Whether hyperuricemia (HU) independently predicts cardiovascular disease (CVD) remains debated, whereas chronic kidney disease (CKD) is a well-established risk factor. This study assessed the independent and mediated association of HU in CKD on long-term CVD mortality in a 30-year nationwide Japanese cohort. Data from NIPPON DATA90 participants aged ≥ 30 years enrolled in 1990 and followed for up to 30 years were used. HU was defined as serum uric acid ≥ 416.4 µmol/L, and CKD as an estimated glomerular filtration rate < 60 mL/min/1.73 m² or positive proteinuria. Four baseline categories were created (neither, HU-only, CKD-only, both conditions), and analyzed via Cox models to estimate hazard ratios (HR) for CVD mortality, adjusted for age, sex, hypertension, diabetes mellitus, dyslipidemia, BMI, and history of smoking/alcohol. Among 7,336 participants (58.5

Introduction: Sleep quality could be an important risk factor for cardiovascular disease, beyond the influence of sleep duration. In particular, difficulty falling asleep, a symptom of poor sleep quality, may be associated with cardiovascular disease; however, evidence in Asian populations is limited. Objective: To examine the association between difficulty falling asleep and incident major cardiovascular events (MACE) beyond the effect of sleep duration in the general population. Methods: We followed 2,507 participants (1,038 men and 1,469 women) enrolled in the NIPPON DATA 2010 study in 2010, excluding those with prior cardiovascular events, until December 31, 2019. Sleep information was obtained from self-administered questionnaires and assessed by difficulty falling asleep (frequent, occasional/rare, none) and sleep duration (short: <6, moderate: 6–<8, long: ≥8 hours). The outcome was incident MACE (stroke, myocardial infarction, PCI, or heart failure). Hazard ratios (HRs) for difficulty falling asleep and sleep duration were estimated using Cox proportional hazards models adjusted for sex, age, BMI, diabetes, hypertension, dyslipidemia, smoking, alcohol use, K6 score, and physical activity index. Both sleep variables were included in the same model for mutual adjustment. Results: During the 8.3-year observation period, 118 MACE occurred (72 in men, 46 in women). The mean age was 58.1±15.8 years. In the overall analysis, compared with those who frequently had difficulty falling asleep, the HRs (95% CIs) were 0.54 (0.33–0.88) for participants who occasionally or rarely had difficulty and 0.51 (0.26–0.99) for those who never had difficulty. For sleep duration, compared with those with moderate sleep duration, the HR (95% CI) was 0.79 (0.49–1.29) for participants with short sleep duration and 1.48 (0.91–2.41) for those with long sleep duration. In analyses stratified by sex, women with long sleep duration showed a higher HR [HR (95% CI) = 2.70 (1.25-5.83)], while this pattern was not observed in men. Conclusions: This study found that participants with frequent difficulty falling asleep had a higher risk of MACE in both sexes, independent of sleep duration, whereas long sleep duration increased the risk among women. Our findings suggest that evaluating difficulty falling asleep as an indicator of sleep quality is important for cardiovascular risk assessment, as well as sleep duration.

