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Aims The potential effect of alcohol consumption on coronary heart disease (CHD) remains unclear. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in subclinical and clinical CHD. Methods We conducted two Mendelian randomization studies: a cross-sectional study of coronary artery calcification (CAC) on computed tomography of 1029 healthy men (mean age, 63.8 years) and a case–control study of 421 men with CHD [acute coronary syndrome (ACS) or stable angina pectoris] who underwent coronary revascularization and 842 age-matched male controls. Results In the CAC study, medians (25%tiles, 75%tiles) of alcohol consumption by ALDH2-rs671 *2 homozygotes [n = 86 (8.4%)], *1*2 heterozygotes [n = 397 (38.5%)], and *1 homozygotes [n = 546 (53.1%)] were 0.0 (0.0, 0.0), 28.0 (0.0, 129.0), and 224.0 (84.0, 350.0) g/week, respectively. In age-adjusted Poisson regression with robust error variance, compared with *2 homozygotes, relative risks for prevalent CAC score >0, ≥100, and ≥300 in *1 homozygotes were 1.29 (95% confidence interval, 1.06–1.57), 1.76 (1.05–2.96), and 1.81 (0.80–4.09), respectively. In age-adjusted ordinal logistic regression for CAC distributions, we observed higher odds among *1 homozygotes [odds ratio, 2.19 (1.39–3.46)] and even among *1*2 heterozygotes [1.77 (1.11–2.82)] compared with *2 homozygotes. In the case–control study, conditional logistic regression revealed lower prevalence of *1 homozygotes among men with CHD [odds ratio, 0.54 (0.35–0.82)], especially ACS [0.46 (0.27–0.77)], than controls. Conclusion Our findings indicate a positive association of alcohol consumption with CAC burden but an inverse association with clinical CHD, especially ACS.

Objective:We aimed to investigate the effect of ambulatory blood pressure (BP) on aortic valve calcification (AVC) and coronary artery calcification (CAC), which are subclinical atherosclerotic diseases., Methods:In this population-based, cross-sectional study, we assessed office BP, mean ambulatory BP (24-h, awake, and asleep), and variability of ambulatory BP, as determined by the coefficient of variation (awake and asleep). AVC and CAC were quantified using an Agatston score (>0) based on computed tomography scanning. We calculated relative risks (RRs) and 95% confidence intervals (CIs) with a 1-standard deviation increment in each BP index for the presence of AVC and CAC using a multivariate-adjusted Poisson regression with robust error variance., Results:Of 483 participants (mean age: 66.8 years), 154 (31.9%) and 310 (64.2%) had AVC and CAC, respectively. The presence of AVC was associated with office systolic BP (SBP; RR, 1.15; 95% CI, 1.03-1.28), awake diastolic BP (DBP) variability (RR, 1.12; 95% CI, 1.01-1.25), and asleep SBP variability (RR, 1.14; 95% CI, 1.03-1.27). The presence of CAC was associated with office SBP (RR, 1.08; 95% CI, 1.01-1.15), mean 24-h SBP (RR, 1.10; 95% CI, 1.04-1.16), mean awake SBP (RR, 1.11; 95% CI, 1.04-1.17), mean asleep SBP (RR, 1.07; 95% CI, 1.01-1.13), and asleep SBP variability (RR, 1.07; 95% CI, 1.01-1.13)., Conclusion:These findings highlight the association of ambulatory BP indices with both AVC and CAC, but with different effects on their presences.

Introduction: Growing evidence supports the bidirectional brain-gut microbiome interaction that contributes to brain health. However, no prior study has assessed the association between gut microbiomes and structural brain features in a healthy general population. Hypothesis: We assess the hypothesis that the gut microbiome composition is associated with structural brain features in healthy humans. Methods: Healthy Japanese men (n=623) aged 40-79 years participated in the examination of the Shiga Epidemiological Study of Subclinical Atherosclerosis II (SESSA II) between 2010 and 2014. Gut microbiota composition including diversity was assessed using 16S rRNA sequencing with DNA extracted from stool samples, and brain volumes (i.e., total brain volume, white matter, gray matter, and hippocampus) and white matter lesion volume (WMLV, reflecting Cerebral small vessel disease) were quantified using brain magnetic resonance imaging (MRI). We performed principal coordinate analysis (PCoA), multivariable-adjusted linear regression models, and linear discriminant analysis (LDA) by measuring effect size (Lefse). Results: Higher alpha diversity was associated with lower brain volumes of gray matter, white matter, and hippocampus (FDR adjusted Q Conclusions: In conclusion, the gut microbiome was associated with the brain gray and white matter structural alterations in healthy Japanese adult men. Persons with higher amount of Lachnospiraceae butyrate-producing bacteria had higher gray and white matter volumes compared to those with lower amount of the bacteria.

