Details of a Researcher - Okamura, Tomonori

Papers - Okamura, Tomonori

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A nutrient-wide association study on blood pressure

Tzoulaki Ioanna, Patel Chirag J., Okamura Tomonori, Chan Queenie, Brown Ian J., Miura Katsuyuki, Ueshima Hirotsugu, Zhao Liancheng, Van Horn Linda, Daviglus Martha L., Stamler Jeremiah, Butte Atul J., Ioannidis John P A, Elliott Paul

Circulation 126 ( 21 ) 2456 - 2464 2012.11

Research paper (scientific journal), Joint Work, Accepted, ISSN 0009-7322

BACKGROUND: A nutrient-wide approach may be useful to comprehensively test and validate associations between nutrients (derived from foods and supplements) and blood pressure (BP) in an unbiased manner. METHODS AND RESULTS: Data from 4680 participants aged 40 to 59 years in the cross-sectional International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were stratified randomly into training and testing sets. US National Health and Nutrition Examination Survey (NHANES) four cross-sectional cohorts (1999-2000, 2001-2002, 2003-2004, 2005-2006) were used for external validation. We performed multiple linear regression analyses associating each of 82 nutrients and 3 urine electrolytes with systolic and diastolic BP in the INTERMAP training set. Significant findings were validated in the INTERMAP testing set and further in the NHANES cohorts (false discovery rate <5% in training, P<0.05 for internal and external validation). Among the validated nutrients, alcohol and urinary sodium-to-potassium ratio were directly associated with systolic BP, and dietary phosphorus, magnesium, iron, thiamin, folacin, and riboflavin were inversely associated with systolic BP. In addition, dietary folacin and riboflavin were inversely associated with diastolic BP. The absolute effect sizes in the validation data (NHANES) ranged from 0.97 mm Hg lower systolic BP (phosphorus) to 0.39 mm Hg lower systolic BP (thiamin) per 1-SD difference in nutrient variable. Inclusion of nutrient intake from supplements in addition to foods gave similar results for some nutrients, though it attenuated the associations of folacin, thiamin, and riboflavin intake with BP. CONCLUSIONS: We identified significant inverse associations between B vitamins and BP, relationships hitherto poorly investigated. Our analyses represent a systematic unbiased approach to the evaluation and validation of nutrient-BP associations. © 2012 American Heart Association, Inc.

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A multicenter study on the precision and accuracy of homogeneous assays for LDL-cholesterol

Miida Takashi, Nishimura Kunihiro, Okamura Tomonori, Hirayama Satoshi, Ohmura Hirotoshi, Yoshida Hiroshi, Miyashita Yoh, Ai Masumi, Tanaka Akira, Sumino Hiroyuki, Murakami Masami, Inoue Ikuo, Kayamori Yuzo, Nakamura Masakazu, Nobori Tsutomu, Miyazawa Yukihisa, Teramoto Tamio, Yokoyama Shinji

Atherosclerosis 225 ( 1 ) 208 - 215 2012.11

Research paper (scientific journal), Joint Work, Accepted, ISSN 0021-9150

Background: Homogeneous assays for low-density lipoprotein-cholesterol (LDL-C) have good precision and are pretreatment-free procedures. However, their accuracies have been questioned, especially in diseased subjects. In this study, we aimed to verify whether LDL-C levels determined by homogeneous assays [LDL-C (H)] agree with those determined by a beta-quantification method [LDL-C (BQ)] in fresh clinical samples. Methods: We determined LDL-C levels in 49 non-diseased and 124 diseased subjects whose triglyceride (TG) levels were less than 11.29 mmol/L (1000 mg/dL) using 12 homogeneous assays and a BQ method simultaneously. Results: In total, 30.6% of non-diseased subjects and 46.0% of diseased subjects were in the postprandial state. The maximum inter- and intra-assay CVs were 1.8% and 1.5%, and 8 reagents had a CV of 1.0% or less. The mean bias ranged from -0.5% to 1.8% for non-diseased subjects and from -0.7% to 1.6% for diseased subjects. For non-diseased subjects, all but one reagent achieved the National Cholesterol Education Program (NCEP) total error requirement in more than 90% of samples. However, for diseased subjects, the number of reagents that met this requirement was low. With some reagents, LDL-C (H) was higher than LDL-C (BQ), especially in subjects with hypertriglyceridemia. While for other reagents, the difference between the two methods was not associated with hypertriglyceridemia except for type I (n = 2) and type III hyperlipidemia (n = 1). Postprandial sampling was not the main factor for discordant results. Conclusions: LDL-C (H) agrees with LDL-C (BQ) in non-diseased subjects, but exhibits positive bias for subjects with hypertriglyceridemia in diseased subjects for some reagents. © 2012 Elsevier Ireland Ltd.

