Search

Background: Excessive alcohol intake has been shown to be associated with cardiovascular disease via metabolic pathways. However, the relationship between alcohol intake and obesity has not been fully elucidated. We aimed to examine the association of alcohol consumption with fat deposition and anthropometric measures., Methods: From 2006-2008, we conducted a cross-sectional study in a population-based sample of Japanese men aged 40 through 79 years. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography imaging. Based on a questionnaire, we classified participants into five groups according to weekly alcohol consumption, excluding former drinkers: non-drinkers (0 g/week), 0.1-160.9, 161-321.9, 322-482.9, and ≥483 g/week. Multivariable linear regression was used to estimate adjusted means of obesity indices for each group., Results: We analyzed 998 men (mean age and body mass index [BMI], 63.8 years and 23.6 kg/m 2 , respectively). Higher weekly alcohol consumption was strongly and significantly associated with higher abdominal VAT area, percentage of VAT, and VAT-to-SAT ratio (all P for trend <0.001), and also with waist circumferences and waist-to-hip ratio (P for trend = 0.042 and 0.007, respectively). These associations remained significant after further adjustment for BMI, whereas alcohol consumption had no significant association with abdominal SAT area., Conclusions: Higher alcohol consumption was associated with higher VAT area, VAT%, and VAT-to-SAT ratio, independent of confounders, including BMI, in general Japanese men. These results suggest that alcohol consumption may have a potential adverse effect on visceral fat deposition.

Background/objectives: Clinical trials of eicosapentaenoic acid (EPA) among high-risk groups in Japan in which consumption of mairne-omega-3 fatty acids (OM3) is much higher than other countries showed slower progression of coronary atherosclerosis. We aimed to determine the cross-sectional associations of coronary artery calcification (CAC) and calcium density with OM3, EPA, and docosahexaenoic acid (DHA), two principal OM3, in the general population in Japan., Subjects/methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis examined a population-based sample of 1074 men aged 40-79 in 2006-08 for computed tomography-measured CAC score (CCS), a well-established biomarker of coronary atherosclerosis, CAC density score (CDS), a potential marker of plaque stabilization, serum levels of OM3, and risk factors., Results: Prevalence of CCS > 0, ≥ 100, and ≥ 300 was 65.8%, 25.9%, and 12.9%, respectively; the mean (SD) OM3, EPA, and DHA were 10.1% (3.2), 3.2% (1.7), and 5.9% (1.6), respectively. Odds ratios (95% CI, p-value) of CCS 0, 100, and 300 in ordinal logistic regression associated with 1 SD increase of OM3, EPA, and DHA were 0.91 (0.81-1.03, p = 0.12), 0.99 (0.88-1.11, p = 0.87) and 0.84 (0.74-0.94, p = < 0.01), respectively. The inverse association of DHA with CCS remained significant in multivariate-adjusted model: odds ratio of 0.87 (0.77-0.99, p = 0.03). Blood levels of OM3, EPA, or DHA did not have any significant associations with CDS., Conclusions: DHA but not EPA had a significant inverse association with coronary atherosclerosis in the general population with high levels of OM3. Future trials are warranted comparing the effect of high-dose DHA and EPA on atherosclerosis and cardiovascular outcomes.

Aims: Calcification in the coronary and aortic arteries has been linked to cardiovascular morbidity and mortality. The pathophysiological influence of aortic artery calcification (AAC) differs from that of coronary artery calcification (CAC). We aimed to compare the relationships between CAC and AAC and cardiovascular disease (CVD) risk factors., Methods: We examined a random sample of 1035 Japanese men aged 40-79 years. CAC and AAC were measured by computed tomography and scored according to the Agatston method. Using a logistic regression, we calculated the odds ratio (OR) as being in the highest quintile (Q5) of the calcification score compared to the lower quintiles (Q1-Q4) per 1 standard deviation higher CVD risk factor. Models were simultaneously adjusted for age, body mass index (BMI), systolic blood pressure, smoking (pack-year), alcohol intake, hemoglobin A1c, uric acid, estimated glomerular filtration rate (eGFR), serum lipids, and C-reactive protein. Differences in ORs were investigated using a generalized estimating equation. We performed a multiple linear regression using log-transformed CAC and AAC values as dependent variables., Results: CAC and AAC were independently associated with age (OR, 95% CI: 2.30 [1.77-2.98] for CAC and 3.48 [2.57-4.73] for AAC), p for difference ＜0.001), systolic blood pressure (1.29 [1.08-1.53] and 1.28 [1.07-1.54], p for difference=0.270), and smoking (1.22, [1.04-1.43] and 1.34 [1.13-1.58]) p for difference=0.071). Alcohol correlated with AAC only (1.17 [0.97-1.41] for CAC and 1.42 [1.16-1.73] for AAC, p for difference= 0.020)., Conclusions: CAC and AAC were associated with similar CVD risk factors. The strength of association slightly differed between CAC and AAC.

