Published papers

Objectives　Although self-reported questionnaires are widely used to collect information on medication use in epidemiological studies, their validity for studies involving older adults has not been sufficiently assessed. This study evaluated the validity of self-reported medication use using questionnaires in comparison with drug notebooks.Methods　The study enrolled 370 older community dwellers who participated in an aging sub-study survey of the Tsuruoka Metabolomics Cohort Study between April 2019 and March 2021. Medication use was assessed by comparing self-reported questionnaire data with drug notebook records. We analyzed medications used for hypertension, dyslipidemia, myocardial infarction, angina, diabetes, rheumatism, osteoporosis/metabolic bone disease, constipation, anxiety/depression, dementia, asthma, allergy, thrombosis, and thyroid disease. Moreover, gastrointestinal (GI) medications, steroids, and antipyretic analgesics were assessed, and data on injectable medications for osteoporosis/metabolic bone disease was collected. Using drug notebook records, we identified regular medication users by assessing whether they had received oral medication prescriptions covering over 28 days and took the medication within the 90 days preceding the day of their survey. To define medication categories, we used Anatomical Therapeutic Chemical (ATC) classification codes. Sensitivity, specificity, and kappa statistics were calculated for each medication using drug notebooks as standards. Those who did not bring their drug notebooks on the day of the survey were defined as non-medication users.Results　The mean age (standard deviation) of the 370 participants (146 men and 224 women) was 73.3 (4.0) years. The sensitivity and specificity for each medication were as follows: hypertension (0.97, 0.97), dyslipidemia (0.93, 0.98), myocardial infarction (0.24, 0.99), diabetes (0.94, 1.00), rheumatism (1.00, 1.00), osteoporosis/metabolic bone disease (0.82, 0.99), constipation (0.71, 0.98), GI conditions (0.63, 0.97), anxiety/depression (0.36, 1.00), dementia (0.67, 1.00), asthma (0.67, 0.98), allergy (0.57, 0.99), thrombosis (0.88, 0.98), steroids (0.80, 0.99), thyroid disease (1.00, 1.00) and antipyretic analgesics (0.75, 0.96).Conclusions　Although sensitivity and specificity differed by medication categories, the results of our population-based cohort study suggested that self-reported questionnaires on medication use among older adults are valid, especially for medications with high sensitivity (≥ 0.8).

BACKGROUND: The gender-specific characteristics of individuals at an increased risk of developing depression currently remain unclear despite a higher prevalence of depression in women than in men. This study clarified socioeconomic and lifestyle factors associated with an increased risk of subclinical depression in general Japanese men and women. METHODS: Study participants were residents not receiving psychiatric treatments in 300 sites throughout Japan in 2010 (1152 men, 1529 women). Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95%CIs) for socioeconomic factors and lifestyle factors were calculated using a logistic regression analysis. RESULTS: Risk of depressive tendencies was significantly higher in men who were single and living alone (OR, 3.27; 95% CI, 1.56-6.88) than those married. The risk was significantly lower in women who were not working and aged ≥ 60 years (OR, 0.39; 95% CI, 0.22-0.68) and higher in men who were not working and aged < 60 years (OR, 3.57; 95%CI, 1.31-9.72) compared with those who were working. Current smoking was also associated with a significantly increased risk of depressive tendencies in women (OR, 2.96; 95% CI, 1.68-5.22) but not in men. CONCLUSIONS: Socioeconomic and lifestyle factors were associated with an increased risk of depressive tendencies in general Japanese. Related factors were different by sex.

