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Background and purpose: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new target for reducing low‐density lipoprotein cholesterol and incident cardiovascular disease, including stroke. However, the clinical relevance of circulating PCSK9 levels has been poorly elucidated in the general population, particularly in association with subclinical cerebrovascular disease including cerebral small vessel disease (CSVD) and intracranial artery stenosis (ICAS). Methods: In community‐dwelling Japanese men (n = 526) aged 46–82 years without a history of cardiovascular disease, the associations of serum PCSK9 levels with the prevalence of CSVD and ICAS were assessed using magnetic resonance imaging. CSVD included lacunar infarction, deep and subcortical white matter hyperintensity, periventricular hyperintensity and cerebral microbleeds. Results: The median (interquartile range) age at baseline and serum PCSK9 levels were 69 (63–74) years and 240 (205–291) ng/ml, respectively. After adjusting for traditional cardiovascular risk factors including low‐density lipoprotein cholesterol, multivariable Poisson regression with robust error variance revealed a significant association between PCSK9 levels (per 1 SD) and ICAS (relative risks 1.18, 95% confidence interval 1.02–1.37). Multivariable ordinal logistic regression for ICAS, with stenosis graded as mild (<50%) or moderate–severe (≥50%), revealed a similar association (common odds ratio 1.31, 95% confidence interval 1.04–1.64). However, no significant association was observed between serum PCSK9 levels and CSVD. Conclusions: Higher circulating PCSK9 levels were independently associated with an ICAS prevalence but not with CSVD prevalence. The quantification of circulating PCSK9 levels may help to identify individuals at high risk for cerebrovascular disease in the general population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the incidence rates and predictors of lower limb fractures in a general Japanese population. Methods: NIPPON DATA is a nationwide, long-term, prospective cohort study of individuals who participated in the National Cardiovascular Survey Japan and the National Nutrition Survey in 1990. Overall, 3,134 individuals (1,827 women, 1,307 men) who participated in follow-up assessments in 1995, 2000, and/or 2006 were included in the present analysis. The outcomes of this study were lower limb fractures (including proximal femur fractures). Results: The mean age at baseline was 63.8 years in women and 63.1 years in men. The average body mass index (BMI) was 23.3 kg/m2 in women and 22.9 kg/m2 in men. During a mean follow-up of 12.1 years, 271 total lower limb fractures were observed. In women, older age, lower BMI, and less intake of vegetables were associated with increased risks of proximal femur fractures. With regard to the outcome of total lower limb fractures, less intake of vegetables and regular exercise were significant predictors in women. Calcium intake was not significantly associated with proximal femur or total lower limb fractures. There were no significant predictors of proximal femur or total lower limb fractures in men, except for age. Conclusions: Aging was a significant risk factor for proximal femur and total lower limb fractures in both men and women. With regard to modifiable risk factors, low BMI and low intake of vegetables were associated with increased risks of proximal femur and/or total lower limb fractures in the general population of Japanese women. [ABSTRACT FROM AUTHOR]

