小谷 和彦

BACKGROUND: Circulating lipoprotein(a) [Lp(a)] and arterial stiffness are markers associated with the atherosclerotic processes. With regard to cardiovascular outcomes, the relationship between Lp(a) and arterial stiffness has not been sufficiently summarized. The present review focuses on the existing association between Lp(a) and arterial stiffness parameters. SUMMARY: This review included human clinical studies that were published between 1980 and 2015. The metrics of arterial stiffness parameters, 'pulse wave velocity' (PWV) and 'cardio-ankle vascular index' (CAVI), were used for this search, which yielded only 4 cross-sectional studies on this topic. Of these 4 studies, 3 reports were based on the use of PWV, while 1 study was based on the use of CAVI. Three studies (including the study using CAVI) reported that high Lp(a) levels were positively associated with arterial stiffness. CONCLUSION: The present review indicates a positive association between Lp(a) and arterial stiffness, as assessed by PWV and CAVI. To definitively establish these findings, there is a need for further prospective outcome studies that simultaneously measure Lp(a) and the oxidative form of Lp(a) (as a pathological marker) as well as PWV and CAVI.

OBJECTIVES: To examine the effects of telephone-delivered lifestyle coaching on preventing the development of type 2 diabetes mellitus (T2DM) in participants with impaired fasting glucose (IFG). DESIGN: Cluster randomised trial. SETTING: 40 groups from 17 healthcare divisions in Japan: companies (31), communities (6) and mixed settings (3). PARTICIPANTS: Participants aged 20-65 years with fasting plasma glucose (FPG) of 5.6-6.9 mmol/L were invited from the 17 healthcare divisions. RANDOMISATION: The groups were then randomly assigned to an intervention or a control arm by independent statisticians according to a computer-generated list. INTERVENTION: The intervention arm received a 1-year telephone-delivered intervention provided by three private lifestyle support centres (at different frequencies: low-frequency (3 times), middle-frequency (6 times) and high-frequency (10 times) support calls). The intervention and control arms both received self-help devices such as a weight scale and pedometer. OUTCOMES: Participants were followed up using data from annual health check-ups and a questionnaire regarding lifestyle. The primary outcome was the development of T2DM defined as FPG ≥ 7.0 mmol/L, the diagnosis of diabetes, or use of an antidiabetic drug, confirmed by referring to medical cards. RESULTS: Of 14,473 screened individuals, participants were enrolled in either the intervention (n = 1240) arm or control (n = 1367) arm. Overall, the HR for the development of T2DM in the intervention arm during 5.5 years was 1.00 (95% CI 0.74 to 1.34). In the subanalysis, the HR was 0.59 (95% CI 0.42 to 0.83) in the subgroup that received phone calls the most frequently, compared with the control arm. A limitation of the study includes a lack of blinding. CONCLUSIONS: High-frequency telephone-delivered lifestyle support could effectively prevent T2DM in participants with IFG in a primary healthcare setting, although low-frequency and middle-frequency phone calls did not. TRIAL REGISTRATION NUMBER: This trial has been registered with the University Hospital Medical Information Network (UMIN000000662).

BACKGROUND: With the increasing trend of metabolic syndrome (MetS) and atherothrombotic stroke (which can manifest as stroke lesion multiplicity), studies on the association between MetS and the clinical aspects of atherothrombotic stroke are of great interest. The present study aimed to investigate the association between MetS and multiple atherothrombotic strokes in patients with intracranial atherothrombotic stroke. METHODS: A retrospective study based on medical charts was conducted among patients (n = 202: 137 men/65 women) who were symptomatically admitted to the hospital with the first-ever atherothrombotic stroke. For the occurrence of multiple lesions of stroke, odds ratio [OR: 95% confidence interval (CI)] of MetS or its respective components was calculated using logistic regression models. RESULTS: Fifty-one percent of the men and 38% of women with stroke presented multiple regions. MetS was a significant factor that was associated with an increased risk of multiple regions in women [OR 4.3 (95% CI 1.4-13.5)], but not in men. According to the components of MetS, dyslipidemia was a significant factor that was positively associated with multiple regions in both men [OR 2.0 (95% CI 1.1-3.7)] and women [OR 3.2 (95% CI 1.1-9.1)]. CONCLUSION: MetS may be pathophysiologically associated with intracranial atherothrombotic stroke multiplicity in women in particular. Future studies are warranted to confirm the findings.

OBJECTIVE: Raised plasma endothelin-1 (ET-1) levels may be a risk factor for vascular dysfunction and cardiovascular (CV) disease. This meta-analysis assessed the effect of statins on circulating ET-1 concentrations. METHODS AND RESULTS: The search included PUBMED, Cochrane Library, Web of Science, Scopus, and EMBASE up to September 30, 2014 to identify randomized controlled trials (RCTs) with ET-1 measurement during statin therapy. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Data from 15 RCTs showed that statin therapy significantly reduces plasma ET-1 concentrations (WMD: -0.30 pg/mL, 95%CI: -0.47, -0.13; p < 0.01). This effect was robust in sensitivity analysis, and not largely affected by the duration of statin therapy (<12 weeks - WMD: -0.51 pg/mL, 95%CI: -0.89, -0.14, p < 0.01; >12 week -WMD: -0.19 pg/mL, 95%CI: -0.36, -0.02; p < 0.05) or by dose of statins (<40 mg/day - WMD: -0.27 pg/mL, 95%CI: -0.49, -0.05; p = 0.01; >40 mg/day - WMD: -0.38 pg/mL, 95%CI: -0.68, -0.08; p = 0.01). Lipophilic (atorvastatin, simvastatin, fluvastatin, and cerivastatin - WMD: -0.34 pg/mL, 95%CI: -0.55, -0.13; p < 0.01), but not a hydrophilic statin (pravastatin - WMD: -0.18 pg/mL, 95%CI: -0.44 -0.08; p > 0.05) had a significant effect in promoting ET-1 reduction. CONCLUSIONS: Statin therapy significantly reduces circulating ET-1 concentrations, regardless of treatment duration or dose of statins. This effect of statins may be influenced by statin lipophilicity. There is a need to establish whether lowering ET-1 levels has a beneficial effect on CV events.