Background and Aim: To determine whether a mild decrease in renal function is an indicator of early detection of silent cerebrovascular disease, we conducted a cross-sectional study in 735 community-dwelling Japanese men. Methods: The prevalence of silent cerebrovascular disease was defined as intracranial artery stenosis (ICAS), lacunar infarctions (LIs), cerebral microbleeds (CMBs), periventricular hyperintensities (PVHs: grade ≥2), and deep and subcortical white matter hyperintensities (DSWMHs: grade ≥3), using brain magnetic resonance imaging independently evaluated by two specialists. In addition, a total cerebral small vessel disease (TCSVD) score was used, summing LIs, CMBs, PVHs, and DSWMHs. We calculated the estimated glomerular filtration rate calculated with creatinine or cystatin C (eGFRcr or eGFRcys) using the CKD-EPI formula for Japanese and the equations by the Japanese Society of Nephrology, respectively. The urinary albumin/creatinine ratio (UACR) was dichotomized at 30 mg/gCre, and the low group was further divided into tertiles. eGFRcr and eGFRcys were also dichotomized at 60 ml/min/1.73 m 2 , and the high group was further divided into tertiles. The odds ratios (ORs) and 95% confidence intervals (95%CIs) for the prevalence of silent cerebrovascular disease by renal function were calculated using binary or ordinal multivariable adjusted logistic regression models. Results: The prevalence of ICAS, LIs, CMBs, and white matter lesions (WMLs: the prevalence of PVHs or DSWMHs) was 30% (220/735), 21% (155/735), 14% (102/735), and 32% (237/735), respectively. The multivariable adjusted ORs (95%CI) of the prevalence of CMBs and TCSVD score were higher in the high UACR (>30mg/gCre) group (3.83 (1.90-7.73) and 1.75 (1.12-2.74), respectively) than in the low UACR (≤4.7 mg/gCre) group; the linear trend was significant (p 2 ) eGFRcr or eGFRcys group (1.70 (0.998-2.91) and 1.85 (1.10-3.10), respectively) than in the high eGFRcr group (≥75.9 ml/min/1.73 m 2 ) or the high eGFRcys group (≥83.3 ml/min/1.73 m 2 ); the linear trend was shown (p=0.036 and p=0.072, respectively). The multivariable adjusted ORs (95%CI) of the prevalence of WML was higher in the decreased (2 ) and mildly decreased (60-69.9 ml/min/1.73 m 2 ) eGFRcr groups (2.41 (1.31-4.43) and 1.78 (1.05-3.02), respectively) than in the high eGFRcr group (≥75.9 ml/min/1.73 m 2 ); the linear trend was significant (p Conclusion: Decreased renal function was associated with the presence of silent cerebrovascular disease. Our results suggest that even a mild decline in renal function may be an indicator of early detection of silent cerebrovascular disease.

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.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).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).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.

Background Few studies have compared the strength in the associations of anthropometric and computed tomography (CT)-based obesity indices with coronary artery calcification (CAC), aortic artery calcification (AoAC), and aortic valve calcification (AVC). Methods In healthy 931 men (mean age, 63.7 years) from a population-based cohort, we assessed cross-sectional associations of anthropometric and CT-based obesity indices with CAC, AoAC, and AVC. Anthropometric measures included body mass index (BMI), waist circumference, hip circumference, waist-to-hip circumference ratio, and waist-to-height ratio. CT images at the L4/5 level were obtained to calculate the areas of abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), total adipose tissue (TAT), VAT-to-SAT ratio (VSR), and VAT-to-TAT ratio (VTR). CAC, AoAC, and AVC were quantified using the Agatston score based on CT scanning. Results CAC, AVC, and AoAC were present in 348 (62.6%), 173 (18.6%), and 769 (82.6%) participants, respectively. In multivariable models adjusting for age, lifestyle factors, and CT types, anthropometric and CT-based obesity indices were positively associated with CAC (p

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.

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.

Background and aims: To examine whether smoking habits, including smoking amount and cessation duration at baseline, are associated with atherosclerosis progression., Methods: At baseline (2006-08, Japan), we obtained smoking status, amount of smoking and time since cessation for quitters in a community-based random sample of Japanese men initially aged 40-79 years and free of cardiovascular disease. Coronary artery calcification (CAC) and aortic artery calcification (AAC) as biomarker of atherosclerosis was quantified using Agatston's method at baseline and after 5 years of follow-up. We defined progression of CAC and AAC (yes/no) using modified criteria by Berry., Results: A total of 781 participants was analyzed. Multivariable adjusted odds ratios (ORs) of CAC and AAC progression for current smokers were 1.73 (95% CI, 1.09-2.73) and 2.47 (1.38-4.44), respectively, as compared to never smokers. In dose-response analyses, we observed a graded positive relationship of smoking amount and CAC progression in current smokers (multivariable adjusted ORs: 1.23, 1.72, and 2.42 from the lowest to the highest tertile of pack-years). Among the former smokers, earlier quitters (≥10.7 years) had similar ORs of the progression of CAC and AAC to that of participants who had never smoked., Conclusions: Compared with never smokers, current smokers especially those with greater pack-years at baseline had higher risk of atherosclerosis progression in community-dwelling Japanese men. Importantly, the residual adverse effect appears to be present for at least ten years after smoking cessation. The findings highlight the importance of early avoidance or minimizing smoking exposure for the prevention of atherosclerotic disease.