Introduction: The American Heart Association’s new Life’s Essential-8 (LE8) metrics is considered a comprehensive framework for pursuing optimal cardiovascular health (CVH). However, its relationship with carotid atherosclerotic plaque is inadequately studied globally and not clarified in Asians. Hypothesis: We assessed the hypothesis that LE8 CVH is associated with carotid intima-media thickness (CIMT) and carotid plaque among Japanese men. Methods: We cross-sectionally analyzed data from 938 randomly selected asymptomatic men aged 40-79 years participating in the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA), Kusatsu, Shiga, during 2006-2008. Utilizing diet, physical activity, nicotine exposure, sleep, body mass index, blood lipids, blood glucose, and blood pressure metrics, we quantified and categorized LE8 CVH (high, 80-100 points; moderate, 50-79 points; and low, 0-49 points) as the exposure. Ultrasonography-derived intima-media thickness (IMT) and plaque numbers were quantified from the right and left common carotid artery (CCA) to the internal carotid artery via the carotid bifurcation. The average of these segment-specific IMT values was calculated and defined as the mean CIMT. The prevalence of increased CIMT (mean IMT >1 mm), increased IMT in CCA (mean IMT in CCA >1 mm), and carotid plaque (plaque count ≥1), and the plaque burden (total count) were evaluated as the outcomes. Multivariable (adjusted for age and family history of cardiovascular disease) modified Poisson regression and negative binomial regression analyses were used. Results: Participants (mean [SD] age, 63.7 [10.0] years) had a prevalence of high, moderate, and low CVH of 16.7%, 77.6% and 5.6%, respectively. The prevalences of increased CIMT, increased IMT in CCA, and carotid plaque were 15.0%, 12.6%, and 77.5%, respectively. Compared to individuals with high CVH, those with moderate and low CVH had a higher risk (risk ratio [95% confidence interval]) of increased CIMT (2.06 [1.23-3.43] and 3.04 [1.53-6.05], respectively), increased IMT in CCA (2.01 [1.14-3.56] and 2.87 [1.28-6.46], respectively), and carotid plaque (1.09 [0.99-1.20] and 1.17 [1.01-1.36], respectively), and had a relative increase in the expected plaque counts (1.34 [1.14-1.59] and 1.65 [1.24-2.18], respectively). Conclusions: Lower LE8 CVH is associated with a higher risk of CIMT and carotid plaque in Japanese men. Healthy lifestyle practices may reduce the risk of subclinical carotid atherosclerosis.

Hypertension, encompassing white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH), is an established risk factor for cardiovascular diseases (CVDs), including atherosclerosis. However, among the general population, findings on which target organ is affected by the different phenotypes of hypertension remain unclear. In this community-based observational study of Shiga Epidemiological Study of Subclinical Atherosclerosis, 740 Japanese men underwent brain magnetic resonance imaging to assess the presence of lacunar infarction, white-matter hyperintensities, microbleeds, and intracranial artery stenosis (ICAS) between 2012 and 2015. They also underwent office blood pressure (BP) measurements, home BP monitoring for at least five consecutive days, and coronary artery calcification (CAC) assessments between 2010 and 2014. The final analysis included 686 participants without a history of CVDs. Of the 686 participants, the mean age ( ± SD) was 68.0 ( ± 8.3) years, and 39.3% were taking antihypertensive medication. In multivariable-adjusted models, each of WCH, MH, and SH was significantly associated with a higher risk of microbleeds compared to normotension. However, the association of WCH with microbleeds was evident only among those on antihypertensive medication (adjusted odds ratio [OR] 6.75 [95% CI 1.83–24.86]) and absent in those not on such medication (adjusted OR 1.20 [95% CI 0.31–4.73]). SH was associated with lacunar infarction, ICAS, and CAC. Among Japanese men, WCH, MH, SH were associated with subclinical cerebrovascular diseases, whereas only SH was associated with CAC. Moreover, any elevated BP phenotype increased the risk of microbleeds. Our findings suggest that different hypertension phenotypes distinctly affect target organs, particularly the brain and heart.

