Effects of 1-week inpatient multidisciplinary care for chronic kidney disease prior to outpatient collaborative care.

BACKGROUND: Multidisciplinary care for Chronic Kidney Disease (CKD) has been reported to be effective in preventing deterioration of renal function and avoiding hemodialysis induction using a central venous catheter. METHODS: We included 171 patients who received dialysis at our department between October 2014 and June 2017. Patients were divided into two groups: an inpatient group who received inpatient multidisciplinary care for CKD (educational hospitalization) prior to outpatient collaborative care from their family physician and nephrologist, and a non-inpatient group who did not receive such care. We compared factors related to dialysis induction. RESULTS: There was no significant difference in eGFR between the groups at the start of observation. The mean time from the start of observation to dialysis induction (inpatient group vs. non-inpatient group; 40.8 ± 2.8 vs. 23.9 ± 3.0 months, respectively; P < 0.001) and the rate of hemodialysis induction using a central venous catheter (22.5 vs. 47.1%, respectively; P = 0.002) were significantly different between the groups. Survival analysis showed that the time to dialysis induction was significantly longer in the inpatient group (P = 0.0001). Multivariate analysis revealed that educational hospitalization (odds ratio = 0.30 [95% CI 0.13, 0.67]) was significantly associated with hemodialysis induction using a central venous catheter. CONCLUSION: Educational hospitalization prior to outpatient collaborative care is beneficial for preventing hemodialysis induction using a central venous catheter and postponing dialysis induction.

Association of gut microbiome with COPD in Japanese male residents: the SESSA study.

Background: Altered gut microbiota may contribute to COPD development or progression. Herein, we investigated the association of gut microorganisms with COPD, taking into account the impact of smoking status. Methods: This cross-sectional observational study was a part of the Shiga Epidemiological Study of Subclinical Atherosclerosis, a population-based cohort study of Japanese men aged 46-76 years, conducted from 2010 to 2016. The gut microbiome, determined using 16S rRNA gene sequencing, was compared among 99 never-smokers, 306 non-COPD ever-smokers and 76 patients with COPD while adjusting for age, body mass index, ethanol consumption and treatment for type 2 diabetes mellitus. Results: The abundance of phylum Firmicutes was comparable between patients with COPD and non-COPD ever-smokers but tended to be higher in never-smokers. Similarly, the α- and ß-diversity analysis showed similarity between patients with COPD and non-COPD ever-smokers, which tended to differ from never-smokers. Discriminant analysis identified the genus [Prevotella] to be more prevalent in patients with COPD than in never-smokers or non-COPD ever-smokers. Post hoc analysis confirmed similarity of gut microbiome between COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and non-COPD ever-smokers, which was different from GOLD II. Conclusion: Smoking may alter the overall gut microbial composition, but gut microbial composition itself may not play a role in the development of COPD. Rather, specific gut bacteria, such as [Prevotella], could be a risk factor for the development of COPD; this may be a potential therapeutic target.

Association of Arterial Stiffness and Atherosclerotic Burden With Brain Structural Changes Among Japanese Men.

Background Little is known regarding whether arterial stiffness and atherosclerotic burden are each independently associated with brain structural changes. Simultaneous assessments of both arterial stiffness and atherosclerotic burden in associations with brain could provide insights into the mechanisms of brain structural changes. Methods and Results Using data from the SESSA (Shiga Epidemiological Study of Subclinical Atherosclerosis), we analyzed data among 686 Japanese men (mean [SD] age, 67.9 [8.4] years; range, 46-83 years) free from history of stroke and myocardial infarction. Brachial-ankle pulse wave velocity and coronary artery calcification on computed tomography scans were measured between March 2010 and August 2014. Brain volumes (total brain volume, gray matter, Alzheimer disease signature and prefrontal) and brain vascular damage (white matter hyperintensities) were quantified using brain magnetic resonance imaging from January 2012 through February 2015. In multivariable adjustment models including mean arterial pressure, when brachial-ankle pulse wave velocity and coronary artery calcification were entered into the same models, the ß (95% CI) for Alzheimer disease signature volume for each 1-SD increase in brachial-ankle pulse wave velocity was -0.33 (-0.64 to -0.02), and the unstandardized ß (95% CI) for white matter hyperintensities for each 1-unit increase in coronary artery calcification was 0.68 (0.05-1.32). Brachial-ankle pulse wave velocity and coronary artery calcification were not statistically significantly associated with total brain and gray matter volumes. Conclusions Among Japanese men, higher arterial stiffness was associated with lower Alzheimer disease signature volumes, whereas higher atherosclerotic burden was associated with brain vascular damage. Arterial stiffness and atherosclerotic burden may be independently associated with brain structural changes via different pathways.