Background The risk of coronary heart disease remains low in Japan, although distributions of several coronary risk factors have become comparable with those in the United States. We prospectively compared coronary atherosclerosis burden, measured with coronary artery calcium (CAC) progression, between men in the 2 countries. Methods In 2 population-based samples of 1712 US White, Black, Hispanic, Chinese men (baseline, 2000-2002) and 697 Japanese men in Japan (2006-2008) aged 45-74 years without clinical cardiovascular disease, we quantified CAC progression by serial computed tomography with medians of 3.4 and 5.2 years between scans, respectively. Results Among White, Black, Hispanic, Chinese, and Japanese men free of baseline CAC, CAC incidence was observed in 35.2%, 26.9%, 29.2%, 18.9%, and 29.2%, respectively. After adjustment for times between scans, demographics, behaviors, coronary risk factors, and their changes between scans, White men had significantly higher CAC incidence than Japanese men (relative risk, 1.68; 95% CI, 1.13-2.50). Among those with detectable baseline CAC, after similar adjustments, all the US race/ethnic groups had significantly greater annual changes in CAC score (mean [95% CI]: 39.4 [35.2-43.6] for White, 26.9 [21.4-32.4] for Black, 30.6 [24.7-36.5] for Hispanic, and 30.2 [22.6-37.8] for Chinese men) than Japanese men (15.9 [10.1-21.8]). Conclusions We found a higher CAC incidence among US White men and greater increases in existing CAC among all the US race/ethnic groups than among Japanese men in Japan. These differences persisted despite adjustment for differences in coronary risk factors.

Coronary artery calcium, quantified by computed tomography scanning, is one of the well-known measures of subclinical atherosclerosis. Coronary artery calcium is considered an end result from the long-term exposure to risk factors. CAC has been shown to improve risk stratification in asymptomatic individuals with intermediate-risk(e.g., an option to facilitate decision making)for primary prevention of atherosclerotic cardiovascular disease in the US/western countries. Coronary artery calcium also represents a surrogate of atherosclerosis burden. However, the lack of evidence regarding issues such as costs or radiation exposure related to measuring coronary artery calcium warrants further studies.

Objective: The mechanism by which higher blood pressure (BP) variability causes cardiovascular events remains unclear. Experimental results indicate that alterations in vessel wall tension related to BP variability may initiate atherosclerosis through oscillatory shear stress. We examined associations of home BP variability with subclinical atherosclerosis at four anatomically distinct vascular beds., Methods: In a cross-sectional population-based study of 1033 Japanese (mean age, 64.0 years; men, 88.7%) without known cardiovascular disease, we defined SBP and DBP variability as variability independent of the mean (VIM) across self-measured home BP values during seven consecutive days and quantified coronary and aortic artery calcification (CAC and AAC) by computed tomography, carotid intima-media thickness (CIMT) by ultrasonography, and ankle-brachial index (ABI)., Results: In multivariable adjusted models including mean SBP, higher VIM of SBP was associated with CIMT greater than1.0 mm [relative risk (95% confidence interval) fourth versus first quartile, 1.71 (1.15-2.54)], AAC score greater than 0 [1.08 (1.02-1.15)], and ABI less than 1.1 [1.49 (1.12-1.97)], and linear trends were also statistically significant. However, there was no significant association between VIM of SBP and CAC score greater than 0. Meanwhile, higher VIM of DBP was associated only with AAC score greater than 0. The associations were similar when modeling subclinical atherosclerosis severity as continuous outcomes and were consistent across subgroups based on demographics, behavioural, and cardiovascular risk factors., Conclusion: Higher variability in home BP, particularly in home SBP, was associated with greater carotid, aortic, and peripheral but not coronary atherosclerosis burdens independent of the mean home BP.

