Low-density lipoprotein particle profiles compared with standard lipids measurements in the association with asymptomatic intracranial artery stenosis.

The Shiga Epidemiological Study of Subclinical Atherosclerosis was conducted in Kusatsu City, Shiga, Japan, from 2006 to 2008. Participants were measured for LDL-p through nuclear magnetic resonance technology. 740 men participated in follow-up and underwent 1.5 T brain magnetic resonance angiography from 2012 to 2015. Participants were categorized as no-ICAS, and ICAS consisted of mild-ICAS (1 to < 50%) and severe-ICAS (≥ 50%) in any of the arteries examined. After exclusion criteria, 711 men left for analysis, we used multiple logistic regression to examine the association between lipid profiles and ICAS prevalence. Among the study participants, 205 individuals (28.8%) had ICAS, while 144 individuals (20.3%) demonstrated discordance between LDL-c and LDL-p levels. The discordance "low LDL-c-high LDL-p" group had the highest ICAS risk with an adjusted OR (95% CI) of 2.78 (1.55-5.00) in the reference of the concordance "low LDL-c-low LDL-p" group. This was followed by the concordance "high LDL-c-high LDL-p" group of 2.56 (1.69-3.85) and the discordance "high LDL-c-low LDL-p" group of 2.40 (1.29-4.46). These findings suggest that evaluating LDL-p levels alongside LDL-c may aid in identifying adults at a higher risk for ICAS.

Heart Rate Fragmentation, Ambulatory Blood Pressure, and Coronary Artery Calcification: A Population-Based Study.

Background: Little is known regarding whether ultra-rapid patterns of heart rate variability (eg, heart rate fragmentation [HRF]) are associated with coronary artery calcification (CAC) in a general population. Objectives: This study aimed to assess the association between HRF and CAC, and whether these associations are independent of systolic blood pressure (SBP) levels. Methods: From SESSA (the Shiga Epidemiological Study of Subclinical Atherosclerosis), we used data from 24-hour ambulatory blood pressure monitoring to identify awake and asleep SBP levels, and data from concurrent 24-hour Holter monitoring to quantify HRF using the awake and asleep percentage of inflection points (PIP). CAC on computed tomography scanning was quantified using an Agatston score. We used multivariable binomial logistic regression to assess the associations of PIP and ambulatory SBP with the presence of CAC, as defined by Agatston score >0. Results: Of the 508 participants in this study (mean age: 66.5 ± 7.3 years), 325 (64%) had CAC and 183 (36%) did not. In fully adjusted models of prevalent CAC that also included office SBP, the ORs with 95% CIs for awake PIP, awake SBP, asleep PIP, and asleep SBP were 1.23 (95% CI: 0.99-1.54), 1.40 (95% CI: 1.11-1.77), 1.31 (95% CI: 1.05-1.62), and 1.28 (95% CI: 1.02-1.60), respectively. There was no evidence of interaction between PIP and ambulatory SBP in association with CAC. Results were similar when other HRF indices instead of PIP were used. Conclusions: Higher HRF and SBP levels during sleep are each associated with the presence of CAC in a general male population.

Relationship Between Hemoglobin Concentration and Cardiovascular Disease Mortality in a 25-Year Follow-up Study of a Japanese General Population　- NIPPON DATA90.

BACKGROUND: Deviations of hemoglobin from normal levels may be a factor in cardiovascular disease (CVD) risk; however, conclusive evidence is lacking. In addition, preclinical conditions may influence hemoglobin concentrations, but studies focusing on reverse causation are limited. Thus, we examined the relationship between hemoglobin concentrations and CVD mortality risk, considering reverse causation.Methods and Results: In a prospective cohort representative of the general Japanese population (1990-2015), we studied 7,217 individuals (mean age 52.3 years; 4,219 women) without clinical CVD at baseline. Participants were categorized into sex-specific hemoglobin quintiles (Q1-Q5) and data were analyzed using the Cox proportional hazards model adjusted for possible confounders. During a 25-year follow-up, 272 men and 334 women died from CVD. Adjusted hazard ratios for CVD mortality across sex-specific quintiles, using Q3 as the reference, were significantly higher for Q1 (1.40; 95% confidence interval [CI] 1.08-1.82) and Q5 (1.49; 95% CI 1.14-1.96), and remained significant after excluding deaths within the first 5 years of follow-up to consider reverse causation (1.35 [95% CI 1.02-1.79] and 1.45 [95% CI 1.09-1.94], respectively). A similar U-shaped association was seen between transferrin saturation levels and CVD mortality, but after excluding deaths within the first 5 years the association was significant only for Q1. CONCLUSIONS: Low and high hemoglobin concentrations were associated with an increased risk of CVD mortality.

