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.

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.

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.

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

Comparison of Publications on Heated Tobacco Products With Conventional Cigarettes and Implied Desirability of the Products According to Tobacco Industry Affiliation: A Systematic Review.

INTRODUCTION: Heated tobacco products (HTPs) have been advertised as "reduced-harm" tobacco products compared to conventional cigarettes (CC); however, no direct evidence supporting HTPs being desirable for human health exists. A previous systematic review reported that evidence on HTPs published in 2017 or earlier was primarily drawn from industry-related papers. We aimed to investigate whether tobacco industry-affiliated studies are more likely to conclude that HTPs are more desirable than CC. METHODS: PubMed and Ichushi-Web were searched up to March 15, 2022, for studies on HTPs published in 2017 or after. We selected studies that assessed any measures of HTPs and CC, including secondary analyses using gray literature in English or Japanese. We excluded review articles except for a meta-analysis that met the aforementioned criteria. Data on the authors' affiliations, grant, conflict of interest, category of research subjects, and interpretation were extracted. Research members in two groups independently assessed the papers; discrepancies were solved by discussion between the groups. RESULTS: Overall, 134 studies met the criteria. Eighty-seven (64.9%) of them were affiliated with the tobacco industry. Of the 134 studies, 56.3% (49/87) of the industry-affiliated studies versus 19.1% (9/47) of nonindustry-affiliated studies concluded that HTPs were more desirable than CC (p < .01). No study investigated clinically relevant outcomes, such as disease occurrence. CONCLUSIONS: Publications on HTPs in the biomedical literature from January 2017 to March 2022 were dominated by tobacco industry-affiliated studies. More than half of them concluded that HTPs were more desirable than CC compared to independent studies. IMPLICATIONS: Tobacco industry advertises HTPs as "reduced-harm" tobacco products compared to CC. HTP users tend to consider HTPs as alternative tobacco products less harmful than CC (ie, products for "harm reduction"). Our results demonstrated that papers written by tobacco industry-affiliated authors concluded that HTPs were more desirable than CC compared to papers by independent authors. However, all their judgments were based on surrogate outcomes. Surrogate outcomes are not necessarily linked to clinically relevant outcomes such as disease occurrence. Further studies on HTPs using clinically relevant outcomes are warranted by independent authors from tobacco industry.

Varying Definitions of Carotid Intima-Media Thickness and Future Cardiovascular Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Carotid intima-media thickness (cIMT) has been widely used as a predictor of future cardiovascular disease (CVD); however, various definitions of cIMT exist. This study provides a systematic review and meta-analysis of the associations between different cIMT definitions and CVD. METHODS AND RESULTS: A systematic review of the different cIMT definitions used in prospective cohort studies was performed. The relationships between cIMT of different definitions (common carotid artery IMT [CCA-IMT], internal carotid artery IMT [ICA-IMT], combined segments [combined-IMT], mean CCA-IMT, and maximum CCA-IMT) with future stroke, myocardial infarction (MI), and CVD events were analyzed using random effects models. Among 2287 articles, 18 articles (14 studies) with >10 different cIMT definitions were identified and included in our meta-analysis. After adjusting for age and sex, a 1-SD increase in CCA-IMT was associated with future stroke (hazard ratio [HR], 1.32 [95% CI, 1.27-1.38]), MI (HR, 1.27 [95% CI, 1.22-1.33]), and CVD events (HR, 1.28 [95% CI, 1.19-1.37]). A 1-SD increase in ICA-IMT was related to future stroke (HR, 1.25 [95% CI, 1.11-1.42]) and CVD events (HR, 1.25 [95% CI, 1.04-1.50]) but not MI (HR, 1.26 [95% CI, 0.98-1.61]). A 1-SD increase in combined-IMT was associated with future stroke (HR, 1.30 [95% CI, 1.08-1.57]) and CVD events (HR, 1.36 [95% CI, 1.23-1.49]). Maximum CCA-IMT was more strongly related than mean CCA-IMT with risk of MI, and both measures were similarly associated with stroke and CVD events. CONCLUSIONS: Combined-IMT is more strongly associated with CVD events compared with single-segment cIMT definitions. Maximum CCA-IMT shows a stronger association with MI than mean CCA-IMT. Further research is warranted to validate our findings and to standardize the cIMT measurement protocol, as well as to explore underlying mechanisms.

Appendicular Muscle Mass Index was Stronger than Body Mass Index in Association with Atherosclerosis in the Community-Dwelling Elderly.