Relationship between Serum Irisin Levels and MRI-Measured Cerebral Small Vessel Disease in Japanese Men.

AIM: Irisin, an exercise-induced myokine, is a potential neurotrophic factor; however, its relationship with cerebral small vessel disease (CSVD) remains unknown. Therefore, we investigated whether serum irisin levels are associated with CSVD in healthy Japanese men. METHODS: We analyzed data from 720 men free of stroke and participated in this observational study. Serum irisin levels were measured by enzyme-linked immunosorbent assay. CSVD was assessed on deep and subcortical white matter hyperintensities (DSWMHs), periventricular hyperintensities (PVHs), lacunar infarcts (LIs), and cerebral microbleeds (CMBs) on brain magnetic resonance imaging. We calculated the total CSVD score (ranges 0-4) to express the total CSVD burden. We computed the adjusted odds ratios (ORs), with 95% confidence intervals (CIs), of the total CSVD score and individual CSVD features using logistic regression models according to the quartiles of irisin (reference: Q1). RESULTS: Serum irisin levels were associated with lower ORs of higher (vs. zero or lower score) total CSVD score, with the lowest risk (OR, 0.63; 95% CI, 0.41-0.97) being observed in Q3 compared to Q1 after adjustment of potential covariates. Similar results were obtained for younger adults (＜65 years). Among individual CSVD features, irisin was associated with a reduced risk of LIs in the total sample and PVHs, LIs, and CMBs in younger adults. No relationship was observed in older adults (≥ 65 years). CONCLUSIONS: Serum irisin levels were associated with less burden of total CSVD in healthy Japanese men. Serum irisin levels were also related with a reduced risk of PVHs, LIs, and CMBs, but not DSWMHs.

Relationship between Serum Proprotein Convertase Subtilisin/Kexin Type 9 Concentration and Prevalence of Coronary Artery Calcium in a Community-Based Sample of Japanese Men.

AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for reducing low-density lipoprotein cholesterol (LDL-C) and cardiovascular events in high-risk patients. However, the influence of circulating PCSK9 concentration on atherosclerotic plaque formation in the general population remains unknown. We assessed the relationship between serum PCSK9 concentration and coronary artery calcium (CAC) prevalence in the general population. METHODS: Community-dwelling Japanese men (n=622) aged 46-82 years without a history of cardiovascular disease and lipid-lowering medications were included. Serum PCSK9 concentration and CAC score were measured using the Agatston method, and the multivariable analysis was used to assess their association. CAC was defined as an Agatston score of ＞10. We conducted further analysis stratified by age (＜60, 60-69, and ≥ 70 years). RESULTS: The average age, LDL-C, and median serum PCSK9 concentration were 68 years, 122 mg/dL, and 240 ng/mL, respectively. After multivariable adjustment for traditional cardiovascular risk factors, no significant association was observed between serum PCSK9 concentration and CAC prevalence (adjusted relative risk [aRR] 1.05, 95% confidence interval [CI] 0.97-1.13). With age stratification, serum PCSK9 concentration was significantly associated with CAC prevalence in men aged ＜60 years (aRR 1.38, 95% CI 1.01-1.88) but not in men aged 60-69 years (aRR 0.96, 95% CI 0.85-1.10) or ≥ 70 years (aRR 1.08, 95% CI 0.99-1.19). CONCLUSIONS: A higher serum PCSK9 concentration was associated with a higher CAC prevalence in men aged ＜60 years, which was independent of traditional cardiovascular risk factors.

Differential Association of Serum n-3 Polyunsaturated Fatty Acids with Various Cerebrovascular Lesions in Japanese Men.