BACKGROUND: Coffee is one of the major dietary modulators of oxidative stress conditions. Whether coffee consumption is associated with oxidative stress markers, such as derivatives of reactive oxygen metabolites (d-ROMs), remains to be investigated in women, despite one recent report describing their significant association in men. METHODS: A total of 415 women (49 ± 9 years) attending a general clinic were evaluated regarding their self-reported coffee consumption habits and blood d-ROMs levels. RESULTS: Women who reported ≥ 3 cups/day of coffee consumption displayed a lower d-ROMs level than those who reported consuming 0-2 cups/day (336 ± 67 vs. 358 ± 80 Carr U; p < 0.05). In the multivariate-adjusted analysis, the association between coffee consumption and the d-ROMs level remained to be significant (p < 0.05). CONCLUSIONS: Daily coffee consumption (i.e., ≥ 3 cups) may be associated with a reduced oxidative stress status, as measured by the d-ROMs level, among women.

The expected role of medical technologists within diabetes mellitus education teams was surveyed. In addition to items regarding laboratory examinations and results themselves, good communication with patients and education team members was highly required. When medical technologists sufficiently follow this role, it would aid patients to cope with life with diabetes mellitus.

OBJECTIVE: Heterogeneous particles of intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) vary in atherogenesis. We investigated the association between the metabolic syndrome (MetS) score and lipoprotein subclasses. DESIGN AND METHODS: A total of 260 outpatients were scored into six groups, based on their number of MetS components. Lipoprotein subclass determined by polyacrylamide tube gel electrophoresis separates IDL particles into three midbands (MID-A to C) and LDL into larger-buoyant (LDL1 and LDL2) and small-dense LDL (LDL3 to LDL6). RESULTS: Mean concentrations of VLDL, MIDC, LDL2, and LDL3 to LDL6 positively correlated with increasing MetS score, but those of MIDA, LDL1 and HDL-C inversely correlated. LDL2 and LDL3 to LDL6 increased while MIDA and LDL1 decreased with increasing visceral fat, HOMA-IR, and triglycerides, with a reverse pattern for HDL-C. MIDB and MIDC were unchanged. By logistic regression, LDL1 and LDL3 to LDL6 significantly associates with the MetS score (odds ratio=0.957 and 1.077, respectively). The ratio of (LDL3 to LDL6)/LDL1 in the presence of HDL-C, showed the strongest association with MetS. CONCLUSIONS: Respective subpopulations of IDL and LDL particles can vary in their ability to identify MetS. Because of the most strongly associated with MetS, (LDL3 to LDL6)/LDL1 ratio is proposed as an excellent marker for evaluating lipid metabolic status in patient with MetS.

Background: Although cardiovascular health is a crucial problem for Mongolian people, little information about metabolic syndrome, which is well known to be associated with the development of cardiovascular disease, is available in Mongolia. The aim of this study was to observe the epidemiological features of metabolic syndrome in a general Mongolian population. Methods: This cross-sectional study was performed in 1911 general Mongolian subjects (717 men, 1194 women), who were &gt;= 40 years old and free of ischemic heart disease, by using a dataset from a nationwide population-based cohort study in Mongolia. The prevalence of metabolic syndrome, as defined by International Diabetes Federation criteria, was determined. Alcohol consumption, smoking habits, and physical activity were evaluated. Education, marital status, income, and occupation were also examined as factors of socioeconomic status (SES). Their association with metabolic syndrome was determined by logistic regression models. Results: The prevalence of metabolic syndrome was significantly higher in women (n=488, 40.6%) than in men (n=138, 19.4%). The prevalence of metabolic syndrome was high, especially in the Khangai region, in women. Moderate-to-high alcohol consumption was a significantly positively associated factor of metabolic syndrome in men [odds ratio (OR)=2.01; 95% confidence interval (CI) 1.15-3.51; adjusted odds ratio (AOR)=2.41; 95% CI 1.31-4.44] and widowed status was a significantly positively associated factor of metabolic syndrome in women (OR=1.61, 95% CI 1.18-2.18; AOR=1.49, 95% CI 1.07-2.08). Conclusions: Metabolic syndrome was prevalent in women compared with men among Mongolian adults. Preventive strategies aimed at men with a higher alcohol consumption and women with widowed status may help reduce metabolic syndrome, thereby improving cardiovascular health conditions in Mongolia.

We conducted ultrasound thyroid screening in cohort of 4,365 children aged between 3 to 18 years in three Japanese prefectures (Aomori, Yamanashi, and Nagasaki) using the same procedures as used in the Fukushima Health Survey. Forty-four children had nodules ≥ 5.1 mm in diameter or cysts ≥ 20.1 mm in diameter detected at the first screening, and 31 of these children underwent the second follow-up survey. We collected information from thyroid ultrasound examinations and final clinical diagnoses and re-categorized the thyroid findings after the second examination. Twenty children had nodules ≥ 5.1 mm in diameter or cysts ≥ 20.1 mm in diameter at the second examination; of these, one child was diagnosed with a thyroid papillary carcinoma and the remaining 19 children were diagnosed with possibly benign nodules such as adenomas, adenomatous nodules, and adenomatous goiters. A further 11 children were re-categorized as "no further examinations were required." Our results suggest that ultrasound thyroid findings in children may change with a relatively short-term passing period, and that thyroid cancer may exist at a very low but certain frequency in the general childhood population.

We assessed the relationship between the number of daily steps and changes in cardiovascular disease (CVD) risk factors in a year-long pedometer-based walking program for physically active older people. A total of 36 physically active older people (68.3 ± 5.8 years) completed this 59-week program. The CVD risk parameters were measured at baseline and at weeks 21 and 59. The mean number of steps increased by week 21 and was maintained at week 59 (approximately 10 000 steps, increase in 1500 steps from the baseline; P < .05). Following a significant reduction in body mass index at week 21, systolic blood pressure levels were significantly reduced, and high-density lipoprotein cholesterol levels were significantly increased at week 59 (P < .05). In summary, even active older people can achieve further protection against CVD risks by minor, but sustained, physical activity using pedometers for a period of more than 1 year.