AIMS: Low muscle mass is associated with advanced atherosclerosis. However, only very few studies on the elderly have investigated a dose-response relationship between muscle mass and atherosclerosis. Furthermore, whether the relationship between muscle mass and atherosclerosis is stronger than that between body mass index (BMI) and atherosclerosis among the elderly population remains to be determined. METHODS: A community-based sample of apparently healthy elderlies (≥ 65 years) was cross-sectionally examined for the association between appendicular skeletal muscle mass (ASM) and brachial-ankle pulse wave velocity (baPWV), a measure of atherosclerosis. We categorized the participants according to sex-specific quintiles of the ASM index (ASM/height2) or BMI. Using multivariable linear regression, we compared the slope of one standard deviation higher ASM index for baPWV with the corresponding slope of BMI, separately (single-index model) and jointly (simltaneously-adjusted model). RESULTS: The ASM index and BMI of a total of 995 participants (60.0% women, mean age 73 years) were significantly inversely associated with baPWV in a dose-response manner across the quintiles in both sexes. The slope for the ASM index tended to be greater than that for BMI in the single-index and simultaneously-adjusted models in both sexes after adjusting for confounders. CONCLUSIONS: Among a community-dwelling elderly population, the association between ASM and baPWV was stronger than, and independent of that between BMI and baPWV. These findings suggest that ASM provides more important information on atherosclerosis in the elderly than BMI does.

[Efforts to improve workplaces considering for older workers: A questionnaire survey focusing on company size in Wakayama Prefecture, Japan].

OBJECTIVES: The "Guidelines for Ensuring the Safety and Health of Older Workers (hereafter referred to as "Guidelines")," formulated in 2021, require employers to implement measures that proactively prevent occupational accidents among older workers. This study aimed to clarify the status of awareness of the Guidelines and workplace improvement efforts with consideration of older workers, focusing on company size. METHODS: Overall, 780 businesses in Wakayama Prefecture, Japan, were randomly selected from a Wakayama Occupational Health Support Center workplace list. Anonymous self-administered questionnaires were distributed by mail. The questionnaires comprised questions about the workplace, status of awareness of the Guidelines, comprehensive management of safety and health, considerations for working conditions, workers, workload reduction, work posture, work environment, and safety and health. RESULTS: One hundred and seventy-one businesses (effective response rate: 21.9%) provided questionnaires with complete responses. For the Guidelines, 39.0% of small-sized (less than 50 employees) businesses answered, "never even heard of the name," while many medium-sized (50-99 employees) and large-sized (100 or more employees) businesses answered that they had heard of the name but did not exactly know about it (33.3% of medium-sized businesses and 47.8% of large-sized businesses). Regarding the system that subsidizes the expenses required for the improvement of a working environment for older workers to work safely and securely (hereinafter referred to as the subsidy system), many businesses of all sizes answered that they had "never even heard of the name." In the comprehensive management of safety and health, half of the businesses of all sizes had developed a system that made it easy to consult about the risk against occupational accidents of older workers. Regardless of size, more than half of businesses were able to consider working conditions and workers. However, there were only a few items where more than half of the businesses considered workload reduction, work posture, work environment, and safety and health, regardless of business size. It became clear that workplace improvement had not progressed very much. CONCLUSIONS: These results suggest that to promote workplace improvement that considers older workers, it is necessary to disseminate the Guidelines and proactively take on workplace improvement by utilizing the subsidy system.

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.

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.

Circulating plasma phospholipid fatty acid levels as a biomarker of habitual dietary fat intake: The INTERMAP/INTERLIPID Study.

BACKGROUND: Accurate assessment of fat intake is essential to examine relationships between diet and disease risk. However, estimating individual intakes of fat quantity by dietary assessment is difficult. OBJECTIVE: We assessed the association of plasma phospholipid fatty acid levels with dietary intake of fatty acids in the INTERMAP/INTERLIPID study, conducted with a standardized protocol. METHODS: The study participants were 1339 men and women ages 40-59 years from five Japanese populations one from Hawaii; four from Japan. Fatty acid intake was estimated from four standardized 24-hour dietary recalls. Plasma phospholipid fatty acid composition was analyzed by gas chromatography. We illustrated the relationship between intake and circulating fatty acid levels using Spearman's rank-correlation coefficients, mean, and median values. RESULTS: Spearman's rank-correlation coefficients between intake (g/d) and circulating fatty acid levels (µg/ml) were -0.03 to 0.21 for saturated fatty acids and monounsaturated fatty acids and -0.04 to 0.32 for trans fatty acids. The coefficients for essential n-3 and n-6 fatty acids were moderate to high, especially for eicosapentaenoic acid (EPA), 0.60; docosahexaenoic acid (DHA), 0.41; and EPA+DHA, 0.51. The circulating levels and intake of marine-derived n-3 fatty acids showed a linear association, at least for the intake of EPA+DHA up to 2.1 g/d. CONCLUSION: We observed high correlation between intake and circulating levels of marine-derived n-3 fatty acids in participants from Japanese and Japanese-American populations with high and low fish intake. Plasma phospholipid marine-derived n-3 fatty acid measurements are a simple and reliable biomarker for assessing dietary intake.

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.

[Support for a balance between work schedules and treatment regimens among workers with illness: A questionnaire survey focusing on company size in Wakayama Prefecture, Japan].