Aim: We aimed to investigate the association between reduced lung function and cerebral small vessel diseases via cranial magnetic resonance imaging (MRI) in the cross-sectional study of the general Japanese population., Methods: We recruited participants aged ≥40 years from the general population of a single city in Japan. We clarified the comorbidities and treatments, smoking habits, second-hand smoke exposure, current alcohol consumption, education level, exercise habits, and occupation. The pulmonary function test was performed to assess the forced expiratory volume in 1 second (FEV 1 ) % predicted and forced vital capacity (FVC) % predicted values. Cranial MRI was performed to evaluate the white matter lesions (WMLs) and lacunar infarcts. We examined the association of the WMLs and lacunar infarcts with a 1-standard deviation (SD) lower in the FEV 1 % predicted and FVC % predicted, on the basis of the smoking status., Results: A total of 473 men were examined. The association of WMLs and lacunar infarcts with the spirometry-based indices were significant only in never smokers. The association between lung function impairment and cerebral small vessel disease did not change after further adjusting for second-hand smoke exposure., Conclusion: In a community-based sample of Japanese men, we found an association between reduced lung function and WMLs and lacunar infarcts in never smokers.

Background: Pericardial fat volume (PFV), defined as the volume of ectopic fat in and around the heart, is associated with the atherosclerotic process in coronary arteries. The magnitude of change in PFV over time and the factors affecting this change in a general population, however, have not been investigated. Methods and Results: Cardiac computed tomography (CT) was carried out at baseline and at follow-up in 623 Japanese men aged 40-79 years without a history of cardiovascular disease who were selected randomly in Kusatsu (Shiga, Japan). PFV was measured on cardiac CT in a qualified laboratory. Age, heart rate, triglycerides, and obesity measurements (weight, body mass index, and waist circumference) were significantly and positively associated with PFV at baseline. Over an average interval of 4.7 years, median PFV increased significantly from 64.1 cm 3 (IQR, 47.2-90.0 cm 3 ) to 73.6 cm 3 (IQR, 53.3-98.1 cm 3 ; P<0.001). Current smoking and heart rate were significantly and independently associated with changes in PFV (B=3.336, P<0.001 and B=6.409, P=0.003, respectively)., Conclusions: PFV increased significantly over time in a population-based observational study of Japanese men. PFV change was significantly and independently associated with smoking status and heart rate, suggesting that quitting smoking might help reduce PFV, which could be expected to decrease the risk of coronary artery disease.

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., (Copyright © 2018. Published by Elsevier B.V.)

Background: Carotid plaque has emerged as a marker of coronary heart disease (CHD) risk. Comparison of carotid plaque burden between different race/ethnic groups may provide a relative estimate of their future CHD risk., Methods: We conducted a population-based study among apparently healthy middle-aged men aged 40-49 years (ERA JUMP study (n = 924)) and recruited 310 Whites in Pittsburgh, US, 313 Japanese in Otsu, Japan, and 301 Koreans in Ansan, South Korea. The number of carotid plaque and CHD risk factors was assessed using a standardized protocol across all centers. The burden of carotid plaque was compared between race/ethnic groups after adjustment for age and BMI, and after multivariable adjustment for other CHD risk factors using marginalized zero-inflated Poisson regression models. Cross-sectional associations of risk factors with plaque were examined., Results: Whites (22.8%) had more than four-fold higher prevalence (p < 0.01) of carotid plaque than Japanese men (4.8%) while the prevalence among Koreans was 10.6%. These differences remained significant after adjustment for age, BMI as well as other risk factors - incidence density ratio (95% confidence interval) for plaque was 0.13 (0.07, 0.24) for Japanese and 0.32 (0.18, 0.58) for Koreans as compared to Whites. Age, hypertension and diabetes were the only risk factors significantly associated with presence of carotid plaque in the overall population., Conclusion: Whites have significantly higher carotid plaque burden than men in Japan and Korea. Lower carotid plaque burden among Japanese and Koreans is independent of traditional CVD risk factors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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 ± 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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: There are few data regarding associations between sleep duration and subclinical atherosclerosis in Japan. The aim of this study was to evaluate associations of self-reported sleep duration with calcification in the coronary arteries (CAC) and carotid intima media thickness (IMT) in Japanese men., Methods: This was a cross-sectional survey of 1093 randomly selected men from Kusatsu City, Japan. Average sleep duration on weekdays was estimated through questionnaire; CAC by computed tomography; and carotid IMT by ultrasonography., Results: The prevalence of CAC was 50.0% for participants with sleep duration ＜5.5 h, 43.9% with 5.5-6.4 h, 50.0% with 6.5-7.4 h, 49.3% with 7.5-8.4 h, and 62.5% with ≥8.5 h. In univariate analysis, participants with sleep duration ≥8.5 h had significantly higher prevalence of CAC than those with 6.5-7.4 h (p=0.043). After adjustment for age and other risk factors, however, the association was not significant (p=0.776). The average IMT was 0.85 mm for participants with sleep duration ＜5.5 h, 0.83 mm with 5.5-6.4 h, 0.85 mm with 6.5-7.4 h, 0.88 mm with 7.5-8.4 h, and 0.90 mm with ≥8.5 h. None of the differences in IMT observed in crude or multivariable-adjusted analyses was significant (all p＞0.1)., Conclusion: Self-reported sleep duration was not associated with increased CAC or carotid IMT in a general population of Japanese men.

