Classifications of moderate to severe asthma phenotypes in Japan and analysis of serum biomarkers: A Nationwide Cohort Study in Japan (NHOM Asthma Study).

BACKGROUND: Asthma is a heterogeneous disease, and phenotyping can facilitate understanding of disease pathogenesis and direct appropriate asthma treatment. This nationwide cohort study aimed to phenotype asthma patients in Japan and identify potential biomarkers to classify the phenotypes. METHODS: Adult asthma patients (n = 1925) from 27 national hospitals in Japan were enrolled and divided into Global Initiative for Asthma (GINA) steps 4 or 5 (GINA 4, 5) and GINA Steps 1, 2, or 3 (GINA 1-3) for therapy. Clinical data and questionnaires were collected. Biomarker levels among GINA 4, 5 patients were measured. Ward's minimum variance hierarchical clustering method and tree analysis were performed for phenotyping. Analysis of variance, the Kruskal-Wallis, and chi-square tests were used to compare cluster differences. RESULTS: The following five clusters were identified: 1) late-onset, old, less-atopic; 2) late-onset, old, eosinophilic, low FEV1; 3) early-onset, long-duration, atopic, poorly controlled; 4) early-onset, young, female-dominant, atopic; and 5) female-dominant, T1/T2-mixed, most severe. Age of onset, disease duration, blood eosinophils and neutrophils, asthma control questionnaire Sum 6, number of controllers, FEV1, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes. CONCLUSIONS: Five distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.).

Distribution of bone mineral content is associated with body weight and exercise capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Although low bone mineral density is highly prevalent in patients with chronic obstructive pulmonary disease (COPD), the distribution of the reduced bone mass has not been fully elucidated. OBJECTIVES: To determine regional bone mass loss in patients with COPD and investigate whether the change in distribution may be associated with body weight loss and functional capacity. METHODS: Body mass index (BMI) was assessed, and height squared indices were derived for the bone mineral content index (BMCI) of the arms, legs and trunk by dual-energy X-ray absorptiometry in 45 male patients with COPD and 12 age- and sex-matched control subjects. Pulmonary function tests were performed, and maximal oxygen uptake (VO2max) was measured. RESULTS: The BMCI was lower in the total bone, legs and trunk of patients with COPD than in control subjects, although the BMCI in the arms was similar between the groups. BMI correlated significantly with the BMCI in all 3 segments. Bone mineral content (BMC) in the trunk, expressed as a percentage of total BMC (BMC trunk/total BMC), correlated significantly with BMI. The BMCI in the trunk was closely related with VO2max but not with airflow limitation. CONCLUSIONS: There was a regional difference in BMC reduction, but a predominant reduction of bone mass in the trunk was not associated with the severity of airflow limitation but rather with body weight loss and exercise intolerance. These data suggest that body weight loss and exercise intolerance are important risk factors for vertebral fracture in patients with COPD.

The impact of obstructive sleep apnea and nasal CPAP on circulating adiponectin levels.

PURPOSE: Although obstructive sleep apnea syndrome (OSAS) is known to be an important risk factor for cardiovascular diseases, the mechanism behind this association has not been fully elucidated. Transendothelial migration of monocytes mediated by adhesion molecules is a crucial step in the pathogenesis of atherosclerosis. We investigated the effect of hypoxic stress on plasma adiponectin and tumor necrosis factor-α (TNF-α) levels and whether adiponectin and TNF-α modulate adhesion molecules in patients with OSAS. METHODS: In 22 patients, plasma adiponectin and TNF-α levels and serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) were determined early in the morning after polysomnography and after nasal continuous positive airway pressure (nCPAP) treatment. RESULTS: Plasma adiponectin levels were inversely correlated with the apnea-hypopnea index (AHI) (r = -0.582, p < 0.005) and % time in SpO2 <90 % (r = -0.539, p < 0.01) but not with the body mass index (BMI). TNF-α levels were positively correlated with the AHI (r = 0.462, p < 0.05) and BMI (r = 0.452, p < 0.05). Serum sICAM-1 levels were inversely correlated with plasma adiponectin levels (r = -0.476, p < 0.05) but not with TNF-α levels. Although plasma TNF-α levels decreased after overnight nCPAP treatment (p < 0.05), plasma adiponectin levels increased after long-term nCPAP (3 months) treatment (p < 0.02) in ten patients. CONCLUSIONS: Our findings suggest that reduced adiponectin and elevated TNF-α levels in plasma are associated with OSAS-induced hypoxic stress. Decreased adiponectin levels are associated with sICAM-1 levels.