BACKGROUND: Although socioeconomic status (SES) may affect food and nutrient intakes, few studies have reported on sodium (Na) and potassium (K) intakes among individuals with various SESs in Japan. We investigated associations of SES with Na and K intake levels using urinary specimens in a representative Japanese population. METHODS: This was a cross-sectional study of 2,560 men and women (the NIPPON DATA2010 cohort) who participated in the National Health and Nutrition Survey Japan in 2010. Casual urine was used to calculate estimated excretion in 24-hour urinary Na (E24hr-Na) and K (E24hr-K). The urinary sodium-to-potassium (Na/K) ratio was calculated from casual urinary electrolyte values. An analysis of covariance was performed to investigate associations of aspects of SES, including equivalent household expenditure (EHE), educational attainment, and job category, with E24hr-Na, E24hr-K, and the Na/K ratio for men and women separately. A stratified analysis was performed on educational attainment and the job category for younger (<65 years) and older (≥65 years) participants. RESULTS: In men and women, average E24hr-Na was 176.2 mmol/day and 172.3, average E24hr-K was 42.5 and 41.3, and the average Na/K ratio was 3.61 and 3.68, respectively. Lower EHE was associated with a higher Na/K ratio in women and lower E24hr-K in men and women. A shorter education was associated with a higher Na/K ratio in women and younger men, and lower E24hr-K in older men and women. CONCLUSION: Lower EHE and a shorter education were associated with a lower K intake and higher Na/K ratio estimated from casual urine specimens in Japanese men and women.

OBJECTIVE: We conducted a cross-sectional study to clarify whether home blood pressure (HBP) is more strongly associated with coronary artery calcification (CAC) than accurately measured office blood pressure (OBP) among the general population of Japanese men. METHODS: We analyzed the data of 919 Japanese male participants who were randomly selected from general population (mean age 64.5 years). OBP was measured twice consecutively by a trained nurse using electrical device after 5 min of complete rest alone in a sitting position in a silent room. The participants were asked to measure HBP with an electrical device once in the morning during 7 consecutive days. CAC was assessed using computed tomography. Presence of CAC was defined as Agatston score at least 10. We calculated odds ratios for the presence of CAC per one SD higher OBP and HBP adjusted for age and other cardiovascular risk factors. RESULTS: The mean systolic OBP (SD) and HBP (SD) were 136.8 (19.0) and 137.2 (18.5) mmHg, respectively, without statistical difference between the two (P = 0.595). OBP and HBP were highly correlated (r = 0.74 P < 0.001). CAC was found in 454 (49.4%) participants. Multivariable-adjusted odds ratios [95% confidence interval (CI)] for the presence of CAC were comparable between OBP (1.32, 95% CI: 1.12-1.56) and HBP (1.35, 95% CI: 1.14-1.60) (P heterogeneity = 0.813). CONCLUSION: The strength of association of accurately measured OBP with CAC was comparable with that of HBP among randomly selected male general population aged 40-79 years.

AIM: To examine the relationship between the intake of dietary vegetable protein and CVD mortality in a 15-year follow-up study of a representative sample of the Japanese population. METHODS: A total of 7,744 participants aged 30 years or older (3,224 males and 4,520 females) who were free of CVD at baseline were included in this analysis. Vegetable protein intake (% energy) was assessed using a three-day semi-weighed dietary record at baseline. Multivariable-adjusted hazard ratios (HRs) were calculated using Cox's proportional hazards model after adjusting for confounding factors. RESULTS: The total person-years studied were 107,988 with a mean follow-up period of 13.9 years. There were 1,213 deaths during the follow-up period, among which 354 (29.2%) were due to CVD. Vegetable protein intake was associated inversely with CVD and cerebral hemorrhage mortality, with the HRs for a 1% energy increment in vegetable protein intake being 0.86 (95% CI, 0.75-0.99) and 0.58 (95% CI, 0.35-0.95), respectively. In the subgroup analysis of participants with or without hypertension, the inverse association between vegetable protein intake and CVD mortality was more evident in the nonhypertensive group, with the HRs for CVD and stroke being 0.68 (95% CI, 0.50-0.94) and 0.50 (95% CI, 0.30-0.84), respectively. CONCLUSIONS: Vegetable protein intake may prevent future CVD, particularly in nonhypertensive subjects in the Japanese population. However, further studies are necessary to examine the biological mechanisms of this effect.

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], mu g cs/L) were 5341 mu g cs/L (4093-7125). The mean average IMT of the common carotid artery was highest in the fourth LAB quartile (842 mu m) compared with the first quartile (797 mu m) 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 mu m (12.7), 856 mu m (16.7) in the low LAB/hypercholesterolemia group, and 833 mu m (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. (C) 2016 National Lipid Association. All rights reserved.