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Relation between serum total cholesterol level and cardiovascular disease stratified by sex and age group

Nagasawa Sin ya, Okamura Tomonori, Iso Hiroyasu, Tamakoshi Akiko, Yamada Michiko, Watanabe Makoto, Murakami Yoshitaka, Miura Katsuyuki, Ueshima Hirotsugu, Evidence for Cardiovascular Prevention from Observational for Cardiovascular Prevention from Observational, Cohorts in Japan (EPOCH-JAPAN) Research Group in Japan (EPOCH-JAPAN) Research Group

Journal of the American Heart Association 1 ( 5 ) e001974 2012.10

Research paper (scientific journal), Joint Work, Accepted

The relation between serum total cholesterol (TC) and cardiovascular disease in women and in the elderly is unclear, especially in Asian populations. We examined this relation in the largest-scale pooled analysis of the Japanese population, the Evidence for Cardiovascular Prevention from Observational Cohorts in Japan (EPOCH-JAPAN) study. A total of 65 594 participants who were 40 to 89 years of age and did not have a past history of cardiovascular disease were examined. Cox proportional-hazards models were used to estimate hazard ratios for death from total stroke, cerebral infarction, intracranial cerebral hemorrhage, or coronary heart disease. The mean follow-up period was 10.1 years, with the number of deaths from total stroke, cerebral infarction, cerebral hemorrhage, and coronary heart disease being 875, 457, 212, and 374, respectively. The participants were divided into 2 age groups: middle-aged (40 to 69 years; mean age 55 years) and elderly (70 to 89 years; mean age 75 years). In men, the multivariate-adjusted hazard ratios for coronary heart disease in the highest TC category (≥6.21 mmol/L) compared with the lowest category (<4.14 mmol/L) were 2.52 (95% confidence interval: 1.15-5.07) in middle-aged participants and 2.77 (1.09-7.03) in elderly participants. In women, the hazard ratios of the highest TC category (≥6.72 mmol/L) compared with the lowest category (<4.66 mmol/L) were 3.20 (1.44-7.09) in middle-aged participants and 1.02 (0.42-2.49) in elderly participants. TC levels were not associated with cerebral infarction in any age or sex group and were associated negatively with total stroke and cerebral hemorrhage. High serum TC levels are associated with coronary heart disease in middle-aged Japanese men and women, but evidence in elderly Japanese individuals is still limited.

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Blood cholesterol level and risk of stroke in community-based or worksite cohort studies

Tanaka Taichiro, Okamura Tomonori

Keio Journal of Medicine 61 ( 3 ) 79 - 88 2012.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 0022-9717

Evidence of the causal relationship between hypercholesterolemia and coronary artery disease (CAD) has been established worldwide. However, little attention has been paid to the relationship between hypercholesterolemia and stroke, despite stroke being the most common cardiovascular disease in Japan. We therefore reviewed cohort studies that investigated this relationship in the Japanese population over the past 20 years, and compared their findings with clinical trials and cohort studies in Western countries. Fourteen cohort studies were carried out in Japan during this period. The number of subjects in the studies ranged from 1621 to 91,219 and the mean follow-up period ranged from 7.6 to 32 years. The majority of studies showed no association between hypercholesterolemia and total stroke. However, one report showed a positive association between low-density lipoprotein cholesterol and atherothrombotic cerebral infarction. The relationship between hypercholesterolemia and cerebral infarction may be modified by the proportion of atherothrombotic infarctions in the population surveyed. Randomized controlled trials on statins have shown a substantial reduction in cerebral infarction, and so the discrepancy between cohort studies and clinical trials requires further study. However, some studies have reported that subjects with low blood cholesterol are more susceptible to intracerebral hemorrhage. Two hypotheses have been proposed to explain this association between low cholesterol and intracerebral hemorrhage. First, low blood cholesterol may induce angionecrosis, possibly in combination with hypertension, and second, low blood cholesterol may reflect a poor nutritional status. Either way, further continuous research in various fields of medical science is required to clarify the overall effect of blood cholesterol on stroke in humans. © 2012 by The Keio Journal of Medicine.