BACKGROUND: An association between a high intake of marine-derived n-3 polyunsaturated fatty acids (n-3 PUFAs) with a lower risk of coronary heart disease was previously reported. However, the association between n-3 PUFAs and cerebrovascular lesions remains unclear. We evaluated this association in a general-population-based sample of Japanese men. METHODS: Participants were community-dwelling men (40-79 years old) living in Kusatsu City, Shiga, Japan. Serum concentrations of n-3 PUFAs, defined as the sum of eicosapentaenoic and docosahexaenoic acids, were measured via gas-liquid chromatography between 2006 and 2008. Magnetic resonance imaging was used to assess cerebrovascular lesions (including intracerebral large-artery stenosis, lacunar infarction, and microbleeds) and white matter lesions between 2012 and 2015. Logistic regression adjusting for conventional cardiovascular risk factors was used to estimate the odds ratio of prevalent cerebrovascular lesions per 1 standard deviation higher serum concentration of n-3 PUFAs. RESULTS: Of a total of 739 men, the numbers (crude prevalence in %) of prevalent cerebral large-artery stenoses, lacunar infarctions, microbleeds, and white matter lesions were 222 (30.0), 162 (21.9), 103 (13.9), and 164 (22.2), respectively. A 1 standard deviation higher concentration of n-3 PUFAs (30.5 µmol/L) was independently associated with lower odds of cerebral large-artery stenosis (multivariable-adjusted odds ratio, 0.80; 95% confidential interval, 0.67-0.97). There were no significant associations of n-3 PUFAs with the other types of lesions. CONCLUSIONS: n-3 PUFAs may have protective effects against large-artery stenosis, but not small vessel lesions, in the brain.

Premature Atrial Contractions and Their Determinants in a General Population of Japanese Men.

BACKGROUND: Premature atrial contractions (PACs) are predictors of atrial fibrillation, stroke, and cardiovascular mortality. The present study aimed to assess relevant factors for PACs among a general population of Japanese men.Methods and Results: This study conducted a population-based, cross-sectional study among 517 men, aged 40-79 years, with neither apparent myocardial infarction nor atrial fibrillation. 24-h Holter electrocardiography to assess PAC frequency was used. Age, body mass index, height, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, mean heart rate, diabetes mellitus, hypertension, physical activity, smoking, alcohol consumption, and lipid-lowering therapy were included in multivariable negative binomial regression analyses to assess correlation for the number of PACs per hour. Almost all participants (99%) had at least 1 PAC in 1 h (median number 2.84 PACs per h). In multivariable negative binomial regression after adjusting for all covariates simultaneously, age (relative risk [95% confidence interval], 1.30 [1.08-1.57] per 1-standard deviation [SD] increment), height (1.19 [1.02-1.39] per 1-SD increment), triglycerides (0.79 [0.65-0.97] per 1-SD increment), mean heart rate (0.69 [0.59-0.80] per 1-SD increment), physical activity (0.63 [0.43-0.93]), current smoking (1.69 [1.06-2.69]), current moderate (1.97 [1.23-3.16]) and heavy (1.84 [1.12-3.01]) alcohol consumption were independently associated with PAC frequency. CONCLUSIONS: PAC frequency was independently associated with age, height, smoking, alcohol consumption, heart rate, physical activity, and triglycerides.

Ventricular Premature Complexes and Their Associated Factors in a General Population of Japanese Men.

