研究者詳細 - 岡村　智教

論文 - 岡村　智教

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Relationship of three different types of low-carbohydrate diet to cardiometabolic risk factors in a Japanese population: the INTERMAP/INTERLIPID Study.

Nakamura Y, Ueshima H, Okuda N, Miura K, Kita Y, Miyagawa N, Yoshita K, Nakagawa H, Sakata K, Saitoh S, Okamura T, Okayama A, Choudhry SR, Rodriguez B, Masaki KH, Chan Q, Elliott P, Stamler J

European journal of nutrition 55 （ 4 ） 1515 - 24 2015年06月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1436-6207

Purpose: Low-carbohydrate diets (LCD) are a popular dietary strategy for weight reduction. The effects of LCD on long-term outcome vary depending on type of LCD, possibly due to the fact that effects on cardiometabolic risk factors may vary with different types of LCD. Accordingly, we studied these relations. Methods: We assessed serum concentrations of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), high-sensitivity C-reactive protein (CRP), total cholesterol, glycated hemoglobin, and uric acid, and nutrient intakes by standardized methods in men and women ages 40–59 years from four population samples of Japanese in Japan (553 men and 544 women, combined). For people consuming usual, animal-based, and plant-based LCDs, we calculated LCD scores, based on relative level of fat, protein, and carbohydrate, by modifying the methods of Halton et al. Instead of calculating scores based on animal or vegetable fat, we used saturated fatty acids (SFA) or monounsaturated fatty acids (MUFA) + polyunsaturated fatty acids (PUFA). Results: In multivariate regression analyses with adjustment for site, age, sex, BMI, smoking, alcohol intake, physical activity, and years of education, all three LCD scores were significantly positively related to HDLc (all P < 0.001), but not to LDLc. The plant-based LCD score was significantly inversely related to log CRP (coefficient = −0.010, P = 0.018). Conclusions: All three LCD scores were significantly positively related to HDLc. The plant-based LCD score was significantly inversely related to CRP. Carbohydrate intake below 50 % of total energy with higher intakes of vegetable protein and MUFA + PUFA, and lower intakes of SFA may be favorable for reducing cardiometabolic risk factors.

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Relationship of type of work with health-related quality of life.

Kawabe Y, Nakamura Y, Kikuchi S, Suzukamo Y, Murakami Y, Tanaka T, Takebayashi T, Okayama A, Miura K, Okamura T, Fukuhara S, Ueshima H

Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation 24 （ 12 ） 2927 - 32 2015年06月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0962-9343

Purpose: To examine the relation of work type with health-related quality of life (HRQoL) in healthy workers. Methods: We cross-sectionally examined 4427 (3605 men and 822 women) healthy workers in Japan, aged 19–69 years. We assessed HRQoL based on scores for five scales of the SF-36. Multiple regression was applied to examine the relation of work type (nighttime, shift, day to night, and daytime) with the five HRQoL norm-based scores, lower scores of which indicate poorer health status, adjusted for confounding factors, including sleeping duration. Results: Shiftwork was inversely related to role physical [regression estimate (β) = −2.12, 95 % confidence intervals (CI) −2.94, −1.30, P < 0.001], general health (β = −1.37, 95 % CI −2.01, −0.72, P < 0.001), role emotional (β = −1.24, 95% CI −1.98, −0.50, P < 0.001), and mental health (β = −1.31, 95% CI −2.01, −0.63, P < 0.001) independent of confounding factors, but not to vitality. Day-to-nighttime work was inversely related to all the five HRQoL subscales (Ps 0.012 to <0.001). Conclusion: Shiftwork was significantly inversely related to four out of the five HRQoL, except for vitality, and day-to-nighttime work was significantly inversely related to all five HRQoL, independent of demographic and lifestyle factors.

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Associations between inflammatory markers and subclinical atherosclerosis in middle-aged white, Japanese-American and Japanese men

Nagasawa Shin Ya, Ohkubo Takayoshi, Masaki Kamal, Barinas-Mitchell Emma, Miura Katsuyuki, Seto Todd B., El-Saed Aiman, Kadowaki Takashi, Willcox Bradley J., Edmundowicz Daniel, Kadota Aya, Evans Rhobert W., Kadowaki Sayaka, Fujiyoshi Akira, Hisamatsu Takashi, Bertolet Marianne H., Okamura Tomonori, Nakamura Yasuyuki, Kuller Lewis H., Ueshima Hirotsugu, Sekikawa Akira

Journal of Atherosclerosis and Thrombosis 22 （ 6 ） 590 - 598 2015年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1340-3478