Relationship between health-related quality of life and clustering of metabolic syndrome diagnostic components

Katano Sayuri, Nakamura Yasuyuki, Nakamura Aki, Suzukamo Yoshimi, Murakami Yoshitaka, Tanaka Taichiro, Okayama Akira, Miura Katsuyuki, Okamura Tomonori, Fukuhara Shunichi, Ueshima Hirotsugu

Quality of Life Research 21 ( 7 ) 1165 - 1170 2012.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 0962-9343

Purpose To examine the association of the number of metabolic syndrome diagnostic components (MetS-DC) with health-related quality of life (HR-QOL). Methods We examined the baseline data from 4,480 healthy workers in Japan (3,668 men and 812 women) aged 19-69 years. We assessed HR-QOL based on scores for five scales of the SF-36. We defined four components for MetS in this study as follows: (1) high blood pressure (BP); (2) dyslipidemia; (3) impaired glucose tolerance; and (4) overweight: a body mass index ≥25 kg/m ². Logistic regression analysis adjusted for lifestyle factors was used to examine the association of the number of MetS-DC with the HR-QOL sub-scales. Results Those who had 0-4 MetS-DC accounted for 2,287, 1,135, 722, 282, and 54 participants. The number of MetS-DC inversely contributed significantly to General Health (norm-based scoring >50) (odd ratios [OR] 0.59-0.82, P≪0.05) and positively associated with Mental Health (OR 1.37, P<0.05). Conclusion When adjusted for lifestyle factors, the number of MetS-DC was inversely associated with General Health and positively with Mental Health in men and women. © Springer Science+Business Media B.V. 2011.

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Blood pressure categories and long-term risk of cardiovascular disease according to age group in Japanese men and women

Fujiyoshi Akira, Ohkubo Takayoshi, Miura Katsuyuki, Murakami Yoshitaka, Nagasawa Shin Ya, Okamura Tomonori, Ueshima Hirotsugu

Hypertension Research 35 ( 9 ) 947 - 953 2012.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 0916-9636

Blood pressure (BP) categories defined by systolic BP (SBP) and diastolic BP (DBP) are commonly used. However, the BP category-specific risk of cardiovascular disease (CVD) has not been thoroughly investigated in different age groups. The aim of this study was to assess long-term CVD risk and its impact according to BP categories and age group. Pooling individual data from 10 cohorts, we studied 67 309 Japanese individuals (40-89 years old) who were free of CVD at baseline: we categorized them as belonging to three age groups: middle-aged (40-64 years), elderly (65-74 years) and very elderly (75-89 years). BP was classified according to the 2009 Japanese Society of Hypertension Guidelines. Cox models were used to estimate adjusted hazard ratios for CVD deaths. We observed 1944 CVD deaths over a mean follow-up of 10.2 years. In all age groups, the overall relationship between BP category and CVD risk was positive, with a greater strength observed for younger age groups. We observed a trend of increased risk from SBP/DBP130/85 mm Hg in the very elderly, and a significant increase from SBP/DBP120/80 mm Hg in the other age groups. The population attributable fractions (PAFs) of CVD death in reference to the SBP/DBP120/80 mm Hg category ranged from 23.4% in the very elderly to 60.3% in the middle-aged. We found an overall graded increase in CVD risk with higher BP category in the very elderly. The PAFs suggest that keeping BP levels low is an important strategy for primary CVD prevention, even in an elderly population. © 2012 The Japanese Society of Hypertension All rights reserved.

