (OR, 2.96; 95% CI, 1.68-5.22) but not in men. CONCLUSIONS: Socioeconomic and lifestyle factors were associated with an increased risk of depressive tendencies in general Japanese. Related factors were different by sex.

The association of home and accurately measured office blood pressure with coronary artery calcification among general Japanese men.

OBJECTIVE: We conducted a cross-sectional study to clarify whether home blood pressure (HBP) is more strongly associated with coronary artery calcification (CAC) than accurately measured office blood pressure (OBP) among the general population of Japanese men. METHODS: We analyzed the data of 919 Japanese male participants who were randomly selected from general population (mean age 64.5 years). OBP was measured twice consecutively by a trained nurse using electrical device after 5 min of complete rest alone in a sitting position in a silent room. The participants were asked to measure HBP with an electrical device once in the morning during 7 consecutive days. CAC was assessed using computed tomography. Presence of CAC was defined as Agatston score at least 10. We calculated odds ratios for the presence of CAC per one SD higher OBP and HBP adjusted for age and other cardiovascular risk factors. RESULTS: The mean systolic OBP (SD) and HBP (SD) were 136.8 (19.0) and 137.2 (18.5) mmHg, respectively, without statistical difference between the two (P = 0.595). OBP and HBP were highly correlated (r = 0.74 P < 0.001). CAC was found in 454 (49.4%) participants. Multivariable-adjusted odds ratios [95% confidence interval (CI)] for the presence of CAC were comparable between OBP (1.32, 95% CI: 1.12-1.56) and HBP (1.35, 95% CI: 1.14-1.60) (P heterogeneity = 0.813). CONCLUSION: The strength of association of accurately measured OBP with CAC was comparable with that of HBP among randomly selected male general population aged 40-79 years.

Association Between Body Mass Index and All-Cause Death in Japanese Population: Pooled Individual Participant Data Analysis of 13 Cohort Studies.

BACKGROUND: We sought to investigate the optimal values of BMI for the lowest risk of all-cause death and whether the optimal BMI differs according to smoking status in large-scale pooled analysis of 13 Japanese cohorts. METHODS: Data from 179,987 participants of 13 well-qualified cohort studies conducted throughout Japan were used for our analysis. A cohort-stratified Cox proportional hazard model was used. P values for interactions were calculated based on the cross product of BMI and age, sex, or smoking status. RESULTS: In the entire study population, all-cause mortality risk was lowest when the BMI was 22.0-24.9 kg/m2. This was also the case for selected healthy participants (never smoked, baseline total cholesterol level ≥4.1 mmol/L; the first 5 years of follow-up data were excluded). No effect modification of age, sex, or smoking status was observed. Regardless of their BMI, never smokers always had a lower all-cause mortality risk than did current smokers even with an ideal BMI in terms of mortality risk. CONCLUSION: A BMI of 22-24.9 kg/m2 correlated with the lowest risk of mortality, regardless of whether all participants or selected healthy participants were analyzed. The fact that smoking was more strongly associated with mortality than obesity emphasizes the urgency for effective anti-smoking programs.

The Relationship Between Evaluation Methods for Chemotherapy-Induced Peripheral Neuropathy.

Numbness and pain are currently evaluated using subjective methods such as the visual analogue scale (VAS). PainVision (PV) is an analytical instrument that was designed to quantitatively assess sense perception and nociception in patients. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most important adverse events that renders prolonged chemotherapy difficult. To assess the features of CIPN, we aimed to compare PV methods with existing methods. A total of 73 patients received oxaliplatin for metastatic colorectal cancer. Registered patients included 37 men and 36 women in the range of 37 to 89 years (median 70). CIPN was evaluated a total of 483 times (median per patient six times). Our study examined the correlation between evaluation methods of CIPN using VAS and PV, respectively. The average VAS (hand), VAS (foot) and PV scores of CIPN were 18.4 (range: 0-100), 23.8 (range: 0-100), and 24.7 (range: 0-496), respectively. VAS (hand), VAS (foot), and FACT/GOG-NTX (NTX2, NTX4 and NTX8) were significantly correlated with PV. PV showed no correlation with a Disk-Criminator or the monofilament test used as a quantitative evaluation. The evaluation of CIPN is complex, and further improvement is required for evaluation with PV.

Pooled Analysis of the Associations between Body Mass Index, Total Cholesterol, and Liver Cancer-related Mortality in Japan

Objective: We employed a large-scale pooled analysis to investigate the association of liver cancer-related mortality with being overweight/obese and total cholesterol (TC) levels, since limited and inconsistent data on these associations exist in Japan. Methods: A total of 59,332 participants (23,853 men and 35,479 women) from 12 cohorts without a history of cancer who were followed for a median of 14.3 years were analyzed. A sex-specific stratified Cox proportional hazards model adjusted for age and other potential confounders was used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for liver cancer-related mortality. Results: A total of 447 participants (266 men and 181 women) died of liver cancer within the follow-up period. Individuals classified as having a high BMI (≥25.0 kg/m2) and low TC levels (<160 mg/dL) had a significantly increased risk for liver cancer-related mortality (HR 7.05, 95% CI 4.41­11.26 in men; HR 8.07, 95% CI 4.76­13.67 in women) when compared with those in the intermediate BMI (18.5­24.9 kg/m2) and TC (160­219 mg/dL) categories. These associations remained after limiting the follow-up duration to >5 years. Conclusion: Being overweight/obese, combined with low TC levels, was strongly associated with liver cancer-related mortality in the EPOCH-JAPAN.