The predictive value of serum non-high-density lipoprotein cholesterol (non-HDL-C) levels for the incidence of ischemic stroke and its subtypes has not yet been established. The present cohort study investigated their relationships in a Japanese population. The first incidence of ischemic stroke and its subtypes was documented as the primary outcome. A total of 249 ischemic stroke patients (men/women = 145/104) were identified during a follow-up period of 10.7 years among 10 760 community-dwelling subjects (men/women = 4212/6548). Cox proportional hazard model analyses revealed that when compared with the lowest tertile of non-HDL-C, multivariate-adjusted hazard ratios for the highest tertile were 0.55 (95% confidence interval = 0.32-0.95, P =.03) on ischemic stroke and 0.29 (95% confidence interval = 0.08-1.05, P =.06) on cardioembolic infarction in women. Men did not show such significant relationships. Low serum non-HDL-C levels may be a predictive marker associated with an increase in the incidence of ischemic stroke and possibly of cardioembolic infarction in Japanese women.

Hyperglycemia predicts cardiovascular disease (CVD)-related outcomes. The resting heart rates (HRs) and serum amyloid A (SAA), an inflammatory marker, are respectively factors associated with CVD-related outcomes; however, little is known regarding the associations between these two factors. This study aimed to investigate the correlation between the HRs and SAA levels under hyperglycemic conditions. This study included 298 subjects (males, 44%; mean age, 61.1 years) without a history of CVD and/or hypertensive levels. Clinical data, including general laboratory measurements, HRs and SAA, were measured. The analyses were performed after dividing all of the subjects into two groups based on the blood glucose level (< or ≥ 6.1 mmol/L). There was a higher SAA level in the hyperglycemic group (n = 143; median [interquartile range] 6.1 [4.1-10.6] μg/mL) than in the counterpart group (n = 155; 6.0 [3.5-8.5] μg/mL; p < 0.01). There was a trend toward increased HRs in the hyperglycemic group (mean [standard deviation] 65.3 [11.2] bpm) compared to the counterpart group (63.2 [9.4] bpm; p = 0.08). In the hyperglycemic group, there was a significant positive correlation between the HRs and SAA levels (multiple variables-adjusted analysis: β = 0.21, p = 0.02), while no correlation was found in the counterpart group (β = 0.06, p = 0.50). In summary, a positive correlation between the HRs and SAA levels can present under hyperglycemic conditions. These findings may provide relevant insights into the CVD-related pathologies associated with hyperglycemia. Further studies are warranted.

AIM: A noninvasive approach to assess atherosclerosis in young people is of great concern. The cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) reflect the arterial conditions, although the CAVI has not fully been studied in Russian populations. This study aimed to determine the CAVI and ABI in young Russians, to compare these findings with those in their Japanese peers and to investigate the lifestyle correlates and genetic associations with the CAVI and ABI in the Russians. METHODS: In addition to several atherosclerotic parameters and self-reported lifestyle factors, the CAVI and ABI levels were measured in 114 Russians (mean 21 years). Four gene polymorphisms, including cholesteryl ester transfer protein (CETP) Taq1B polymorphism, were typed in some of the subjects. RESULTS: The Russians exhibited significantly higher CAVI levels compared to their Japanese counterparts (5.87 vs. 5.36; p＜0.05), while the ABI levels were similar between the two populations. In the Russians, the ABI was significantly correlated with the mean blood pressure (r=-0.26) and heart rate (r=-0.43), while the CAVI did not show such correlations. No significant associations existed between lifestyle-related factors and the CAVI or ABI levels. A lower ABI level was found in carriers with the T-allele of CETP Taq1B in the Russians. CONCLUSIONS: The reference CAVI value can be specified for individual ethnic populations. Our findings suggest that Russians may develop atherosclerosis-related conditions at a younger age compared to Japanese subjects, although this must be verified in additional studies. The possible association between CETP polymorphisms and the ABI deserves further investigation.

The aim of this study is to determine which indicator of chronic kidney disease most closely correlates with 10-year Framingham coronary heart disease (CHD) risk among serum creatinine, serum cystatin C (S-CysC), urine albumin-creatinine ratio (UACR), estimated creatinine-based GFRs (eGFRcre), and estimated CysC-based GFRs (eGFRcys) in patients with obesity and diabetes. Serum creatinine, S-CysC, UACR, and cardio-ankle vascular index (CAVI) were examined in 468 outpatients with obesity and type 2 diabetes, free of severe renal dysfunction or previous history of cardiovascular disease, as a cross-sectional survey using baseline data from the multi-centered Japan Diabetes and Obesity Study. S-CysC and eGFRcys had significantly stronger correlations with the 10-year Framingham CHD risk than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.318; S-CysC, ρ = 0.497; UACR, ρ = 0.174; eGFRcre, ρ = -0.291; eGFRcys, ρ = -0.521; P < 0.01 by Fisher's z-test). S-CysC and eGFRcys had significantly stronger correlations with CAVI than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.198; S-CysC, ρ = 0.383; UACR, ρ = 0.183; eGFRcre, ρ = -0.302; eGFRcys, ρ = -0.444; P < 0.05 by Fisher's z-test). The receiver operating characteristic curves to distinguish the high-risk patients for CHD revealed significantly larger areas under the curve of S-CysC and eGFRcys than those of serum creatinine, UACR, and eGFRcre (serum creatinine, 0.64; S-CysC, 0.75; UACR, 0.56; eGFRcre, 0.63; eGFRcys, 0.76; P < 0.01). The data suggested that eGFRcys can be more predictive of the 10-year CHD risk than eGFRcre in Japanese patients with obesity and diabetes.