Background and Aims: Several studies have reported a significant inverse association of light to moderate alcohol consumption with coronary heart disease (CHD). However, studies assessing the relationship between alcohol consumption and atherosclerosis have reported inconsistent results. The current study was conducted to determine the relationship between alcohol consumption and aortic calcification., Methods: We addressed the research question using data from the population-based ERA-JUMP Study, comprising of 1006 healthy men aged 40-49 years, without clinical cardiovascular diseases, from four race/ethnicities: 301 Whites, 103 African American, 292 Japanese American, and 310 Japanese in Japan. Aortic calcification was assessed by electron-beam computed tomography and quantified using the Agatston method. Alcohol consumption was categorized into four groups: 0 (non-drinkers), ≤1 (light drinkers), >1 to ≤3 (moderate drinkers) and >3 drinks per day (heavy drinkers) (1 drink = 12.5 g of ethanol). Tobit conditional regression and ordinal logistic regression were used to investigate the association of alcohol consumption with aortic calcification after adjusting for cardiovascular risk factors and potential confounders., Results: The study participants consisted of 25.6% nondrinkers, 35.3% light drinkers, 23.5% moderate drinkers, and 15.6% heavy drinkers. Heavy drinkers [Tobit ratio (95% CI) = 2.34 (1.10, 4.97); odds ratio (95% CI) = 1.67 (1.11, 2.52)] had significantly higher expected aortic calcification score compared to nondrinkers, after adjusting for socio-demographic and confounding variables. There was no significant interaction between alcohol consumption and race/ethnicity on aortic calcification., Conclusions: Our findings suggest that heavy alcohol consumption may be an independent risk factor for atherosclerosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: A few studies have examined the longitudinal association of blood pressure (BP) with arterial stiffness progression, and the results were inconsistent. The objective of this study was to investigate the roles of initial BP and its longitudinal change on the progression of arterial stiffness measured using brachial-ankle pulse wave velocity (baPWV)., Method: Study participants (n = 656) were from population-based samples of healthy men aged 40-49 years at baseline (213 White Americans, 47 African-Americans, 152 Japanese Americans and 244 Japanese in Japan). BP measures, baPWV and other factors were examined at baseline and 4-7 years later. General linear regression was applied for statistical analyses., Result: Annual change in SBP (standardized coefficient: 0.33, P < 0.001), but not its baseline level (standardized coefficient: 0.03, P = 0.495), had a positive significant association with the progression of baPWV after adjusting for a wide range of standard cardiovascular risk factors. Similarly, annual changes in DBP (standardized coefficient: 0.35, P < 0.001), pulse pressure (standardized coefficient: 0.15, P = 0.001) and mean arterial pressure (standardized coefficient: 0.37, P < 0.001) were positively associated with the progression of baPWV. None of the baseline measures were related to the progression of baPWV., Conclusion: Our findings imply that, regardless of initial BP, effective monitoring and controlling of BP is important to slow down arterial wall stiffening and hence reduce cardiovascular risk.