Association of step counts with cognitive function in apparently healthy middle-aged and older Japanese men.

Background: Increasing physical activity may prevent cognitive decline. Previous studies primarily focused on older adults and used self-reported questionnaires to assess physical activity. We examined the relationship between step count, an objective measure of physical activity, and cognitive function in community-based middle-aged and older Japanese men. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis randomly recruited community-dwelling healthy men aged 40-79 years from Shiga, Japan, and measured their step counts over 7 consecutive days using a pedometer at baseline (2006-2008). Among men who returned for follow-up (2009-2014), we assessed their cognitive function using the Cognitive Abilities Screening Instrument (CASI) score. We restricted our analyses to those with valid 7-day average step counts at baseline and those who remained free of stroke at follow-up (n = 676). Using analysis of covariance, we calculated the adjusted means of the CASI score according to the quartiles of the average step counts. Results: The mean (standard deviation) of age and unadjusted CASI score were 63.8 (9.1) years and 90.8 (5.8), respectively. The CASI score was elevated in higher quartiles of step counts (90.2, 90.4, 90.6, and 91.8 from the lowest to the highest quartile, respectively, [p for trend = 0.004]) in a model adjusted for age and education. Further adjustment for smoking, drinking, and other cardiovascular risk factors resulted in a similar pattern of association (p for trend = 0.005). Conclusion: In apparently healthy middle-aged and older Japanese men, a greater 7-day average step count at baseline was associated with significantly higher cognitive function score.

Alcohol Consumption and Cerebral Small- and Large-Vessel Diseases: A Mendelian Randomization Analysis.

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.

Association of Anthropometric and CT-Based Obesity Indices with Subclinical Atherosclerosis.

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.

High blood pressure and colorectal cancer mortality in a 29-year follow-up of the Japanese general population: NIPPON DATA80.

Onco-hypertension has been proposed, although associations of high blood pressure (BP) with cancer risk remain inconsistent. We examined associations of high BP with risk of mortality from stomach, lung, colorectal, liver, and pancreatic cancers independent of possible confounders in an analysis that excluded deaths within the first 5 years of follow-up to consider the reverse causality. In a prospective cohort representative of the general Japanese population (1980-2009), we studied 8088 participants (mean age, 48.2 years; 56.0% women) without clinical cardiovascular disease or antihypertensive medication at baseline. Fine-Gray competing risks regression was used to estimate hazard ratios for 10 mmHg higher BP adjusted for confounders including smoking, alcohol-drinking, obesity, and diabetes mellitus. During 29-year follow-up, 159 (2.0%), 159 (2.0%), 89 (1.1%), 86 (1.1%), and 68 (0.8%) participants died from stomach, lung, colorectal, liver, and pancreatic cancers, respectively. We observed a positive association of high BP with risk of colorectal cancer mortality but not with mortality risks from any other cancers. The association with colorectal cancer mortality for systolic and diastolic BP was evident in those aged 30-49 years (hazard ratios 1.43 [95% confidence interval, 1.22-1.67] and 1.86 [1.32-2.62], respectively) but not in those aged 50-59 years and ≥60 years (P for age interaction <0.01 for systolic and diastolic BP). The associations with colorectal cancer mortality were similar in the analyses stratified by smoking, alcohol-drinking, obesity, and diabetic status. In conclusion, high BP among young to middle-aged adults was independently associated with risk of colorectal cancer mortality later in life.

The gut microbiota and coronary artery calcification in Japanese men.

BACKGROUND: The gut microbiota differs between patients with coronary artery disease (CAD) and healthy controls; however, it currently remains unclear whether these differences exist prior to the onset of CAD. We herein investigated the gut microbiota associated with subclinical coronary artery calcification (CAC) in a Japanese population. METHODS: A total of 663 Japanese men were enrolled in this cross-sectional study. Computed tomography and gut microbiology tests were performed, and CAC scores were calculated using the Agatston method. Participants were categorized into 4 groups based on their CAC scores: CAC = 0, 0

Association and dose-response relationship between exposure to alcohol advertising media and current drinking: a nationwide cross-sectional study of Japanese adolescents.