Hypertension (HTN) is a major risk factor for atherosclerosis. Flow-mediated vasodilation (FMD) is an ultrasonic method used to evaluate endothelial function, which is associated with HTN and related complications. We summarized clinical trials focusing on the effects of non-antihypertensive drugs on endothelial function, as evaluated by FMD, in patients with HTN. Hypercholesterolemic patients with HTN who used the cholesterol- lowering drugs HMG-CoA reductase inhibitors (statins) had improved FMD with a reduction in cholesterol levels and no significant change in blood pressure (BP). Non-diabetic patients with HTN who used the insulinsensitizing drug pioglitazone had improved FMD with a reduction in insulin resistance. Obese patients with HTN who used the anti-obesity drug orlistat had improved FMD with a reduction in BP and weight, and the improvement in FMD was correlated with weight reduction. Patients with HTN who used the selective cyclocxygenase-2 inhibitor celecoxib had improved FMD with no significant change in BP. Hypercholesterolemic patients with HTN who used aspirin added to a statin had improved FMD with a reduction in BP. Patients with HTN who used the advanced glycation endproduct crosslink breaker alagebrium had improved FMD with no significant change in BP. Postmenopausal women with HTN who used estrogen-replacement therapy had improved FMD. The possibility of improvement in FMD levels has, therefore, been suggested with several non-antihypertensive drugs. In addition to the direct effects of antihypertensive drugs on endothelial function, use of these non-antihypertensive drugs may give important insights into HTN management.

BACKGROUND: Cardiac lesions, such as coronary dilatation, aneurysms, narrowing, myocardial infarction, and valvular lesions, sometimes occur in Kawasaki disease, but most studies have only evaluated cardiac lesions in the later phase of the disease. This study was undertaken to clarify the related factors between cardiac lesions and laboratory data in the initial phase of Kawasaki disease. METHODS: We conducted a cross-sectional study using data for 26 691 patients from the 22nd nationwide survey of Kawasaki disease in Japan, the observation period of which was from January 2011 through December 2012. We excluded patients with recurrent Kawasaki disease and who were more than seven days from the start of symptoms at admission. We analyzed 23 155 cases (13 353 boys; mean age: 923 ± 734 days) with available laboratory data for white blood cell count, platelet count, serum albumin, and C-reactive protein (CRP). RESULTS: Cardiac lesions were detected in 984 cases (656 boys and 328 girls); lesions were classified as coronary dilatation (764 cases), coronary aneurysm (40), giant coronary aneurysm (6), coronary narrowing (3), and valvular lesions (204). The significant related factors of initial coronary dilatation were male sex (odds ratio [OR] 1.73), older age (OR per 100 days increase 1.03), higher platelet count (OR per 10 000 cells/µL increase 1.006), lower albumin (OR per 1 g/dL increase 0.66), and higher CRP (OR per 1 mg/dL increase 1.02). The factors related to coronary aneurysm were higher platelet count (OR 1.01) and lower albumin (OR 0.34). No factors were significantly related to giant coronary aneurysm. The related factors of valvular lesions were age (OR 0.98), and higher CRP (OR 1.05). CONCLUSIONS: Clinicians should consider male sex, older age, higher platelet count, lower albumin levels, and higher CRP levels when assessing risk of cardiac lesions in the initial phase of Kawasaki disease.

BACKGROUND: Clock genes regulate circadian rhythm and are involved in various physiological processes, including digestion. We therefore investigated the association between the CLOCK 3111T/C single nucleotide polymorphism and the Period3 (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in length) with morning gastric motility. METHODS: Lifestyle questionnaires and anthropometric measurements were performed with 173 female volunteers (mean age, 19.4 years). Gastric motility, evaluated by electrogastrography (EGG), blood pressure, and heart rate levels were measured at 8:30 a.m. after an overnight fast. For gastric motility, the spectral powers (% normal power) and dominant frequency (DF, peak of the power spectrum) of the EGG were evaluated. The CLOCK and PER3 polymorphisms were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism analysis. RESULTS: Subjects with the CLOCK C allele (T/C or C/C genotypes: n = 59) showed a significantly lower DF (mean, 2.56 cpm) than those with the T/T genotype (n = 114, 2.81 cpm, P < 0.05). Subjects with the longer PER3 allele (PER34/5 or PER35/5 genotypes: n = 65) also showed a significantly lower DF (2.55 cpm) than those with the shorter PER34/4 genotype (n = 108, 2.83 cpm, P < 0.05). Furthermore, subjects with both the T/C or C/C and PER34/5 or PER35/5 genotypes showed a significantly lower DF (2.43 cpm, P < 0.05) than subjects with other combinations of the alleles (T/T and PER34/4 genotype, T/C or C/C and PER34/4 genotypes, and T/T and PER34/5 or PER35/5 genotypes). CONCLUSIONS: These results suggest that minor polymorphisms of the circadian rhythm genes CLOCK and PER3 may be associated with poor morning gastric motility, and may have a combinatorial effect. The present findings may offer a new viewpoint on the role of circadian rhythm genes on the peripheral circadian systems, including the time-keeping function of the gut.

STUDY DESIGN: Cized, single-blind, controlled trial. OBJECTIVE: To investigate the efficacy of the Arthrokinematic approach (AKA)-Hakata (H) method for chronic low back pain. SUMMARY OF BACKGROUND DATA: The AKA-H method is used to manually treat abnormalities of intra-articular movement. METHODS: One hundred eighty-six patients with chronic nonspecific low back pain randomly received either the AKA-H method (AKA-H group) or the sham technique (S group) monthly for 6 months. Data were collected at baseline and once a month. Outcome measures were pain intensity (visual analogue scale [VAS]) and quality of life (the Roland-Morris Disability Questionnaire [RDQ] and Short Form SF-36 questionnaire [SF-36]). RESULTS: At baseline, the VAS, RDQ, and SF-36 scores showed similar levels between the groups. After 6 months, the AKA-H group had more improvement in the VAS (42.8% improvement) and RDQ score (31.1% improvement) than the sham group (VAS: 10.4% improvement; RDQ: 9.8% improvement; both, P < 0.001). The respective scores for the SF-36 subscales (physical functioning, role physical, bodily pain, social functioning, general health perception, role emotional, and mental health) were also significantly more improved in the AKA-H group than in the sham group (all, P < 0.001). The scores for the physical, psychological, and social aspects of the SF-36 subscales showed similar improvement in the AKA-H group. CONCLUSION: The AKA-H method can be effective in managing chronic low back pain. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000006250.

