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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. 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

Background: Ne-Zake is the drinking of alcohol before sleeping for helping to fall asleep and sleep well, and Mukae-Zake is the drinking of alcohol in the morning for "calming down" or "curing hangovers".Objective: We sought to examine the relationship of insomnia with Ne-Zake and Mukae-Zake among healthy middle-aged Japanese farmers.Methods: In a cross-sectional study of 746 participants (mean age, 59.5 years; women, 25.9%), Ne-Zake and Mukae-Zake were defined based on a self-administered questionnaire. Insomnia was defined as the Athens Insomnia Scale Japanese version ≥6 or usage of sleeping pills in the previous year. Logistic regression was used to calculate odds ratio (OR) of insomnia related to Ne-Zake and Mukae-Zake adjusting for sex, age, presence of sleep-related disorders, frequency of alcohol consumption, and quantity of alcohol consumed per one occasion.Results: We observed insomnia, Ne-Zake, and Mukae-Zake in 174 (23.3%), 140 (18.8%), and 37 (5.0%) participants, respectively. After adjustment for demographic and confounding factors, participants with Ne-Zake had a significantly higher prevalence of insomnia (OR 2.00 [95% confidence interval, 1.27-3.16]), compared to those without Ne-Zake. Mukae-Zake was also independently associated with a higher prevalence of insomnia among men (OR 3.26 [1.55-6.87]). Participants with both Ne-Zake and Mukae-Zake had a highly significant association with insomnia (OR 4.77 [2.01-11.3]) than those with neither Ne-Zake nor Mukae-Zake. Additionally, for insomnia, the association of Mukae-Zake was more pronounced than that of Ne-Zake (OR 4.09, 95% CI 1.14-14.7, p = 0.031; and OR 1.81, 95% CI 1.08-3.06, p = 0.026, respectively).Conclusion: Ne-Zake and Mukae-Zake were associated with insomnia independent of the quantity and frequency of alcohol consumption among Japanese farmers. This finding can be used for stratifying individuals with insomnia not only to improve sleep hygiene but also to prevent alcohol dependence by informing the general population that alcohol has a negative effect on sleep, contrary to popular beliefs. [ABSTRACT FROM AUTHOR]

Background The relationship between mutation locations in KCNQ1 which is a major gene in long QT syndrome (LQTS) and phenotype has been analyzed and used for risk stratification. Mutations in the transmembrane region (TM) or cytoplasmic-loop (C-loop) are associated with more frequent cardiac events than those in other regions. However, accumulation of LQTS type 1 (LQT1) patients poses the question of whether the location specific risk stratification is really effective. Methods The study cohort consisted of 67 KCNQ1 mutation carriers and 13 family members who were suspected as having LQTS due to sudden cardiac death or syncope from 36 unrelated families. The KCNQ1 mutations were L250H, V254M, H258P, and R259C located in segment 4–5 linker (C-loop), G269S, and S277L in segment 5 (TM). Results More than half of the patients with V254M or S277L suffered sudden cardiac death or syncope. In contrast, those with other mutations showed mild phenotype. In these two mutations related to severe phenotype, gender frequency and the age of onset were contrasting, 14 out of 23 patients with V254M were male, 19 out of 22 patients with S277L were female. In the patients we could confirm the age of onset, all of the patients with V254M showed symptoms at less than 15 years old, while 5 out of 12 patients with S277L suffered symptoms after 16 years old. Conclusion Clinical characteristics were not specific for mutation locations but specific for respective mutations in our LQT1 patients. Patients should be evaluated by their own mutations to prevent severe cardiac events. [ABSTRACT FROM AUTHOR]