Background:The association of proteinuria and reduced estimated glomerular filtration rate (eGFR) with cognition needs more clarification. We cross-sectionally examined whether proteinuria and reduced eGFR, even in moderate stages, were independently associated with lower cognition in a community-based sample of elderly men., Methods:Our cohort initially comprised 1,094 men aged 40-79 years from a random sample from Shiga, Japan in 2006-2008. Of 853 men who returned for the follow-up examination (2009-2014), we analyzed 561 who were ≥65 years, free of stroke, and completed the Cognitive Abilities Screening Instrument (CASI) at follow-up (higher CASI scores [range 0 to 100] indicate better cognition). Proteinuria was assessed via dipstick. eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration Equation. Participants were divided into three groups either by eGFR (≥60, 59-40, and, Results: Significant trends of lower cognition were observed across the groups of worse proteinuria and lower eGFR independently: multivariable-adjusted mean CASI scores were 90.1, 89.3, and 88.4 for proteinuria (Ptrend = 0.029), and 90.0, 88.5, and 88.5 for eGFR (Ptrend = 0.015) in mutual-adjustment model., Conclusions: Proteinuria and reduced eGFR, even in their moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. The results suggest the importance of proteinuria and low eGFR for early detection and prevention of cognitive decline.

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.

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.

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.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).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).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.

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.

Background Premature atrial contractions (PACs) are known predictor of atrial fibrillation; however very little has been revealed on its factors among Asian general population. We assessed the frequency of higher PAC counts and its association with relevant factors in general Japanese men. Methods We have conducted a population based cross sectional study among 517 healthy men from Kusatsu, Japan, aged between 40 and 79 years. 24 hours Holter electrocardiogram was performed to assess the PAC frequency. We divided participants into quartiles based on number of PACs/hour to compare the characteristics by using Cochran–Mantel–Hanzal test and ANOVA. We defined the highest quartile as event and multivariable logistic regression was performed to assess the significance with relevant factors. Results Median number of PACs was 2.84 PACs/hour. The highest quartile of PAC counts was >7.86PACs/hour. Age, triglycerides, blood pressure, ventricular contractions and heart rates were different among quartiles. In multivariable logistic regression analysis, higher age (OR, 95% CI: 1.35, 1.01-1.67), lower mean heart rates (OR, 95% CI: 0.97, 0.94-0.99), higher heart rate difference in a day (OR, 95% CI: 1.40, 1.12-1.75) and lower triglyceride (OR, 95% CI: 0.53, 0.33-0.82) were independently, significantly associated with highest quartile of PACs. Conclusions Higher PACs evaluated by Holter ECG was associated with higher age, lower heart rate, higher heart rate difference, and lower triglyceride in general Japanese men. Key messages The PAC frequency was high. Age, mean heart rates, difference between maximum and resting heart rates, triglycerides are possible risk factors for frequent PAC counts.

Background and purpose The association between an increased supraventricular ectopic beat (SVEB) and subclinical cerebrovascular disease remains unclear. Given the emerging concept that an increased SVEB is a marker of atrial cardiomyopathy or atherosclerosis burden, we sought to determine whether excessive supraventricular ectopic activity (ESVEA) is associated with a higher burden of subclinical cerebrovascular disease in the middle-aged to older cohort with neither apparent stroke nor atrial fibrillation. Methods We conducted a cross-sectional population-based study of 462 men (mean age, 68.1 years) who underwent 24-h Holter electrocardiography and brain magnetic resonance imaging. ESVEA was defined as the presence of >10 SVEBs/h. Subclinical cerebrovascular diseases were defined as silent brain infarct (SBI), white matter hyperintensity (WMH) and intracranial atherosclerotic stenosis (ICAS). The association of ESVEA with the presence of subclinical cerebrovascular diseases was adjusted for potential confounding covariates. Results A total of 88 (19.0%) participants had ESVEA and 81 (17.5%), 91 (19.7%) and 109 (23.6%) had SBI, WMH and ICAS, respectively. In multivariable-adjusted Poisson regression with robust error variance, ESVEA was associated with the presence of WMH (relative risk, 1.58; 95% confidence interval, 1.06-2.36) and ICAS (relative risk, 1.49; 95% confidence interval, 1.02-2.18), but not with that of SBI (relative risk, 1.32; 95% confidence interval, 0.86-2.01). These associations were consistent when the graded distributions of subclinical cerebrovascular diseases were applied as outcomes in ordinal logistic regression. Conclusions The ESVEA was independently associated with higher burdens of WMH and ICAS. This suggests that increased SVEBs might improve risk stratification of individuals at high risk of subclinical cerebrovascular disease and consequently apparent ischaemic stroke.