BACKGROUND: Underage drinking is a public health concern. However, few studies have examined the association between alcoholic beverage advertising and underage drinking, particularly in countries with low underage drinking rates, such as Japan. Therefore, we aimed to investigate the relationship between exposure to advertising in various media and alcohol drinking among Japanese adolescents. METHODS: We conducted a cross-sectional study involving 15,683 adolescents (51% girls) using data from a nationwide lifestyle survey in 2021 among junior and senior high schools across Japan. Media types were websites, stores, and public transportation. We defined current drinking as alcohol consumption of ≥1 day in the 30 days preceding the survey. Multivariable logistic regression was used to examine the association between exposure to alcohol advertisements and current drinking, adjusting for sex, grades, school area, lifestyle (bedtime and having fun at school), and addictive behaviors (smoking status and parents' alcohol consumption). RESULTS: The prevalence of current drinking was 2.2% (2.3% of boys and 2.0% of girls). Students who were exposed to any alcohol advertising media had higher odds of current drinking compared with those who were not (odds ratio, 1.48; 95% confidence interval [CI], 1.18-1.87). Students who were exposed to web, in-store, and public transportation advertisements had odds ratios of 1.44 (95% CI, 1.14-1.81), 1.62 (1.28-2.05), and 1.45 (1.06-1.98) of current drinking, respectively, compared with those who were not. The association of exposure to alcohol advertising media with the prevalence of current drinking was similar among boys and girls (all p for sex interaction >0.1), except for that of exposure to web advertisements; its association with current drinking was more pronounced in girls (p for sex interaction = 0.046). Exposure to a larger cumulative number of different alcohol advertising media was independently associated with a higher prevalence of current drinking among all students, boys, and girls (p-values for trend <0.001, 0.031, and <0.001, respectively; p for sex interaction = 0.085). CONCLUSIONS: We found an association with a dose-response relationship between exposure to alcohol advertisements and current drinking among adolescents in junior and senior high schools across Japan. Our findings highlight the need for further advertising regulations to prevent underage drinking.

Coronary Artery Calcium in Assessment of Atherosclerotic Cardiovascular Disease Risk and its Role in Primary Prevention.

Coronary artery calcium (CAC), which is detected using computed tomography scanning, is a well-established indicator of subclinical atherosclerosis. The CAC score is independently associated with atherosclerotic cardiovascular disease (ASCVD) outcomes and provides improved predictive values for estimating the risk of ASCVD beyond traditional risk factors. Thus, CAC is considered to have important implications for reclassification as a decision aid among individuals in the preclinical phase and as the primary prevention of ASCVD. This review is focused on epidemiological evidence on CAC in asymptomatic population-based samples from Western countries and Japan. We also discuss the usability of CAC as a tool for assessing ASCVD risk and its role in the primary prevention of ASCVD. A lack of evidence for the CAC score in ASCVD risk assessment beyond traditional risk factors in populations other than those in Western countries (including Japan) warrants further investigation. Clinical trials are also necessary to demonstrate the usefulness and safety of CAC screening in the primary prevention of ASCVD.

Relationships of rapid eating with visceral and subcutaneous fat mass and plasma adiponectin concentration.

Rapid eating has been demonstrated to be associated with obesity and overweight. However, few studies have characterized the separate relationships of eating speed with visceral and subcutaneous fat mass or circulating adiponectin concentration. We hypothesized that rapid eating is associated with the larger visceral fat tissue (VFT) area and lower adiponectin concentration, but not with the subcutaneous fat tissue (SFT) area in men and women. We performed a cross-sectional study of 712 adults aged 20-86 years (528 men and 184 women; mean ± SD age 59.36 ± 13.61 years). The participants completed a self-reported questionnaire, and underwent anthropometric and laboratory measurements and computed tomographic imaging of the abdomen as a part of annual medical check-ups. Multivariate linear regression analyses revealed that rapid eating was associated with larger visceral (B = 24.74; 95% CI 8.87-40.61, p = 0.002) and subcutaneous fat areas (B = 31.31; 95% CI 12.23-50.38, p = 0.001), lower adiponectin concentration (B = - 2.92; 95% CI - 4.39- - 1.46, p < 0.001), higher body mass index (BMI) (B = 2.13; 95% CI 1.02-3.25, p < 0.001), and larger waist circumference (B = 5.23; 95% CI 2.16-8.30, p < 0.001) in men, which is partially consistent with the hypothesis. In contrast, rapid eating was found to be associated only with BMI, and not with abdominal adipose area or adiponectin concentration in women, which is a result that is not consistent with the hypothesis. These results suggest that there is no difference in the association of rapid eating with VFT and SFT areas.