Objective The utility of lipoprotein particle profiles measured by nuclear magnetic resonance (NMR) spectroscopy beyond standard serum lipids remains inconclusive. Furthermore, few studies have compared NMR measurements with standard lipids in association with coronary artery calcification (CAC) in Japanese, where the coronary atherosclerotic burden is low. We examined whether NMR-based lipoprotein particle profiles are associated with CAC, and compared them with standard lipid and lipid ratios in the Japanese general population. Methods and Results We conducted a cross-sectional study in 851 men aged 40–79 years without cardiovascular diseases and lipid-lowering therapies. Adjusted odds ratios (ORs) (95% confidence intervals) for the top versus the bottom quartile of NMR-measured particle concentrations were 2.01 (1.24–3.23) for low-density lipoprotein (LDL-P), 1.04 (0.62–1.75) for high-density lipoprotein (HDL-P), 1.82 (1.13–2.95) for very-low-density lipoprotein (VLDL-P), and 1.92 (1.18–3.17) for LDL-P/HDL-P ratio. Similarly adjusted ORs of NMR-measured particle sizes were 0.59 (0.36–0.97) for LDL-P, 0.66 (0.40–1.10) for HDL-P, and 0.67 (0.40–1.12) for VLDL-P. The corresponding ORs were 1.82 (1.14–2.90) for total cholesterol (TC), 2.06 (1.28–3.30) for low-density lipoprotein cholesterol (LDL-C), 0.56 (0.34–0.91) for high-density lipoprotein cholesterol (HDL-C), 2.02 (1.24–3.29) for triglycerides, 2.08 (1.29–3.36) for non-high-density lipoprotein cholesterol (non-HDL-C), 2.27 (1.37–3.78) for TC/HDL-C ratio, and 1.73 (1.06–2.85) for LDL-C/HDL-C ratio. After mutual adjustment for total LDL-P concentration and TC/HDL-C ratio or non-HDL-C, LDL-P was no longer associated, whereas TC/HDL-C ratio remained significantly associated with CAC. Conclusions In community-based Japanese men, the overall association of CAC with NMR-measured lipoprotein indices is comparable, but not superior, to that with standard lipids. [ABSTRACT FROM AUTHOR]

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

Background The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than usual lipid parameters; however, the relationship between LAB and carotid intima-media thickness (IMT) was not clear even in Asian populations. Methods A total of 992 community-dwelling Japanese men, aged 40 to 79 years, were enrolled in the present study. Serum LAB levels were measured by enzyme-linked immunosorbent assays (ELISAs) with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody. Results Serum LAB levels (median [interquartile range], μg cs/L) were 5341 μg cs/L (4093–7125). The mean average IMT of the common carotid artery was highest in the fourth LAB quartile (842 μm) compared with the first quartile (797 μm) after adjustment for age, high-density lipoprotein cholesterol, triglyceride, body mass index, hypertension, diabetes, high sensitivity C-reactive protein, smoking, and alcohol drinking. However, this statistically significant difference was lost after further adjustment for total cholesterol (TC). After stratification using the combination of median LAB and hypercholesterolemia (serum TC ≥ 6.21 mmol/L and/or lipid-lowering medication), the adjusted mean average IMT (standard error) in the high LAB/hypercholesterolemia group was 886 μm (12.7), 856 μm (16.7) in the low LAB/hypercholesterolemia group, and 833 μm (8.4) in the low LAB/normal cholesterol group ( P = .004). After further adjustment for TC, mean average IMT in the high LAB group was significantly higher than that measured in the low LAB group in hypercholesterolemic participants not taking lipid-lowering medication. Conclusion Serum LAB was associated with an increased carotid IMT in Japanese men, especially those with hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Objective Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is an enzyme predominantly bound to low-density lipoprotein (LDL). Lp-PLA 2 is recognized as playing a key role in inflammatory processes and the development of atherosclerosis. This study aimed to investigate whether Lp-PLA 2 is related to subclinical atherosclerosis, independently from traditional risk factors, in a general Japanese population by analyses of both the observational study and Mendelian randomization using V279F polymorphism. Methods and results We cross-sectionally examined community-based sample of 929 Japanese men aged 40–79 years, without statin treatment, who were randomly selected from the resident registration. Multiple regression analyses of Lp-PLA 2 activity and concentration were undertaken separately for men aged 40–49 years and 50–79 years, to clarify interactions of age and Lp-PLA 2 . Lp-PLA 2 activity for men aged 50–79 years was significantly and positively related to intima-media thickness (IMT) ( P = 0.013) and plaque index ( P = 0.008) independent of traditional risk factors including small LDL particles, but not to coronary artery calcification (CAC) score. Associations with Lp-PLA 2 concentration were qualitatively similar to those of activity. Corresponding relationships were not observed in men aged 40–49 years. Mendelian randomization analyses based on V279F genotype did not show any significant associations with subclinical atherosclerosis, although the homozygote and heterozygote of V279F showed low Lp-PLA 2 activity and concentration. Conclusions Lp-PLA 2 activity in Japanese men aged 50–79 years was associated significantly and positively with IMT and plaque in the carotid artery but Mendelian randomization did not support that Lp-PLA 2 is a causative factor for subclinical atherosclerosis. [ABSTRACT FROM AUTHOR]