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, 70.0 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-hour ambulatory BP monitoring in 468 of the men. Variability indices included day-by-day, daytime, and nighttime 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 systolic BP 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 systolic BP (all heterogeneity P-values >0.1). Independent of mean systolic BP, greater nocturnal decline or morning pressor surge, but not day-by-day, daytime, or nighttime variability, in systolic BP was associated with higher burden of any or severe ICAS. CONCLUSIONS: 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.

Background: Few studies have compared accurately measured office, self-measured home, and ambulatory blood pressure (BP) for asymptomatic intracranial artery stenosis (ICAS). Relationship of day-by-day or short-term variability in BP to asymptomatic ICAS remains unclear. Objectives: To examine the association of office, home (mean value and day-by-day variability), and ambulatory BP indices (24-hour/daytime/nighttime mean values, short-term variability, nocturnal decline, and morning pressor surge) with asymptomatic ICAS. Methods: Data on office and 7-day home BP and magnetic resonance angiography to assess ICAS were obtained in 677 men (mean age, 70.0 years) from a population-based cohort. Among them, 468 underwent 24-hour ambulatory BP monitoring. Mild- or severe-ICAS was defined as 1-49% or ≥50% stenosis, respectively, and any-ICAS as either mild or severe-ICAS. Results: We observed mild- and severe-ICAS in 153 (22.6%) and 36 (5.3%) participants, respectively. In multivariable Poisson regression with robust error variance, higher systolic BP at 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 systolic BP (all heterogeneity Ps >0.1). Independent of mean systolic BP, greater nocturnal decline or morning pressor surge in systolic BP was associated with higher burden of any- or severe-ICAS. Conclusion: The magnitude of association of BP accurately measured at office for asymptomatic ICAS was comparable with that of BP at home or ambulatory BP monitoring. Circadian BP variation based on ambulatory BP monitoring may be considered when assessing ICAS in apparently healthy individuals.

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, Research members：Minoru Horie, Yoshihisa Nakagawa, Takashi Yamamoto, Yasutaka Nakano, Emiko Ogawa, Hiroshi Maegawa, Katsutaro Morino, Itsuko Miyazawa, Yoshiyuki Watanabe, Kazuhiko Nozaki, Ikuo Tooyama, Akihiko Shiino, Akira Andoh, Teruhiko Tsuru, Hisakazu Ogita, Naomi Miyamatsu, Yasuyuki Nakamura, Aya Kadota, Keiko Kondo, Sayuki Torii, Takashi Kadowaki, Sayaka Kadowaki, Sentaro Suzuki, Takahiro Ito, Ayako Kunimura, Hiroyoshi Segawa, Akira Fujiyoshi, Aya Higashiyama, Tomonori Okamura, Koichiro Azuma, Tatsuya Sawamura, Michiya Igase, Yasuharu Tabara, Akira Sekikawa, Emma J M Barinas-Mitchell, Daniel Edmundowicz, Takayoshi Ohkubo, Atsushi Hozawa, Yoshitaka Murakam, Nagako Okuda, Hisatomi Arima, Atsushi Satoh, Yoshikuni Kita, Takashi Hisamatsu, Masahiko Yanagita, Robert D Abbott, Seiko Ohno, Naoyuki Takashima, Naoko Miyagawa, Maryam Zaid, Yoshino Saito

Background: Blood pressure (BP) indexes (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], mean arterial pressure [MAP]) shows association with subclinical cerebrovascular diseases (SCVDs). Although various studies reported this association, there are still controversy in the effect size of long period versus short period of these indexes to SCVDs. Aim: Identifying the effect size of four BP indexes measured at two visits on SCVDs assessed by magnetic resonance imaging (MRI) in general Japanese men. Methods: Four office BP indexes were measured at two visits 4.5 years apart in general Japanese men aged 40-79 years. Participants without myocardial infarction or stroke history were analyzed (N=629). MRI obtained at 3 rd visit were investigated for prevalent of five SCVDs diagnosed as follows; lacunar infarction (LI)= any presence, periventricular hyperintensity (PVH)= Fazekas grade ≥2, deep subcortical white matter hyperintensity (DSWMH)= Fazekas grade ≥3, microbleeds= any presence, and intracranial arterial stenosis (ICAS)= ≥1% stenosis. Using multivariable logistic regression, we computed and compared odds ratio OR (95% CI) of each prevalent SCVD for 1 standard deviation higher of each of 4 BP indexes after adjusting for SCVDs’ conventional risk factors. Results: Participants’ mean age at Visit 1 was 63.9 years. Our results show all office BP indexes, except PP, similar association with MRI outcomes at both Visit 1 and Visit 2. SBP, DBP and MAP were associated with LI, PVH, DSWMH, microbleed and ICAS, while PP was associated with LI and ICAS only. Conclusion: In general Japanese men, BP indexes SBP, DBP and MAP measured at two distinct visits show similar association to all future MRI assessed SCVD, while PP shows association to LI and ICAS only.