&lt;b&gt;Background: &lt;/b&gt;The number of patients and incidence rate of Kawasaki disease (KD) are increasing in Japan. We have therefore characterized the latest epidemiological information on KD.&lt;BR&gt;&lt;b&gt;Methods: &lt;/b&gt;The 22nd nationwide survey of KD, which targeted patients diagnosed with KD in 2011 and 2012, was conducted in 2013 and included a total of 1983 departments and hospitals. In order to report o

BACKGROUND AND OBJECTIVES: The portion size of food is a determinant of energy intake, linking with obese traits. A healthy plate for portion control has recently been made in a Japanese style. The aim of the current study was to assess the efficacy of a lifestyle intervention program using the Japanese-style healthy plate on weight reduction in overweight and obese diabetic Japanese subjects. METHODS: We randomized overweight and obese diabetic subjects (n = 19, 10 women) into an intervention group including educational classes on lifestyle modification incorporating the healthy plate (n = 10) or a waiting-list control group (n = 9). The intervention period was three months, and the educational classes using the healthy plate were conducted monthly in a group session for the intervention group. The body weight, blood glycemic and metabolic measures, and psychosocial variables were measured at the baseline and after the 3-month intervention in both groups. The impression of the intervention was interviewed using a structured questionnaire. RESULTS: There was one drop-out in the control group. No adverse events were reported in the groups. Subjects in the intervention group had a greater weight change from baseline to the end of the 3-month intervention period (-3.7 +/- 2.5 [SD] kg in the intervention group vs. -0.1 +/- 1.4 kg in the control group, P = 0.002). Most subjects recorded that the use of a healthy plate could be recommended to other people. CONCLUSIONS: The lifestyle intervention program using the Japanese-style healthy plate, which was developed for portion control, may effectively reduce body weight in overweight and obese diabetic subjects in Japan. Further studies are needed to establish the efficacy of this methodology on weight management.

AIM: We have recently demonstrated the quick ex vivo transfer of paraoxonase 1 (PON1) activity from high-density lipoprotein (HDL) to small, dense low-density lipoprotein (sdLDL). We set out to assess whether sdLDL contains active PON1 in vivo. METHODS: We conducted a nested case-control, proof of principle study with the Japanese healthy subjects with normal lipids (n = 23) and age and gender-paired dyslipidemic subjects (n = 17). Lipid panels, lactonase and arylesterase assays, and PON1 zymogram in the LDL and HDL subclasses were assessed. RESULTS: PON1 specific activity in the high-molecular weight lipoprotein fraction corresponding to LDL migration was found in 48% of normo and in 29% of dyslipidemic Japanese subjects. This band co-localizes with apoB100 and not Lp(a) and displays a lower molecular mass than the bulk of LDL. CONCLUSION: We provide evidence, for the first time, that native sdLDL contains up to 4% of the total PON1 activity in the serum of up to 48% of the Japanese subjects. Could the PON1-containing sdLDL represent a set of particles with a defense mechanism from oxidation and therefore its levels actually prove to be atheroprotective? If further studies confirm this contention, a zymogram of PON1 in LDL subclasses could be a functional assay that complements the current methods that only inform on the size and lipid concentration of these particles.

BACKGROUND: White blood cell (WBC) count and C-reactive protein (CRP) level are the most common markers of inflammation. There is a growing need for point-of-care testing (POCT) of WBC and CRP, and more advances in convenient devices are required. We developed an analyzer-free POCT system for measuring WBC and CRP using a low volume blood sample. METHODS: The POCT-WBC is based on the granulocyte esterase assay, while the POCT-CRP is based on the immunochromatographic assay. These kits were examined for precision as well as correlation with currently used popular commercial automated assays. The correlations were clinically analyzed in children with acute infection (n=62; mean age 4.2y). The correlations regarding the monitoring of values were further examined in several follow-up subjects. RESULTS: The POCT-WBC and POCT-CRP kits demonstrated good precision. POCT-WBC exhibited a significantly close correlation with those of the control assay (r=0.94, p<0.05). The results of POCT-CRP also exhibited a significantly close correlation with those of the control assay (r=0.94, p<0.05). In the follow-up study, the results of the respective kits were similar to those of the control assays. CONCLUSIONS: The POCT-WBC and POCT-CRP are promising tools for assessing infection in clinical practice.

Sleep apnea is a prevalent disorder associated with an increased risk of cardiovascular disease (CVD). While arterial stiffness is a surrogate marker for the development of CVD, the cardio-ankle vascular index (CAVI) is a recently developed metric for evaluating arterial stiffness. Clinical studies have shown that the CAVI is higher in patients with the sleep apnea syndrome. In particular, a reduction in the CAVI can clearly be seen during short-term therapy for these patients. Although clinical evidence on sleep apnea using the CAVI is currently limited, the CAVI is expected to be useful for identifying patients with an increased risk of CVD and for monitoring treatment effectiveness in sleep apnea practice.

CONTEXT: The use of the Palliative Prognostic Index (PPI) in relation to the clinical time course has not yet been established. OBJECTIVES: To investigate the association between the changes in the PPI over time and the survival of terminal cancer patients in a palliative care unit (PCU). METHODS: This retrospective cohort study analyzed data from 374 terminal cancer patients who were admitted to the PCU of a university hospital in Japan. Clinical data, such as age, gender, body mass index, vital signs, initial PPI, and subsequent PPI, were collected from the medical records. The PPI change per day (ΔPPI) was calculated using the initial PPI at admission and the one after five to seven days. The factors associated with death within three weeks were identified using Cox proportional hazards model analysis. RESULTS: After their admission to the PCU, 147 (39.3%) patients were deceased within three weeks. The multivariate-adjusted analysis showed that body temperature (hazard ratio [HR] 0.7; 95% CI 0.5, 1.0), initial PPI (HR 1.3; 95% CI 1.2, 1.4), and ΔPPI (HR 6.6; 95% CI 4.9, 9.0) were significantly and independently associated with death within three weeks. In the subanalysis, the ΔPPI was significantly associated with death within three weeks in the group with initial PPI ≤ 4 (HR 9.3; 95% CI 5.8, 15.0), 4 < initial PPI ≤ 6 (HR 14.4; 95% CI 5.7, 36.2), and initial PPI > 6 (HR 9.0; 95% CI 4.1, 20.0). CONCLUSION: Our data suggest that the ΔPPI may be useful for predicting the survival of terminally ill cancer patients.