Low birth weight has been associated with cardiovascular diseases. The waist-to-height ratio is a good indicator of risks for these diseases. The objective of this study was to examine the associations between birth weight and adult waist-to-height ratio in a Japanese population. A cross-sectional study, comprised of 851 subjects (401 men and 450 women) aged 35-62 years who were born at full term, was conducted at a medical checkup. The subjects responded to a questionnaire about weight at birth, and data on physical characteristics were collected from the results of the medical checkup. The subjects were stratified with sex and a Body Mass Index of 25 kg/m² to elucidate the effects of birth weight on adult waist-to-height ratio. Analysis of covariance was used to compare the physical condition among the 4 birth weight categories. After adjusting for age, alcohol consumption, smoking status and exercise, the height was significantly lower in the birth weight < 2,500 g category among men (P < 0.001) and women (P < 0.001), while the waist-to-height ratio was significantly higher in the birth weight < 2,500 g category, compared with the > 3,500 g category in the non-obese women (P = 0.004), but not in the obese women. In conclusion, low birth weight was independently associated with a low adult height among men and women and with a high adult waist-to-height ratio among non-obese women. Our results suggest that intrauterine environmental insults might lead to accumulation of visceral fat among non-obese women. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Low-density lipoprotein particle (LDL-P) has recently been found to be a stronger predictor of cardiovascular disease (CVD) than LDL-cholesterol (LDL-C). Objectives Whether LDL-P is associated with subclinical atherosclerosis, independent of LDL-C, as well as other lipid measures has not been fully examined. We aimed to analyze LDL-P associations with measures of subclinical atherosclerosis. Methods We examined 870 Japanese men randomly selected from Kusatsu City, Shiga, Japan, aged 40–79 years from 2006–2008, free of clinical CVD and not using lipid-lowering medication. Cross-sectional associations of lipid measures with carotid intima-media thickness (cIMT) and coronary artery calcification (CAC; >0 Agatston score) were examined. Results LDL-P was significantly positively associated with cIMT and maintained this association after adjustments for LDL-C and other lipid measures. Although these lipid measures were positively associated with cIMT, model adjustment for LDL-P removed any significant relationships. Higher LDL-P was associated with a significantly higher odds ratio of CAC and further adjustment for LDL-C did not affect this relationship. In contrast, the LDL-C association with CAC was no longer significant after adjustment for LDL-P. Other lipid measures attenuated associations of LDL-P with CAC. Likewise, associations of these measures with CAC were attenuated when model adjustments for LDL-P were made. Conclusions In a community-based sample of Japanese men, free of clinical CVD, LDL-P was a robust marker for subclinical atherosclerosis, independent of LDL-C and other lipid measures. Associations of LDL-C and other lipid measures with either cIMT or CAC were generally not independent of LDL-P. [ABSTRACT FROM AUTHOR]

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 β-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., Competing Interests: Conflict of interest: The authors declare that they have no competing interests., (Copyright ©The authors 2024.)

Aims: It remains inconclusive regarding alcohol intake and stroke risk because determining risk factors depends on the specific pathogenesis of stroke. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in cerebral small- and large-vessel diseases., Methods: We studied 682 men (mean age, 70.0 years), without stroke, in a cross-sectional Mendelian randomization analysis. We assessed small-vessel diseases (SVDs), which comprised lacunar infarcts, white matter hyperintensities (WMHs), and cerebral microbleeds, and large intracranial artery stenosis (ICAS) on brain magnetic resonance imaging., Results: The median (25%tiles, 75%tiles) alcohol consumption by ALDH2-rs671 inactive A allele (n=313 [45.9%]) and non-A allele (n=369 [54.1%]) carriers was 3.5 (0.0, 16.0) and 32.0 (12.9, 50.0) g/day, respectively. Non-A allele carriers had higher prevalent hypertension and lower low-density lipoprotein cholesterol concentrations than A allele carriers. In age-adjusted ordinal logistic regression for graded burden, odds ratios (95% confidence intervals) for total SVDs, lacunar infarcts, WMHs, cerebral microbleeds, and ICAS in non-Aallele carriers were 1.46 (1.09-1.94), 1.41 (0.95-2.08), 1.39 (1.05-1.85), 1.69 (1.06-2.69), and 0.70 (0.50-0.98), respectively, compared with A allele carriers. These associations attenuated to statistical non-significance after considering covariates and amount of alcohol intake., Conclusions: Our findings suggest a positive association of alcohol consumption with risk of cerebral SVDs and its inverse association with risk of large-vessel disease through intermediaries, such as hypertension or low-density lipoprotein cholesterol. These findings provide insight into potential causal mechanisms linking alcohol consumption with stroke risk.

