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Background/objectives: Clinical trials of eicosapentaenoic acid (EPA) among high-risk groups in Japan in which consumption of mairne-omega-3 fatty acids (OM3) is much higher than other countries showed slower progression of coronary atherosclerosis. We aimed to determine the cross-sectional associations of coronary artery calcification (CAC) and calcium density with OM3, EPA, and docosahexaenoic acid (DHA), two principal OM3, in the general population in Japan.Subjects/methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis examined a population-based sample of 1074 men aged 40-79 in 2006-08 for computed tomography-measured CAC score (CCS), a well-established biomarker of coronary atherosclerosis, CAC density score (CDS), a potential marker of plaque stabilization, serum levels of OM3, and risk factors.Results: Prevalence of CCS > 0, ≥ 100, and ≥ 300 was 65.8%, 25.9%, and 12.9%, respectively; the mean (SD) OM3, EPA, and DHA were 10.1% (3.2), 3.2% (1.7), and 5.9% (1.6), respectively. Odds ratios (95% CI, p-value) of CCS 0, 100, and 300 in ordinal logistic regression associated with 1 SD increase of OM3, EPA, and DHA were 0.91 (0.81-1.03, p = 0.12), 0.99 (0.88-1.11, p = 0.87) and 0.84 (0.74-0.94, p = < 0.01), respectively. The inverse association of DHA with CCS remained significant in multivariate-adjusted model: odds ratio of 0.87 (0.77-0.99, p = 0.03). Blood levels of OM3, EPA, or DHA did not have any significant associations with CDS.Conclusions: DHA but not EPA had a significant inverse association with coronary atherosclerosis in the general population with high levels of OM3. Future trials are warranted comparing the effect of high-dose DHA and EPA on atherosclerosis and cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

To examine whether smoking habits, including smoking amount and cessation duration at baseline, are associated with atherosclerosis progression. At baseline (2006–08, Japan), we obtained smoking status, amount of smoking and time since cessation for quitters in a community-based random sample of Japanese men initially aged 40–79 years and free of cardiovascular disease. Coronary artery calcification (CAC) and aortic artery calcification (AAC) as biomarker of atherosclerosis was quantified using Agatston's method at baseline and after 5 years of follow-up. We defined progression of CAC and AAC (yes/no) using modified criteria by Berry. A total of 781 participants was analyzed. Multivariable adjusted odds ratios (ORs) of CAC and AAC progression for current smokers were 1.73 (95% CI, 1.09–2.73) and 2.47 (1.38–4.44), respectively, as compared to never smokers. In dose-response analyses, we observed a graded positive relationship of smoking amount and CAC progression in current smokers (multivariable adjusted ORs: 1.23, 1.72, and 2.42 from the lowest to the highest tertile of pack-years). Among the former smokers, earlier quitters (≥10.7 years) had similar ORs of the progression of CAC and AAC to that of participants who had never smoked. Compared with never smokers, current smokers especially those with greater pack-years at baseline had higher risk of atherosclerosis progression in community-dwelling Japanese men. Importantly, the residual adverse effect appears to be present for at least ten years after smoking cessation. The findings highlight the importance of early avoidance or minimizing smoking exposure for the prevention of atherosclerotic disease. • Longitudinal study on relationship between smoking habits and atherosclerosis. • Continued smokers had artery calcification progression two times than never smokers. • Residual effect on atherosclerosis appears at least ten years after smoking cessation. [ABSTRACT FROM AUTHOR]