INTRODUCTION: Oxidative stress, assessed using 8-hydroxy-2'-deoxyguanosine (8-OHdG), can be associated with arterial stiffness in patients with type 2 diabetes mellitus (T2DM) and/or hypertension (HT). We investigated the correlation between urinary 8-OHdG and pulse wave velocity (PWV) in hypertensive and non-hypertensive T2DM patients with fair glycaemic control to determine the clinical significance of HT as a comorbidity in the diabetic state. METHODS: Clinical data, including traditional cardiovascular risk factors, diabetic complications, prescribed agents, urinary 8-OHdG level and brachial-ankle PWV, was collected from T2DM patients with and without HT. RESULTS: There were 76 patients (45 men, 31 women; mean age 61 years; mean haemoglobin A1c level 6.5%) in the study cohort. T2DM patients with HT had significantly higher mean PWV than patients without HT (1,597 cm/s vs 1,442 cm/s; p < 0.05). Patients with HT showed no significant difference in 8-OHdG levels relative to those without HT (median 7.9 ng/mg creatinine vs 8.8 ng/mg creatinine; p > 0.05). Simple linear correlation and stepwise multiple linear regression analyses revealed that 8-OHdG levels correlated independently, significantly and positively with PWV among T2DM patients with HT (r = 0.33, p < 0.05; β= 0.23, p < 0.05). No significant correlation was observed between 8-OHdG levels and PWV among T2DM patients without HT. CONCLUSION: In the hypertensive state, oxidative stress can be responsible for the development of arterial stiffness, even in patients with fairly well controlled T2DM. Oxidative stress management may be necessary for the prevention of cardiovascular disease in this population.

INTRODUCTION: Gamma-glutamyltransferase (GGT), bilirubin (Bil) and small dense low-density lipoprotein (sdLDL) particles are each known to be risk markers for cardiometabolic diseases which are characterised by oxidative stress conditions. These markers are connected with the oxidative milieu; however, the association between GGT, Bil, and sdLDL has been hardly examined. This hospital-based study investigated the association between GGT and sdLDL, as well as the association between Bil and sdLDL, in asymptomatic subjects. MATERIALS AND METHODS: Cardiometabolic variables, GGT, Bil and the mean LDL particle size were measured in 100 asymptomatic subjects attending a clinic for screening dyslipidaemias (36 men and 64 women, mean age 64 years). Correlation analyses of the association between the mean LDL particle size and other variables, such as GGT and Bil, were performed. RESULTS: The mean (standard deviation) levels of GGT, Bil, and the mean LDL particle size were found to be 21.7 (8.3) IU/L, 14.0 (4.3) μmol/L, and 26.7 (0.6) nm, respectively. An univariate correlation test showed both a significant inverse correlation between the mean LDL particle size and GGT (r = - 0.33, P <0.01) and a significant positive correlation between the mean LDL particle size and Bil (r = 0.32, P <0.01). A multiple regression analysis revealed similarly significant results of their correlations, independent of the other cardiometabolic variables. CONCLUSION: These results suggest that the correlation of GGT and sdLDL, as well as that of Bil and sdLDL, may be cooperatively associated with cardiometabolic processes. Further research is warranted in order to confirm the observed association.

OBJECTIVES: Soy isoflavones have received great attention for their beneficial effects on health and disease, i.e., in patients with diabetes. Equol is a biologically active isoflavone-related metabolite with interindividual differences in its production. The current study investigated the relationship between an equol-producing state and the levels of adipocytokine markers in a prediabetic and diabetic population. SUBJECTS AND METHODS: A total of 79 subjects (34 males/45 females) in a prediabetic or diabetic state recruited from the general population were examined regarding their ability to produce equol using urine samples. Clinical data, such as age, smoking as well as anthropometric and biochemical variables, including body mass index (BMI), lipids, insulin, glucose, hemoglobin A1c, leptin and adiponectin, were recorded. RESULTS: Equol producers exhibited lower leptin and leptin/BMI than non-producers among females. Simple correlation tests and stepwise multiple regression analyses revealed a significant inverse correlation between the leptin/BMI and equol-production. This relationship was not found in males. CONCLUSIONS: Female equol producers can have favorable metabolic traits in relation to leptin metabolism in this population. Further studies are needed to confirm these results.

BACKGROUND: While alcohol consumption is associated with levels of high-density lipoprotein (HDL)-cholesterol (HDL-C), a cardiovascular risk marker, HDL size distribution has yet to be characterized in subjects with alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD). METHODS: The present study compared HDL subfractional characteristics between subjects with AFLD (36 men, age 61 +/- 14) and NAFLD (35 men, age 65 +/- 13), recruited during general health check-ups. Serum HDL subfractions were measured with the electrophoretic separation of lipoproteins employing the Lipoprint system. RESULTS: The subjects with AFLD had a significantly greater proportion of small-sized HDL part (6.6 +/- 5.7%) than those with NAFLD (3.8 +/- 4.9%, p = 0.029). CONCLUSIONS: More percentages of small-sized HDL part were observed in the subjects with AFLD than in those with NAFLD in Japanese general population. Whether the difference of HDL size is associated with cardiovascular manifestations should be studied further.

Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. It exhibits N-linked glycosylation in its second half. There are both glycosylated and nonglycosylated forms in plasma and the ratio of these two forms varies among individuals. This study was conducted to examine the influence of genetic polymorphism of SAA4 on its glycosylation status. In 55 healthy subjects, SAA4 polymorphism was analyzed by PCR combined direct sequencing and its glycosylation status was analyzed by immunoblotting. The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P < 0.05) higher than that in subjects with the wild type. The polymorphism had no influence on the plasma concentration of SAA4. These findings suggest that the changes in protein structures alter the efficiency of glycosylation in the SAA4 molecule. The functional implication of this should be of interest.