Aim:Coronary artery calcification (CAC) is an independent predictor of stroke and dementia, in which subclinical cerebrovascular diseases (SCVDs) play a vital pathogenetic role. However, few studies have described the association between CAC and SCVDs. Therefore, the aim of this study was to assess the clinical relationship between CAC and SCVDs in a healthy Japanese male population., Methods:In this observational study, 709 men, free of stroke, were sampled from a city in Japan from 2010 to 2014. CAC was scored using the Agatston method. The following SCVDs were assessed using magnetic resonance imaging: intracranial arterial stenosis (ICAS), lacunar infarction, deep and subcortical white matter hyperintensity (DSWMH), periventricular hyperintensity (PVH), and microbleeds. The participants were categorized according to CAC scores as follows: no CAC (0), mild CAC (1-100), and moderate-to-severe CAC (＞100). The adjusted odds ratios of prevalent SCVDs were computed in reference to the no-CAC group using logistic regression., Results:The mean (standard deviation) age of the participants was 68 (8.4) years. Participants in the moderate-to-severe CAC category showed significantly higher odds of prevalent lacunar infarction, DSWMH, and ICAS in age-adjusted and risk-factor-adjusted models. Microbleeds and PVH, in contrast, did not show any significant associations. The trends for CAC with lacunar infarction, DSWMH, and ICAS were also significant (all P-values for trend ≤ 0.02)., Conclusions:Higher CAC scores were associated with higher odds of lacunar infarction, DSWMH, and ICAS. The presence and degree of CAC may be a useful indicator for SCVDs involving small and large vessels.

Background Reducing the urinary sodium-to-potassium ratio is important for reducing both blood pressure and risk of cardiovascular disease. Among free-living Japanese individuals, we carried out a randomized trial to clarify the effect of lifestyle modification for lowering urinary sodium-to-potassium ratio using a self-monitoring device. Methods This was an open, prospective, parallel randomized, controlled trial. Ninety-two individuals were recruited from Japanese volunteers. Participants were randomly allocated into intervention and control groups. A month-long dietary intervention on self-monitoring urinary sodium-to-potassium ratio was carried out using monitors (HEU-001F, OMRON Healthcare Co., Ltd., Kyoto, Japan). All participants had brief dietary education and received a leaflet as usual care. Monitors were handed out to the intervention group, but not to the control group. The intervention group was asked to measure at least one spot urine sodium-to-potassium ratio daily, and advised to lower their sodium-to-potassium ratio toward the target of less than 1. Outcomes included changes in 24-hour urinary sodium-to-potassium ratio, sodium excretion, potassium excretion, blood pressure, and body weight in both groups. Results Mean measurement frequency of monitoring was 2.8 times/day during the intervention. Changes in urinary sodium-to-potassium ratio were -0.55 in the intervention group and -0.06 in the control group (P = 0.088); respective sodium excretion changes were -18.5 mmol/24 hours and -8.7 mmol/24 hours (P = 0.528); and corresponding potassium excretion was 2.6 mmol/24 hours and -1.5 mmol/24 hours (P = 0.300). No significant reductions were observed in either blood pressure or body weight after the intervention. Conclusions Providing the device to self-monitor a sodium-to-potassium ratio did not achieve the targeted reduction of the ratio in "pure self-management" settings, indicating further needs to study an effective method to enhance the synergetic effect of dietary programs and self-monitoring practice to achieve the reduction. However, we cannot deny the possibility of reducing sodium-to-potassium ratio using a self-monitoring device.

Aim: We investigated whether 2 types of personalized health guidance (repeated and single counseling) in the Japanese nationwide cardiovascular prevention system promoted smoking cessation among smokers. Methods: The study included 47,745 Japanese smokers aged 40 to 74 years classified into 2 personalized health guidance schemes. After a 1-year follow-up, we compared the rates of smoking cessation between individuals who had received counseling (“supported”) and those who had not received counseling (“unsupported”). Using propensity score matching analysis, we estimated the average treatment effect (ATE) of each approach on smoking cessation after balancing out the characteristics between the supported and unsupported groups. The propensity score regression model included age, medical insurance type, weight gain since the age of 20 years, exercise, eating habits, alcohol intake, quality of sleep, readiness to modify lifestyle, willingness to receive support, and body mass index. Results: In the repeated counseling scheme, the age-adjusted rates of smoking cessation in the supported and unsupported groups were 8.8% and 6.3% for males, and 9.8% and 9.1% for females respectively. In the single counseling scheme, the corresponding rates were 8.4% and 7.3% for supported and unsupported males, and 11.0% and 11.7% for supported and unsupported females respectively. The ATE of repeated counseling was + 2.64% (95% confidence interval: + 1.51% to + 3.77%) for males and + 3.11% (−1.85% to +8.07%) for females. The ATE of single counseling was +0.61% (−1.17% to +2.38%) for males and −1.06% (−5.96% to +3.85%) for females. Conclusions: In the Japanese cardiovascular prevention system, repeated counseling may promote smoking cessation among male smokers.