Efficacy of tezepelumab against uncontrolled severe non-type 2 asthma refractory to bronchial thermoplasty, benralizumab, dupilumab and mepolizumab.

Severe asthma affects approximately 5%-10% of patients with asthma. Herein, we describe a case of non-type 2 asthma that progressively worsened over the years. An 80-year-old woman was diagnosed with asthma 11 years back. She experienced repeated exacerbations requiring treatment with systemic corticosteroid despite therapy with medications including high-dose inhaled corticosteroids/long-acting beta-agonists plus long-acting muscarinic antagonist. The patient presented with non-eosinophilic asthma. Therefore, the patient was initially treated with bronchial thermoplasty, which was effective for 1 year only. Treatment with bronchial thermoplasty, benralizumab, dupilumab, and mepolizumab was ineffective. The fourth treatment, which included tezepelumab, was initiated. The patient's symptoms and quality of life improved significantly. This is the first case of a patient who did not respond to sequential bronchial thermoplasty, benralizumab, dupilumab, and mepolizumab but who presented with good clinical response to tezepelumab. Therefore, tezepelumab may be useful for patients with non-type 2 asthma.

Difficulties in Differentiating Osteosclerosis in Patients With Multifocal Micronodular Pneumocyte Hyperplasia and Cancer.

A 52-year-old woman with multifocal micronodular pneumocyte hyperplasia in bilateral lungs and multiple sclerotic bone lesions (SBLs) visited our hospital. Tuberous sclerosis complex (TSC) was suspected but did not meet the diagnostic criteria. Ten years later, at age 62, the patient developed ureteral cancer. Cisplatin-containing chemotherapy ameliorated ureteral tumor, concomitant with exacerbation of SBLs. It was difficult to distinguish whether the exacerbation of SBLs was due to exacerbation of TSC or bone metastasis of cancer. The administration of cisplatin made the diagnosis even more difficult because its molecular biological effects can exacerbate the complications of TSC.

Antiviral Effect of Candies Containing Persimmon-Derived Tannin against SARS-CoV-2 Delta Strain.

Inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the mouth has the potential to reduce the spread of coronavirus disease 2019 (COVID-19), due to the virus being readily transmitted by dispersed saliva. Persimmon-derived tannin has strong antioxidant and antimicrobial activity owing to its strong adhesion to proteins, and it also exhibited antiviral effects against non-variant and Alpha-variant SARS-CoV-2 in our previous study. In this study, we first demonstrated the antiviral effects of persimmon-derived tannin against the Delta variant of SARS-CoV-2 in vitro via the plaque assay method. We then examined the effects of candy containing persimmon-derived tannin. Remarkably, the saliva samples provided by healthy volunteers while they were eating tannin-containing candy showed that the virus titers of the SARS-CoV-2 Delta variant were suppressed. In addition, we found that the SARS-CoV-2 viral load in saliva from patients with COVID-19 collected immediately after they had eaten the tannin-containing candy was below the level of detection via PCR for SARS-CoV-2. These data suggest that adding persimmon-derived tannin to candy and holding such candy in the mouth is an effective method for inactivating SARS-CoV-2 in saliva, and the application of this approach shows potential for inhibiting the transmission of COVID-19.

Reduced larger von Willebrand factor multimers at dawn in OSA plasmas reflect severity of apnoeic episodes.