The purpose of the study is to examine whether, among patients who visited hospitals and underwent brain MRI or MRA scan tests, there was a relationship between the existence of clinically significant abnormal findings and the relevance of primary care physicians' referrals. A case-control study was carried out at six teaching hospitals in Japan. We identified cases with significant abnormal MRI/MRA findings from radiologists' reports based on certain explicit criteria and controls with outpatients who underwent MRI/MRA scans but did not have stroke. We also collected clinical data independently from medical records. The findings of 156 cases and 721 controls were collected for the analysis. A multivariate analysis adjusted by age group, sex, and the number of comorbidity factors showed that those who had visited the hospitals after referral were more likely to have significant abnormal findings in their MRI/MRA scan results (odds ratio [OR] = 1.6, 95% CI: 1.1 to 2.4). The present study suggests that referral from gatekeepers such as primary care physicians is effective in determining the appropriate use of brain MRI/MRA tests for hospital outpatients.

Reactive AA amyloidosis develops secondary to chronic inflammatory disorders. Serum amyloid A protein (SAA) and its degradation products, named AAs, are the main components of amyloid deposits, while apolipoprotein E (apoE) fragments are the minor components. To further understand the molecular mechanism of AA amyloidosis, we examined SAA/AAs moieties and apoE in the spleen and plasma throughout the amyloid-generating and amyloid-absorbing phases in a mouse model. SAA and four AA species (8.5kDa, 7.8kDa, 7.0kDa, and 6.2kDa) were detected in the spleen. SAA and the 8.5 kDa and 7.8 kDa AAs were prominent in the acute phase, whereas the 7.0kDa AA, the second smallest AA corresponding to the most common form in the human disease, was prominent in the chronic phase. These results indicate that the higher molecular weight species first constituted the fibril, followed by the 7.0kDa species, which were finally absorbed. ApoE was a component of the amyloid deposits at a degradation size from the beginning and was absorbed without being converted to another size. Degradation products, either from SAA or apoE, did not appear in the plasma during the course of the disease. A more detailed understanding of the moieties of amyloid-related peptides may help in the development of a method that can indicate the disease activity of AA amyloidosis.

BACKGROUND: A low ratio of eicosapentaenoic acid (EPA)/arachidonic acid (AA) is considered a risk factor for cardiovascular disease. Smoking is also a risk factor for cardiovascular disease even in an elderly population. This study investigated the relationship between EPA/AA ratio and smoking status among elderly patients with type 2 diabetes mellitus (T2DM). FINDINGS: A total of 188 elderly patients with T2DM (men/women, 114/74; mean age, 65.0 ± 7.5 years) were studied in terms of their smoking status, diabetic conditions, and blood data, including EPA and AA. Current smokers showed a lower EPA/AA ratio than non-smokers (current smokers: 0.29, n = 49; non-smokers: 0.39, n = 139, p < 0.01). This relationship remained significant after adjusting for multiple variables. CONCLUSIONS: Smoking may affect the EPA/AA ratio among elderly patients with T2DM, suggesting a possible mechanism of cardiovascular disease development and indicating the importance of smoking secession in such patients.

OBJECTIVES: Generalizable data on current satisfaction levels are required to establish a scientific basis for the political advancement of measures to improve satisfaction with hospital care among patients with diabetes. The present study made secondary use of existing official statistics in order to demonstrate the range of satisfaction levels with hospital care among diabetic outpatients and to closely examine related factors. METHODS: Data sets that consolidated the Patient Survey, the Survey of Medical Care Institutions, and the Patient Behavior Survey (all from 2008) were created. Shared medical institution survey reference numbers were used to consolidate the data from the Patient Survey and the Survey of Medical Care Institutions, and in addition, sex and date of birth were used to consolidate the Patient Behavior Survey data. The range of satisfaction levels with hospital care among diabetic outpatients was investigated along with any relationship with the following potentially related factors: visitation status (first or repeat examination); waiting time until examination; examination duration; care-seeking status (any use of other medical facilities, etc.); diabetic complications; other complications; coverage under the Public Assistance Act; smoking cessation outpatient services; hospitals that specialized in treating diabetes (metabolic medicine); medical care on Saturday, Sunday, and public holidays; and provision of health checkups. RESULTS: Overall, 62.3% of diabetic outpatients were either fairly or extremely satisfied with their hospital care, whereas 5.6% expressed dissatisfaction. Satisfaction levels with hospital care were found to be significantly related to visitation status, waiting time until examination, examination duration, care-seeking status, and Saturday medical care. Multivariate analysis with the factors demonstrated to be significantly related to satisfaction revealed significant relationships between high satisfaction levels and repeat examinations, short waiting times, no use of any other medical facilities, and long examinations. CONCLUSION: Consolidating official statistics from multiple sources indicated the range of satisfaction levels with hospital care among diabetic outpatients and facilitated the clarification of factors affecting satisfaction. Reducing waiting times and ensuring sufficient time spent on examinations are important for increasing satisfaction levels with hospital care among patients with diabetes. It is hoped that official statistics can be further applied to many future public health policy studies.

OBJECTIVES: To determine the effects of a lifestyle intervention on the development of type 2 diabetes mellitus (T2DM) among participants with impaired glucose tolerance (IGT), in particular in the subgroup with baseline glycated hemoglobin (HbA1c) levels ≥5.7%, in primary healthcare settings. DESIGN: Randomized controlled trial. SETTING: 32 healthcare centers in Japan. PARTICIPANTS: Participants with IGT, aged 30-60 years, were randomly assigned to either an intensive lifestyle intervention group (ILG) or a usual care group (UCG). INTERVENTIONS: During the initial 6 months, participants in the ILG received four group sessions on healthy lifestyles by public health providers. An individual session was further conducted biannually during the 3 years. Participants in the UCG received usual care such as one group session on healthy lifestyles. OUTCOME MEASURES: The primary endpoint was the development of T2DM based on an oral glucose tolerance test. RESULTS: The mean follow-up period was 2.3 years. The annual incidence of T2DM were 2.7 and 5.1/100 person-years of follow-up in the ILG (n=145) and UCG (n=149), respectively. The cumulative incidence of T2DM was significantly lower in the ILG than in the UCG among participants with HbA1c levels ≥5.7% (log-rank=3.52, p=0.06; Breslow=4.05, p=0.04; Tarone-Ware=3.79, p=0.05), while this was not found among participants with HbA1c levels <5.7%. CONCLUSIONS: Intensive lifestyle intervention in primary healthcare setting is effective in preventing the development of T2DM in IGT participants with HbA1c levels ≥5.7%, relative to those with HbA1c levels <5.7%. TRIAL REGISTRATION NUMBER: UMIN000003136.