High sodium-to-potassium ratios are associated with elevated blood pressure levels and an increased risk of cardiovascular diseases. We aimed to determine whether urinary sodium-to-potassium ratios fluctuate diurnally during the day to understand measured values of casual urinary sodium-to-potassium ratios. A total of 13,277 casual urine specimens were collected under free-living conditions from 122 Japanese normotensive and hypertensive individuals. Participants collected all casual urine samples in aliquot tubes, reported urine volumes and the time at each voiding for 10–22 days. Then, specimens were classified into hourly data. Diurnal patterns of urinary sodium-to-potassium ratios and urinary concentrations of sodium and potassium were evaluated. Overall mean values of hourly urinary sodium-to-potassium ratios were highest (4.1–5.0) in the early morning, lower (3.3–3.8) in the daytime and higher (4.0–4.4) toward evening hours. The mean urinary sodium and potassium concentrations were the lowest (90–110 and 24–32 mmol l−1, respectively) during the early morning and higher (110–140 and 35–43 mmol l−1, respectively) after mid-morning. Diurnal variability of potassium concentrations was larger than for sodium concentrations. Diurnal variations in urinary sodium-to-potassium ratios were comparable between normotensive and hypertensive individuals, between hypertensive individuals with and without antihypertensive medications, and among age and gender-specific subgroups. Overall mean hourly urinary sodium-to-potassium ratios fluctuated diurnally under free-living conditions and were higher during the morning and evening and lower during the daytime compared with 24-h urinary sodium-to-potassium ratios. Diurnal variation in urinary sodium-to-potassium ratios should be considered to understand actual daily dietary levels and avoid over- and under-estimation in clinical practice.

Background and Purpose— Few community-based studies have reported the prevalence of intracranial artery stenosis (ICAS) assessed with magnetic resonance angiography. The aim was to determine the prevalence of ICAS using magnetic resonance angiography in a general population of Japanese men and to investigate the associations between ICAS and conventional cardiovascular risk factors. Methods— The Shiga Epidemiological Study of Subclinical Atherosclerosis randomly recruited and examined participants from Kusatsu City, Shiga, Japan, in 2006 to 2008 (baseline); 740 men returned for follow-up and underwent 1.5 T brain magnetic resonance angiography in 2012 to 2015. Participants were categorized as having no-ICAS, mild-ICAS (1 to Results— The participants’ mean age was 68.0 years. The age-standardized prevalences of mild and severe-ICAS were 20.7% and 4.5%, respectively (with the population of the 2010 Japanese vital statistics as the reference). Age, hypertension, diabetes mellitus, and dyslipidemia were associated with a higher prevalence of severe-ICAS after simultaneous adjustment for conventional cardiovascular risk factors. Conclusions— In a community-based sample of Japanese men, ICAS was estimated to be present in 25.2%, and related to metabolic risk factors, in addition to hypertension and age. These results support the importance of comprehensive management of conventional cardiovascular risk factors for stroke prevention.