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Hypertension and life expectancy among Japanese

Turin Tanvir Chowdhury, Murakami Yoshitaka, Miura Katsuyuki, Rumana Nahid, Kita Yoshikuni, Hayakawa Takehito, Okamura Tomonori, Okayama Akira, Ueshima Hirotsugu

Hypertension Research 35 ( 9 ) 954 - 958 2012.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 0916-9636

Life expectancy (LE) is a measure that describes the health status of a population. The few published studies that have examined the impact of hypertension on LE were predominantly performed in Western populations. The effect of hypertension on LE has not been reported in an Asian population. Thus, we examined the impact of hypertension on LE in the Japanese population, which has the highest LE worldwide. The abridged life table method was applied to calculate the LEs of both normotensive and hypertensive men and women aged 40-85 years. Hypertensive participants were categorized as having either stage 1 or stage 2 hypertension. Age-specific mortality rates across different groups were estimated using the person-year method based on the follow-up data from a representative Japanese population in a national survey (NIPPON DATA80). The proportion of hypertensive patients in the baseline survey was 50.5% for men and 41.4% for women. The LE of 40-year-old men and women was 41.7 years and 48.7 years, respectively, in normotensive participants and 39.5 and 45.8 years, respectively, in hypertensive participants. The LE difference between normotensive and hypertensive participants was 2.2 years for men and 2.9 years for women. LE decreased with increasing stages of hypertension. Similar patterns of LE, with respect to blood pressure (BP) status, were observed in all index ages and for both genders. At the population level, hypertension leads to decreased LE and affects both genders similarly. Our findings highlight the importance of preventing high BP and the consequences of hypertension in Japanese population. © 2012 The Japanese Society of Hypertension All rights reserved.

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Diabetes and life expectancy among Japanese - NIPPON DATA80

Turin Tanvir Chowdhury, Murakami Yoshitaka, Miura Katsuyuki, Rumana Nahid, Kadota Aya, Ohkubo Takayoshi, Okamura Tomonori, Okayama Akira, Ueshima Hirotsugu, Ueshima Hirotsugu, Okayama Akira, Okamura Tomonori, Saitoh Shigeyuki, Sakata Kiyomi, Hozawa Atsushi, Hayakawa Takehito, Nakamura Yosikazu, Matsumura Yasuhiro, Nishi Nobuo, Okuda Nagako, Izumi Toru, Ojima Toshiyuki, Tamakoshi Koji, Nakagawa Hideaki, Miura Katsuyuki, Ohkubo Takayoshi, Kita Yoshikuni, Kadota Aya, Nakamura Yasuyuki, Yoshita Katsushi, Kodama Kazunori, Kasagi Fumiyoshi, Yutaka Kiyohara Kiyohara

Diabetes Research and Clinical Practice 96 ( 2 ) e18 - 22 2012.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 0168-8227

Life expectancy (LE) among the Japanese population with or without diabetes mellitus was estimated. LE in 40-year old men and women was 41.1 and 47.5. years in those without diabetes and 32.3 and 40.9. years in those with diabetes. The LE of 40-year old men and women with diabetes was 8.8 and 6.6. years shorter than in those without diabetes. Diabetes mellitus leads to a decrease in LE. The presence of impaired glucose tolerance also affected LE inversely. © 2012 Elsevier Ireland Ltd.

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Influence of smoking combined with another risk factor on the risk of mortality from coronary heart disease and stroke

Nakamura Koshi, Nakagawa Hideaki, Sakurai Masaru, Murakami Yoshitaka, Irie Fujiko, Fujiyoshi Akira, Okamura Tomonori, Miura Katsuyuki, Ueshima Hirotsugu

Cerebrovascular Diseases 33 ( 5 ) 480 - 491 2012.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 1015-9770