Equol, a metabolite of the dietary isoflavone daidzein, is produced by the action of gut bacteria in some individuals who are termed as equol-producers. It is proposed to have stronger atheroprotective properties than dietary isoflavones. We examined a cross-sectional association of dietary isoflavones and equol-producer status with coronary artery calcification (CAC), a biomarker of coronary atherosclerosis, among men in Japan. A population-based sample of 272 Japanese men aged 40-49 years recruited from 2004 to 2007 was examined for serum isoflavones, serum equol, CAC and other factors. Equol-producers were classified as individuals having a serum level of equol >83 nm. The presence of CAC was defined as a coronary Ca score 10 Agatston units. The associations of dietary isoflavones and equol-producers with CAC were analysed using multiple logistic regression. The median of dietary isoflavones, equol and CAC were 5127 (interquartile range (IQR) 1941, 11700), 91 (IQR 010, 331) and 00 (IQR 00, 10) nm, respectively. Prevalence of CAC and equol-producers was 96 and 160 %, respectively. Dietary isoflavones were not significantly associated with CAC. After multivariable adjustment, the OR for the presence of CAC in equol-producers compared with equol non-producers was 010 (95 % CI 001, 090, P<004). Equol-producers had significantly lower CAC than equol non-producers, but there was no significant association between dietary isoflavones and CAC, suggesting that equol may be a key factor for atheroprotective properties of isoflavones in Japanese men. This finding must be confirmed in larger studies or clinical trials of equol that is now available as a dietary supplement.

The objective of this study was to determine the optimal number and type of casual (spot) urine specimens required to estimate an individual's urinary sodium/potassium (Na/K) ratio. A total of 48 participants, 25 men and 23 women, aged between 25 and 59 years, was recruited from healthy volunteers. The Na/K ratio in each casual urine and 7-day 24-h urine sample was measured. Correlation analysis and the quality of agreement by the Bland and Altman method between casual urine and 24-h urine were analyzed. The mean Na/K ratio of 7-day 24-h urine was 4.3. The mean Na/K ratio of six random specimens of daytime (collected between 09 and 17 hours) casual urine correlated most strongly with the Na/K ratio of 7-day 24-h urine (r=0.87). The bias for the mean Na/K ratio between 7-day 24-h urine and daytime casual urine was almost negligible (0.03), and the quality of agreement for the mean of the six random, daytime casual urine specimens on different days was similar to that of the 2-day 24-h urine samples for estimating 7-day 24-h values. Our findings show that the mean Na/K ratio of six random daytime casual urine specimens on different days was a good substitute for the 2-day 24-h urine Na/K ratio.

Background-Smoking is an overwhelming, but preventable, risk factor for cardiovascular diseases (CVD), although smoking prevalence remains high in developed and developing countries in East Asia. Methods and Results-In a population-based sample of 1019 Japanese men aged 40 to 79 years, without CVD, we examined cross-sectional associations of smoking status, cumulative pack-years, daily consumption, and time since cessation, with subclinical atherosclerosis at 4 anatomically distinct vascular beds, including coronary artery calcification, carotid intima-media thickness (CIMT) and plaque, aortic artery calcification (AoAC), and ankle-brachial index. Current, former, and never smoking were present in 32.3%, 50.0%, and 17.7%, respectively. Compared to never smokers, current smokers had significantly higher risks of subclinical atherosclerosis in all 4 circulations (eg, odds ratios for coronary artery calcification >0, 1.79 [95% CIs, 1.16-2.79]; CIMT >1.0 mm, 1.88 [1.02-3.47]; AoAC >0, 4.29 [2.30-7.97]; and ankle-brachial index <1.1, 1.78 [1.16-2.74]) and former smokers did in carotid and aortic circulations (CIMT >1.0 mm, 1.94 [1.13-3.34]; and AoAC >0, 2.55 [1.45-4.49]). Dose-response relationships of pack-years and daily consumption, particularly with CIMT, carotid plaque, AoAC, and ankle-brachial index, were observed among both current and former smokers, and even a small amount of pack-years or daily consumption among current smokers was associated with coronary artery calcification and AoAC, whereas time since cessation among former smokers was linearly associated with lower burdens of all atherosclerotic indices. Conclusions-Cigarette smoking was strongly associated with subclinical atherosclerosis in multiple vascular beds in Japanese men, and these associations attenuated with time since cessation.