Introduction: The biomarkers and the mechanisms underlying the cognitive decline in ageing are not fully clarified although they might be effective for dementia prevention. We comprehensively explore metabolites associated with cognitive function by conducting metabolomics analysis in a cohort study of general Japanese men. Methods: The study population was 672 Japanese men aged 46-83 years without stroke, who were randomly selected for the SESSA study from Kusatsu City, Japan. Metabolomics using liquid chromatography mass spectrometry (LC-MS) was conducted on plasma samples, focusing on lipid metabolism. The 442 metabolites were identified. The cognitive function was assessed by Cognitive Abilities Screening Instrument (CASI), and CASI score less than 82 was defined as having mild cognitive impairment (MCI). We examined the metabolites among groups with and without MCI using principal component analysis and partial least squares regression (PLS) or PLS rank order of groups. Multivariable adjusted logistic regression estimated the odds ratios (ORs) and 95%CI of MCI for the extracted metabolites per standard deviation. The 9 domain specific MCI using median value of each domain specific CASI score as cutoff points were also examined. KEGG pathway analysis was done to clarify the linked pathway for the extracted metabolites. Results: The prevalence of MCI was 5.5%. The 22 metabolites were statistically significantly associated with CASI score (q <0.05 in PLS, 21 metabolites in the positive direction and 1 metabolite in the negative direction). Phosphatidylcholines (PC) and Lysophosphatidylcholines (LPC) were associated with low risk of MCI (OR(95%CI): PC16:0/20:3; 0.51(0.32-0.51), LPC18:2/0.0; 0.59 (0.36-0.96), LPC20:3/0.0; 0.48(0.28-0.82)), phenacetylcarnitine was associated with the high risk of MCI (OR (95%CI); 1.33 (1.01-1.75)) (q <0.05). The analysis for domain specific MCI extracted the metabolites for short term memory, language abilities and category fluency. The Linoleic acid metabolism pathway was statistically significantly associated with CASI score. Conclusion: Glycerophosphocolines such as PC16:0/20:3, LPC18:2/0.0 and LPC20:3/0.0 were reduced in participants with MCI, and those metabolites associated with low risk of MCI. Linoleic acid metabolism might be important for prevention of dementia among Japanese.

BACKGROUND:Circulating n-3 polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), have been linked to brain structural integrity. However, much of the existing evidence stems from Western populations with relatively low n-3 PUFA exposure. Data from Japan-where fish consumption and n-3 PUFAs concentrations are substantially higher-remain scarce, and few studies have contrasted the differential associations of DHA and eicosapentaenoic acid (EPA) with brain structure. OBJECTIVES:The aim of our study was to examine the association between circulating EPA, DHA, and EPA + DHA concentrations and brain volume in older Japanese women. METHODS:This cross-sectional study included 527 community-dwelling women aged 60 to 85 y residing in Kusatsu City, Shiga, Japan. Serum concentrations of EPA and DHA were measured using gas chromatography, and their combined concentration (EPA + DHA) was calculated. Brain volume (total brain, gray matter, white matter, and hippocampal volume) was assessed using 1.5-Tesla magnetic resonance imaging. Analysis of covariance was performed to compare the adjusted mean values for brain volume according to the quartile of EPA, DHA, and EPA + DHA concentrations. Covariates included age, total intracranial volume, body mass index, years of education, smoking and drinking status, step count, diabetes, hypertension, and statin use. RESULTS:Participants' mean age was 74.2 y. Serum concentrations of DHA were significantly and positively associated with gray matter volume (P for trend = 0.036), whereas EPA concentrations were not. Notably, serum concentrations of EPA + DHA exhibited a positive trend with gray matter volume (P for trend = 0.085). No significant associations were found between EPA, DHA, or EPA + DHA concentrations and white matter volume, total brain volume, or hippocampal volume. CONCLUSIONS:DHA exhibits a stronger positive association with gray matter volume than EPA, for which associations are limited, supporting the importance of DHA-rich diets for healthy brain aging.

The association between body mass index (BMI) and pancreatic cancer remains elusive in Asian populations. Clarifying the causal relationship between type 2 diabetes (T2D) and pancreatic cancer warrants triangulation of evidence, with Mendelian Randomization (MR) providing a robust approach. A two-sample, multivariable MR analysis was performed to investigate the associations between BMI, T2D, and pancreatic cancer risk in the Japanese population. Single nucleotide polymorphisms (SNPs) associated with BMI and T2D were selected from the Genome-Wide Association Study (GWAS) Catalog, and summary statistics for pancreatic cancer were derived from our previous GWAS in the Japanese population. MR analyses were performed using a random-effects inverse variance-weighted (IVW) method as well as sensitivity analyses. Genetic predisposition to T2D, assessed using 891 SNPs, was associated with increased pancreatic cancer risk (IVW odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.08-1.25 per 1-unit increase in the ln odds of T2D). MR-Egger and weighted median MR analyses yielded similar results. By contrast, genetically indexed BMI showed no association with pancreatic cancer risk (IVW OR: 1.00; 95% CI: 0.95-1.04 per 1 kg/m2 increase). The association between T2D and pancreatic cancer remained significant after adjusting for BMI (OR: 1.15; 95% CI: 1.07-1.24), while BMI was not significant in univariable or multivariable analyses. Our MR study supports a modest causal association of T2D, independent of BMI, with pancreatic cancer risk.