Aim: 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: We assessed cross-sectcional associations of anthropometric and CT-based obesity indices with CAC, AoAC, and AVC. Anthropometric measures included body mass index (BMI), waist circumference, hip ircumference, waist-to-hip circumference ratio, and waist-to-height ratio in 931 men (mean age, 63.7 years) from a population-based cohort. 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 (electron beam CT and multidetector row CT), anthropometric and CT-based obesity indices were positively associated with CAC (p＜0.01). Conversely, VAT-to-SAT ratio and VAT-to-TAT ratio were positively associated with AoAC (p＜0.01). Any obesity indices were not associated with AVC., Conclusions: The strength of the associations of obesity indices with subclinical atherosclerosis varied according to the anatomically distinct atherosclerotic lesions, among men.

Background: The association between alcohol consumption and atherosclerotic cardiovascular disease (ASCVD) was controversial, and no previous studies have shown the impact of dyslipidemia on the association. We aimed to clarify the association between alcohol consumption and death from cardiovascular disease (CVD) and its subtypes and the impact of dyslipidemia on the association., Methods: We conducted a 20-year cohort study to clarify the association between alcohol intake and death from CVD and its subtypes in 2,909 Japanese men. We estimated the hazard ratio (HR) and 95% confidence intervals (CIs) for current drinkers with non-drinkers as the reference, after adjusting for potential confounders using Cox proportional hazards models. We also investigated the association between alcohol consumption and ASCVD or CVD death stratified by the presence or absence of dyslipidemia., Results: During 50,782 person-years of follow-up period, 223 participants died from total CVD, 110 participants died from ASCVD, and 25 participants died from cerebral hemorrhage. Current drinkers with 1 gou/day were significantly associated with lower risk of ASCVD (HR: 0.60, 95%CI: 0.37-0.98), which is more apparent in those without dyslipidemia, and current drinkers with ≥3 gou/day were significantly associated with higher risk of cerebral hemorrhage (HR: 4.13, 95%CI: 1.12-15.19)., Conclusions: Small amounts of alcohol drinking were associated with lower risk of ASCVD in Japanese men, especially those without dyslipidemia. Meanwhile, excessive alcohol drinking was associated with higher risk of cerebral hemorrhage. Our findings suggest that it is important for current Japanese drinkers to reduce alcohol consumption for preventing ASCVD or cerebral hemorrhage.

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.

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.

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 β (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 β (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.

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/1.73m 2 ) (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 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.

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.

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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: 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 <40 mL/min/1.73 m 2 ) or by proteinuria (no, trace, and positive), considered normal, moderate, and advanced, respectively. Using linear regression, we computed mean CASI score, with simultaneous adjustment for proteinuria and eGFR in addition to other potential confounders., 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 (P trend = 0.029), and 90.0, 88.5, and 88.5 for eGFR (P trend = 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: Excessive alcohol intake has been shown to be associated with cardiovascular disease via metabolic pathways. However, the relationship between alcohol intake and obesity has not been fully elucidated. We aimed to examine the association of alcohol consumption with fat deposition and anthropometric measures., Methods: From 2006-2008, we conducted a cross-sectional study in a population-based sample of Japanese men aged 40 through 79 years. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography imaging. Based on a questionnaire, we classified participants into five groups according to weekly alcohol consumption, excluding former drinkers: non-drinkers (0 g/week), 0.1-160.9, 161-321.9, 322-482.9, and ≥483 g/week. Multivariable linear regression was used to estimate adjusted means of obesity indices for each group., Results: We analyzed 998 men (mean age and body mass index [BMI], 63.8 years and 23.6 kg/m 2 , respectively). Higher weekly alcohol consumption was strongly and significantly associated with higher abdominal VAT area, percentage of VAT, and VAT-to-SAT ratio (all P for trend <0.001), and also with waist circumferences and waist-to-hip ratio (P for trend = 0.042 and 0.007, respectively). These associations remained significant after further adjustment for BMI, whereas alcohol consumption had no significant association with abdominal SAT area., Conclusions: Higher alcohol consumption was associated with higher VAT area, VAT%, and VAT-to-SAT ratio, independent of confounders, including BMI, in general Japanese men. These results suggest that alcohol consumption may have a potential adverse effect on visceral fat deposition.