Increased ventricular premature complexes (VPCs) are associated with a higher risk of cardiac morbidities. However, little information is available on the risk factors of Western general populations. Therefore, we aimed to assess the frequency and associated factors of VPCs in healthy general Japanese men. We conducted a population-based cross-sectional study in 517 men, aged 40 to 79 years, using 24-hour Holter electrocardiography. Age, body mass index, height, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, resting heart rate, diabetes mellitus, hypertension, physical activity, smoking, alcohol consumption, lipid-lowering therapy were included in multivariable negative binomial regression to assess independent correlates for the number of VPCs per hour. We observed at least 1 VPC in 1 hour in 429 men (83%). In multivariable negative binomial regression adjusted for all covariates simultaneously, age (risk ratio [95% confidence interval] 1.91 [1.56 to 2.33] per 1-SD increment), height (1.17 [1.04 to 1.49] per 1-SD increment), resting heart rate(1.34 [1.02 to 1.77] per 1-SD increment), diabetes mellitus (2.36 [1.17 to 4.76] ), hypertension (1.90 [1.03 to 3.50]), physical activity (0.67 [0.47 to 0.97] ), current smoking (4.23 [1.86 to 9.60] ), past smoking (2.08 [1.03 to 4.19] ), current light alcohol consumption (0.16 [0.04 to 0.64] ), and lipid-lowering therapy (0.47 [0.23 to 0.96] ) were independently associated with VPCs frequency. In conclusion, VPCs frequency was independently associated with age, height, resting heart rate, diabetes mellitus, hypertension, physical activity, smoking, alcohol consumption, and lipid-lowering therapy.

Relationship of Four Blood Pressure Indexes to Subclinical Cerebrovascular Diseases Assessed by Brain MRI in General Japanese Men.

AIM: The relationship of blood pressure (BP) indexes (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], mean arterial pressure [MAP]) to subclinical cerebrovascular diseases (SCVDs) remains unclear. This study aimed to elucidate the relationship of four BP indexes measured at two visits on SCVDs assessed by magnetic resonance imaging (MRI) in general Japanese men. METHODS: In general Japanese men aged 40-79 years (N=616), office BP indexes were measured at two visits (Visits 1 [2006-2008] and 2 [2010-2014]). MRI images obtained on the third visit (2012-2015) were examined for prevalent SCVDs: lacunar infarction, periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), microbleeds, and intracranial artery stenosis (ICAS). Using a multivariable logistic regression analysis, we computed and estimated the odds ratio of each prevalent SCVD for one standard deviation higher BP indexes. The same analyses were performed using home BP. RESULTS: All four office BP indexes at both visits associated with lacunar infarction. Visit 1 and 2 DBP and Visit 1 MAP associated with PVH and DSWMH, and Visit 1 SBP associated with DSWMH. All Visit 2 BP indexes appear to show stronger association with microbleeds than Visit 1 indexes, and Visit 1 and 2 SBP, PP, and MAP showed similar associations with ICAS. Additional analyses using home BP indexes revealed similar relationships; however, the significance of some relationships decreased. CONCLUSION: In general Japanese men, BP indexes were associated with most of SCVDs, and BP indexes measured at different periods associated with different SCVDs assessed by MRI.

Relationship between Kidney Function and Subclinical Atherosclerosis Progression Evaluated by Coronary Artery Calcification.

AIMS: The roles of urinary albumin, eGFRcystatin (eGFRcys), and eGFRcreatinine (eGFRcre) in the progression of coronary artery calcification (CAC) remain unclear. Therefore, the present study investigated the relationship between kidney function and CAC progression. METHODS: A total of 760 Japanese men aged 40-79 years were enrolled in this population-based study. Kidney function was measured using eGFRcre, eGFRcys, and the urine albumin-to-creatinine ratio. CAC scores were calculated using the Agatston method. CAC progression was defined as an annual increase of ＞10 Agatston units (AU) among men with 0＜CAC＜100 AU at baseline, that of ＞10% among those with CAC ≥ 100 AU, and any progression for those with CAC=0 at baseline. The relative risk (RR) of CAC progression based on kidney function was assessed using a robust Poisson regression model. RESULTS: The mean follow-up period was 4.9 years. CAC progression was detected in 45.8% of participants. Positive associations between CAC progression and albuminuria (＞30mg/g) (RR: 1.29; 1.09 to 1.53; p=0.004) and low eGFRcys (＜60ml/min/1.73m2) (RR: 1.27; 1.05 to 1.53; p=0.012) remained significant after adjustments for age, the follow-up time, and computerized tomography type. Following further adjustments for hypertension, diabetes mellitus, dyslipidemia, C-reactive protein, and lifestyle factors, CAC progression was associated with albuminuria (RR: 1.20; 1.01 to 1.43; p=0.04) and low eGFRcys (RR: 1.19; 0.99 to 1.43; p=0.066), but not with eGFRcre. CONCLUSION: CAC progression was associated with albuminuria; however, its relationship with eGFRcys was weakened by adjustments for risk factors.