Background: In spite of the importance of a multifactorial approach to preventing cardiovascular disease in smokers, most information on the combined adverse effects of smoking and hypertension or high serum cholesterol on cardiovascular disease has been derived from Western populations, and coronary heart disease was often used as the only endpoint. Therefore, the present large-scale pooled analysis attempted to provide reliable information on the adverse effects of the coexistence of smoking and hypertension or high serum cholesterol on the risk of mortality from coronary heart disease and stroke in both, individuals and the entire population in Japan. Methods: A total of 27,385 male and 39,207 female participants aged 40-89 years were enrolled from 10 well-qualified Japanese cohort studies with a mean follow-up of 10.1 years. Hazard ratios and their corresponding 95% confidence intervals in smokers who had hypertension or high serum cholesterol were estimated for men and women separately using a Cox proportional hazards regression model that included age, body mass index, cohort and either serum total cholesterol or systolic blood pressure as covariates. Fractions of deaths attributable to the coexistence of these risk factors were also calculated. Results: The multivariate-adjusted hazard ratios in male and female current smokers with hypertension, compared with those with neither factor were 2.57 (95% confidence intervals, 1.51-4.38) and 6.14 (3.49-10.79) for coronary heart disease, and 3.28 (1.89-5.71) and 1.61 (0.81-3.18) for cerebral infarction, respectively. The fractions of deaths attributable to the coexistence of current smoking and hypertension in men and women were 24.6 and 9.6% for coronary heart disease and 28.1 and 2.0% for cerebral infarction, respectively. Smokers with high serum cholesterol were broadly comparable to hypertensive smokers only with respect to coronary mortality risk; the hazard ratios, compared with those with neither factor were 4.19 (2.33-7.53) for men and 3.90 (1.57-9.67) for women. The fraction of coronary deaths attributable to the coexistence of current smoking and high serum cholesterol was 6.3% in men and 2.2% in women. There was no interaction between smoking habit and blood pressure or serum total cholesterol for these two subtypes in both men and women. Conclusions: Particular attention should be given to smokers who have concomitant hypertension or high serum cholesterol for preventing deaths due to cardiovascular disease. From a public health perspective in Japan, priority should be given to hypertensive smokers, since this group makes a large contribution to the burden of both coronary and cerebral infarction deaths. Copyright © 2012 S. Karger AG, Basel.

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Prognostic values of clockwise and counterclockwise rotation for cardiovascular mortality in Japanese subjects

Nakamura Yasuyuki, Okamura Tomonori, Higashiyama Aya, Watanabe Makoto, Kadota Aya, Ohkubo Takayoshi, Miura Katsuyuki, Kasagi Fumiyoshi, Kodama Kazunori, Okayama Akira, Ueshima Hirotsugu

Circulation 125 ( 10 ) 1226 - 1233 2012.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 0009-7322

Background: Although clockwise rotation and counterclockwise rotation are distinct findings of the ECG, their prognostic significance is rarely studied. Methods and Results: We studied prognostic values of clockwise and counterclockwise rotation on total, cardiovascular disease (CVD), and subtype mortality using the National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in the Aged, 1980-2004 (NIPPON DATA80) database with a 24-year follow-up. At baseline in 1980, data were collected on study participants aged ≥30 years from randomly selected areas in Japan. We followed 9067 participants (44% men; mean age, 51 years). During the 24-year follow-up, mortality was as follows: 2581 total, 887 CVD, 179 coronary heart disease, 173 heart failure, and 411 stroke. The multivariate-adjusted hazard ratio (HR) with the use of the Cox model including biochemical and other ECG variables revealed that clockwise rotation was significantly positively associated with heart failure in men and women combined (HR=1.79; 95% confidence interval [CI], 1.13-2.83; P=0.013), CVD in men and in men and women combined (HR=1.49; 95% CI, 1.12-1.98; P=0.007 in men; HR=1.28; 95% CI, 1.02-1.59; P=0.030 in combined), and total mortality in men and in men and women combined (HR=1.19; 95% CI, 1.00-1.49; P=0.0496inmen; HR=1.15; 95% CI, 1.00-1.32; P=0.045 in combined). Counterclockwise rotation was significantly inversely associated stroke in men and women combined (HR=0.77; 95% CI, 0.62-0.96; P=0.017), CVD in men and in men and women combined (HR=0.74; 95% CI, 0.59-0.94; P=0.011 in men; HR=0.81; 95% CI, 0.70-0.94; P=0.006 in combined), and total mortality in women (HR=0.87; 95% CI, 0.77-0.98; P=0.023). Conclusions: We found a significant positive association of clockwise rotation and a significant inverse association of counterclockwise rotation with CVD mortality in men and in men and women combined, independent of confounding factors including other ECG changes. © 2012 American Heart Association, Inc.

