研究者詳細 - 岡村　智教

論文 - 岡村　智教

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Associations of serum LDL particle concentration with carotid intima-media thickness and coronary artery calcification.

Zaid M, Miura K, Fujiyoshi A, Abbott RD, Hisamatsu T, Kadota A, Arima H, Kadowaki S, Torii S, Miyagawa N, Suzuki S, Takashima N, Ohkubo T, Sekikawa A, Maegawa H, Horie M, Nakamura Y, Okamura T, Ueshima H, SESSA Research Group.

Journal of clinical lipidology 10 （ 5 ） 1195 - 1202.e1 2015年12月

研究論文（学術雑誌）, ISSN 1933-2874

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.

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Advance in cardiac CT

Yamada Yoshitake, Matsumoto Shunsuke, Suzuki Tatsuya, Hashimoto Masahiro, Okamura Teppei, Sugiura Hiroaki, Jinzaki Masahiro, Yamada Minoru

Respiration and Circulation 63 （ 12 ） 1199 - 1207 2015年12月

ISSN 0452-3458

Erratum

Nagai Masato, Ohkubo Takayoshi, Murakami Yoshitaka, Takashima Naoyuki, Kadota Aya, Miyagawa Naoko, Saito Yoshino, Nishi Nobuo, Okuda Nagako, Kiyohara Yutaka, Nakagawa Hideaki, Nakamura Yoshikazu, Fujiyoshi Akira, Abbott Robert D., Okamura Tomonori, Okayama Akira, Ueshima Hirotsugu, Miura Katsuyuki

Hypertension Research 38 （ 11 ） 798 2015年11月

ISSN 0916-9636

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Secular trends of the impact of overweight and obesity on hypertension in Japan, 1980-2010.

Nagai M, Ohkubo T, Murakami Y, Takashima N, Kadota A, Miyagawa N, Saito Y, Nishi N, Okuda N, Kiyohara Y, Nakagawa H, Nakamura Y, Fujiyoshi A, Abbott RD, Okamura T, Okayama A, Ueshima H, Miura K, NIPPON DATA80/90/2010 Research Group.

Hypertension research : official journal of the Japanese Society of Hypertension 38 （ 11 ） 790 - 795 2015年11月

研究論文（学術雑誌）, ISSN 0916-9636

The prevalence of overweight (body mass index (BMI)=25.0-29.9 kg m - 2) and obesity (≥30.0 kg m - 2) has been increasing over the last several decades in Japan. We examined trends of the impact of overweight and obesity on hypertension (systolic/diastolic blood pressure ≥140/90 mm Hg or antihypertensive drugs use) using four national surveys in Japan, from which the participants were randomly sampled from the entire population. Study participants aged 30-79 years were selected for each survey (10 370 in 1980, 8005 in 1990, 5327 in 2000 and 2547 in 2010). The results showed that the impact of overweight and obesity on hypertension had increased significantly (P=0.040 and 0.006 in men and women, respectively). From 1980 to 2010, the multivariable-adjusted odds ratios for hypertension, comparing overweight and obesity with normal weight (BMI =18.5-24.9 kg m - 2), went from 1.94 (95% confidence intervals: 1.64, 2.28) to 2.82 (2.07, 3.83) in men, and from 2.37 (2.05, 2.73) to 3.48 (2.57, 4.72) in women. Most of the association was observed in overweight participants, as only 3% of the Japanese were obese. In addition to the relationship between excessive BMI and other adverse health conditions, the rise in the association with hypertension increases the urgency in addressing weight control. We need to address the overweight and obesity epidemic.

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Smoking increases the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease.

Nakamura K, Nakagawa H, Murakami Y, Kitamura A, Kiyama M, Sakata K, Tsuji I, Miura K, Ueshima H, Okamura T, EPOCH–JAPAN research group.