Association of self-measured home, ambulatory, and strictly measured office blood pressure and their variability with intracranial arterial stenosis.

OBJECTIVE: Hypertension and intracranial artery stenosis (ICAS) are closely related; however, few studies have compared the strength of the relationship between strictly measured office and out-of-office blood pressure (BP) measurements. The relationship of day-by-day or short-term variability in BP to asymptomatic ICAS also remains unclear. METHODS: In apparently healthy 677 men (mean age, 70 years) from a population-based cohort, we examined the association of strictly measured office BP and 7-day home BP with ICAS on magnetic resonance angiography. We conducted 24-h ambulatory BP monitoring in 468 of the men. Variability indices included day-by-day, daytime, and night-time variability, nocturnal decline, and morning pressor surge. Any ICAS was defined as either mild (1-49%) or severe (≥50%) stenosis. RESULTS: We observed mild and severe ICAS in 153 (22.6%) and 36 (5.3%) participants, respectively. In multivariable-adjusted Poisson regression with robust error variance, higher SBP in office, home, or ambulatory BP monitoring was associated with the presence of any or severe ICAS. The associations with ICAS were comparable between office, home, and ambulatory SBP (all heterogeneity P values >0.1). Independent of mean SBP, greater nocturnal decline or morning pressor surge, but not day-by-day, daytime, or night-time variability, in SBP was associated with higher burden of any or severe ICAS. CONCLUSION: The magnitude of association of strictly measured office BP for asymptomatic ICAS was comparable with that of BP measured at home or in ambulatory BP monitoring. Circadian BP variation based on ambulatory BP monitoring was positively associated with asymptomatic ICAS burden.

Lipoprotein Particle Profiles Compared With Standard Lipids in the Association With Subclinical Aortic Valve Calcification in Apparently Healthy Japanese Men.

BACKGROUND: Risk factors for atherosclerotic disease including dyslipidemia have been shown to be associated with aortic valve calcification (AVC). Nuclear magnetic resonance (NMR)-measured lipoprotein particles, low-density and high-density lipoprotein particles (LDL-p, HDL-p) in particular, have emerged as novel markers of atherosclerotic disease; however, whether NMR-measured particles are associated with AVC remains to be determined. This study aimed to examine the association between NMR-based lipoprotein particle measurements and standard lipids with AVC. The primary variables of interest were LDL-p (nmol/L), HDL-p (µmol/L), LDL-cholesterol, and HDL-cholesterol (both in mg/dL).Methods and Results:A community-based random sample of Japanese men aged 40-79 years examined in 2006-2008, in Shiga, Japan was studied. Presence of AVC was defined as an Agatston score >0. Lipoprotein particles were measured using NMR spectroscopy. In the main analysis, multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for the prevalence of AVC across the higher quartiles of lipids in reference to the lowest ones were obtained. Of 874 participants analyzed, 153 men had AVC. Multivariable-adjusted ORs of prevalent AVC for the highest vs. the lowest quartile were significantly elevated for LDL-p (OR, 2.20; 95% CI: 1.23-3.93) and LDL-cholesterol (OR, 2.16; 95% CI: 1.23-3.78). In contrast, neither HDL-p nor HDL-cholesterol was associated with AVC. CONCLUSIONS: The association of prevalent AVC with NMR-based LDL-p was comparable to that with LDL-cholesterol.

Urinary sodium/potassium ratio as a screening tool for hyperaldosteronism in men with hypertension.