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Effects of public education by television on knowledge of early stroke symptoms among a japanese population aged 40 to 74 years

Miyamatsu Naomi, Kimura Kazumi, Okamura Tomonori, Iguchi Yasuyuki, Nakayama Hirofumi, Toyota Akihiro, Watanabe Makoto, Morimoto Akiko, Morinaga Miho, Yamaguchi Takenori

Stroke 43 ( 2 ) 545 - 549 2012.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 0039-2499

Background and Purpose-: An educational campaign by mass media has been associated with great increases in the knowledge about early symptoms of stroke. However, few studies were conducted with a controlled community intervention study. Methods-: To clarify the effects of a 1-year television campaign for the whole population on improvement of knowledge about stroke symptoms in 2 cities, a campaign area and a control area in Japan were selected. Before and after the campaign, 1960 randomly selected residents aged 40 to 74 years answered a telephone survey regarding knowledge of early stroke symptoms. We calculated the percentage and 95% CIs of participants who correctly chose all 5 early symptoms of stroke in each area and in each year. Results-: Before the campaign, 53% of participants (95% CI, 50%-55%) in the campaign area and 46% (95% CI, 44%-49%) in the control area correctly chose 5 early symptoms. After the 1-year television campaign, knowledge was significantly improved only in the campaign area (campaign area, 63%; 95% CI, 60%-66%; control area, 51%; 95% CI, 48%-54%). After sex stratification, only women showed improved knowledge of early symptoms. The audience rate for the campaign television programs was found to be higher in women than in men. Conclusions-: A 1-year stroke educational television campaign effectively improved knowledge about early stroke symptoms among Japanese women aged 40 to 74 years. No impact was found among men in this age group. Future studies should examine the impact of this approach on stroke knowledge among younger individuals and whether there are any behavioral changes that contribute to earlier presentation for treatment. © 2011 American Heart Association, Inc.

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CDH13 Gene coding T-cadherin influences variations in plasma adiponectin levels in the Japanese population

Morisaki Hiroko, Yamanaka Itaru, Iwai Naoharu, Miyamoto Yoshihiro, Kokubo Yoshihiro, Okamura Tomonori, Okayama Akira, Morisaki Takayuki

Human Mutation 33 ( 2 ) 402 - 410 2012.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 1059-7794

Adiponectin is most abundantly expressed in adipose tissue and well known to play an important role in metabolic regulation. Several studies have attempted to identify the genetic determinants of metabolic syndrome (MetS), though no study has revealed a cis- or transsingle nucleotide polymorphism (SNP) that affects plasma adiponectin levels, except the adiponectin structure gene and genes encoding adiponectin-regulatory proteins. We performed a genome-wide association study in regards to plasma adiponectin concentrations in 3,310 Japanese subjects. We identified the strongest statistically associated SNP (rs4783244) with adiponectin levels (P = 3.8 × 10 ^-19) in the first intron of CDH13 (T-cadherin) gene in a 30-kb haplotype block covering the promoter region to first intron. In addition, rs12051272 SNP genotypes in linkage disequilibrium with rs4783244 were found to be more significantly associated with adiponectin levels (P = 9.5×10 ^-20) and specifically with the levels of high-molecular weight (HMW) adiponectin, a subtype form associated with parameters related to glucose metabolism. Our results did show more significant association with adiponectin levels than rs12444338 (in CDH13) SNP genotypes reported recently. We suggest that the phenotype-affecting haplotype tagged by rs12051272 SNP would affect the plasma adiponectin levels and that we have to take the CDH13 genotype into account before considering the functional relevance of the adiponectin level. © 2011 Wiley Periodicals, Inc.

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[Effect of cardiovascular risk factors on individual and population medical expenditures

Okamura Tomonori, Nakamura Koshi, Hayakawa Takehito, Kanda Hideyuki, Miura Katsuyuki, Okayama Akira, Ueshima Hirotsugu

Nihon eiseigaku zasshi. Japanese journal of hygiene 67 ( 1 ) 38 - 43 2012.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 0021-5082