Relationship of serum irisin levels to prevalence and progression of coronary artery calcification: A prospective, population-based study.

BACKGROUND: The mechanisms by which exercise reduces the risk of coronary heart disease remain poorly understood. Irisin, an exercise-induced polypeptide secreted from skeletal muscles, is proposed to potentially mediate beneficial effects of exercise, especially in metabolic regulation and development of atherosclerosis. We examined whether higher serum irisin levels are associated with lower prevalence and progression of coronary atherosclerosis. METHODS AND RESULTS: We performed a prospective, population-based study of Japanese men aged 40-79 years without known coronary heart disease. We measured baseline serum irisin levels using an enzyme-linked immunosorbent assay and quantified coronary artery calcification (CAC) from serial computed tomography scans. Of 1038 participants (mean age, 63.9 years) at baseline, 670 (64.6%) had prevalent CAC. Of 810 participants at follow-up (median, 5.1 years), 407 (50.3%) experienced CAC progression. In Poisson regression with robust error variance adjusted for age and behavioral factors, serum irisin levels were inversely associated with CAC prevalence (relative risk [RR] of 4th versus 1st quartiles [95% confidence interval], 0.88 [0.78-0.99]; trend P = 0.016) and CAC progression (RR, 0.76 [0.63-0.91]; trend P = 0.002). After further adjustment for cardiometabolic risk factors, the inverse association with CAC prevalence disappeared (RR, 0.95 [0.84-1.08]; trend P = 0.319), but that with CAC progression persisted (RR, 0.77 [0.64-0.93]; trend P = 0.003). These associations were consistent when we applied ordinal logistic regression and across subgroups by cardiometabolic risk factor status. CONCLUSIONS: Higher serum irisin levels were associated with less burden of coronary atherosclerosis. This association would be mediated through and beyond traditional cardiometabolic pathways.

Serum magnesium, phosphorus, and calcium levels and subclinical calcific aortic valve disease: A population-based study.

BACKGROUND AND AIMS: Calcific aortic valve disease (CAVD) is the most common valve disease. Although micronutrients are known to contribute to cardiovascular disease, the relationship with CAVD remains poorly evaluated. We examined the association of serum levels of magnesium, phosphorus, and calcium with prevalence, incidence, and progression of aortic valve calcification (AVC). METHODS: We conducted a prospective study in a population-based sample of Japanese men aged 40-79 years without known cardiovascular disease and chronic kidney disease at baseline, and quantified AVC from serial computed tomographic images with the Agatston method. RESULTS: Of 938 participants at baseline (mean age, 63.7 ±â€¯9.9 years), AVC prevalence was observed in 173 (18.4%). Of 596 participants without baseline AVC at follow-up (median duration, 5.1 years), AVC incidence was observed in 138 (23.2%). After adjustment for demographics, behaviors and cardiovascular risk factors, relative risks (95% confidence intervals) in the highest versus lowest categories of serum magnesium, phosphorus, and calcium were 0.62 (0.44-0.86), 1.45 (1.02-2.04), and 1.43 (0.95-2.15), respectively, for AVC prevalence and 0.62 (0.42-0.92), 1.93 (1.28-2.91), and 1.09 (0.77-1.55), respectively, for AVC incidence. Their linear trends of serum magnesium and phosphorus were also all statistically significant. Of 131 participants with baseline AVC, there was no association of any serum micronutrients with AVC progression. CONCLUSIONS: Serum magnesium was inversely associated, while serum phosphorus was positively associated with AVC prevalence and incidence, suggesting that these serum micronutrients may be potential candidates for risk prediction or prevention of CAVD, and warranting further studies.

A small-molecule DS44170716 inhibits Ca2+-induced mitochondrial permeability transition.

Mitochondria are involved in a variety of physiological and pathological processes. Ca2+ uptake is one of the important functions of the organelle for maintenance of cellular Ca2+ homeostasis. In pathological conditions such as ischemia reperfusion injury, Ca2+ overload into mitochondria induces mitochondrial permeability transition (MPT), a critical step for cell death. Because inhibition of MPT is a promising approach to protecting cells and organs, it is important for drug discovery to identify novel chemicals or mechanisms to inhibit MPT. Here we report upon a small-molecule compound DS44170716 that inhibits Ca2+-induced MPT in rat liver isolated mitochondria. DS44170716 protects human liver HepG2 cells from Ca2+-induced death with a level of protection similar to cyclosporin A (CsA). The inhibitory mechanism of DS44170716 against MPT is independent on PPIF, a target of CsA. DS44170716 blocks Ca2+ flux into the mitochondria by decreasing mitochondrial membrane potential, while potently inhibiting mitochondrial complex III activities and weakly inhibiting complex IV and V activities. Similarly, complex III inhibitor antimycin A, complex IV inhibitor KCN or complex V inhibitor oligomycin inhibits Ca2+ uptake of isolated mitochondria. These results show that DS44170716 is a novel class inhibitor of MPT by blocking of mitochondrial complexes and Ca2+-overload into mitochondria.