Background The mechanisms by which exercise reduces the risk of coronary heart disease remain poorly understood. Irisin, an exercise-induced polypeptide secreted from skeletal muscles, is proposed to potentially mediate beneficial effects of exercise, especially in metabolic regulation and development of atherosclerosis. We examined whether higher serum irisin levels are associated with lower prevalence and progression of coronary atherosclerosis. Methods and results We performed a prospective, population-based study of Japanese men aged 40–79 years without known coronary heart disease. We measured baseline serum irisin levels using an enzyme-linked immunosorbent assay and quantified coronary artery calcification (CAC) from serial computed tomography scans. Of 1038 participants (mean age, 63.9 years) at baseline, 670 (64.6%) had prevalent CAC. Of 810 participants at follow-up (median, 5.1 years), 407 (50.3%) experienced CAC progression. In Poisson regression with robust error variance adjusted for age and behavioral factors, serum irisin levels were inversely associated with CAC prevalence (relative risk [RR] of 4th versus 1st quartiles [95% confidence interval], 0.88 [0.78–0.99]; trend P  = 0.016) and CAC progression (RR, 0.76 [0.63–0.91]; trend P  = 0.002). After further adjustment for cardiometabolic risk factors, the inverse association with CAC prevalence disappeared (RR, 0.95 [0.84–1.08]; trend P  = 0.319), but that with CAC progression persisted (RR, 0.77 [0.64–0.93]; trend P   =  0.003). These associations were consistent when we applied ordinal logistic regression and across subgroups by cardiometabolic risk factor status. Conclusions Higher serum irisin levels were associated with less burden of coronary atherosclerosis. This association would be mediated through and beyond traditional cardiometabolic pathways. [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 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]

The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45–54, 55–64, or 65–74 years). We used community-based samples of Caucasian men in the United States (2000–2002; n = 1,067) and Japanese men in Japan (2006–2008; n = 832) aged 45–74 years, stratifying them into groups with 0, 1, 2, or ≥3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian men's having Agatston scores of ≥10, ≥100, and ≥400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian men's having an Agatston score of ≥100 were 2.05, 2.43, and 3.86 among those aged 45–54, 55–64, and 65–74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups. [ABSTRACT FROM PUBLISHER]

Abstract: Although moderate alcohol intake in diabetic Caucasians is associated with a reduction in coronary heart disease mortality, no study in Japanese with diabetes has examined the association between alcohol intake and mortality outcomes. We analyzed the relationship between alcohol intake and all-cause and cause-specific mortality using the database from NIPPON DATA80. At the baseline in 1980, data on history, lifestyle, and physical examinations were collected on study participants aged 30 years and older from randomly selected areas in Japan. After excluding participants with comorbidities, we followed 4,018 male participants (3,614 nondiabetics, 195 with impaired glucose tolerance and 209 diabetic) for 19 years. During the 19 years of follow-up, there were 990 deaths; 328 were from cardiovascular disease and 157 from all-heart diseases. With the never-drinking category serving as a reference, the Cox multivariate-adjusted hazard ratios for non-daily and daily drinkers for cardiovascular mortality were 0.43 (95% confidence intervals: 0.19–0.95) and 0.45 (0.25–0.80), respectively, and 0.33 (0.12–0.91) and 0.31 (0.15–0.67) for all-heart disease mortality in the combined impaired glucose tolerance and diabetic Japanese men. Alcohol drinking in men with glucose intolerance was associated with a significant reduction in cardiovascular and all-heart disease mortality as seen in the general population in Japan. [Copyright &y& Elsevier]

Aims: Ectopic fat accumulation is related to insulin resistance and diabetes mellitus (DM). However, the effect of fatty liver on DM in non-obese individuals has not been clarified. We investigated whether liver fat accumulation assessed by computed tomography (CT) is associated with the incidence of DM.Methods: In a prospective population-based study, 640 Japanese men were followed up for 5 years. The liver to spleen (L/S) ratio of the CT attenuation value was used as the liver fat accumulation index. We calculated the odds ratio (OR) and 95% confidence interval (CI) for the DM incidence of per 1 standard deviation (SD) lower L/S and those of L/S < 1.0 compared with L/S ≥ 1.0, using logistic regression models.Results: Both per 1 SD lower L/S and L/S < 1.0 were significantly associated with a risk for DM incidence (1 SD lower L/S: OR = 1.57, 95%CI = 1.14-2.16; L/S < 1.0: OR = 2.27, 95%CI = 1.00-5.14). The relationship between L/S and incidence of DM was consistent in the obese and non-obese groups, with thresholds of BMI 25 kg/m2, waist circumference 85 cm, or visceral adipose tissue 100 cm2.Conclusions: Liver fat accumulation assessed by CT was associated with the incidence of DM. [ABSTRACT FROM AUTHOR]