【目的】循環器疾患危険因子の正しい知識を持つ者ほど、循環器疾患発症に予防的な健康行動をとることが報告されている。そこで本研究では本邦国民における循環器疾患危険因子の認知度を明らかにするとともに、危険因子保有と認知度との関連を検討した。【方法】平成22年国民健康・栄養調査に参加した全国300地区からの20歳以上の男女2,891名に対し、「心筋梗塞または脳卒中の原因として正しいと思うもの」を選択する質問調査を実施した。正答は高血圧、糖尿病、高コレステロール血症、喫煙、不整脈、HDLコレステロール低値である。ロジスティック回帰分析で、各危険因子の保有者をそれぞれの非保有者と比較し、危険因子を認知している年齢調整オッズ比を算出した。【結果】循環器疾患危険因子の認知度はそれぞれ、85.8%(高血圧)、72.6%(高コレステロール血症)、58.5%(喫煙)、49.8%(不整脈)、45.1%(糖尿病)、38.5%(HDLコレステロール低値)であった。男性では、各危険因子の非保有者を基準とした時、高血圧者の高血圧認知度、高コレステロール血症を有する者の高コレステロール血症認知度、過去の喫煙習慣を有する者で喫煙に関する認知度、糖尿病者の糖尿病認知度が有意に高かった(オッズ比1.33〜2.73)。女性では、高コレステロール血症を有する者の高コレステロール血症認知度、過去の喫煙習慣を有する者で喫煙に関する認知度、糖尿病者の糖尿病認知度が有意に高かった(オッズ比1.54〜1.80)。【結論】循環器疾患危険因子の認知度は、高血圧で8割を超える一方、不整脈、糖尿病、HDLコレステロール低値では5割に満たなかった。また、危険因子保有者は保有する危険因子が循環器疾患危険因子であることを認知している傾向が観察されたが、その他の危険因子の認知度は非保有者と同程度、または低い傾向であった。国民に対する循環器疾患危険因子の周知が必要である。(著者抄録)

AIM: To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors. METHODS: Overall, 1,241 (aged 40-59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker's 1 H-nuclear magnetic resonance spectrometer for the primary outcome. Modifiable lifestyle factors included body mass index (BMI), physical activity, alcohol and smoking habits, and 70 nutrient parameters. We evaluated the different lipids between the groups using partial least squares-discriminant analysis and association between extracted lipids and lifestyle factors using multivariable linear regression analysis. RESULTS: Concentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8- mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI. CONCLUSIONS: Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.

The Japan Multi-Institutional Collaborative Cohort Study, the Yamagata Molecular Epidemiological Cohort Study, and the Tsuruoka Metabolomics Cohort Study use a 47-item food frequency questionnaire (FFQ) developed in central Japan in 2004. We applied regression analyses to estimate nutrient intakes in the FFQ. The regression equations, however, may not be so robust and may vary among areas, even in Japan. We aimed to evaluate the reproducibility and validity of the FFQ over an expanded area of Japan. Healthy volunteers aged 34–70 years from 13 areas of Japan provided 12-day weighed dietary records (WDRs) and completed two FFQs over 1 year. We evaluated reproducibility and validity by comparing the intakes of 27 nutrients between the two FFQs and the first FFQ (FFQ1) and WDRs, respectively. Spearman's rank correlation coefficients (SRs) between estimates from the FFQs and WDRs were calculated and corrected for intra-individual variation in the WDRs. Intakes of the selected nutrients estimated from the two FFQs were equivalent. The median energy-adjusted SRs between FFQ1 and the second FFQ were 0.66 for both men and women. Regarding validity adjusted for within-individual variation, energy-adjusted SRs for WDRs vs FFQ1 ranged from 0.13 (thiamin) to 0.79 (alcohol) for men, and the median was 0.35. The energy-adjusted SRs ranged from 0.20 (protein) to 0.71 (alcohol) for women, and the median was 0.43. The FFQ demonstrated high reproducibility and moderate validity, which suggests that it is appropriate to clarify associations between diet and health and/or disease among adults in Japan.