Aim: To examine whether the inflammatory markers C-reactive protein (CRP) and fibrinogen are associated with biomarkers of atherosclerosis [carotid intima-media thickness (IMT) and coronary artery calcification (CAC)] in the general male population, including Asians. Methods: Population-based samples of 310 Japanese, 293 Japanese-American and 297 white men 40-49 years of age without clinical cardiovascular disease underwent measurement of IMT, CAC and the CRP and fibrinogen levels as well as other conventional risk factors using standardized methods. Statistical associations between the variables were evaluated using multiple linear or logistic regression models. Results: The Japanese group had significantly lower levels of inflammatory markers and subclinical atherosclerosis than the Japanese-American and white groups (P-values all <0.001). The mean level of CRP was 0.66 vs. 1.11 and 1.47 mg/L, while that of fibrinogen was 255.0 vs. 313.0 and 291.5 mg/dl, respectively. In addition, the mean carotid IMT was 0.61 vs. 0.73 and 0.68 mm, while the mean prevalence of CAC was 11.6% vs. 32.1% and 26.3%, respectively. Body mass index (BMI) showed significant positive associations with both the CRP and fibrinogen levels. Although CRP showed a significant positive association with IMT in the Japanese men, this association became non-significant following adjustment for traditional risk factors or BMI. In all three populations, CRP was not found to be significantly associated with the prevalence of CAC. Similarly, fibrinogen did not exhibit a significant association with either IMT or the prevalence of CAC. Conclusions: The associations between inflammatory markers and subclinical atherosclerosis may merely reflect the strong associations between BMI and the levels of inflammatory markers and incidence of subclinical atherosclerosis in both Eastern and Western populations.

Fruit and vegetable intake and mortality from cardiovascular disease in Japan: a 24-year follow-up of the NIPPON DATA80 Study.

Okuda N, Miura K, Okayama A, Okamura T, Abbott RD, Nishi N, Fujiyoshi A, Kita Y, Nakamura Y, Miyagawa N, Hayakawa T, Ohkubo T, Kiyohara Y, Ueshima H, NIPPON DATA80 Research Group

European journal of clinical nutrition 69 （ 4 ） 482 - 488 2015年04月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0954-3007

Background/Objectives:There have been few studies on the association of fruit and vegetable (FV) intake with cardiovascular disease (CVD) risk in Asian populations where both dietary habits and disease structure are different from western countries. No study in Asia has found its significant association with stroke. We examined associations of FV intake with mortality risk from total CVD, stroke and coronary heart diseases (CHDs) in a representative Japanese sample.Methods:A total of 9112 participants aged from 24-year follow-up data in the NIPPON DATA80, of which baseline data were obtained in the National Nutrition Survey Japan in 1980, were studied. Dietary data were obtained from 3-day weighing dietary records. Participants were divided into sex-specific quartiles of energy adjusted intake of FV. Multivariate-adjusted hazard ratios (HRs) were calculated between strata of the total of FV intake, fruit intake and vegetable intake. The adjustment included age, sex, smoking, drinking habit and energy adjusted intakes of sodium and some other food groups.Results:Participants with higher FV intake were older, ate more fish, milk and dairy products and soybeans and legumes and ate less meat. Multivariate-adjusted HR (95% confidence interval; P; P for trend) for the highest versus the lowest quartile of the total of FV intake was 0.74 (0.61-0.91; 0.004; 0.003) for total CVD, 0.80 (0.59-1.09; 0.105; 0.036) for stroke and 0.57 (0.37-0.87; 0.010; 0.109) for CHD.Conclusions:The results showed that higher total intake of FVs was significantly associated with reduced risk of CVD mortality in Japan.

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High-density lipoprotein particle concentration and subclinical atherosclerosis of the carotid arteries in Japanese men.

Zaid M, Fujiyoshi A, Miura K, Abbott RD, Okamura T, Takashima N, Torii S, Saito Y, Hisamatsu T, Miyagawa N, Ohkubo T, Kadota A, Sekikawa A, Maegawa H, Nakamura Y, Mitsunami K, Ueshima H, SESSA Research group.

Atherosclerosis 239 （ 2 ） 444 - 450 2015年04月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0021-9150

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.

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Combined effect of blood pressure and total cholesterol levels on long-term risks of subtypes of cardiovascular death: Evidence for Cardiovascular Prevention from Observational Cohorts in Japan.

Satoh M, Ohkubo T, Asayama K, Murakami Y, Sakurai M, Nakagawa H, Iso H, Okayama A, Miura K, Imai Y, Ueshima H, Okamura T, Evidence for Cardiovascular Prevention From Observational Cohorts in Japan (EPOCH–JAPAN) Research Group*.