Among individuals with hypertension, the prevalence of secondary hypertension has been reported to be ≈10%. More than half of individuals with secondary hypertension have associated hyperaldosteronism. However, given the current clinical environment, these patients often remain undiagnosed. We hypothesized that the urinary sodium/potassium ratio (Na/K) could be used as a simple, low-cost method of screening for hyperaldosteronism among individuals with hypertension in primary care and health examination settings. We recruited hypertensive individuals aged 30-69 years old who were not taking any antihypertensive medications from among participants in health examinations. Urinary Na and K were measured using second morning urine samples, and the plasma aldosterone concentration (PAC) was also measured. We evaluated the association of the second morning urine Na/K ratio (SMU Na/K) with a high PAC, defined as ≥90th percentile (24.3 ng/dL), using receiver operating characteristic (ROC) curves. Overall, 160 participants (108 men and 52 women) with a mean age of 54.3 years were eligible for this study. The area under the ROC curve for the relationship between SMU Na/K and high PAC was 0.77 (95% confidence interval [CI]: 0.59-0.95) in men and 0.64 (95% CI: 0.36-0.93) in women. In men, SMU Na/K values <1.0 could detect hyperaldosteronism with a sensitivity of 45.5%, a specificity of 97.9%, a positive predictive value of 71.4%, and a negative predictive value of 94.1%. The use of the urinary Na/K ratio may be appropriate as a method of screening for hyperaldosteronism in hypertensive men.

Relationships of Alcohol Consumption with Coronary Risk Factors and Macro- and Micro-Nutrient Intake in Japanese People: The INTERLIPID Study.

Several studies have reported a J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk. However, the mechanisms of this relationship remain unclear. This study aimed to evaluate the relationships of alcohol consumption with established CHD risk factors and with macro-/micro-nutrient intake among Japanese people. Participants were 1,090 Japanese men and women aged 40-59 y enrolled in the INTERLIPID study, excluding former drinkers. Based on two 7-d alcohol records, participants were classified as non-drinkers (0 g/wk), light-drinkers (<100 g/wk), moderate-drinkers (100-299 g/wk), or heavy-drinkers (≥300 g/wk). Detailed macro-/micro-nutrient intake was evaluated using four in-depth 24-h dietary recalls and adjusted for total energy intake excluding alcohol. We analyzed the associations of CHD risk factors and nutrient intake with alcohol consumption. Serum high-density lipoprotein cholesterol and blood pressure were higher and low-density lipoprotein cholesterol was lower among those with higher alcohol consumption. J-shaped relationships with alcohol consumption were observed for the proportion of current smokers, number of cigarettes smoked, and prevalence of hypertension; these risk factors were lowest among light-drinkers. Carbohydrate and total fiber intakes were lower and protein and dietary cholesterol intakes were higher among those with higher alcohol consumption. These associations were similar for men and women. Alcohol consumption was related to nutrient intake as well as established CHD risk factors. Non-drinkers were higher on some CHD risk factors than were light-drinkers. These findings may influence the J-shaped relationship between alcohol consumption and CHD risk.

Seven-Day Pedometer-Assessed Step Counts and Brain Volume: A Population-Based Observational Study.

BACKGROUND: To investigate the association between step counts and brain volumes (BVs)-global and 6 a priori selected cognition-related regions of interest-in Japanese men aged 40-79 years. METHODS: The authors analyzed data from 680 cognitively intact participants of the Shiga Epidemiological Study of Subclinical Atherosclerosis-a population-based observational study. Using multivariable linear regression, the authors assessed cross-sectional associations between 7-day step counts at baseline (2006-2008) and BVs at follow-up (2012-2015) for age-stratified groups (<60 y and ≥60 y). RESULTS: In the older adults ≥60 years, step counts at baseline (per 1000 steps) were associated with total BV at follow-up (ß = 1.42, P = .022) while adjusted for potential covariates. Regions of interest-based analyses yielded an association of step counts with both prefrontal cortexes (P < .05) in older adults, while the left entorhinal cortex showed marginally significant association (P = .05). No association was observed with hippocampus, parahippocampal, cingulum, and cerebellum. No association was observed in younger adults (<60 y). CONCLUSIONS: The authors found a positive association between 7-day step counts and BVs, including prefrontal cortexes, and left entorhinal cortex in apparently healthy Japanese men.

Alcohol drinking and brain morphometry in apparently healthy community-dwelling Japanese men.