BACKGROUND: Oral health is thought to be associated with diet quality, and socioeconomic status (SES) affects both oral health and diet. The aim of this study was to investigate the association between the number of teeth and dietary intake as well as nutritional biomarker, considering the subjects' SES. METHODS: We conducted a cross-sectional analysis of data from 2049 individuals aged ≥ 50 years from the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 2010. The number of remaining teeth was categorized into age-specific quartiles (Q1 to Q4). We assessed the adjusted means and 95% confidence intervals for dietary variables by the number of teeth using analysis of covariance. Stratified analyses by SES were also conducted. RESULTS: The intake of grain products was 31 g higher, and those of vegetables and meat were 30 g and 8 g lower, respectively, in Q1 (fewer teeth) than in Q4 (more teeth). Carbohydrate intake was higher whereas protein, minerals (potassium, magnesium, and zinc), vitamins (vitamins A, E, B1, B6, β-carotene, and folic acid), and dietary fiber intakes were lower among individuals with fewer teeth. Adjusted mean serum albumin levels were low in Q1. The associations between the number of teeth and dietary intake were more evident in individuals with a low SES. CONCLUSIONS: Having few remaining teeth was associated with a low nutrient intake and low serum albumin levels in middle-aged and older Japanese adults, and these associations were more evident in individuals with low SES.

BACKGROUND: A lower socioeconomic status (SES) may be related to the intake of unhealthy food; however, this relationship has not been examined in detail. This study was undertaken to examine relationships among food group intakes and SES in a representative Japanese population. METHODS: This was a cross-sectional study using the baseline data of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey in Japan. A total of 2,898 participants were included in the baseline survey in 2010. The effects of age (<65 years and ≥65 years), equivalent household expenditure (EHE), and education attainment on food group intakes (gram per 1,000 kcal) were analyzed using a two-way analysis of variance. RESULTS: When EHE was lower, cereal intake was higher in men and women. Among men, fish, milk, and alcohol intakes were reduced with lower EHE. Among women, vegetable intake was reduced with lower EHE. In men and women, cereal intake was higher with lower education attainment. In contrast, meat intake was reduced with lower education attainment. CONCLUSIONS: Lower SES was associated with a higher cereal intake and lower vegetable, fish, meat, and milk intakes in a representative Japanese population. Socioeconomic discrepancies need to be considered in order to promote healthier dietary habits.

Background: Increased resting heart rate (RHR) independently predicts cardiovascular mortality. Meanwhile, long-chain n-3 fatty acids (LCn3FAs) have a cardioprotective effect. Our aim was to evaluate whether higher LCn3FAs intake attenuates the elevated risk of cardiovascular mortality associated with increased RHR. Methods: We conducted a population-based 24-year prospective cohort study of Japanese, whose LCn3FAs intake is relatively high. Study participants included 8807 individuals aged 30-95 years from randomly selected areas across Japan without cardiovascular diseases and anti-hypertensive drugs at baseline. The primary endpoint was cardiovascular mortality, and the secondary endpoints were cardiac and stroke mortality during 24 years of follow-up. Individual dietary LCn3FAs intake was estimated from household-based 3-day weighed food records. RHR was obtained from 3 consecutive R-wave intervals on 12-lead electrocardiography. Cox models were used to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) adjusting for possible confounders. Results: During the follow-up period, 617 cardiovascular deaths were observed. The median daily intake of LCn3FAs was 0.37% kcal (0.86 g/day). The interaction between dietary LCn3FAs intake and RHR in the risk of cardiovascular mortality was statistically significant (p = 0.033). The risk of cardiovascular mortality was significantly higher in the low-intake group (<0.37% kcal) with an RHR >85 beats/min (bpm) [hazard ratio (HR), 1.67; 95% confidence interval (CI), 1.15-2.43], but not in the high-intake group (>= 0.37% kcal) with an RHR >85 bpm (HR, 0.92; 95% CI, 0.61-1.38), compared with those in the high-intake group with an RHR <70 bpm. Similar results were observed with stroke mortality, but not with cardiac mortality. Conclusions: The risk of cardiovascular mortality associated with increased RHR is elevated in participants with low dietary LCn3FAs intake, but not in participants with high dietary LCn3FAs intake in a representative Japanese general population. These results suggest that high dietary LCn3FAs intake may prevent cardiovascular mortality associated with increased RHR. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