Arterial stiffness is established as an independent predictor of cardiovascular morbidity and mortality. The objective was to prospectively evaluate association of aortic calcification burden with progression of arterial stiffness in population-based samples of healthy middle-aged men from ERA JUMP cohort (Electron-Beam Computed Tomography and Risk Factor Assessment in Japanese and US Men in the Post-World War II Birth Cohort). Men (n=635) aged 40 to 49 years (207 white American, 45 black American, 142 Japanese American, and 241 Japanese in Japan) were examined at baseline and 4 to 7 years later. Aortic calcification was evaluated from level of aortic arch to iliac bifurcation. Arterial stiffness progression was measured as annual change in brachial-ankle pulse wave velocity. Multivariable-adjusted general linear models were applied to investigate associations of longitudinal change in aortic calcification with arterial stiffness progression in participants overall, as well as in subgroups without or with prevalent aortic calcification at baseline. Annual change in aortic calcification was positively and significantly associated with arterial stiffness progression. In participants with annual changes in aortic calcium score of ≤0, 1 to 10, 11 to 100, and >100, the adjusted means (SD) for the annual change in brachial-ankle pulse wave velocity were 3.8 (2.2), 7.2 (2.2), 12.2 (1.8), and 15.6 (2.6) cm/s, respectively (P for trend <0.01) adjusted for baseline aortic calcification, arterial stiffness, and standard cardiovascular risk factors. Arterial stiffness was associated with the incidence of aortic calcification over the follow-up period among participants without aortic calcification (n=297) and with an increase in aortic calcification among participants with prevalent aortic calcification at baseline (n=388). Our findings suggest aortic calcification may be causally linked to arterial stiffness., Competing Interests: 6. Conflict of Interests: None, (© 2016 American Heart Association, Inc.)

Background and Aims: While alcohol consumption is known to increase plasma high-density lipoprotein (HDL) cholesterol levels, its relationship with low-density lipoprotein (LDL) cholesterol levels is unclear. Aldehyde dehydrogenase 2 (ALDH2) is a rate-controlling enzyme in alcohol metabolism, but a large number of Japanese people have the inactive allele. Here, we conducted a Mendelian randomization analysis using the ALDH2 genotype to clarify a causal role of alcohol on circulating cholesterol levels and lipoprotein particle numbers., Methods: This study was conducted in three independent general Japanese populations (men, n = 2289; women, n = 1940; mean age 63.3 ± 11.2 years). Alcohol consumption was assessed using a questionnaire. Lipoprotein particle numbers were determined by nuclear magnetic resonance spectroscopy., Results: Alcohol consumption increased linearly in proportion to the number of subjects carrying the enzymatically active *1 allele in men (p < 0.001). The *1 allele was also positively associated with HDL cholesterol level (adjusted mean ± standard error, *1*1: 60 ± 0.5, *1*2: 56 ± 0.6, *2*2: 55 ± 1.3 mg/dl, p < 0.001) and inversely associated with LDL cholesterol level (116 ± 0.9, 124 ± 1.1, 130 ± 2.6 mg/dl, p < 0.001). The *1 allele was also positively associated with HDL particle numbers (per-allele: 2.60 ± 0.32 μmol/l, p < 0.001) and inversely associated with LDL particle numbers (-67.8 ± 19.6 nmol/l, p = 0.001). Additional Mendelian randomization analysis failed to clarify the involvement of cholesteryl ester transfer protein in alcohol-related changes in lipoprotein cholesterol levels. No significant association was observed in women, presumably due to their small amount of alcohol intake., Conclusions: Alcohol consumption has a causal role in not only increasing HDL cholesterol levels but also decreasing LDL cholesterol levels and particle numbers., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Studies from Western countries suggest that smokers tend to display greater abdominal obesity than non-smokers, despite showing lower weight. Whether this holds true in a leaner population requires clarification. Using indices of abdominal obesity including visceral adipose tissue, we examined whether lifetime cigarette smoking is associated with unfavorable fat distribution among Japanese men. From 2006 to 2008, we conducted a cross-sectional investigation of a community-based sample of Japanese men at 40-64 years old, free of cardiovascular diseases and cancer. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography. We divided participants into four groups: never-smokers; and tertiles of pack-years of smoking among ever-smokers. Using multivariable linear regression, we calculated adjusted means of obesity indices (VAT, SAT, VAT-SAT ratio [VSR], and waist-hip ratio [WHR]) for each group, and mean differences between consecutive groups. We analyzed 513 men (median age, 58.2 years; current smokers, 40.1%). Two-thirds showed body mass index (BMI) < 25 kg/m(2) (median, 23.5 kg/m(2)). Overall, greater lifetime smoking group was associated with greater WHR and VSR. On average, one higher smoking group was associated with 0.005 higher WHR (95% CI, 0.001-0.008; P = 0.005) and 0.041 greater VSR (95% CI, 0.009-0.073; P = 0.012) after adjustment for potential confounders, including BMI. In this sample of relatively lean Japanese men, greater lifetime smoking was associated with a metabolically more adverse fat distribution. Although smoking is commonly associated with lower BMI, minimizing the amount of lifetime smoking should be advocated.