The clinical implications of alcohol consumption have been extensively examined; however, its effects on brain structures in apparently healthy community-dwellers remain unclear. Therefore, we investigated the relationship between alcohol consumption and brain gray matter volume (GMV) in community-dwelling Japanese men using voxel-based morphometry (VBM). We recruited cognitively intact Japanese men, aged 40-79 years, from a population-based cohort in Shiga, Japan. Brain magnetic resonance imaging was performed, on average, 2 years after demographic and medical information was obtained in 2010-2014. A multivariable linear regression analysis of 639 men was conducted to elucidate the relationship between the amount of alcohol consumed and GMV. VBM statistics were analyzed by threshold-free cluster enhancement with a family-wise error rate of <0.05. The results obtained demonstrated that the amount of alcohol consumed was associated with lower GMV. The VBM analysis showed lower GMV within the parahippocampal, entorhinal, cingulate, insular, temporal, and frontal cortices and cerebellum in very heavy drinkers (≥42 ethanol g/day) than in non-drinkers. Furthermore, alcohol consumption was associated with a higher white matter lesion volume. These results suggest subclinical structural changes similar to alcohol-related neurological diseases.

Association of Red Meat Intake with the Risk of Cardiovascular Mortality in General Japanese Stratified by Kidney Function: NIPPON DATA80.

The consumption of red meat has been recommended for individuals with reduced kidney function. However, red meat intake was recently suspected to increase cardiovascular disease (CVD) risk. We evaluated the association of red meat intake with CVD mortality risk in Japanese with/without reduced kidney function. Overall, 9112 participants of a Japanese national survey in 1980, aged ≥30 years, were followed for 29 years. Red meat intake was assessed using weighed dietary record. Cox proportional hazards models were used to estimate the hazard ratio (HR) of CVD mortality according to sex-specific tertiles of red meat intake. We also performed stratified analyses with/without reduced kidney function defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m2. Red meat intake was not associated with CVD mortality risk in men and women. In stratified analyses, the HR of the highest compared with the lowest tertile of red meat intake was lower only in women with reduced kidney function (0.67, 95% confidence interval 0.46-0.98). In conclusion, there were no clear associations between red meat intake and CVD mortality risk in Japanese population; however, a higher intake of red meat was associated with lower risk of future CVD mortality in women with reduced kidney function.

Relationship Between Step Counts and Cerebral Small Vessel Disease in Japanese Men.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population. METHODS: We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006-2008) using a pedometer. CSVD was assessed at follow-ups (2012-2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression. RESULTS: Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175-10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30-0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29-0.86]), and lacunar infarcts (0.52 [95% CI, 0.30-0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors. CONCLUSIONS: We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.

The relationship between serum levels of LOX-1 ligand containing ApoAI as a novel marker of dysfunctional HDL and coronary artery calcification in middle-aged Japanese men.

BACKGROUND AND AIMS: Dysfunctional high-density lipoprotein (HDL) is a risk factor for cardiovascular disease (CVD) beyond HDL concentrations. Recently, a novel method has been introduced to measure LOX-1 ligand containing apolipoprotein AI (LAA), which is an indicator of various types of modified HDL with binding capacity to LOX-1 and related to impaired anti-atherogenic functions of HDL. This study aimed to examine the relationship between LAA as a novel marker of dysfunctional HDL and coronary artery calcification (CAC). METHODS: We selected 910 community-dwelling Japanese men aged 40-79 years without a history of CVD. The odds ratios per 1SD of LAA for the presence of CAC (Agatston score >10) were estimated using logistic regression model adjusted for confounders, including HDL-C or HDL particle (HDL-P) concentration. In addition, we performed further analysis stratified by age (<65 and ≥ 65 years). RESULTS: The mean age of the participants was 63.6 years, and the median LAA was 187.0 ng/mL. The prevalent CAC was 46.2%. The multivariable adjusted odds ratio (95% confidence interval) per 1SD of LAA for CAC was 1.14 (0.96-1.36) for all participants. After stratification by age, multivariable adjusted odds ratios per 1SD of LAA were 1.34 (1.02-1.76) and 0.97 (0.77-1.23) in men aged <65 and ≥ 65 years, respectively. CONCLUSIONS: The present study showed that LAA was associated with CAC independent of HDL-C or HDL-P in middle-aged Japanese men. This finding suggests that LAA might be an early marker for CVD events. Future longitudinal studies are warranted.