Obesity has been linked to progressive loss of kidney function, but the independent and combined associations of body mass index (BMI) and visceral fat accumulation remain uncertain in healthy individuals. This study aimed to clarify the longitudinal relationship between BMI, visceral fat area (VFA), and chronic kidney disease (CKD), defined as an estimated glomerular filtration rate based on serum cystatin C (eGFRcys) < 60 mL/min/1.73 m² among the Kobe Study participants targeting healthy urban residents in Japan. A total of 897 participants (267 men, 630 women) without CKD and with a mean age of 61.4 years were analyzed. VFA was measured using the impedance method, and participants were followed for a median of 8.3 years. Participants were classified into four groups based on baseline BMI (kg/m²) and VFA (cm²): G1 (VFA < 100 and BMI < 25), G2 (VFA < 100 and BMI ≥ 25), G3 (VFA ≥ 100 and BMI < 25), G4 (VFA ≥ 100 and BMI ≥ 25). Multivariable linear regression models were used to estimate adjusted mean annual changes in eGFRcys, and Cox proportional hazards models were applied to calculate hazard ratios (HRs) for incident CKD, adjusting for potential confounders (age, sex, smoking status, alcohol consumption, dyslipidemia, diabetes, hypertension and eGFRcys at baseline). During follow-up, 85 participants (9.5

BackgroundThe aging population in Japan highlights the public health need to maintain functional abilities, with activities of daily living (ADL) being essential for healthy aging.AimWe prospectively examined the association between protein intake (g/BWkg/day) and the ADL decline or death risk among older Japanese adults.MethodsData from 1773 Japanese adults aged ≥65 years in the NIPPON DATA90 cohort were analyzed. Protein intake was assessed using data from the 1990 National Nutrition Survey of Japan, and individual intakes were estimated from household dietary records. Protein intake (g/BWkg/day) was categorized into sex-specific quartiles. ADL decline was defined as requiring assistance in ≥1 of ADL tasks during follow-up surveys (1995-2012). Logistic regression was used to estimate odds ratios for ADL decline or death by survey year, and Cox proportional hazards models examined hazard ratios for time-to-event ADL decline or death.SummaryDuring follow-up, 515 participants experienced ADL decline, and 1015 died. Among women, moderate protein intake (second quartile, 1.15-1.38 g/BWkg/day) was associated with a 35% lower risk of ADL decline (adjusted hazard ratio 0.65) compared with the lowest quartile. A similar pattern was observed for the combined outcome of ADL decline or death, whereas higher intake levels did not show additional benefit. No clear association was observed among men. These findings suggest that moderate protein intake was associated with the lowest risks of ADL decline and death, particularly among women. Adequate, but not excessive, protein consumption may help support functional health in older Japanese adults.