Associations of socioeconomic status with prevalence, awareness, treatment, and control of hypertension in a general Japanese population: NIPPON DATA2010.

OBJECTIVE: To investigate associations between socioeconomic status (SES) and prevalence, awareness, treatment, and control of hypertension in Japan's general population. METHODS: In 2010, we established a cohort of participants in the National Health and Nutrition Survey of Japan. The cohort included 2623 adults from 300 randomly selected areas across Japan. Using baseline data, four cross-sectional analyses were performed: association of SES with prevalent hypertension in 2623 participants; association of SES with unawareness of hypertension and with no treatment in 1282 hypertensive patients; and association of SES with uncontrolled hypertension in 720 treated hypertensive patients. SES was classified according to employment status, length of education, marital and living status, and household expenditure. RESULTS: The overall prevalence of hypertension was 48.9%. Among hypertensive participants, the proportions of unawareness and no treatment were 33.1 and 43.8%, respectively. Target blood pressure levels were not achieved among 61.2% of treated hypertensive patients. Hypertension was more prevalent in the unmarried and living alone group than in the married group (odds ratio 1.76; 95% confidence interval 1.26-2.44), after adjustment for age, sex, BMI, smoking, alcohol consumption, habitual exercise, history of cardiovascular diseases, diabetes mellitus, hypercholesterolemia, dietary sodium, and potassium intake. SES was not clearly associated with unawareness, no treatment, nor poor control of hypertension. CONCLUSION: Being unmarried and living alone was associated with increased prevalence of hypertension. There was no clear association of SES with unaware, untreated, and uncontrolled hypertension.

Efficacy of trastuzumab in Japanese patients with HER2-positive advanced gastric or gastroesophageal junction cancer: a subgroup analysis of the Trastuzumab for Gastric Cancer (ToGA) study.

BACKGROUND: The Trastuzumab for Gastric Cancer (ToGA) study is the first international trial to include Japanese patients with human epidermal growth factor 2 (HER2) positive advanced/metastatic gastric or gastroesophageal junction cancer. ToGA showed that trastuzumab plus chemotherapy (capecitabine/cisplatin or 5-fluorouracil/cisplatin) improved overall survival in the overall population (hazard ratio 0.74). Regional differences in outcome in favor of Japanese populations were observed in other studies; therefore, subgroup analyses of ToGA may contribute to the evaluation of the potential benefits of this regimen in Japanese patients. METHODS: We performed subgroup analyses on 101 Japanese patients enrolled into ToGA (trastuzumab plus chemotherapy, n = 51; chemotherapy, n = 50). RESULTS: Median overall survival in the Japanese subgroup was 15.9 months (95% confidence interval 12-25) for trastuzumab plus chemotherapy and 17.7 months (95% confidence interval 12-24) for chemotherapy (hazard ratio 1.00; 95% confidence interval 0.59-1.69). After adjusting for prespecified covariates, the estimated hazard ratio for overall survival was 0.68 (95% confidence interval 0.36-1.27). Further post hoc and exploratory examinations supported the robustness of the adjusted hazard ratios. CONCLUSIONS: After adjusting for imbalanced patient backgrounds between arms, overall survival of Japanese patients with human epidermal growth factor 2 positive advanced/metastatic gastric or gastroesophageal junction cancer who received trastuzumab plus chemotherapy was improved compared with patients who received chemotherapy alone.

Regulation of oxidative stress by pituitary adenylate cyclase-activating polypeptide (PACAP) mediated by PACAP receptor.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional peptide that has been shown to be neuroprotective following a diverse range of cell injuries. Although several mechanisms regulating this effect have been reported, no direct evidence has linked PACAP to the regulation of oxidative stress, despite the fact that oxidative stress is a factor in the injury progression that occurs in most models. In the present study, we investigated the plasma oxidative metabolite and anti-oxidation potential levels of PACAP-deficient mice, as well as those of wild-type animals treated with PACAP38. These were assayed by the determination of Reactive Oxidative Metabolites (d-ROMs) and the Biological Anti-oxidant Potential (BAP) using the Free Radical Electron Evaluator system. We also investigated the direct radical scavenging potency of PACAP38 and the functional role of its receptor in the regulation of oxidative stress by PACAP, by using vasoactive intestinal peptide (VIP) and the PACAP receptor antagonist, PACAP6-38. Although younger PACAP null mice displayed no significant effect, greater d-ROMs and lower BAP values were recorded in older animals than in their wild-type littermates. Intravenous injection of PACAP38 in wild-type mice decreased the plasma d-ROMs and BAP values in a dose-dependent manner. These effects were not reproduced using VIP and were abolished by co-treatment with PACAP38 and the PAC1R antagonist PACAP6-38. Taken together, these results suggest that PACAP plays an important role in the physiological regulation of oxidative stress.