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme predominantly bound to low-density lipoprotein (LDL). Lp-PLA2 is recognized as playing a key role in inflammatory processes and the development of atherosclerosis. This study aimed to investigate whether Lp-PLA2 is related to subclinical atherosclerosis, independently from traditional risk factors, in a general Japanese population by analyses of both the observational study and Mendelian randomization using V279F polymorphism., Methods and Results: We cross-sectionally examined community-based sample of 929 Japanese men aged 40-79 years, without statin treatment, who were randomly selected from the resident registration. Multiple regression analyses of Lp-PLA2 activity and concentration were undertaken separately for men aged 40-49 years and 50-79 years, to clarify interactions of age and Lp-PLA2. Lp-PLA2 activity for men aged 50-79 years was significantly and positively related to intima-media thickness (IMT) (P = 0.013) and plaque index (P = 0.008) independent of traditional risk factors including small LDL particles, but not to coronary artery calcification (CAC) score. Associations with Lp-PLA2 concentration were qualitatively similar to those of activity. Corresponding relationships were not observed in men aged 40-49 years. Mendelian randomization analyses based on V279F genotype did not show any significant associations with subclinical atherosclerosis, although the homozygote and heterozygote of V279F showed low Lp-PLA2 activity and concentration., Conclusions: Lp-PLA2 activity in Japanese men aged 50-79 years was associated significantly and positively with IMT and plaque in the carotid artery but Mendelian randomization did not support that Lp-PLA2 is a causative factor for subclinical atherosclerosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than usual lipid parameters; however, the relationship between LAB and carotid intima-media thickness (IMT) was not clear even in Asian populations., Methods: A total of 992 community-dwelling Japanese men, aged 40 to 79 years, were enrolled in the present study. Serum LAB levels were measured by enzyme-linked immunosorbent assays (ELISAs) with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody., Results: Serum LAB levels (median [interquartile range], μg cs/L) were 5341 μg cs/L (4093-7125). The mean average IMT of the common carotid artery was highest in the fourth LAB quartile (842 μm) compared with the first quartile (797 μm) after adjustment for age, high-density lipoprotein cholesterol, triglyceride, body mass index, hypertension, diabetes, high sensitivity C-reactive protein, smoking, and alcohol drinking. However, this statistically significant difference was lost after further adjustment for total cholesterol (TC). After stratification using the combination of median LAB and hypercholesterolemia (serum TC ≥ 6.21 mmol/L and/or lipid-lowering medication), the adjusted mean average IMT (standard error) in the high LAB/hypercholesterolemia group was 886 μm (12.7), 856 μm (16.7) in the low LAB/hypercholesterolemia group, and 833 μm (8.4) in the low LAB/normal cholesterol group (P = .004). After further adjustment for TC, mean average IMT in the high LAB group was significantly higher than that measured in the low LAB group in hypercholesterolemic participants not taking lipid-lowering medication., Conclusion: Serum LAB was associated with an increased carotid IMT in Japanese men, especially those with hypercholesterolemia., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Aims/hypothesis: At the same level of BMI, white people have less visceral adipose tissue (VAT) and are less susceptible to developing type 2 diabetes than Japanese people. No previous population-based studies have compared insulin resistance and insulin secretion between these two races in a standardised manner that accounts for VAT. We compared HOMA-IR, HOMA of beta cell function (HOMA-β%) and disposition index (DI) in US white men and Japanese men in Japan., Methods: We conducted a population-based, cross-sectional study, comprising 298 white men and 294 Japanese men aged 40-49 years without diabetes. Insulin, glucose, VAT and other measurements were performed at the University of Pittsburgh. We used ANCOVA to compare geometric means of HOMA-IR, HOMA-β% and DI, adjusting for VAT and other covariates., Results: White men had higher HOMA-IR, HOMA-β% and DI than Japanese men, and the difference remained significant (p < 0.01) after adjusting for VAT (geometric mean [95% CI]): 3.1 (2.9, 3.2) vs 2.5 (2.4, 2.6), 130.8 (124.6, 137.3) vs 86.7 (82.5, 91.0), and 42.4 (41.0, 44.0) vs 34.8 (33.6, 36.0), respectively. Moreover, HOMA-IR, HOMA-β% and DI were significantly higher in white men even after further adjustment for BMI, impaired fasting glucose and other risk factors., Conclusions/interpretation: The higher VAT-adjusted DI in white men than Japanese men may partly explain lower susceptibility of white people than Japanese people to developing type 2 diabetes. The results, however, should be interpreted with caution because the assessment of insulin indices was made using fasting samples and adjustment was not made for baseline glucose tolerance. Further studies using formal methods to evaluate insulin indices are warranted.