Objective The association of high-density lipoprotein particle (HDL-P) with atherosclerosis may be stronger than that of HDL-cholesterol (HDL-C) and independent of conventional cardiovascular risk factors. Whether associations persist in populations at low risk of coronary heart disease (CHD) remains unclear. This study examines the associations of HDL-P and HDL-C with carotid intima-media thickness (cIMT) and plaque counts among Japanese men, who characteristically have higher HDL-C levels and a lower CHD burden than those in men of Western populations. Methods We cross-sectionally examined a community-based sample of 870 Japanese men aged 40–79 years, free of known clinical cardiovascular disease (CVD) and not on lipid-lowering medication. Participants were randomly selected among Japanese living in Kusatsu City in Shiga, Japan. Results Both HDL-P and HDL-C were inversely and independently associated with cIMT in models adjusted for conventional CHD risk factors, including low-density lipoprotein cholesterol (LDL-C) and diabetes. HDL-P maintained an association with cIMT after further adjustment for HDL-C (P < 0.01), whereas the association of HDL-C with cIMT was noticeably absent after inclusion of HDL-P in the model. In plaque counts of the carotid arteries, HDL-P was significantly associated with a reduction in plaque count, whereas HDL-C was not. Conclusion HDL-P, in comparison to HDL-C, is more strongly associated with measures of carotid atherosclerosis in a cross-sectional study of Japanese men. Findings demonstrate that, HDL-P is a strong correlate of subclinical atherosclerosis even in a population at low risk for CHD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Dietary intake of long-chain n-3 PUFA (LCn3FA) among Japanese is generally higher than that in Western populations. However, little is known whether an inverse association of LCn3FA with cardiovascular disease (CVD) risk exists in a population with higher LCn3FA intake. Objective: To investigate the association between LCn3FA intake and the long-term risk of CVDs in a Japanese general population. Methods: We followed-up a total of 9190 individuals (56.2% women, mean age 50.0 years) randomly selected from 300 areas across Japan and free from CVDs at baseline. Dietary LCn3FA intake was estimated using household weighed food records. Cox models were used to calculate multivariate-adjusted hazard ratios (HR) and confidence intervals (CI) according to sex specific quartiles of LCn3FA intake. Results: During 24-year follow-up (192,897 person-years), 879 cardiovascular deaths were observed. The median daily intake of LCn3FA was 0.37% kcal (0.86 g/day). Adjusted HR for CVD mortality was lower in the highest quartile of LCn3FA intake (HR 0.80; 95% CI 0.66–0.96) compared with the lowest quartile, and the trend was statistically significant (P = 0.038). The similar but statistically non-significant trends were observed for coronary heart disease death and stroke death. In analyses by age groups, the inverse associations of LCn3FA intake with the risk of total CVD death and stroke death were significant in younger individuals (30–59 years at baseline). Conclusion: LCn3FA intake was inversely and independently associated the long-term risk of total CVD mortality in a representative sample of Japanese with high LCn3FA intake. [Copyright &y& Elsevier]