Hypertension (Dallas, Tex. : 1979) 65 （ 3 ） 517 - 524 2015年03月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0194-911X

No large-scale, longitudinal studies have examined the combined effects of blood pressure (BP) and total cholesterol levels on long-term risks for subtypes of cardiovascular death in an Asian population. To investigate these relationships, a meta-analysis of individual participant data, which included 73 916 Japanese subjects (age, 57.7 years; men, 41.1%) from 11 cohorts, was conducted. During a mean follow-up of 15.0 years, deaths from coronary heart disease, ischemic stroke, and intraparenchymal hemorrhage occurred in 770, 724, and 345 cases, respectively. Cohort-stratified Cox proportional hazard models were used. After stratifying the participants by 4 systolic BP ×4 total cholesterol categories, the group with systolic BP ≥160 mm Hg with total cholesterol ≥5.7 mmol/L had the greatest risk for coronary heart disease death (adjusted hazard ratio, 4.39; P<0.0001 versus group with systolic BP <120 mm Hg and total cholesterol <4.7 mmol/L). The adjusted hazard ratios of systolic BP (per 20 mm Hg) increased with increases in total cholesterol categories (hazard ratio, 1.52; P<0.0001 in group with total cholesterol ≥5.7 mmol/L). Similarly, the adjusted hazard ratios of total cholesterol increased with increases in systolic BP categories (P for interaction ≤0.04). Systolic BP was positively associated with ischemic stroke and intraparenchymal hemorrhage death, and total cholesterol was inversely associated with intraparenchymal hemorrhage, but no significant interactions between BP and total cholesterol were observed for stroke. High BP and high total cholesterol can synergistically increase the risk for coronary heart disease death but not for stroke in the Asian population.

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Serum polyunsaturated fatty acid composition and serum high-sensitivity C-reactive protein levels in healthy Japanese residents

Kubota Yoshimi, Higashiyama A., Imano H., Sugiyama D., Kawamura K., Kadota A., Nishimura K., Miyamatsu N., Miyamoto Y., Okamura T.

Journal of Nutrition, Health and Aging 2015年03月

ISSN 1279-7707

Background/Objectives: Serum polyunsaturated fatty acid (PUFA) composition reflects dietary intake and is related to risks for cardiovascular diseases. We hypothesized that serum n-3 PUFA composition, especially including long-chain n-3 PUFA such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is associated with inflammatory status, which is related to increased risk for cardiovascular diseases.Subjects/Methods: We investigated the relationship between serum PUFA composition and high-sensitivity C-reactive protein (hs-CRP) levels in a cross-sectional study among 1,102 healthy men and women aged 40–74 years who reside in Kobe City. Multiple linear regression models that predict hs-CRP level were prepared to confirm the contribution of serum total n-3 PUFA, long-chain n-3 PUFA, EPA and DHA compositions after adjusting for other PUFAs and atherosclerotic risk factors.Results: The serum n-3 PUFA, particularly long-chain n-3 PUFA, compositions were inversely associated with the hs-CRP levels. The standardized regression coefficient was −0.089 (p < 0.01) for total n-3 PUFA, −0.091 (p < 0.01) for long-chain n-3 PUFA, −0.071 (p = 0.03) for EPA, and −0.068 (p = 0.04) for DHA. The n-6 PUFA compositions were also inversely associated with the hs-CRP levels (−0.169 [p < 0.01] for total n-6 PUFA and −0.159 [p < 0.01] for linoleic acid).Conclusions: The serum n-3 PUFA compositions were inversely related with the hs-CRP levels, similar associations were also observed in n-6 PUFA compositions. Our results suggest that dietary PUFA intake was inversely associated with attenuated inflammation in healthy Japanese population.

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Effects of stroke education of junior high school students on stroke knowledge of their parents: Tochigi project.

Matsuzono K, Yokota C, Takekawa H, Okamura T, Miyamatsu N, Nakayama H, Nishimura K, Ohyama S, Ishigami A, Okumura K, Toyoda K, Miyamoto Y, Minematsu K, Tochigi Junior High School Stroke Education Group., Participating Investigators of Tochigi Junior High School Stroke Education Group.

Stroke 46 （ 2 ） 572 - 574 2015年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0039-2499

BACKGROUND AND PURPOSE - : Educating the youth about stroke is a promising approach for spreading stroke knowledge. The aim of this study was to verify communication of stroke knowledge to parents by educating junior high school students about stroke. METHODS - : We enrolled 1127 junior high school students (age, 13-15 years) and their parents in the Tochigi prefecture, Japan. All students received a stroke lesson, watched an animated cartoon, and read the related Manga comic as educational aids. The students took back home the Manga and discussed what they learned with their parents. Questionnaires on stroke knowledge were given to all at baseline and immediately after the lesson. RESULTS - : A total of 1125 students and 915 parents answered the questionnaires. In the students, the frequency of correct answers increased significantly for all questions on stroke symptoms except for headache, and for all questions on risk factors after the lesson. In the parents, the correct answer rates increased for stroke symptoms except for headache and numbness in one side of the body, and for all questions on risk factors except for hypertension. Ninety-one percent of students and 92.7% of parents correctly understood the Face, Arm, Speech, and Time (FAST) mnemonic after the lesson. CONCLUSIONS - : Improvement of stroke knowledge immediately after the stroke lesson was observed in parents as well as their children, which indicated that our teaching materials using the Manga was effective in delivering the stroke knowledge to parents through their children.