Kidney international 88 （ 5 ） 1144 - 1152 2015年11月

研究論文（学術雑誌）, ISSN 0085-2538

Little is known about the magnitude and nature of the combined effect of chronic kidney disease (CKD) and smoking on cardiovascular diseases. We studied this in a Japanese population using a pooled analysis of 15,468 men and 19,154 women aged 40-89 years enrolled in 8 cohort studies. The risk of mortality from all-causes and cardiovascular disease was compared in 6 gender-specific categories of baseline CKD status (non-CKD or CKD) and smoking habits (lifelong never smoked, former smokers, or currently smoking). CKD was defined as a decreased level of estimated glomerular filtration rate (under 60 ml/min per 1.73 m 2) and/or dipstick proteinuria. Hazard ratios were estimated for each category, relative to never smokers without CKD. During the follow-up period (mean 14.8 years), there were 6771 deaths, 1975 of which were due to cardiovascular diseases. In both men and women, current or former smokers with CKD had the first or second highest crude mortality rates from all-cause and cardiovascular diseases among the 6 categories. After adjustment for age and other major cardiovascular risk factors, the hazard ratios in male and female current smokers with CKD were 2.26 (95% confidence interval, 1.95-2.63) and 1.78 (1.36-2.32) for all-causes, and 2.66 (2.04-3.47) and 1.71 (1.10-2.67) for cardiovascular diseases, respectively. Thus, coexistence of CKD and smoking may markedly increase the risk of all-cause and cardiovascular mortality.

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Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men.

Harada S, Takebayashi T, Kurihara A, Akiyama M, Suzuki A, Hatakeyama Y, Sugiyama D, Kuwabara K, Takeuchi A, Okamura T, Nishiwaki Y, Tanaka T, Hirayama A, Sugimoto M, Soga T, Tomita M

Environmental health and preventive medicine 21 （ 1 ） 18 - 26 2015年10月

研究論文（学術雑誌）, ISSN 1342-078X

Objective: Metabolomics is a promising approach to the identification of biomarkers in plasma. Here, we performed a population-based, cross-sectional study to identify potential biomarkers of alcohol intake and alcohol-induced liver injury by metabolomic profiling using capillary electrophoresis-mass spectrometry (CE-MS). Methods: Fasting plasma samples were collected from 896 Japanese men who participated in the baseline survey of the Tsuruoka Metabolomics Cohort Study, and 115 polar metabolites were identified and absolutely quantified by CE-MS. Information on daily ethanol intake was collected through a standardized, self-administered questionnaire. The associations between ethanol intake and plasma concentration of metabolites were examined. Relationships between metabolite concentrations or their ratios and serum liver enzyme levels in the highest ethanol intake group (>46.0 g/day) were then examined by linear regression analysis. Replication analysis was conducted in 193 samples collected from independent population of this cohort. Results: Nineteen metabolites were identified to have an association with daily alcohol consumption both in the original and replication population. Three of these metabolites (threonine, glutamine, and guanidinosuccinate) were found to associate well with elevated levels of serum liver enzymes in the highest ethanol intake group, but not in the non-drinker group. We also found that the glutamate/glutamine ratio had a much stronger relation to serum γ-glutamyltransferase, aspartate transaminase, and alanine transaminase than glutamate or glutamine alone (standardized beta = 0.678, 0.558, 0.498, respectively). Conclusions: We found 19 metabolites associated with alcohol intake, and three biomarker candidates (threonine, guanidinosuccinate and glutamine) of alcohol-induced liver injury. Glutamate/glutamine ratio might also be good biomarker.

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Participants with treated hyperlipidemia may be more health conscious

Hozawa Atsushi, Okamura Tomonori

Journal of Atherosclerosis and Thrombosis 22 （ 10 ） 1025 - 1026 2015年10月

ISSN 1340-3478

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Participants with treated hyperlipidemia may be more health conscious

Hozawa Atsushi, Okamura Tomonori

Journal of Atherosclerosis and Thrombosis 22 （ 10 ） 1030 - 1039 2015年10月

ISSN 1340-3478

Continuous decline in mortality from coronary heart disease in Japan despite a continuous and marked rise in total cholesterol: Japanese experience after the Seven Countries Study.