OBJECTIVES: The support from businesses to create a balance between work schedules and treatment regimens among employees suffering from illnesses, such as cancer and diabetes, seems to be insufficient. This study aimed to investigate efforts of businesses to support the balance of work schedules and treatment regimens among employees with illness, focusing on company size and to identify potential workplace improvements for such employees. METHODS: Overall, 789 businesses in Wakayama Prefecture, Japan were randomly selected from a workplace list of the Wakayama Occupational Health Support Center. Anonymous questionnaires were distributed by mail. The questionnaires consisted of question items on workplace, current employees who had suffered or were suffering from cancer (employees with cancer), employees with illnesses (diseases such as cancer and diabetes), and support for businesses and employees. RESULTS: Questionnaires with complete responses were collected from 187 businesses (response rate: 23.7%). The ratios of businesses where employees with cancer were engaged or had been engaged were 43.4% for small-sized (less than 50 employees), 70.9% for medium-sized (50-99 employees), and 83.1% for large-sized (100 and more employees) businesses. In all business sizes, the most common support in reinstatement or hiring employees with cancer was "absenteeism for treatment." The most common difficulty that occurred in the workplace due to the presence of employees with cancer was "the insufficient number of workers." The information from the attending physician, etc. necessary for deciding the reinstatement was mostly "the current health condition and physical strength." Additionally, in all business sizes, the most common support for employees with illness to balance work schedule and treatment regimens was "considering measures suitable to the situation such as hospital visits and physical condition." The most common challenge was "securing alternative personnel." The information from the attending physician, etc. necessary for deciding the reinstatement was "the current health condition and physical strength," similar to that for employees with cancer. More than 60% of the businesses of varying sizes reported being unaware of the work-treatment balance support coordinator. CONCLUSIONS: Considering measures suitable to the situation, such as hospital visits and physical condition, securing alternative personnel, and actively disseminating information regarding work-treatment balance support coordinators are recommended as workplace improvements for employees with illnesses.

Relationship of Higher-level Functional Capacity With Long-term Mortality in Japanese Older People: NIPPON DATA90.

BACKGROUND: Basic and instrumental activities of daily living (BADL and IADL, respectively) are known predictors of mortality. However, the relationship between higher-level functional capacity (HLFC) and mortality and related sex differences have rarely been investigated. METHODS: A prospective population-based cohort study was conducted in 1,824 older residents (≥65 years) with independent BADL from 300 randomly selected areas in Japan from 1995, and the participants were followed up until 2010. Using the Cox proportional hazards model, the relationship between HLFC and mortality risk was investigated, with adjustment for possible confounders. HLFC was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Baseline data were collected using a questionnaire or by home-visit interviews. RESULTS: During an average 12.2-year follow-up, all-cause death was observed in 836 (45.8%) participants. Impaired HLFC was significantly associated with mortality (hazard ratio [HR] 1.37; 95% confidence interval [CI], 1.13-1.65). Lower social role was significantly associated with higher mortality risk in men (HR 1.38; 95% CI, 1.13-1.68). Lower IADL and intellectual activity were significantly associated with higher mortality risk in women (HR 1.50; 95% CI, 1.15-1.95 and HR 1.46; 95% CI, 1.19-1.79, respectively). The relationship between HLFC and mortality risk showed a similar tendency among cardiovascular diseases, stroke, cancer, and pneumonia. CONCLUSION: Impaired HLFC was associated with a high risk of all-cause mortality among community-dwelling older people with independent BADL. In particular, social role in men and IADL and intellectual activity in women were associated with long-term mortality risk.

Relationship between Serum Proprotein Convertase Subtilisin/Kexin Type 9 Concentration and Prevalence of Coronary Artery Calcium in a Community-Based Sample of Japanese Men.

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.

Cross-sectional association of equol producing status with aortic calcification in Japanese men aged 40-79 years.

Equol is an isoflavone (ISF)-derived metabolite by the gut microbiome in certain individuals termed equol-producers (EP). Equol might be the critical anti-atherogenic component of ISFs. In a population-based study of 979 Japanese men aged 40-79 without cardiovascular (CVD) or chronic kidney disease, we measured the urinary levels of equol and ISFs. Aortic calcification (AC) in the entire aorta was assessed by electron-beam or multi-detector-row computed tomography. Subjects with log10 (urinary equol to daidzein concentration) > - 1.5 were classified as EP. EP was further classified as person with low- and high-equol. We analyzed the association between equol-producing status and AC presence, defined as AC score > 0, by the logistic regressions. We found that EP (50% of the sample) had significantly lower odds of AC presence (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.39, 0.98) compared to non-EP. This association was independent of CVD risk factors. For the dose-response association, compared to non-EP, subjects with low and high levels of equol had ORs of 0.51 (95% CI 0.30, 0.84) and 0.67 (95% CI 0.39, 1.14) after adjusting for major CVD risk factors (p for trend = 0.06). ISFs concentrations were not significantly associated with AC presence (OR: 1.18, 95% CI: 0.82, 1.69). In conclusion, EP had a significantly lower burden of AC than non-EP, while ISFs were not associated with AC presence in Japanese men aged 40-79 years.

Alcohol consumption and subclinical and clinical coronary heart disease: a Mendelian randomization analysis.

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

Association of ambulatory blood pressure with aortic valve and coronary artery calcification.

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