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

Background and Purpose: Intracranial subclinical vessel diseases are considered important indicators of cognitive impairment. However, comprehensive assessment on various types of vessel disease is lacking. We aim to compare various types of intracranial vessel disease in association with cognitive function among a community-based male population. Method: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited and examined participants from Shiga, Japan in 2006-08 at baseline. Among 824 male participants in the follow-up exam (2010-12), we restricted our analyses to those who underwent the Cognitive Abilities Screening Instrument (CASI), cranial magnetic resonance imaging/angiogram (MRI/MRA, 1.5-Tesla), and free of stroke or neurodegenerative disease. Using MRI/MRA, we assessed intracranial arterial stenosis and four types of small vessel diseases: lacunar infarction and microbleed, periventricular hyperintensity (PVH), deep and subcortical white matter hyperintensity (DSWMH). We graded each vessel disease into 3 grades by severity. Cerebral artery stenosis was graded according to the presence of most stenotic lesions in the major 11 vessels: no stenosis (grade 1), 1-50% stenosis at least 1 vessel (grade 2), ≥ 50% stenosis at least 1 vessel (grade 3). Lacunar infarct was graded according to number of infarct: 0 (grade 1), 1-2 (grade 2), >2 (grade 3). Microbleed was graded according to number of microbleed: 0 (grade 1), 1 (grade 2), ≥2 (grade 3). PVH and DSWMH were graded according to Shinohara’s scale (a modified Fazekas scale): scale 0 to 1 (grade 1), scale 2 (grade 2), scale ≥3 (grade 3). Using linear regression, CASI score (ranging from 0 to 100 with a higher score indicating better cognition) was calculated according to the grade of each vessel disease adjusted for age and education year attained. Results: We analyzed 693 men. Mean (standard deviation) age and CASI score was 67.9 (8.1) years, and 91.2 (5.4), respectively. Significant inverse trends were observed between disease grade and CASI score for DSWMH and PVH: adjusted CASI scores of grade 1, 2, and 3 were 91.7, 91.2, and 90.4 (P trend 0.015) for DSWMH, and 91.5, 90.4, and 89.8 (P trend 0.007) for PVH. No clear trend across the grade was observed in other vessel diseases. Conclusion: Among various types of intracranial subclinical vessel diseases assessed with MRA/MRI, white matter hyperintensity (PVH, and DSWMH) had significant dose-response relationships to cognitive function in a community-based male sample that has a relatively well-preserved cognition level. Our finding suggests that white matter hyperintensity is an important early predictor of cognitive functions among subclinical vessel diseases.

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 (FEV1) % 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 FEV1 % 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.

Cerebral small vessel disease (CSVD) is an important cause of stroke and dementia. Recent evidence showed that coronary artery calcium (CAC), a robust measure of subclinical atherosclerosis, independently predicts future dementia. One potential explanation for this observed link between CAC and dementia is that CAC is related to CSVD. However, limited study directly examined such association. Aim: To provide mechanistic explanation for the already-observed positive association between atherosclerosis and dementia. Methods: A total of 702 community dwelling men randomly sampled from Kusatsu City, Japan were analyzed. CAC was scored by Agatston’s method. Using MRI (magnetic resonance imaging) we assessed the following components as the measures of CSVD: lacunar infarcts (LI), microbleeds (MB), deep and subcortical white matter hyperintensity (DSWMH) and periventricular hyperintensity (PVH). CAC were categorized as absent (Agatston score=0), mild (more than zero and Results: Mean age of the participants was 69.7± 8.8 years. Prevalence of CSVD components was significantly higher in groups with higher CAC. LI was significantly associated with mild and moderate-to-severe CAC groups in unadjusted, age and risk factors adjusted analyses. Moreover, DSWMH was significantly associated with moderate-to-severe CAC group in unadjusted analysis as well as in age and risk factors adjusted analyses. But, MB and PVH were significantly associated with mild and moderate-to-severe CAC groups only in unadjusted analysis. After age and risk factors adjusted analyses the associations were no longer significant. Trend for a dose-response relation of CAC with LI and DSWMH were significant in unadjusted, age and risk factors adjusted analyses, but for MB and PVH, trends were significant only in unadjusted analysis. In Conclusion, those with higher CAC were associated with higher odds of having LI and DSWMH. Presence and degree of CAC may be useful in predicting CSVD.

This study was done to clarify the optimal number and type of casual urine specimens required to estimate urinary sodium/potassium (Na/K) ratio in individuals with high blood pressure. A total of 74 individuals with high blood pressure, 43 treated and 31 untreated, were recruited from the Japanese general population. Urinary sodium, potassium and Na/K ratio were measured in both casual urine samples and 7-day 24-h urine samples and then analyzed by correlation and Bland–Altman analyses. Mean Na/K ratio from random casual urine samples on four or more days strongly correlated with the Na/K ratio of 7-day 24-h urine (r=0.80–0.87), which was similar to the correlation between 1 and 2-day 24-h urine and 7-day 24-h urine (r=0.75–0.89). The agreement quality for Na/K ratio of seven random casual urine for estimating the Na/K ratio of 7-day 24-h urine was good (bias: −0.26, limits of agreements: −1.53–1.01), and it was similar to that of 2-day 24-h urine for estimating 7-day 24-h values (bias: 0.07, limits of agreement: −1.03 to 1.18). Stratified analyses comparing individuals using antihypertensive medication and individuals not using antihypertensive medication showed similar results. Correlations of the means of casual urine sodium or potassium concentrations with 7-day 24-h sodium or potassium excretions were relatively weaker than those for Na/K ratio. The mean Na/K ratio of 4–7 random casual urine specimens on different days provides a good substitute for 1–2-day 24-h urinary Na/K ratio for individuals with high blood pressure.