Sekikawa A, Miyamoto Y, Miura K, Nishimura K, Willcox BJ, Masaki KH, Rodriguez B, Tracy RP, Okamura T, Kuller LH

International journal of epidemiology 44 （ 5 ） 1614 - 1624 2015年10月

研究論文（学術雑誌）, ISSN 0300-5771

Background: The Seven Countries Study in the 1960s showed very low mortality from coronary heart disease (CHD) in Japan, which was attributed to very low levels of total cholesterol. Studies of migrant Japanese to the USA in the 1970s documented increase in CHD rates, thus CHD mortality in Japan was expected to increase as their lifestyle became Westernized, yet CHD mortality has continued to decline since 1970. This study describes trends in CHD mortality and its risk factors since 1980 in Japan, contrasting those in other selected developed countries. Methods: We selected Australia, Canada, France, Japan, Spain, Sweden, the UK and the USA. CHD mortality between 1980 and 2007 was obtained from WHO Statistical Information System. National data on traditional risk factors during the same period were obtained from literature and national surveys. Results: Age-adjusted CHD mortality continuously declined between 1980 and 2007 in all these countries. The decline was accompanied by a constant fall in total cholesterol except Japan where total cholesterol continuously rose. In the birth cohort of individuals currently aged 50-69 years, levels of total cholesterol have been higher in Japan than in the USA, yet CHD mortality in Japan remained the lowest: >67% lower in men and > 75% lower in women compared with the USA. The direction and magnitude of changes in other risk factors were generally similar between Japan and the other countries. Conclusions: Decline in CHD mortality despite a continuous rise in total cholesterol is unique. The observation may suggest some protective factors unique to Japanese.

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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 19 （ 7 ） 719 - 728 2015年08月

研究論文（学術雑誌）, 共著, 査読有り, 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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Interaction of Blood Pressure and Body Mass Index With Risk of Incident Atrial Fibrillation in a Japanese Urban Cohort: The Suita Study.

Kokubo Y, Watanabe M, Higashiyama A, Nakao YM, Kobayashi T, Watanabe T, Okamura T, Okayama A, Miyamoto Y

American journal of hypertension 28 （ 11 ） 1355 - 1361 2015年08月

研究論文（学術雑誌）, ISSN 0895-7061

BACKGROUND AND PURPOSE To prevent stroke, strategies for atrial fibrillation (AF) prevention and an early detection of AF by electrocardiogram are essential. However, only a limited prospective studies have examined the risk factors for AF, even in blood pressure (BP) and body mass index (BMI), which are not clear among general populations. We investigated the impacts of BP and BMI on the risk of incident AF in a general population. METHODS A total of 6,906 participants (30-84 years) in the Suita Study were prospectively followed up for incident AF. Participants were diagnosed with AF if AF or atrial flutter was present on an electrocardiogram from a routine health examination (every 2 years) or if AF was indicated as a present illness from health examinations and/or medical records during follow-up. Adjusted Cox proportional hazard ratios (HRs) were calculated. RESULTS During the 12.8-year follow-up, 253 incident AF events occurred. Compared with the systolic BP (SBP) <120mm Hg and normal-weight, the adjusted HRs (95% confidence intervals; CIs) of incident AF in the systolic hypertension and the overweight (BMI ≥ 25kg/m²) groups were 1.74 (1.22-2.49) and 1.35 (1.01-1.80), respectively. Compared with SBP <120mm Hg and normal weight, the adjusted HRs (95% CIs) of incident AF in the SBP = 120-139mm Hg with overweight and the systolic hypertension with normal or overweight were 1.72 (1.01-2.91), 1.66 (1.10-2.50), and 2.31 (1.47-3.65), respectively (P for interaction = 0.04). CONCLUSIONS Systolic prehypertension and overweight are associated with incident AF in Japanese population. The association between SBP and AF may be evident by overweight.

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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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岡村　智教

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