Plasma von Willebrand factor (VWF), produced in and released from vascular endothelial cells by various stimuli including hypoxia, induces platelet aggregation under high shear stress and plays dual pivotal roles in haemostasis and thrombosis within arterioles, which are regulated by the size of vWF multimers (VWFMs). Patients with obstructive sleep apnoea (OSA) have increased risk of thrombotic cardiovascular events, but the pathogenesis is unclear. We examined the relationship between VWF and OSA by measuring VWF antigen (VWF:Ag), VWFMs, VWF collagen binding activity (VWF:CB) and a disintegrin-like, metalloproteinase, and thrombospiondin type 1 motifs 13. A total of 58 OSA patients were enrolled. Blood samples were collected before sleep, after sleep, and after one night of nasal continuous positive airway pressure therapy. Based on VWFM analysis, OSA patients were classified into three groups; consistently normal VWFMs (group 1, n=29), increased high molecular weight (HMW)-VWFMs at 06:00 h (group 2, n=18), and decreased or absent HMW-VWFMs at 06:00 h (group 3, n=11). Patients in group 3 had significantly worse apnoea/hypopnoea index; VWF:CB followed a similar pattern. We observed a significant decrease in platelet count between 21:00 h and 06:00 h in OSA patients, potentially associated with reduced larger VWFMs together with decreased VWF:Ag levels. Severe OSA may contribute to an arterial pro-thrombotic state.

Randomized double-blind placebo-controlled multicenter trial for the effects of a polyherbal remedy, Yokukansan (YiganSan), in smokers with depressive tendencies.

BACKGROUND: Smoking and depression are closely related and form a vicious cycle. Yokukansan (YiganSan) is a polyherbal remedy that has the effect of calming neuropsychiatric symptoms such as anger and irritation. To examine the efficacy of Yokukansan during smoking cessation (SC) therapy in smokers with depressive tendencies but without major depressive disorders requiring pharmacotherapy. METHODS: A multicenter, double-blind, randomized, placebo-controlled, parallel-group comparison trial was conducted between June 2016 and May 2020 at 12 centers of the National Hospital Organization, Japan. This trial targeted smokers who first visited the SC outpatient clinics, did not receive any pharmacological treatment at the psychiatric or psychosomatic department, and scored 39 or more on the self-rating depression scale (SDS). Participants (n = 198) were randomly assigned to either the Yokukansan or placebo groups. The trial drug was initiated with the start of the SC treatment and continued for 12 weeks. The primary outcome was the high success rate of the SC treatment, and the secondary outcomes included changes in scores of the SDS and the Profile of Mood States (POMS) instrument. RESULTS: The success rate of the SC treatment was similar between the placebo (63%) and Yokukansan (67%) groups (P = .649). The SDS scores (placebo: mean difference [MD] = -3.5, 95% confidence interval [CI][-5.8, -1.2], d = 0.42; Yokukansan: MD = -4.6, 95%CI[-6.8, -2.3], d = 0.55), and the "tension-anxiety" POMS-subscale scores (placebo: MD = -1.6, 95%CI[-2.5, -0.7], d = 0.52; Yokukansan: MD = -1.6, 95%CI[-2.9, -0.3], d = 0.36) showed significant improvement in both groups after the SC treatment. However, "depression-dejection" improved in the Yokukansan group (MD = -1.9, 95%CI[-3.1, -0.7], d = 0.44) but not in the placebo group (MD = -0.1, 95%CI[-1.0, 0.7], d = 0.04). Significant improvement in "fatigue" was noted in the Yokukansan group (MD = -2.1, 95%CI[-3.4, -0.9], d = 0.47) but not in the placebo group (MD = -0.5, 95%CI[-1.8, 0.8], d = 0.11). The time × group interaction on the improvement in "depression-dejection" was significant (P = .019). CONCLUSIONS: Yokukansan does not increase the SC treatment's success rate but has additional positive effects on the psychological states due to the SC treatment in smokers with depressive tendencies but without apparent mental disorders. TRIAL REGISTRATION: ID: UMIN000027036. Retrospectively registered at UMIN on April 18, 2017.

Early decrease in α-fetoprotein, but not des-γ-carboxy prothrombin, predicts sorafenib efficacy in patients with advanced hepatocellular carcinoma.