Previous findings for the association of fish intake and its related metabolites on risk of metabolic syndrome (MetS) are inconsistent and limited. The prevalence of fish and shellfish consumers are high in Japan where it contributes to one fourth of the protein intake. We aimed to investigate the relationship of fish and fish-related metabolites with MetS risk factors in a community-dwelling Japanese population. In this cross-sectional study, 1047 Japanese men and women aged 40–59 years were included. Four in-depth multiple-pass 24-h dietary recalls, two timed 24-h urine collections, blood collection, extensive questionnaire and anthropometric measurements were collected for each participant. Urinary and serum profiles were obtained using 1H Nuclear magnetic resonance (NMR) spectroscopy. Mean fish intake was 47.0 (SD 28.8) g per 1000 kcal. Urinary trimethylamine-N-oxide (TMAO) and taurine, and serum creatine and threonine were significantly correlated with fish intake and homarine was associated with shellfish intake (p < 0.01). Significant inverse associations were found between triglycerides and total fish intake, low omega-3 fish, urinary TMAO, taurine and between urinary taurine with systolic blood pressure. Direct association between urinary TMAO and serum threonine with high-density lipoprotein cholesterol were found. We found several metabolites related to fish intake and risk factors of MetS in habitual fish-consuming country, Japan. When stratified by seafood type, raw and high omega-3 fish intake showed the strongest associations with urinary and serum metabolomes, while fried fish had weaker or non-significant correlations, suggesting that cooking methods may modulate the bioavailability or metabolic impact of fish nutrients. The combined panel of urinary TMAO and taurine with plasma creatine and threonine, reflecting seafood intake, was associated with a favorable lipid profile and lower blood pressure. The INTERMAP study is registered as NCT00005271 at www.clinicaltrials.gov .

OBJECTIVES:There is a growing interest in understanding the long-term impact of employment status on psychological stress. We aimed to explore the association between socioeconomic status and psychological stress over a long-term follow-up period across the COVID-19 pandemic, employing the Kessler 6-Item Psychological Distress Scale (K6). METHODS:We evaluated K6 scores from the 2021 follow-up survey of NIPPON DATA2010 using a self-administered questionnaire. The association between employment status and changes in K6 scores over 11 years was examined. Multiple regression analyses were used to estimate both crude and adjusted differences in K6 score changes across various socioeconomic factors including employment category, annual household income, marital status, and household size. Analyses were stratified by age, gender, and prefectural population size. RESULTS:This study included 1532 participants with an average age of 54.9 years. Over 11 years (2010-2021), participants in both gender and age groups showed increases in mean K6 scores (men: 2.79 to 3.06; women: 3.15 to 3.56; <65 years: 3.27 to 3.47; ≥65 years: 2.37 to 3.08). Nonemployed participants, particularly homemakers, showed significantly greater increases in K6 scores, compared with full-time employees, especially among women, younger individuals, and those in densely populated areas, with a significant interaction with age. CONCLUSIONS:Nonemployed individuals, especially homemakers, experienced greater psychological stress over the past 11 years than did their fully employed counterparts. Public interventions, including strengthened social connections and telemental health services, may help mitigate these disparities, enhance mental well-being, and foster a sense of belonging.

Introduction: The westernization and modernization of diet have gradually increased among the Japanese people, resulting in greater consumption of meat. Metabolic profiling can be considered a useful tool to ensure more accurate assessment of meat consumption and to clarify its underlying mechanisms associated with cardiovascular health outcomes. Hypothesis: We hypothesized that greater meat consumption could potentially lead to an elevation in blood pressure (BP), which was elucidated through meat-related candidate serum metabolites. Methods: A total of 1,007 Japanese participants aged 40-59 years residing in Japan were selected from the INTERLIPID study. Data on systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), dietary intakes, urinary, serum metabolites and lifestyle factors were collected. Serum metabolites were measured by nuclear magnetic resonance (NMR) spectroscopy and liquid-chromatography mass spectrometry (LC-MS). Associations between BP and serum metabolites were identified through partial Spearman correlation, and the effect of candidate serum metabolites of meat consumption on BP was explored by stepwise multiple linear regression considering age and sex. Results: The median of self-reported total meat intake was 28.98 g/1000kcal in men and 24.50 g/1000kcal in women. The multivariable linear regression results indicated that total meat and poultry intakes were significantly and positively related to BP. A total of 7 metabolites among 25 NMR and 29 metabolites among 51 LC-MS serum metabolites significantly correlated with meat consumption. Stepwise multiple linear regression indicated that the commonly related metabolites (p-value <0.05) for SBP, DBP and MAP were palmitoylcarnitine, carnitine and octanoylcarnitine. Additionally, the other associated metabolites included isovalerylcarnitine for SBP (β 1.24, CI 0.32-2.15), while for DBP, hexanoylcarnitine (β 1.61, CI 0.78-2.44), and niacinamide (β 0.73, CI 0.16-1.30). Conclusions: Higher meat consumption was significantly associated with elevated BP in Japanese. Some metabolites including palmitoylcarnitine, carnitine and octanoylcarnitine were suggested as important contributors to this association, offering novel insights into the metabolic mechanisms linking diet and BP.