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LOX-1 in atherosclerotic disease.

Sawamura T, Wakabayashi I, Okamura T

Clinica chimica acta; international journal of clinical chemistry 440 157 - 163 2015年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0009-8981

Oxidized low-density lipoprotein (LDL) exhibits various biological activities and accumulates in atheromas. LOX-1 (lectin-like oxidized LDL receptor) is the receptor that mediates oxidized LDL activity in vascular endothelial cells. Activation of LOX-1 results in oxidized LDL-induced endothelial dysfunction and hyperlipidemia-induced vascular lipid deposition. We hypothesized that LOX-1 is a candidate risk factor beyond LDL cholesterol (LDLC) and developed a novel assay to quantify LOX-1 ligand containing apoB (LAB). In men from the United States, serum LAB showed a significant positive association with carotid intima-media thickness, independent of LDLC. LAB and the LOX index (obtained by multiplying LAB by sLOX-1) were significantly associated with the incidence of coronary artery disease and ischemic stroke after adjusting for confounding factors, including non-HDL cholesterol. sLOX-1 is thought to be a better biomarker for early diagnosis of acute coronary syndrome than traditional biomarkers, including troponin T. LAB was associated with various atherosclerotic risk factors such as smoking, obesity, diabetes, diastolic hypertension, hypertriglyceridemia, and metabolic syndrome. Measurement of the soluble form of LOX-1 (sLOX-1) and LAB seems to be useful for evaluating the state and risk of atherosclerosis and atherosclerosis-related diseases. Further prospective studies using large populations and randomized clinical trials on sLOX-1, LAB, and the LOX index are needed.

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HDL cholesterol performance using an ultracentrifugation reference measurement procedure and the designated comparison method.

Nakamura M, Yokoyama S, Kayamori Y, Iso H, Kitamura A, Okamura T, Kiyama M, Noda H, Nishimura K, Nakai M, Koyama I, Dasti M, Vesper HW, Teramoto T, Miyamoto Y

Clinica chimica acta; international journal of clinical chemistry 439 185 - 190 2015年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0009-8981

Background: Accurate high-density lipoprotein cholesterol (HDL-C) measurements are important for management of cardiovascular diseases. The US Centers for Disease Control and Prevention (CDC) and Cholesterol Reference Method Laboratory Network (CRMLN) perform ultracentrifugation (UC) reference measurement procedure (RMP) to value assign HDL-C. Japanese CRMLN laboratory (Osaka) concurrently runs UC procedure and the designated comparison method (DCM). Osaka performance of UC and DCM was examined and compared with CDC RMP. Methods: CDC RMP involved UC, heparin-MnCl₂ precipitation, and cholesterol analysis. CRMLN DCM for samples containing <200mg/dl triglycerides involved 50-kDa dextran sulfate-MgCl₂ precipitation and cholesterol determination. Results: HDL-C regression equations obtained with CDC (x) and Osaka (y) were y=0.992x+0.542 (R²=0.996) for Osaka UC and y=1.004x-0.181 (R²=0.998) for DCM. Pass rates within ±1mg/dl of the CDC target value were 91.9 and 92.1% for Osaka UC and DCM, respectively. Biases at 40mg/dl HDL-C were +0.22 and -0.02mg/dl for Osaka UC and DCM, respectively. Conclusions: Osaka UC and DCM were highly accurate, precise, and stable for many years, assisting manufacturers to calibrate products for clinical laboratories to accurately measure HDL-C for patients, calculate non-HDL-C, and estimate low-density lipoprotein cholesterol with the Friedewald equation.

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The reasonable reliability of a self-administered food frequency questionnaire for an urban, Japanese, middle-aged population: the Suita study.