At-risk internet addiction and related factors among senior high school teachers in Japan based on a Nationwide survey.

BACKGROUND: Internet addiction (IA) has been drawing attention to mental health. However, few reports have been found on the related factors of at-risk IA among regular workers by a nationwide survey. The study aimed to evaluate the characteristics of at-risk IA and identify related factors among senior high school teachers in Japan. METHODS: This survey was a cross-sectional survey of high schools across Japan in 2017. There were 3189 teachers (2088 males and 1098 female) who participated in this survey. The questionnaire asked about their devices, both the time and the activities of using their internet, and sociodemographic factors. IA was measured by the internet addiction test (IAT) by which 40-79 points were classified as at-risk IA, and more as IA. We compared the related factors of at-risk IA and non-IA using descriptive analysis and multivariable regression analysis. RESULTS: The rates of IA and at-risk IA were 0.09% (n = 3) and 6.91% (n = 220), respectively. At-risk IA was positively associated with activities on the internet for gaming, entertainment, net-surfing, and younger ages. In addition, the at-risk IA group had a longer time spent on the internet than the non-IA group. CONCLUSIONS: Around 7% of high school teachers are at-risk IA in this survey, though they have regular work. Our results suggest that at-risk IA may be reinforced not only by the active internet use such as gaming, but also by purposeless behaviors, such as net-surfing. Managing time on the internet may support preventing at-risk IA among senior high school teachers.

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

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

Non-missense variants of KCNH2 show better outcomes in type 2 long QT syndrome.

AIMS: More than one-third of type 2 long QT syndrome (LQT2) patients carry KCNH2 non-missense variants that can result in haploinsufficiency (HI), leading to mechanistic loss-of-function. However, their clinical phenotypes have not been fully investigated. The remaining two-thirds of patients harbour missense variants, and past studies uncovered that most of these variants cause trafficking deficiency, resulting in different functional changes: either HI or dominant-negative (DN) effects. In this study, we examined the impact of altered molecular mechanisms on clinical outcomes in LQT2 patients. METHODS AND RESULTS: We included 429 LQT2 patients (234 probands) carrying a rare KCNH2 variant from our patient cohort undergoing genetic testing. Non-missense variants showed shorter corrected QT (QTc) and less arrhythmic events (AEs) than missense variants. We found that 40% of missense variants in this study were previously reported as HI or DN. Non-missense and HI-groups had similar phenotypes, while both exhibited shorter QTc and less AEs than the DN-group. Based on previous work, we predicted the functional change of the unreported variants-whether they cause HI or DN via altered functional domains-and stratified them as predicted HI (pHI)- or pDN-group. The pHI-group including non-missense variants exhibited milder phenotypes compared to the pDN-group. Multivariable Cox model showed that the functional change was an independent risk of AEs (P = 0.005). CONCLUSION: Stratification based on molecular biological studies enables us to better predict clinical outcomes in the patients with LQT2.

Association between proprotein convertase subtilisin/kexin type 9 and subclinical cerebrovascular disease in the community.

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.

Associations of indoor and outdoor temperatures and their difference with home blood pressure: The Masuda Study.

Ambient temperature and blood pressure (BP) are closely related; however, few studies have examined the association of out-of-office BP with indoor or outdoor temperature. The effect of the difference between indoor and outdoor temperatures on BP also remains unknown. Therefore, this study aimed to investigate the association of indoor and outdoor temperatures and their difference with home BP. We studied healthy 352 participants (mean age, 49.8 years; 46.0% women) from a population-based cohort using 2-year data on temperature and self-measured home BP. We measured home BP and indoor temperature at the same time in the morning and evening every day. Outdoor temperature during the same period was based on national data. We observed 82,900 home BP measurements in the morning and 66,420 in the evening. In the mixed-effects model adjusted for age, sex, and possible confounders, indoor temperature was inversely associated with systolic and diastolic BP in the morning and evening. A 1 °C increase in indoor temperature reduced systolic and diastolic BP by 0.37 and 0.22 mmHg, respectively, in the morning and by 0.45 and 0.30 mmHg, respectively, in the evening (all P-values<0.001). The magnitude of associations was stronger for indoor than outdoor temperature. Similarly, a 1 °C increase in indoor temperature above outdoor temperature decreased systolic and diastolic BP by 0.33 and 0.12 mmHg, respectively, in the morning and by 0.45 and 0.26 mmHg, respectively, in the evening independent of outdoor temperature (all P-values <0.001). In conclusion, controlling indoor temperature is important to stabilize home BP levels.

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

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