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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: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.