The association of high-density lipoprotein particle (HDL-P) with atherosclerosis may be stronger than that of HDL-cholesterol (HDL-C) and independent of conventional cardiovascular risk factors. Whether associations persist in populations at low risk of coronary heart disease (CHD) remains unclear. This study examines the associations of HDL-P and HDL-C with carotid intima-media thickness (cIMT) and plaque counts among Japanese men, who characteristically have higher HDL-C levels and a lower CHD burden than those in men of Western populations.We cross-sectionally examined a community-based sample of 870 Japanese men aged 40-79 years, free of known clinical cardiovascular disease (CVD) and not on lipid-lowering medication. Participants were randomly selected among Japanese living in Kusatsu City in Shiga, Japan.Both HDL-P and HDL-C were inversely and independently associated with cIMT in models adjusted for conventional CHD risk factors, including low-density lipoprotein cholesterol (LDL-C) and diabetes. HDL-P maintained an association with cIMT after further adjustment for HDL-C (P 0.01), whereas the association of HDL-C with cIMT was noticeably absent after inclusion of HDL-P in the model. In plaque counts of the carotid arteries, HDL-P was significantly associated with a reduction in plaque count, whereas HDL-C was not.HDL-P, in comparison to HDL-C, is more strongly associated with measures of carotid atherosclerosis in a cross-sectional study of Japanese men. Findings demonstrate that, HDL-P is a strong correlate of subclinical atherosclerosis even in a population at low risk for CHD.

Introduction: The relationship between chronic kidney disease (CKD) and cognitive function remains to be determined. Existing studies focused primarily on estimated glomerular filtration rate (eGFR) but not proteinuria in relation to cognitive function. Hypothesis: In a community-based sample, lower eGFR and presence of proteinuria are cross-sectionally independently associated with lower cognition. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited and examined participants from Shiga, Japan in 2006-08 at baseline. Among 824 male participants in the follow-up exam (2010-12), we restricted our analyses to those who underwent the Cognitive Abilities Screening Instrument (CASI), age ≥65 years-old, free of stroke, with no missing pertinent covariates. We calculated eGFR (creatinine-based) according to the 2012-guideline by the Japanese Society of Nephrology. We then divided the participants into three groups by eGFR of ≥60, 59-40, and 2 ), and separately divided into three groups according to proteinuria using urine dipstick: (-), (-/+), and ≥(1+). We defined CKD as either eGFR Results: We analyzed 541 men. The mean [standard deviation] of age and unadjusted score were 72.6 [4.3] years and 89.7 [6.0]. Prevalence of CKD was 56%. The score was significantly lower in participants with CKD than those without it (P=0.03). eGFR and proteinuria categories were separately and jointly associated with lower CASI score in a graded fashion (Ps for trend Table 1 ). Conclusions: Lower eGFR and higher degree of proteinuria were independently associated with lower cognitive function in the community-based men. CKD even in its early phase may predispose to lower cognitive function.

Objective The utility of lipoprotein particle profiles measured by nuclear magnetic resonance (NMR) spectroscopy beyond standard serum lipids remains inconclusive. Furthermore, few studies have compared NMR measurements with standard lipids in association with coronary artery calcification (CAC) in Japanese, where the coronary atherosclerotic burden is low. We examined whether NMR-based lipoprotein particle profiles are associated with CAC, and compared them with standard lipid and lipid ratios in the Japanese general population. Methods and Results We conducted a cross-sectional study in 851 men aged 40–79 years without cardiovascular diseases and lipid-lowering therapies. Adjusted odds ratios (ORs) (95% confidence intervals) for the top versus the bottom quartile of NMR-measured particle concentrations were 2.01 (1.24–3.23) for low-density lipoprotein (LDL-P), 1.04 (0.62–1.75) for high-density lipoprotein (HDL-P), 1.82 (1.13–2.95) for very-low-density lipoprotein (VLDL-P), and 1.92 (1.18–3.17) for LDL-P/HDL-P ratio. Similarly adjusted ORs of NMR-measured particle sizes were 0.59 (0.36–0.97) for LDL-P, 0.66 (0.40–1.10) for HDL-P, and 0.67 (0.40–1.12) for VLDL-P. The corresponding ORs were 1.82 (1.14–2.90) for total cholesterol (TC), 2.06 (1.28–3.30) for low-density lipoprotein cholesterol (LDL-C), 0.56 (0.34–0.91) for high-density lipoprotein cholesterol (HDL-C), 2.02 (1.24–3.29) for triglycerides, 2.08 (1.29–3.36) for non-high-density lipoprotein cholesterol (non-HDL-C), 2.27 (1.37–3.78) for TC/HDL-C ratio, and 1.73 (1.06–2.85) for LDL-C/HDL-C ratio. After mutual adjustment for total LDL-P concentration and TC/HDL-C ratio or non-HDL-C, LDL-P was no longer associated, whereas TC/HDL-C ratio remained significantly associated with CAC. Conclusions In community-based Japanese men, the overall association of CAC with NMR-measured lipoprotein indices is comparable, but not superior, to that with standard lipids.