Cigarette smoking is one of the most important risk factors for lung cancer. Genetic studies have shown that smoking behavior-related genetic variants are directly associated with lung cancer, independent of smoking behavior, mainly in European populations. A recent genome-wide association study in Japan identified five loci associated with the number of cigarettes smoked per day. This study aimed to evaluate whether these loci are associated with lung cancer risk directly or indirectly through changing smoking behavior. Here, we conducted a case-control study (1427 cases and 5595 controls) and a prospective cohort study (128 incident cases in 10 520 subjects). Using mediation analysis, we decomposed the total effect of the lead single nucleotide polymorphism (SNP) at each locus on lung cancer risk into direct and indirect effects. The results of the two studies were pooled using a random-effects model to estimate summary relative risks (RRs) and their 95% confidence intervals (CIs). Two studies showed that: (i) rs78277894 (EPHX2-CLU, G > A) had a protective direct effect (RR: 0.84; 95% CI: 0.77-0.93) on lung cancer risk; and (ii) rs56129017 (CYP2A6, C > T) had carcinogenic direct and indirect effects on lung cancer risk (RR: 1.26; 95% CI: 1.15-1.39 and RR: 1.01; 95% CI: 1.00-1.01, respectively). This mediation analysis revealed that two smoking behavior-related SNPs, EPHX2-CLU rs78277894 and CYP2A6 rs56129017, were associated with lung cancer risk through pathways independent of changing smoking behavior. Our findings may contribute to our understanding of lung carcinogenesis pathways that cannot be addressed by changes in smoking behavior.

Background and aims:The American Heart Association's Life's Essential-8 (LE8) cardiovascular health (CVH) metrics is considered a comprehensive framework for optimal cardiovascular wellbeing. However, its relationship with the progression of subclinical atherosclerosis, like coronary artery calcification (CAC), is not clarified. We investigated the associations of LE8 CVH metrics with the prevalence and progression of CAC in Japanese men. Methods:We analyzed data from 760 asymptomatic men participating in the Shiga Epidemiological Study of Subclinical Atherosclerosis. We assessed baseline (2006-2008) LE8 CVH (low, 0-49 points; moderate, 50-79 points; high, 80-100 points) using its eight components (diet, physical activity assessed by step count, smoking, sleep, body mass index, blood lipids, blood glucose, blood pressure). We quantified CAC at baseline and follow-up of 5 years employing Agatston's method and defined its baseline prevalence (CAC >0) and progression (employing Berry's criteria). Modified Poisson regression analyses were used to estimate risk ratio (RR) and 95 % confidence interval (CI), adjusted for age and family history of cardiovascular disease. Results:Participants (mean [SD] age, 63.8 [9.4] years) had 63.2 % and 44.9 % prevalence of CAC at baseline and CAC progression at follow-up, respectively. Individuals with moderate and low CVH at baseline had a higher risk of prevalent CAC (RR [95 % CI], 1.42 [1.18-1.71] and 2.07 [1.67-2.57], respectively) at baseline, compared to those with high CVH. Those with moderate and low CVH at baseline had a higher risk of CAC progression (RR [95 % CI], 1.52 [1.17-1.97] and 1.99 [1.42-2.81], respectively), compared to high CVH individuals. Conclusions:A lower LE8 CVH is significantly associated with a higher risk of prevalence and progression of CAC in general Japanese men.