Maruyama K, Kokubo Y, Yamanaka T, Watanabe M, Iso H, Okamura T, Miyamoto Y

Nutrition research (New York, N.Y.) 35 （ 1 ） 14 - 22 2015年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0271-5317

Because few studies have developed food frequency questionnaires (FFQ) and examined their reliability for Japanese urban populations, FFQ developed for urban Japanese populations may show reasonable reliability for estimating intakes of nutrients and food groups. Therefore, the objective of this study was to examine the reliability of an FFQ developed for a prospective cohort study in a Japanese urban area. A total of 29 men and 29 women aged 47 to 78 years were selected from participants in the Suita study from February 1997 to February 1998. Seven-consecutive-day dietary records (DR) was collected in each season (28-day DR). The FFQ were administered 3 times in total in each season, except in autumn. We calculated Spearman correlation coefficients to assess the validation of the first and third FFQ compared with 28-day DR and to assess the repeatability for 3-, 6-, and 9-month intervals. Reasonable validity of each FFQ compared with 28-day DR were observed for energy intake and for 27 nutrients, and 11 food groups were selected. Median (range) Spearman rank correlation coefficients for energy-adjusted nutrient and food group intakes of the first FFQ were 0.52 (0.14-0.88) and 0.53 (0.24-0.74), and those of the third FFQ were 0.51 (0.07-0.84) and 0.57 (0.16-0.75), respectively. The repeatability of each interval was relatively good; median (range) Spearman correlation coefficients of nutrients for 3-, 6-, and 9-month intervals were 0.67 (0.40-0.85), 0.63 (0.25-0.93), and 0.62 (0.31-0.87), respectively; those for food groups were 0.58 (0.42-0.76), 0.56 (0.24-0.80), and 0.65 (0.30-0.76), respectively. In conclusion, this FFQ is useful for evaluating the associations of nutrient and food intakes with cardiovascular diseases and their risk factors in Japanese urban populations.

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[Effects of a long-term intervention in a work cafeteria on employee vegetable intake].

Misawa A, Yoshita K, Fukumura T, Tanaka T, Tamaki J, Takebayashi T, Kusaka Y, Nakagawa H, Yamato H, Okayama A, Miura K, Okamura T, Ueshima H, HIPOP-OHP Research Group.

Sangyo eiseigaku zasshi = Journal of occupational health 57 （ 3 ） 97 - 107 2015年

研究論文（学術雑誌）, ISSN 1341-0725

OBJECTIVES: We examined the effects on employee vegetable intake of a long-term intervention in an employee work cafeteria.METHODS: The subjects were approximately 1,200 employees (aged 19-61 years) of an industrial company in Fukui prefecture. We promoted the intake of typical Japanese style meals that combined three elements (staple foods, main dishes and vegetable dishes) to increase vegetables intake. We displayed all items on the menus of the employee cafeteria using three colors (yellow, red and green to denote three elements) to indicate healthy food choices for the maintenance of a healthy food environment. We advised employees to choose meals containing the three elements at the time of payment, for nutritional education (appropriate portion choice: APC). We evaluated the ratio of APC at the same time. To calculate the mean daily intake per person, we carried out a questionnaire survey similar to the "semi-quantitative food frequency questionnaire" and asked about the frequency and approximate intake of vegetables.RESULTS: The APC was 63.5% after one year of intervention, significantly increased to 82.1% after two years (p <0.001), and was 80.0% after three years of intervention (p <0.001). Vegetable intake at breakfast (p <0.001), lunch (p <0.001) and dinner (p = 0.011), and from vegetable juice (p = 0.030) significantly increased after three years of intervention. The consumption of pickles significantly decreased after three years of intervention (p = 0.009). It was estimated that the vegetable intake of men increased from 167.3 to 184.6 g, and that of women from 157.9 to 187.7 g.CONCLUSIONS: Employee estimated vegetable intake was significantly increased and that of pickles was significantly decreased by a long-term intervention (three years) in the employee work cafeteria.

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The relationship between lectin-like oxidized low-density lipoprotein receptor-1 ligands containing apolipoprotein B and the cardio-ankle vascular index in healthy community inhabitants

Sugiyama Daisuke, Higashiyama Aya, Wakabayashi Ichiro, Kubota Yoshimi, Adachi Yoshiko, Hayashibe Akiko, Kawamura Kuniko, Kuwabara Kazuyo, Nishimura Kunihiro, Kadota Aya, Nishida Yoko, Hirata Takumi, Imano Hironori, Miyamatsu Naomi, Miyamoto Yoshihiro, Sawamura Tatsuya, Okamura Tomonori

Journal of Atherosclerosis and Thrombosis 22 （ 5 ） 499 - 508 2015年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1340-3478