PURPOSE: Critical illnesses are assessed according to the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation (APACHE) II. Circulating ischemia-modified albumin (IMA) is a biomarker generated under ischemic and oxidative conditions and may reflect disease severity in preoperative patients. This study investigated the correlations of IMA with SOFA and APACHE II scores in inpatients admitted for colorectal surgery. METHODS: We examined 27 patients with advanced colorectal cancers (mean age 69 years, men/women=15/12). Correlations between SOFA and APACHE II scores in addition to preoperative serum IMA and C-reactive protein (CRP) levels were analyzed. RESULTS: The mean IMA level was 0.5 AU, and the median CRP level was 0.6 mg/dL. Median scores for SOFA and APACHE II were 2 and 12 points, respectively. Significant positive correlations between IMA and SOFA (r=0.45, P<0.05) and IMA and APACHE II (r=0.45, P<0.05) were identified which remained significant in confounder-adjusted analyses. In contrast, weak correlations were observed between CRP and the SOFA and APACHE II scores. CONCLUSIONS: The positive correlations between IMA and both SOFA and APACHE II scores suggest that serum IMA measurements reflect the severity of systemic failure in patients admitted for colorectal surgery in the preoperative phase.

Ischemic heart disease (IHD) remains one of the most important disorders associated with disability and mortality worldwide, and is one of the major causes of cardiovascular diseases in Mongolia. The objective of the current study was to determine the prevalence of IHD and its related factors in a general population in Mongolia. We conducted a nationwide cross-sectional survey between March and September, 2009. General participants were recruited from urban to rural regions in a multistage random cluster sampling method. The diagnosis of IHD was based on the Rose questionnaire (World Health Organization) and electrocardiographic findings. A total of 369 (16.2 %) subjects with IHD were diagnosed among 2,280 participants. The prevalence of subjects with IHD was significantly increased by age: from 9.9 % in individuals age 40-44 years compared to 17.7 % in those over 60 years. Smoking habits (former and current) and non-frequent intake of fruits and vegetables were significantly positively associated with IHD in men, while heavy alcohol drinking habits and lower education period of time were significantly positively associated with IHD in women. IHD was found to be prevalent, especially among people aged over 40 years, in Mongolia. Statistical factors related to IHD were found to be significantly different based on sex. The current data may provide relevant information to prevent IHD in the Mongolian population.

OBJECTIVE: Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) consist of heterogeneous particles whose subpopulations may have different atherogenic characteristics. This study investigated the associations between these subpopulations and other lipids, lipoproteins and atherosclerosis-related markers. DESIGN AND METHODS: A total of 416 subjects (124 males and 292 females, mean age: 50.8 years) were enrolled in this study. Using polyacrylamide gel electrophoresis, serum lipoproteins were separated according to their specific electrophoretic mobility based on particle size. The IDL particles were separated into three midbands (MID-A to C), and the LDL particles were separated into seven subfractions (LDL1 to 7). RESULTS: MID-B, MID-C, LDL2 and LDL3 to 6 (as a small LDL fraction) were significantly and positively correlated with very LDL (VLDL), while MID-A and LDL1 were significantly and inversely correlated with VLDL. MID-A and LDL1 were significantly and positively correlated with high-density lipoprotein (HDL). The correlation patterns between MID-A or LDL1 and triglycerides, apolipoprotein A-I, glucose, the insulin resistance index, creatinine and the mean LDL particle size had similar trends to those between HDL and these parameters. CONCLUSIONS: The respective subpopulations of IDL and LDL particles can vary in their ability to predict cardiovascular disease risks. These variations may partially explain why quantitative assessments using LDL-cholesterol concentrations, as typically performed in conventional practice, are not perfect predictors of cardiovascular disease. Further studies are required to determine the clinical relevance of analyzing the IDL and LDL subpopulations.

Prostate cancer is a common disease in modern, developed societies and has a high incidence and mortality. High-density lipoprotein cholesterol (HDL-C) has recently received much attention as a possible risk marker of prostate cancer development and prognosis. In the present article, we summarized findings from epidemiologic studies of the association between HDL-C and prostate cancer. Low HDL-C level was found to be a risk and prognostic factor of prostate cancer in several epidemiologic studies, although the overall linkage between HDL and prostate cancer has not been definitively established. The mechanisms for this association remain uncertain; however, limited data from experimental studies imply a possible role of HDL in the pathophysiology of prostate cancer. More epidemiologic research, in combination with experimental studies, is needed in this field.

While oxidized lipoprotein(a) (oxLp(a)) has been indicated to be involved in atherogenesis more than native lipoprotein(a) (Lp(a)), there is still a need to elucidate the associations among oxLp(a), hypertension, and atherosclerosis. The cardio-ankle vascular index (CAVI) is a recently developed index used to assess arterial stiffness that is independent of blood pressure components. The present study investigated the correlation between oxLp(a) and the CAVI among hypertensive subjects. Clinical data, including general atherosclerotic risk factors, in addition to Lp(a), oxLp(a), and the CAVI, were collected from 72 non-smoking, asymptomatic, and untreated female subjects (mean age: 64.3 years). Correlations between the CAVI and Lp(a) or oxLp(a) were examined in a hypertensive group (n = 34) and a non-hypertensive control group (n = 38). There was a significant and positive correlation between the CAVI and subject age in the control group, while there was a significant and positive correlation between the CAVI and subject age, systolic blood pressure, and oxLp(a) (r = 0.38, p < 0.05) in the hypertensive group. A stepwise multiple linear regression analysis identified the oxLp(a) to be correlated independently, significantly, and positively with the CAVI (β = 0.30, p < 0.05) in the hypertensive group, while this correlation was not significant in the control group. These findings suggest that the oxidative modification of Lp(a) may be associated with arterial stiffness in hypertensive, but not non-hypertensive, female subjects.