Decreased bone mineral density (BMD) is associated with atherosclerosis in postmenopausal women and older men. Limited research has explored this relationship in middle-aged men. Aortic calcification (AC) is a novel biomarker for aortic atherosclerosis. This study aimed to examine whether baseline BMD is associated with the progression of AC in an international multi-ethnic cohort of middle-aged men participating in the ERA-JUMP Study (The Electron-Beam Tomography Risk Factor Assessment Among Japanese and U.S. Men in the Post-World War II Birth Cohort). We hypothesized that higher BMD at baseline would be associated with less progression of AC. This analysis included participants who completed two visits an average of 5.69 years apart. Participants (mean age: 45.3 + 2.9) were recruited from population-based samples in the United States (Pennsylvania and Hawaii) and Japan (Shiga). All participants were free of clinical cardiovascular disease at baseline. BMD was measured via electron-beam tomography images of the T12 to L4 vertebrae. AC was evaluated from the aortic arch to the iliac bifurcation with computed tomography and scored via the Agatston Scoring Method. Incidence of AC was defined as an AC score <100 at baseline and ≥ 100 at follow-up. Linear regression was employed to assess the association between baseline BMD and changes in AC (Visit 2 – Visit 1). Model 1 adjusted for follow-up time, age, and race/ethnicity. Model 2 was further adjusted for cardiovascular risk factors: hypertension, diabetes, LDL-C, HDL-C, and lipid medication. Model 3 additionally adjusted for BMI and smoking status. Logistic regression, with the same models, was used to assess the association between baseline BMD and incident AC at Visit 2. At baseline, the average BMD was 173.1 HU (+ 37.1), and the median AC score was 3.0. The median change in AC score was 39.76 (IQR: 0- 220.3). There were 159 incident cases of AC in the cohort. Baseline BMD was inversely associated with the change in AC in Models 1, 2 (p<0.05) and Model 3 (p<0.1). Similarly, baseline BMD was inversely associated with incident AC in Models 1, 2 (p<0.05), and Model 3 (p=0.10). Our findings suggest that skeletal and cardiovascular health may be linked in middle-aged healthy men. Higher baseline BMD appears to be associated with reduced progression and lower incidence of AC. These results underscore the need for further longitudinal studies to confirm this relationship and explore its clinical implications.

Objective We investigated the associations of nocturnal oxygen saturation (SpO2) with prevalence of coronary artery calcification (CAC) and its level of burden, and whether the associations differ by obesity and mediate through diabetes mellitus (DM), dyslipidaemia and hypertension.Design Observational study.Setting Kusatsu, Shiga.Participants We analysed data from 510 Japanese men (aged 46–76 years) with no history of myocardial infarction.Primary and secondary outcomes Mean SpO2, minimum SpO2 and oxygen desaturation index (ODI) were measured using overnight pulse oximetry (primary exposures), while CAC was assessed using CT. Prevalence of CAC (>0) and its burden (CAC 0, >0–100, >100–400 and>400) were evaluated as outcomes. Body mass index≥25.0 kg/m2 defined as obesity.Results Mean±SD age was 66.7±7.2 years. The prevalence of CAC was 64.7% (CAC scores>0–100, 31.4%; >100–400, 20.0% and>400, 13.3%). In multivariable binary logistic regression, the OR and 95% CI for the prevalence of CAC were 1.25 (1.02 to 1.53) per 1-SD decrement in mean SpO2 and 1.25 (1.01 to 1.55) per 1-SD increment in ODI. The associations lost their significance while further adjusted for DM and dyslipidaemia. Similar trends were observed for the level of CAC burden in multivariable ordinal logistic regression. Obesity did not show significant interaction with SpO2 on CAC. In mediation analysis, the OR (95% CI) for natural indirect effect; percentage mediated through dyslipidaemia in association of 1-SD decrement in mean SpO2 with prevalence of CAC were 1.06 (1.01 to 1.10); 25.4%. These estimates for mediation through DM and dyslipidaemia for 1-SD increment in ODI in the associations were 1.07 (1.01 to 1.12); 29.6% and 1.04 (1.00 to 1.08); 17.5%, respectively.Conclusions Lower mean SpO2 and higher ODI are associated with CAC among Japanese men, independent of age, lifestyle factors and obesity. The associations became non-significant after adjusting for diabetes and dyslipidaemia, but were mediated through these factors.