OBJECTIVES: The aim of this study was to investigate the relationships between early changes in the tumor markers α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), and antitumor response in the early period following administration of sorafenib in patients with advanced hepatocellular carcinoma (HCC). METHODS: Forty-eight advanced HCC patients were evaluated. AFP and DCP were measured at baseline, and after 2 and 4 weeks, and the antitumor responses were evaluated according to the RECIST criteria 4 weeks after starting sorafenib therapy. The ratios of each tumor marker were compared by stratifying the patients into the partial response (PR) + stable disease (SD) group or the progressive disease (PD) group. RESULTS: Both 2 and 4 weeks after starting sorafenib therapy, the AFP ratio in the PR + SD group (n = 32) was significantly lower than in the PD group (n = 16; p = 0.002, p = 0.002). DCP was elevated in both the PR + SD group and the PD group 2 weeks and 4 weeks after starting sorafenib therapy. CONCLUSIONS: Evaluation of AFP ratios 2 and 4 weeks after starting sorafenib therapy may be useful for predicting antitumor response. On the other hand, early elevation of DCP does not necessarily suggest treatment failure by sorafenib, as DCP elevation can occur despite therapeutic efficacy.

A case of diffuse aspiration bronchiolitis due to oesophageal stenosis after radiation therapy.

A 66-year-old woman was hospitalized for recurrent pneumonia twice in 1 year. After treatment for pneumonia, chronic coughing, sputum and low-grade fever continued, so she was referred and admitted to our hospital for investigation. Chest computed tomography revealed a lung infiltrative shadow and diffuse centrilobular micronodules. Histological findings from transbronchial lung biopsy showed chronic inflammation and giant cells in the bronchiole. These findings were compatible with diffuse aspiration bronchiolitis (DAB), which is characterized by chronic inflammation of the bronchioles caused by recurrent aspiration of foreign bodies. Oesophagogastroduodenoscopy revealed stenosis of the oesophageal entrance, which was thought to be caused by radiation therapy for hypopharyngeal cancer 20 years before. Antibiotic treatment ameliorated the centrilobular nodule shadow. After discharge, there was no recurrence. This is the first case report of DAB resulting from oesophageal stenosis associated with hypopharyngeal cancer and will serve as an educational case.

Nocturnal hypoxic stress activates invasive ability of monocytes in patients with obstructive sleep apnoea syndrome.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea syndrome (OSAS) is known to be a risk factor for cardiovascular events. However, the precise mechanism has not been fully elucidated. OSAS-induced hypoxic stress may promote the production of inflammatory cytokines and chemokines by monocytes, which has a crucial role in the development of atherosclerosis. In addition, adhesion to the vascular endothelium and transendothelial migration of monocytes are considered to induce atherosclerosis. The aim of this study was to investigate the effects of hypoxic stress on the invasive ability of monocytes in OSAS. METHODS: Twenty-one male patients with OSAS and 17 healthy male control subjects, who were matched for age and BMI, were enrolled. Venous blood samples were collected before and after sleep, and also after CPAP titration, for the purpose of monocyte isolation. The invasive ability of monocytes was evaluated by counting the number of invading cells using a BD BioCoat Matrigel Invasion Chamber. RESULTS: The number of cells, which represents the invasive ability of monocytes, was significantly higher in patients with OSAS compared with control subjects, in the early morning (P < 0.001). In patients with OSAS, invasive ability in the early morning after sleep was significantly elevated as compared with that before sleep (P < 0.001), and was positively correlated with the oxygen desaturation index (P < 0.05). CPAP titration led to a decrease in the invasive ability (P < 0.001). CONCLUSIONS: These results indicate that OSAS-induced hypoxic stress activates the invasive ability of monocytes, and that the occurrence of this phenomenon during sleep may contribute to the development of atherosclerosis in OSAS.

Effect of serum leptin levels on hypercapnic ventilatory response in obstructive sleep apnea.