The United States has a higher prevalence of metabolic syndrome (MS) and cardiovascular disease (CVD) mortality than Japan, but it is unknown how much of the difference in MS accounts for the mortality difference. The aim of this study was to examine the impact of MS on the excess CVD mortality in the United States compared with that in Japan. Data from the United States Third National Health and Nutrition Examination Survey (NHANES 111; n = 12,561) and the Japanese National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in Aged (NIPPON DATA; n = 7,453) were analyzed. MS was defined as of 5 risk factors (obesity, high blood pressure, decreased high-density lipoprotein cholesterol, elevated glycosylated hemoglobin, and elevated triglycerides). The results show that after a median of 13.8 years of follow-up in the United States, 1,683 patients died from CVD (11.75 per 1,000 person-years), and after a median of 15 years of follow-up in Japan, 369 patients died from CVD (3.56 per 1,000 person-years). The age-adjusted prevalence of MS was 26.7% in the United States and 19.3% in Japan. Of 5 MS factors, obesity, high blood pressure, elevated triglycerides, and glycosylated hemoglobin in the United States, and high blood pressure and elevated glycosylated hemoglobin in Japan were significant risk factors for CVD mortality. Estimates of 13.3% and 44% of the excess CVD mortality for the United States could be explained by the higher prevalence of MS and MS plus baseline CVD history than in Japan. In conclusion, the present study is the first to quantitatively demonstrate that MS and MS plus baseline CVD history may significantly contribute to the explanation of excess CVD mortality in the United States compared with Japan. (C) 2014 Elsevier Inc. All rights reserved.

Objective Higher marine-derived n-3 fatty acids (MDn3FAs) intake reduces the risk of sudden cardiac death via antiarrhythmic effects. The article evaluates whether MDn3FAs intake attenuates the increased risk of cardiac death associated with J-point elevation (JPE), characterised by an elevation of QRS-ST junction (J-point) >= 0.1 mV on electrocardiography. Design A prospective population-based cohort study. Setting The National Survey on Circulatory Disorders and the National Nutrition Survey of Japan. Participants A total of 4348 community-dwelling men (mean age 49.3 years), without cardiovascular diseases at baseline, from randomly selected areas across Japan. Main outcome measures Cardiac death (200 men) during the 24-year follow-up. Results Dietary MDn3FAs intake was assessed using a dietary method to estimate individual intake of household-based weighed food records for 3 days. Cox models were used to calculate HRs and 95% CIs adjusted for possible confounding factors. JPE was present in 340 participants (7.8%). The median daily intake of MDn3FAs was 0.35% kcal (0.92 g/day). The risk of cardiac death was significantly higher in participants with JPE than in those without JPE in the low intake group (<0.35% kcal; adjusted HR 3.51; 95% CI 1.84 to 6.73; p<0.001), but not in the high intake group (>= 0.35% kcal; adjusted HR 1.09; 95% CI 0.56 to 2.16; p=0.795). The interaction between dietary MDn3FAs intake and JPE on the risk of cardiac death was statistically significant (p=0.006). Conclusions The increased risk of cardiac death associated with JPE may be attenuated by higher dietary MDn3FAs intake.

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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme predominantly bound to low-density lipoprotein (LDL). Lp-PLA2 is recognized as playing a key role in inflammatory processes and the development of atherosclerosis. This study aimed to investigate whether Lp-PLA2 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-PLA2 activity and concentration were undertaken separately for men aged 40-49 years and 50-79 years, to clarify interactions of age and Lp-PLA2. Lp-PLA2 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-PLA2 concentration were qualitatively similar to those of activity. Corresponding relationships were not observed in men aged 40e49 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 LpPLA2 activity and concentration. Conclusions: Lp-PLA2 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 LpPLA2 is a causative factor for subclinical atherosclerosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.