A 10-year follow-up cohort study of 4,535 National Health Insurance beneficiaries aged 40 to 69 years in Shiga was performed as part of a research project conducted by the Health Promotion Research Committee of the Shiga National Health Insurance Organizations in 2002. The relationship between cardiovascular risk factors and medical expenditures during the 10-year study period has been examined in this cohort. For example, there was a positively graded correlation between blood pressure and individual total medical expenditures per month. The odds ratio for cumulative hospitalization and hazard ratio for all-cause mortality in severe hypertensives were also higher than those in normotensives. However, from the viewpoint of the entire population, the excess medical expenditures attributable to hypertension within the total medical expenditures were higher for mild-to-moderate hypertensives than for severe hypertensives. On the other hand, although individual medical expenditures per month were 1.7-fold higher for participants with 2 or 3 risk factors and obesity, which was broadly equivalent to metabolic syndrome, than for those without these factors, the excess medical expenditures determined by risk clustering within the total medical expenditures were higher in normal-weight people than in obese people because of the higher prevalence of normal weight. These findings suggest that high-risk individuals are a good target of a high-risk approach, such as intensive health guidance, from the viewpoint of medical expenditures. However, another approach for the majority with a low-to-moderate cardiovascular risk should be considered, because they account for a greater proportion of the excess medical expenditures. Another way to solve this problem may be a population approach with an effective method of providing information to citizens.

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Relation of dietary and lifestyle traits to difference in serum leptin of Japanese in Japan and Hawaii

Nakamura Y., Ueshima H., Okuda N., Miura K., Kita Y., Okamura T., Turin T. C., Okayama A., Rodriguez B., Curb J. D., Stamler J.

Nutrition, Metabolism and Cardiovascular Diseases 22 ( 1 ) 14 - 22 2012.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 0939-4753

Background and Aims: Previously, we found significantly higher serum leptin in Japanese-Americans in Hawaii than Japanese in Japan. We investigated whether differences in dietary and other lifestyle factors explain higher serum leptin concentrations in Japanese living a Western lifestyle in Hawaii compared with Japanese in Japan. Methods and Results: Serum leptin and nutrient intakes were examined by standardized methods in men and women ages 40-59 years from two population samples, one Japanese-American in Hawaii (88 men, 94 women), the other Japanese in central Japan (123 men, 111 women). Multiple linear regression models were used to assess role of dietary and other lifestyle traits in accounting for serum leptin difference between Hawaii and Japan. Mean leptin was significantly higher in Hawaii than Japan (7.2 ± 6.8 vs 3.7 ± 2.3 ng/ml in men, P < 0.0001; 12.8 ± 6.6 vs 8.5 ± 5.0 in women <0.0001). In men, higher BMI in Hawaii explained over 90% of the difference in serum leptin; in women, only 47%. In multiple linear regression analyses in women, further adjustment for physical activity and dietary factors - alcohol, dietary fiber, iron - produced a further reduction in the coefficient for the difference, total reduction 70.7%; P-value for the Hawaii-Japan difference became 0.126. Conclusion: The significantly higher mean leptin concentration in Hawaii than Japan may be attributable largely to differences in BMI. Differences in nutrient intake in the two samples were associated with only modest relationship to the leptin difference. © 2010 Elsevier B.V.

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Defining patients at extremely high risk for coronary artery disease in heterozygous familial hypercholesterolemia

Sugisawa Takako, Okamura Tomonori, Makino Hisashi, Watanabe Makoto, Kishimoto Ichiro, Miyamoto Yoshihiro, Iwamoto Noriyuki, Yamamoto Akira, Yokoyama Shinji, Harada-Shiba Mariko