BACKGROUND: Leptin levels have been reported to be higher in patients with obstructive sleep apnea (OSA) than in control subjects with matching age and body mass index (BMI). Although animal studies have shown that leptin augments hypercapnic ventilatory response (HCVR), the effect of leptin on HCVR has not been clarified in OSA. OBJECTIVES: To investigate whether leptin could augment HCVR during wakefulness in patients with OSA. METHODS: Of 134 consecutive patients with OSA, 13 eucapnic and 16 hypercapnic patients with OSA, and 12 control subjects matched for sex, age, and BMI were selected. Fasting serum leptin levels were collected, and HCVR during wakefulness assessed by the slope between minute ventilation and end-tidal PCO(2). RESULTS: There was a significant positive relationship between serum leptin levels and HCVR in the group including control subjects and eucapnic patients with OSA (r = 0.42, p < 0.05). Subgroup analyses suggest that serum leptin levels and HCVR were significantly higher in eucapnic patients with OSA than in control subjects. On the other hand, hypercapnic patients had lower HCVR than eucapnic patients (p < 0.05), whereas serum leptin levels were similar between the two OSA subgroups. CONCLUSION: Leptin levels and HCVR are correlated as long as the eucapnic condition is maintained. We speculate that a stimulating effect of leptin on HCVR may be masked by the hypoventilation state.

The association between high-density lipoprotein cholesterol level and cholesteryl ester transfer protein TaqIB gene polymorphism is influenced by alcohol drinking in a population-based sample.

Cholesteryl ester transfer protein (CETP) is a key enzyme in high-density lipoprotein (HDL) cholesterol metabolism. We studied the association between CETP TaqIB polymorphism and the HDL cholesterol levels considering environmental factors in a population-based sample consisting of 1729 participants who did not use lipid-lowering agents (659 men and 1070 women). The CETP TaqIB genotypes were determined by PCR-RFLP analysis. The serum HDL cholesterol levels of female participants with the B2B2 genotype were significantly higher than those with other genotypes (p<0.001). Multiple regression analysis with covariates such as age, waist to hip (W/H) ratio, alcohol drinking, current smoking, non-HDL cholesterol, and logarithm of triglyceride revealed that the CETP TaqIB genotype was an independent determinant of HDL cholesterol levels in men (p=0.049) and women (p<0.001). Subgroup analysis revealed that an interaction was observed between the CETP TaqIB polymorphism and alcohol consumption in the regulation of HDL cholesterol levels in men (p=0.049) and women (p=0.022). No interactions were observed between the CETP TaqIB polymorphism and current smoking status, body mass index, or W/H ratio in the regulation of HDL cholesterol levels. The association between the CETP TaqIB polymorphism and HDL cholesterol levels was more evident in alcohol consumers than in non-drinkers.

Elevated circulating plasma adiponectin in underweight patients with COPD.

BACKGROUND: Adiponectin is an adipose tissue-derived specific protein that has antiinflammatory as well as anti-atherosclerotic effects. In the United States, many patients with COPD are obese and die of cardiovascular diseases. However, in Japan, patients with COPD are frequently cachexic and die of respiratory failure. This study was designed to investigate the role of adiponectin in these differences in characteristics of COPD. METHODS: We enrolled normal-weight and underweight male patients with COPD (n = 31; age, 71 +/- 1 years; body mass index [BMI], 20.1 +/- 0.6 kg/m(2)) and age-matched, healthy, male, control subjects (n = 12). The adiponectin levels were measured by enzyme-linked immunosorbent assay. Correlation of adiponectin levels with pulmonary function and serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin-6) were estimated. RESULTS: Adiponectin levels in patients with COPD were significantly higher than those in control subjects (p<0.01) and inversely correlated with BMI (r = - 0.55, p<0.01). Even in the normal-weight patients with COPD, adiponectin levels were significantly higher than those in control subjects (p<0.01). Adiponectin levels in patients with COPD significantly correlated with percentage of predicted residual volume (r = 0.40, p<0.05). In patients with TNF-alpha levels > 5 pg/mL, there was a significant correlation between plasma adiponectin and serum TNF-alpha levels (r = 0.68, p<0.05). CONCLUSIONS: Plasma adiponectin levels in patients with COPD were elevated and correlated with body weight loss, hyperinflation, and systemic inflammation. Increased adiponectin may reduce cardiovascular events in underweight patients with COPD.