Aim: Pulse wave velocity (PWV) is a simple and valid clinical method for assessing arterial stiffness. Coronary artery calcification (CAC) is an intermediate stage in the process leading to overt cardiovascular disease (CVD) and an established determinant of coronary artery disease. This study aimed to examine the association between PWV and CAC in a population-based sample of Japanese men., Methods: This is a cross-sectional study of 986 randomly selected men aged 40-79 years from Shiga, Japan. CVD-free participants were examined from 2006 to 2008. Brachial-ankle PWV (baPWV) was measured using an automatic waveform analyzer. CAC was assessed using computed tomography. Agatston scores ≥ 10 were defined as the presence of CAC., Results: Prevalence of CAC progressively increased with rising levels of baPWV: 20.6%, 41.7%, 56.3%, and 66.7% across baPWV quartiles ＜ 1378, 1378-1563, 1564-1849, and ＞ 1849 cm/s (P ＜ 0.001 for trend). Associations remained significant after adjusting for age and other factors, including body mass index, systolic blood pressure, pulse rate, total and high-density lipoprotein cholesterol, hemoglobin A1c, drinking, smoking and exercise status, and the use of medication to treat hypertension, dyslipidemia and diabetes (P=0.042 for trend). The optimal cutoff level of baPWV to detect CAC was 1612 cm/s using receiver operating characteristic curve analysis., Conclusions: Arterial stiffness as defined by an elevated baPWV is associated with an increased prevalence of CAC in a general population-based setting among Japanese men.

Background: Brachial-ankle pulse wave velocity (baPWV) is a simple and reproducible measure of arterial stiffness and is extensively used to assess cardiovascular disease (CVD) risk in eastern Asia. We examined whether baPWV is associated with coronary atherosclerosis in an international study of healthy middle-aged men., Methods: A population-based sample of 1131 men aged 40-49 years was recruited - 257 Whites and 75 Blacks in Pittsburgh, US, 228 Japanese-Americans in Honolulu, US, 292 Japanese in Otsu, Japan, and 279 Koreans in Ansan, Korea. baPWV was measured with an automated waveform analyzer (VP2000, Omron) and atherosclerosis was examined as coronary artery calcification (CAC) by computed-tomography (GE-Imatron EBT scanner). Association of the presence of CAC (defined as ≥ 10 Agatston unit) was examined with continuous measure as well as with increasing quartiles of baPWV., Results: As compared to the lowest quartile of baPWV, the multivariable-adjusted odds ratio (95% Confidence Interval [CI]) for the presence of CAC in the combined sample was 1.70 (0.98, 2.94) for 2nd quartile, 1.88 (1.08, 3.28) for 3rd quartile, and 2.16 (1.19, 3.94) for 4th quartile (p-trend = 0.01). The odds for CAC increased by 19% per 100 cm/s increase (p < 0.01), or by 36% per standard-deviation increase (p < 0.01) in baPWV. Similar effect-sizes were observed in individual races, and were significant among Whites, Blacks and Koreans., Conclusion: baPWV is cross-sectionally associated with CAC among healthy middle-aged men. The association was significant in Whites and Blacks in the US, and among Koreans. Longitudinal studies are needed to determine its CVD predictive ability., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aim: To examine whether the inflammatory markers C-reactive protein (CRP) and fibrinogen are associated with biomarkers of atherosclerosis [carotid intima-media thickness (IMT) and coronary artery calcification (CAC)] in the general male population, including Asians., Methods: Population-based samples of 310 Japanese, 293 Japanese-American and 297 white men 40-49 years of age without clinical cardiovascular disease underwent measurement of IMT, CAC and the CRP and fibrinogen levels as well as other conventional risk factors using standardized methods. Statistical associations between the variables were evaluated using multiple linear or logistic regression models., Results: The Japanese group had significantly lower levels of inflammatory markers and subclinical atherosclerosis than the Japanese-American and white groups (P-values all ＜0.001). The mean level of CRP was 0.66 vs. 1.11 and 1.47 mg/L, while that of fibrinogen was 255.0 vs. 313.0 and 291.5 mg/dl, respectively. In addition, the mean carotid IMT was 0.61 vs. 0.73 and 0.68 mm, while the mean prevalence of CAC was 11.6% vs. 32.1% and 26.3%, respectively. Body mass index (BMI) showed significant positive associations with both the CRP and fibrinogen levels. Although CRP showed a significant positive association with IMT in the Japanese men, this association became non-significant following adjustment for traditional risk factors or BMI. In all three populations, CRP was not found to be significantly associated with the prevalence of CAC. Similarly, fibrinogen did not exhibit a significant association with either IMT or the prevalence of CAC., Conclusions: The associations between inflammatory markers and subclinical atherosclerosis may merely reflect the strong associations between BMI and the levels of inflammatory markers and incidence of subclinical atherosclerosis in both Eastern and Western populations.