Aims: Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 ligands containing apolipoprotein B (LAB) and lectin-like oxidized LDL receptor-1 (LOX-1) are known as LOX-1-related modified LDL indicators. These indicators play an important role in the early phase atherosclerosis, but the relationship between these indicators and subclinical atherosclerosis, as represented by the cardioankle vascular index (CAVI), has not been assessed. We herein investigated the association of LOX-1- related modified LDL indicators and the CAVI in healthy, Japanese urban community inhabitants who were considered to be at low risk for cardiovascular disease (CVD). Methods: The participants were 515 healthy Japanese (310 men and 205 women) without a history of CVD, cancer or the use of medication for hypertension, diabetes or dyslipidaemia. To estimate the association between LOX-1-related modified LDL indicators (LAB, soluble form of LOX-1 (sLOX- 1)) and the CAVI, we performed multivariable linear regression analyses with possible confounders such as the serum LDL cholesterol level. Results: The plasma LAB showed a positive association with the CAVI in men (standardized coefficient: 0.11, p= 0.04). This relationship was not observed in women. On the other hand, no clear association was observed between the CAVI and the plasma sLOX-1 level in either sex. Conclusions: The plasma LAB levels may represent a useful marker for detecting potential atherosclerosis in healthy individuals considered to be at low risk for atherosclerosis and CVD. Further studies are needed to confirm the present findings.

Risk of hypercholesterolemia for cardiovascular disease and the population attributable fraction in a 24-year Japanese cohort study.

Sugiyama D, Okamura T, Watanabe M, Higashiyama A, Okuda N, Nakamura Y, Hozawa A, Kita Y, Kadota A, Murakami Y, Miyamatsu N, Ohkubo T, Hayakawa T, Miyamoto Y, Miura K, Okayama A, Ueshima H, NIPPON DATA 80/90 Research Group.

Journal of atherosclerosis and thrombosis 22 （ 1 ） 95 - 107 2015年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1340-3478

Aims: The population-attributable fraction (PAF) is an indicator of the disease burden. In Western countries, the PAF of hypercholesterolemia in cardiovascular disease (CVD) is the highest among that for traditional risk factors; however, data for Asian populations are limited. Methods: A 24-year cohort study was conducted among 9,209 randomly selected participants who were not taking statins. We estimated the hazard ratio (HR) after adjusting for covariates and PAF associated with the serum total cholesterol (TC) levels in relation to CVD mortality. Results: The TC level was found to be positively associated with an increased risk of CVD, coronary heart disease (CHD) and cardiac death (CHD plus heart failure), with an HR of 1.08 (95% confidence interval [CI]: 1.00-1.16), 1.33 (95% CI: 1.14-1.55) and 1.21 (95% CI: 1.08-1.35) for a 1-SD increment in the serum TC level, respectively. Similar positive associations between the TC level and both CHD and cardiac death were observed after classifying the patients by age and sex. Furthermore, the highest serum TC level (≥6.72 mmol/L) was positively associated with CVD death, with an HR of 1.76 (95% CI: 1.25-2.47), as well as both CHD death and cardiac death. In contrast, no significant relationships were observed between the serum TC level and stroke. Meanwhile, the PAF for CVD, CHD, and cardiac deaths due to hypercholesterolemia (serum TC level ≥5.69 mmol/L, defined by the Japan Atherosclerosis Society) was 1.7%, 10.6% and 5.6%, respectively. Conclusions: The estimated PAF of CVD death due to hypercholesterolemia is moderately high, but lower than that for other risk factors, such as hypertension.

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Association between serum long-chain n-3 and n-6 polyunsaturated fatty acid profiles and glomerular filtration rate assessed by serum creatinine and cystatin C levels in Japanese community-dwellers.

Higashiyama A, Kubota Y, Marumo M, Konishi M, Yamashita Y, Nishimura K, Fukuda Y, Okamura T, Wakabayashi I

Journal of epidemiology 25 （ 4 ） 303 - 311 2015年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0917-5040

Background: Plasma concentration of n-3 polyunsaturated fatty acids (PUFAs) has been reported to be associated with renal function in Western populations. However, few studies have investigated the association between serum long-chain n-3 and n-6 PUFA profiles and renal function in a Japanese population with high marine-derived longchain n-3 PUFA intake. Methods: A cross-sectional study was performed in 549 Japanese rural community-dwellers aged 40 to 64 years. In adjusted analysis of covariance, we assessed the relationship between estimated glomerular filtration rate (eGFR) and tertiles of serum long-chain n-3 and n-6 PUFA profiles ([eicosapentaenoic acid {EPA} + docosahexaenoic acid {DHA}]:arachidonic acid [AA]). GFR was estimated by Japanese specific equations using serum creatinine and cystatin C (eGFR<inf>cre</inf> and eGFR<inf>cys</inf>). Using multivariate-adjusted linear regression models, we also assessed the relationships between eGFRs and several n-3 and n-6 PUFAs, which have been suggested to be associated with renal function. Results: In all participants, higher dietary fish intake as assessed by a semi-quantitative questionnaire was associated with higher serum value of (EPA+DHA):AA. Participants in the higher (EPA+DHA):AA tertiles had nonsignificantly higher eGFR<inf>cre</inf> and significantly higher eGFR<inf>cys</inf> (P = 0.016). In addition, eGFR<inf>cys</inf> in T2+T3 of (EPA+DHA):AA was significantly higher than that in T1 (adjusted mean eGFR<inf>cys</inf>, T1: 87 ml/min/1.73m2, T2+T3: 91 ml/min/1.73m2; P < 0.01). Among the PUFAs, only (EPA+DHA) was significantly associated with eGFR<inf>cys</inf>. Conclusions: Serum (EPA+DHA):AA, which reflects an individual's fish intake, might be associated with eGFR<inf>cys</inf> in Japanese community-dwellers.