Fish consumption and early atherosclerosis in middle-aged men.

To investigate the association between fish consumption and early atherosclerosis, we analyzed the relationship between fish consumption and average intima-media thickness (AveIMT) by carotid ultrasound in middle-aged Japanese men. Participants were 250 randomly selected, community-based Japanese men aged 40 to 49 years without a prior history of cardiovascular disease. AveIMT was calculated from the mean of 1-cm lengths of both the right and the left carotid arteries at 8 locations. A lifestyle survey was carried out using a self-administered questionnaire including the frequency of fish intake. There were 147 men in the fewer than 4 times per week fish consumption group and 103 men in the 4 or more times per week group. The mean AveIMT was significantly higher in the low fish consumption group than in the high fish consumption group (0.623+/-0.068 vs 0.605+/-0.065 mm, P=.03). After adjustment for age, waist circumference, pack-years of smoking, alcohol consumption, diabetes, and lipid-lowering medications, the significant difference in the AveIMT between the 2 groups remained. However, after further adjustment for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and C-reactive protein in the model, the significant difference disappeared. Fish consumption may be protective against early atherosclerosis in middle-aged men, probably through its beneficial effects on inflammation.

Alcohol consumption and coronary artery calcium in middle-aged Japanese men.

Epidemiologic studies have investigated the relation between alcohol intake and coronary calcification, with controversial results. Furthermore, the influence of heavy drinking has not been well elucidated. In the present study, a random sample of community-based Japanese men aged 40 to 49 years without a history of cardiovascular disease (n=245) were examined for coronary artery calcium (CAC) determined by electron-beam computed tomography and drinking status. There was a J-shaped association between alcohol intake and CAC. There was an increase of CAC in heavy drinkers (>or=46 g/day), and participants who were drinking>or=69 g/day showed a significant increase in CAC compared with never drinkers after adjusting for other cardiovascular risk factors.

Impact of paraoxonase polymorphism (Q192R) on endothelial function in intact coronary circulation.

Paraoxonase-1 (PON1) can protect endothelial function by preventing the oxidation of low-density lipoprotein (LDL) cholesterol and retarding the development of atherosclerosis. We examined whether PON1 polymorphism influences endothelium-dependent coronary vasomotor responses. Sixty-seven patients underwent diagnostic cardiac catheterization, but showed no significant coronary artery stenosis. In all patients, PON1 genotypes (Q/Q, Q/R and R/R) were determined, and provocative testing was performed by the intracoronary administration of graded doses of bradykinin (BK; 0.2, 0.6 and 2.0 mug/min) and acetylcholine (ACh; 3, 10 and 30 mug/min). Coronary blood flow (CBF) was evaluated by a Doppler guide wire. The patients were divided into 2 groups on the basis of ACh testing: one with coronary spastic angina (CSA) and one with non-CSA. The frequencies of the PON1 genotype in the CSA group did not differ significantly from those in the non-CSA group. In the non-CSA group, the patients were subdivided into 2 groups: a group with the Q/Q or Q/R genotypes and a group with the R/R genotype. The vasoconstrictive responses of the epicardial coronary artery to ACh were comparable between the Q/Q + Q/R and R/R groups. Also, the coronary vasodilations induced by BK in the R/R group were similar to those in the QR + QQ group. There were no significant differences in the CBF responses induced by BK or ACh between the Q/Q + Q/R and R/R groups. In conclusion, as estimated by BK and ACh testing, our findings suggest that PON1 genotypes may not play a critical role in the modulation of endothelial vasomotor function in the intact coronary circulation.

The association between morning hypertension and metabolic syndrome in hypertensive patients.