The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45-54, 55-64, or 65-74 years). We used community-based samples of Caucasian men in the United States (2000-2002; n = 1,067) and Japanese men in Japan (2006-2008; n = 832) aged 45-74 years, stratifying them into groups with 0, 1, 2, or ≥3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian men's having Agatston scores of ≥10, ≥100, and ≥400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian men's having an Agatston score of ≥100 were 2.05, 2.43, and 3.86 among those aged 45-54, 55-64, and 65-74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: An early repolarization pattern, characterized by an elevation of the QRS-ST junction (J-point) on 12-lead electrocardiography (ECG) is associated with cardiac and sudden death. However, little is known about the prognostic significance of J-point elevation for various disease-specific cardiovascular outcomes, including coronary artery disease (CAD)., Methods and Results: To investigate the association between the presence of J-point elevation≥0.1 mV and various disease-specific cardiovascular outcomes, we conducted a 15-year prospective study in a representative general Japanese population of 7,630 individuals (41% men, mean age 52.4 years) who participated in the National Survey of Circulatory Disorders. Cox models were used to estimate the hazard ratios (HRs) adjusted for possible confounding factors. J-point elevation was present in 264 individuals (3.5%) and was associated with an increased risk of cardiac death (adjusted HR, 2.54; 95% confidence interval [CI] 1.40-4.58; P=0.002) and death from CAD (adjusted HR, 4.66; 95% CI 2.30-9.46; P<0.001). In a subgroup analysis by age, the association between J-point elevation and cardiovascular outcomes was more remarkable in middle-aged (<60 years) than in older individuals (≥60 years) (all P for interaction<0.05)., Conclusions: J-point elevation on standard 12-lead ECG was an independent predictor of cardiac death and death from CAD in a representative sample of the general Japanese population, particularly among the middle-aged.

We studied 316 adults with community-and hospital-acquired bacterial pneumonia admitted from January 1998 to July 2003. Of these, 66 (20.9%) died. Classified by age, none under 70 died, but mortality increased to 22.6% in the 70-79 age group, 31.6% in the 80-89 age group and 24.2% in the group over 90. Mortality was 3.4% (6/177) for mild pneumonia, 32.0% (24/75) for moderate pneumonia, and 56.3% (36/64) for severe pneumonia. Mortality in hospital-acquired pneumonia (69.1%) was significantly higher than that in community-acquired pneumonia (10.7%). This may result from the higher percentage of moderate by and severe by ill patients who contracted hospital-acquired pneumonia, since 80% of those with hospital-acquired pneumonia were in the moderate and severe group compared to 36.4% of those with community-acquired pneumonia. For antibiotic regimens, mortality was 18.2% to 36.4% for patients who underwent Penicillins-Cephems therapy compared with 51.6% to 66.7% for Carbapenems-Quinolones therapy. The reasons for these differences remain unclear. Our study indicates that severity of illness, age, and antibiotic therapy were factors correlated with death from pneumonia. Underlying diseases such as respiratory failure, chronic heart failure, cerebrovascular disease, renal failure, malignancy, and senile dementia may also be associated with mortality.

A 50-year-old male with left cervical lymphadenopathy visited our hospital. Infectious and lymphomatous diseases were suspected in the patient. Since the patient owned a dog, which often licked the patient's face, Bartonella infection was also suspected. Histopathological examination in the lymph node biopsy revealed the epithelioid granuloma, but B. henselae was not detected from the culture of the lymphnode. B. henselae DNA also was not detected from the lymph node. Since the antibody titer (lgG) to B. henselae showed 1:128 by immunofluorescent antibody technique (IFA), he was serdogicalg diagnosed as cat-scratch disease. 'Cat-scratch disease' is named after cat scratch, however we propose 'B. henselae infection' which is more appropriate since other animals could serve as a cause of infection.