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The relationship between Asian dust events and out-of-hospital cardiac arrests in Japan.

Nakamura T, Hashizume M, Ueda K, Kubo T, Shimizu A, Okamura T, Nishiwaki Y

Journal of epidemiology 25 （ 4 ） 289 - 296 2015年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0917-5040

Background: Asian dust events are caused by dust storms that originate in the deserts of China and Mongolia and drift across East Asia. We hypothesized that the dust events would increase incidence of out-of-hospital cardiac arrests by triggering acute events or exacerbating chronic diseases. Methods: We analyzed the Utstein-Style data collected in 2005 to 2008 from seven prefectures covering almost the entire length of Japan to investigate the effect of Asian dust events on out-of-hospital cardiac arrests. Asian dust events were defined by the measurement of light detection and ranging. A time-stratified case-crossover analysis was performed. The strength of the association between Asian dust events and out-of-hospital cardiac arrests was shown by odds ratios and 95% confidence intervals in two conditional logistic models. A pooled estimate was obtained from area-specific results by random-effect meta-analysis. Results: The total number of cases of out-of-hospital cardiac arrest was 59 273, of which 35 460 were in men and 23 813 were in women. The total number of event days during the study period was smallest in Miyagi and Niigata and largest in Shimane and Nagasaki. There was no significant relationship between Asian dust events and out-ofhospital cardiac arrests by area in either of the models. In the pooled analysis, the highest odds ratios were observed at lag day 1 in both model 1 (OR 1.07; 95% CI, 0.97-1.19) and model 2 (OR 1.08; 95% CI, 0.97-1.20). However, these results were not statistically significant. Conclusions: We found no evidence of an association between Asian dust events and out-of-hospital cardiac arrests.

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HOMA-IR Values are Associated With Glycemic Control in Japanese Subjects Without Diabetes or Obesity: The KOBE Study.

Hirata T, Higashiyama A, Kubota Y, Nishimura K, Sugiyama D, Kadota A, Nishida Y, Imano H, Nishikawa T, Miyamatsu N, Miyamoto Y, Okamura T

Journal of epidemiology 25 （ 6 ） 407 - 414 2015年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0917-5040

Background: Several studies have reported that insulin resistance was a major risk factor for the onset of type 2 diabetes mellitus in individuals without diabetes or obesity. We aimed to clarify the association between insulin resistance and glycemic control in Japanese subjects without diabetes or obesity. Methods: We conducted a community-based cross-sectional study including 1083 healthy subjects (323 men and 760 women) in an urban area. We performed multivariate regression analyses to estimate the association between the homeostasis model assessment of insulin resistance (HOMA-IR) values and markers of glycemic control, including glycated haemoglobin (HbA1c), 1,5-anhydroglucitol (1,5-AG), and fasting plasma glucose (FPG) levels, after adjustment for potential confounders. Results: Compared with the lowest tertile of HOMA-IR values, the highest tertile was significantly associated with HbA1c and FPG levels after adjustment for potential confounders, both in men (HbA1c: β = 1.83, P = 0.001; FPG: β = 0.49, P < 0.001) and women (HbA1c: β = 0.82, P = 0.008; FPG: β = 0.39, P < 0.001). The highest tertile of HOMA-IR values was inversely associated with 1,5-AG levels compared with the lowest tertile (β = -18.42, P = 0.009) only in men. Conclusions: HOMA-IR values were associated with markers of glycemic control in Japanese subjects without diabetes or obesity. Insulin resistance may influence glycemic control even in a lean, non-diabetic Asian population.

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Nationwide distribution of cardiovascular practice in Japan - results of Japanese circulation society 2010 annual survey.

Tomoike H, Yokoyama H, Sumita Y, Hanai S, Kada A, Okamura T, Yoshikawa J, Doi Y, Hori M, Tei C, Scientific Committee of the JCS.