Morning hypertension (MHT) and metabolic syndrome (MS) have been reported as important risk factors for stroke and cardiovascular events. We investigated the prevalence of MHT and MS among hypertensive patients in our outpatient clinic from June to August, 2005. We studied 181 hypertensive patients (91 men and 90 women) in our outpatient clinic using home-use electronic sphygmomanometers. Seventy-nine of these 181 patients (43.6%) demonstrated MHT, defined as systolic blood pressure (SBP) > or = 135 mmHg in the morning. Only 48.1% of the patients demonstrated normal SBP both at the clinic and in the morning at home, whereas 72.9% of the patients demonstrated normal diastolic blood pressure (DBP) under the same conditions. Sixty-one patients (33.7%) had MS, and 34 patients had both MHT and MS. Twenty-seven of the 102 patients (26.5%) without MHT had MS. The frequency of MS was significantly higher among those with MHT than those without MHT (p = 0.019). Multiple logistic regression analysis including smoking, alcohol consumption, sex, and age as confounding factors showed significant association between MHT and MS (odds ratio: 1.99; 95% confidence interval: 1.04-3.80; p = 0.039). In conclusion, although 1 year has passed since the JSH 2004 guidelines, 43.6% of our patients still showed MHT, and there was a significantly higher prevalence of MS among those with MHT. Our results suggest the need for a more vigorous intervention for controlling BP.

Relationship between metabolic syndrome and Trp64arg polymorphism of the beta-adrenergic receptor gene in a general sample: the Shigaraki study.

It has been reported that the beta3-adrenergic receptor gene (ADRB3) is associated with abnormal metabolic risk factors. Therefore, we examined whether the Trp64Arg polymorphism of ADRB3 affects the occurrence of metabolic syndrome (MS). The participants were 2,395 subjects who underwent a medical examination in Shigaraki in Shiga, Japan. Among them, 1,416 subjects who gave informed consent for genetic analysis and were not receiving treatment for hypertension, diabetes, or hyperlipidemia were enrolled in this study. MS was diagnosed in 86 (16.0%) of 537 men, and 8 (0.9%) of 879 women. There was no significant relationship between ADRB3 polymorphism and the frequency of MS. Multiple logistic regression analysis including smoking, sex, and age as confounding factors showed no interaction between MS and ADRB3 polymorphism (odds ratio: 0.94; 95% confidence interval: 0.59-1.49; p=0.78). Subjects were also analyzed according to differences in the number of abnormal metabolic risk factors. However, there was no significant relationship between ADRB3 polymorphism and the number of such factors. In conclusion, in a general sample, the frequency of MS was 16.0% in men, and 0.9% in women. There was no relationship between ADRB3 polymorphism and MS.

Association between fish consumption and all-cause and cause-specific mortality in Japan: NIPPON DATA80, 1980-99.

PURPOSE: Although high consumption of fish may be one of the contributing factors for Japanese longevity, no epidemiological study using Japanese data has tested this hypothesis. SUBJECTS AND METHODS: The relationship between fish consumption and all-cause as well as cause-specific mortality was analyzed using the database of NIPPON DATA80. At baseline in 1980, history, physical, and blood biochemical measurement and a nutritional survey by the food-frequency method were performed in randomly selected community-based subjects aged 30 years and over in Japan. After exclusion of subjects with significant comorbidities at baseline, we followed 3945 men and 4934 women for 19 years. Men and women were analyzed comprehensively. Age- and sex-adjusted and multivariate adjusted relative risk for all-cause or cause-specific mortality was calculated using a Cox proportional hazards model with delayed entry. RESULTS: During 19 years of followup, there were 1745 deaths. Subjects were divided into 5 groups according to fish consumption frequency. The multivariate Cox analyses showed that relative risks for subjects who ate fish more than twice daily compared with those of subjects who ate 1 to 2 times weekly were 0.99 (95% confidence intervals: 0.77-1.27) for all-cause, 1.26 (0.70-2.29) for stroke, 0.92 (0.20-4.23) for cerebral hemorrhage, 1.09 (0.48-2.43) for cerebral infarction, and 0.91 (0.35-2.35) for coronary heart disease mortality. CONCLUSION: Our results did not provide evidence in support of the fish hypothesis, perhaps because the majority of the Japanese subjects in the study ate fish more than the threshold level shown to be beneficial in the previous studies.