Journal of Atherosclerosis and Thrombosis 19 ( 4 ) 369 - 375 2012

Research paper (scientific journal), Joint Work, Accepted, ISSN 1340-3478

Aim: Heterozygous patients with familial hypercholesterolemia (FH) are known to be associated with a high risk of coronary artery disease (CAD), which is a major determinant of their clinical outcome. The prognosis of heterozygous FH patients substantially varies, being dependent on the level of their CAD risk, and their therapeutic regimen should be individualized. We assessed critical levels of LDLcholesterol (LDL-C) and Achilles tendon thickness (ATT) to identify heterozygous FH patients at "very high" risk for CAD. Methods: One hundred and nine heterozygous FH patients who had no history of CAD and had had their plasma lipid profile and ATT assessed before treatment were followed up until their first CAD event or 31 December 2010. Multivariable logistic regression models were used to analyze the correlation of LDL-C and/or ATT levels with the risk of developing CAD. Results: During the follow-up period, 21 of the 109 patients had a CAD event, diagnosed by coronary angiogram. Individuals in the highest tertile of LDL-C had a CAD risk 8.29-fold higher than those in the lowest tertile. Individuals in the highest tertile of the ATT group had a 7.82-fold higher CAD risk than those in the lowest tertile. Those who had either LDL-C ≥260 mg/dL or ATT ≥14.5 had a 23.94-fold higher CAD risk than those with LDL-C ≥260 mg/dL and ATT ≥14.5 mm. Conclusions: In heterozygous FH patients, LDL-C 260 mg/dL or higher and/or ATT 14.5 mm or thicker are useful markers for extracting patients at "very high" risk for CAD.

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Relation of dietary and lifestyle traits to difference in serum leptin of Japanese in Japan and Hawaii: the INTERLIPID study

Nakamura Y, Ueshima H, Okuda N, Miura K, Kita Y, Okamura T, Turin TC, OkayamaA, Rodriguez B, Curb JD, Stamler J; INTERLIPID Research Group

Nutr Metab Cardiovasc Dis 22 ( 1 ) 14-22 2012

Research paper (scientific journal), Joint Work, Accepted

生活習慣病の予防と医療費：10年間の追跡調査による健診所見と医療費の関連：滋賀国保コホート研究の知見から

岡村智教、中村幸志、早川岳人、神田秀幸、三浦克之、岡山明、上島弘嗣

日本衛生学雑誌 67 ( 1 ) 38-43 2012

Research paper (scientific journal), Joint Work, Accepted

循環器病の体質と予防戦略－日米比較研究・移民研究からの検証－

岡村智教

日本体質医学会雑誌 74 ( 1 ) 46-52 2012

Research paper (scientific journal), Single Work

前期高齢者におけるBMI別医療費と医療費高値群の特性．29,490人の大規模データを用いた検討．

鈴木（斎藤）智子、安村誠司、岡村智教、坂田清美、日高秀樹、三浦克之、岡山　明

日本公衆衛生雑誌 59 ( 7 ) 466-473 2012

Research paper (scientific journal), Joint Work, Accepted

Prognostic value of cardiac magnetic resonance imaging for idiopathic pulmonary arterial hypertension before initiating intravenous prostacyclin therapy

Yamada Yoshitake, Okuda Shigeo, Kataoka Masaharu, Tanimoto Akihiro, Tamura Yuichi, Abe Takayuki, Okamura Tomonori, Fukuda Keiichi, Satoh Toru, Kuribayashi Sachio

Circulation Journal 76 ( 7 ) 1737 - 1743 2012

Research paper (scientific journal), Joint Work, Accepted, ISSN 1346-9843

Background: Because few have reported the prognostic significance of cardiac magnetic resonance imaging (CMR) for idiopathic pulmonary arterial hypertension (IPAH), in this study we evaluated the value of CMR measurements as a prognostic predictor of IPAH before starting intravenous prostacyclin therapy. Methods and Results: A total of 121 consecutive CMR studies for evaluating right ventricular (RV) function were reviewed. Forty-one patients were diagnosed with IPAH and served as the study group. Factors, such as age, sex, New York Heart Association functional class (NYHAFC), 6-min walk test, plasma brain natriuretic peptide level, serum uric acid level and CMR measurements were analyzed as predictors of first hospitalization and death. The mean follow- up period was 1,350±769 days. Nine patients were hospitalized because of heart failure, and 4 patients died from cardiopulmonary causes. The univariate analyses suggested that the left ventricular (LV) mass index, the left and right ventricular end-diastolic volume indices (LVEDVI, RVEDVI), the LV and RV end-systolic volume indices (LVESVI, RVESVI) and NYHAFC predicted the risk for hospitalization and that RVEDVI, RVESVI and NYHAFC predicted mortality. The multivariate analyses suggested that RVEDVI and NYHAFC are independent predictors of both hospitalization and mortality. The effects of RVEDVI and NYHAFC on hospitalization were not substantially affected by the concomitant medication. Conclusions: In IPAH patients, the RVEDVI predicts both hospitalization for right heart failure and mortality before initiating intravenous prostacyclin therapy.

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