Circulation journal : official journal of the Japanese Circulation Society 79 （ 5 ） 1058 - 1067 2015年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1346-9843

Background: The geographic distribution of cardiovascular (CV) health-care services has not been assessed systematically. Methods and Results: Data of the Japanese Circulation Society (JCS) annual survey were provided to the JCS working group with the permission of the JCS Scientific Committee. The status of CV practice in 2010 was then assessed in 47 prefectures retrospectively, along with national census and gross domestic product (GDP) data. The surveyed indices included resources (hospitals, beds and cardiologists), burden (number of inpatients), and outcome (CV mortality and autopsy) in each prefecture, which correlated well with respective populations or GDP. Inequality of geographic distribution was evident for pediatrics among the 47 prefectures, according to Lorenz curve, Gini coefficient or the maximum/minimum ratio for each index. According to the Gini coefficients, only the number of inpatients (medical or acute myocardial infarction) and beds for the total number of general hospitals or the hospitals surveyed in the present JCS study were lower than expected with regard to GDP. Conclusions: Geographic disparity of CV resources or burden was larger in pediatrics than in CV medicine or surgery. Improvement of equality in CV practice with regard to appropriateness and quality are the coming challenges for the JCS.

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Changes in Waist Circumference and the Incidence of Type 2 Diabetes in Community-Dwelling Men and Women: The Suita Study.

Tatsumi Y, Watanabe M, Nakai M, Kokubo Y, Higashiyama A, Nishimura K, Kobayashi T, Takegami M, Nakao YM, Watanabe T, Okayama A, Okamura T, Miyamoto Y

Journal of epidemiology 25 （ 7 ） 489 - 495 2015年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0917-5040

Backgrounds: The association between weight gain and the incidence of type 2 diabetes is well known. The aim of our study was to investigate the relationship between change in waist circumference (WC) and type 2 diabetes incidence. Methods: The participants in the Suita Study, a population-based cohort study in an urban area of Japan, underwent a baseline survey between 1989 and 1994 (Exam 1) and were examined at follow-up every 2 years. We performed a 9.3-year cohort study of 946 men and 1327 women with no history of diabetes who underwent Exam 1 and Exam 2 (between 1997 and 1999). Participants were stratified by sex and median WC at Exam 1, and, in each stratum, participants were further classified into three categories by tertile of WC change per year between Exam 1 and Exam 2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for type 2 diabetes incidence were calculated by Cox proportional hazard models. The endpoints were first diagnosis of type 2 diabetes or March 2011. Results: During follow-up, 287 participants developed type 2 diabetes. In both sexes with median WC or higher, participants in the highest tertile of WC change had a significantly higher risk of developing type 2 diabetes. Multivariable adjusted HRs were 1.84 (95% CI, 1.10-3.08) in men and 2.30 (95% CI, 1.31-4.04) in women. No significant association was observed among participants with WC below median. Conclusions: Preventing WC gain is important in preventing type 2 diabetes in the Japanese population, especially among individuals with a relatively high WC.

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Alcohol consumption, hospitalization and medical expenditure: a large epidemiological study on the medical insurance system in Japan.

Nakamura K, Okuda N, Okamura T, Miura K, Nishimura K, Yasumura S, Sakata K, Hidaka H, Okayama A

Alcohol and alcoholism (Oxford, Oxfordshire) 50 （ 2 ） 236 - 243 2015年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0735-0414

Aims: This study investigated the relationship between alcohol drinking habits and the onset of high medical expenditure in a Japanese male population. Methods: The cohort comprised 94,307 male beneficiaries 40-69 years of age of the Japanese medical insurance system, who had daily alcohol drinking habits. The likelihood of incurring high medical expenditure, defined as the ≥90th percentile of the medical expenditure distribution in the study population 1 year after baseline, as well as the likelihood of undergoing hospitalization that year were compared among the participants grouped according to their alcohol consumption amount (<2, 2-3.9, 4-5.9, ≥6 drinks/day). Results: Participants who ranked in the top 10% medical expenditure group within the 1 year after baseline each incurred at least 2152 euros/year. The top 10% medical expenditure group accounted for 61.1% of the total medical expenditure in the study population. The odds ratios (95% confidence intervals) for ranking in the top 10% group during the 1-year period, compared with the <2 drinks (23 g of alcohol)/day group, were 1.08 (1.02-1.15) for 2-3.9 drinks/day, 1.11 (1.05-1.19) for 4-5.9 drinks/day, and 1.31 (1.18-1.45) for ≥6 drinks/day after adjustment for age, body mass index, and smoking and exercise habits. The adjusted odds ratios for undergoing hospitalization were 1.11 (1.04-1.19), 1.14 (1.06-1.24) and 1.39 (1.24-1.56), respectively. Conclusion: The likelihood of incurring high medical expenditure and undergoing hospitalization increased with daily alcohol consumption amount.

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