Details of a Researcher - Okamura, Tomonori

Papers - Okamura, Tomonori

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虚血性心疾患の最近の疫学的動向からみた実地診療のすすめかた.

田中太一郎、岡村智教

Medical Practice (文光堂) 28 ( 9 ) 1506-1512 2011

Research paper (scientific journal), Joint Work

動脈硬化性疾患の絶対リスクの評価.

岡村智教、杉山大典

日本医師会雑誌 140 ( 6 ) 1208-1212 2011

Research paper (scientific journal), Joint Work

ホモシステインの動脈硬化リスクについてのpros and cons.

岡村智教、久保田芳美、吉野佳織

循環器内科 (科学評論社) 70 ( 2 ) 202-209 2011

Research paper (scientific journal), Joint Work

心血管病の危険因子としての喫煙

岡村智教、森本明子

日本臨床 (日本臨床社) 69 ( 増刊号7. 冠動脈疾患動脈（上巻） ) 599-603 2011

Research paper (scientific journal), Joint Work

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Okamura T in The International Consortium for Blood Pressure Genome-Wide Association Studies

Nature 478 103-109 2011

Research paper (scientific journal), Joint Work, Accepted

脂質異常症と動脈硬化性疾患（世界と日本の違い

岡村智教

臨床と研究 (大道学館出版部) 88 ( 10 ) 1229-1234 2011

Research paper (scientific journal), Single Work

虚血性心疾患の一次予防：心臓を護るためになすべきこと.

中村幸志、岡村智教

Heart View（11月増刊号） (メジカルビュー社) 15 ( 12 ) 216-220. 2011

Research paper (scientific journal), Joint Work

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

Okamura T in the International Consortium for Blood Pressure Genome-wide Association Studies (ICBP-GWAS)

Hum Mol Genet 20 ( 11 ) 2273-84 2011

Research paper (scientific journal), Joint Work, Accepted

Relationship between dietary and other lifestyle habits and cardiometabolic risk factors in men

Katano Sayuri, Nakamura Yasuyuki, Okuda Nagako, Murakami Yoshitaka, Chiba Nagako, Yoshita Katsushi, Tanaka Taichiro, Tamaki Junko, Takebayashi Toru, Okayama Akira, Miura Katsuyuki, Okamura Tomonori, Ueshima Hirotsugu

Diabetology and Metabolic Syndrome 3 ( 1 ) 30 2011

Research paper (scientific journal), Joint Work, Accepted

Background: Prevalence of men with cardiometabolic risk factors (CMRF) is increasing in Japan. Few studies have comprehensively examined the relation between lifestyles and CMRF. Methods. We examined the baseline data from 3,498 male workers ages 19 to 69 years who participated in the high-risk and population strategy for occupational health promotion (HIPOP-OHP) study at 12 large-scale companies throughout Japan. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). Dietary intake was surveyed by a semi-quantitative Food Frequency Questionnaire. We defined four CMRF in this study as follows: 1) high blood pressure (BP): systolic BP 130 mmHg, or diastolic BP ≥85 mmHg, or the use of antihypertensive drugs; 2) dyslipidemia: high-density lipoprotein-cholesterol concentration < 40 mg/dl, or triglycerides concentration ≥150 mg/dl, or on medication for dyslipidemia; 3) impaired glucose tolerance: fasting blood sugar concentration ≥110 mg/dl; 4) obese: a body mass index ≥25 kg/m ². Results: Those who had 0 to 4 CMRF accounted for 1,597 (45.7%), 1,032 (29.5%), 587 (16.8%), 236 (6.7%), and 44 (1.3%) participants, respectively, in the Poisson distribution. Poisson regression analysis revealed that independent factors that contributed to the number of CMRF were age (b = 0.020, P < 0.01), IPAQ (b = -0.091, P < 0.01), alcohol intake (ml/day) (b = 0.001, P = 0.03), percentage of protein intake (b = 0.059, P = 0.01), and total energy intake (kcal)(b = 0.0001, P < 0.01). Furthermore, alcohol intake and its frequency had differential effects. Conclusions: Alcohol intake, percent protein and total energy intake were positively associated, whereas drinking frequency and IPAQ were inversely associated, with the number of CMRF. © 2011 Katano et al; licensee BioMed Central Ltd.

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Residual lifetime risk of cardiovascular diseases in Japan

Turin Tanvir Chowdhury, Rumana Nahid, Okamura Tomonori

Journal of Atherosclerosis and Thrombosis 18 ( 6 ) 443 - 447 2011

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

Risk assessment of cardiovascular diseases (CVD) is shifting from the relative risk to an absolute risk approach. The residual lifetime risk (LTR), which provides an absolute risk assessment, is an epidemiologic measure that expresses the probability of someone of a given age and sex developing a disease condition during their remaining lifespan. The LTR estimation is important because it could be more easily comprehended by clinicians and patients. The LTR for CVD was not estimated for the Japanese population until recently, when the LTR of stroke and acute myocardial infarction (AMI) was reported. The reported LTR of stroke and AMI for middle-aged adults is substantial. The observed probabilities illustrated that approximately 1 in 5 men and women of middle age will suffer from a stroke in their remaining lifetime. On the other hand, approximately 1 in 6 men and 1 in 9 women of middle age will suffer from AMI in their remaining lifetime. Aaginst the backdrop of the aging population and worsening risk factor scenario, these estimates re-emphasize that CVD is a public health burden that requires preventive interventions. These estimates provide a means to communicate the absolute risk of CVD to the lay population, policy makers, as well as health service providers in predicting the disease burden of CVD. This easily comprehended knowledge can be used as an important index to assist in public health education and planning.

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The combined impact of blood pressure category and glucose abnormality on the incidence of cardiovascular diseases in a Japanese urban cohort

Kokubo Yoshihiro, Okamura Tomonori, Watanabe Makoto, Higashiyama Aya, Ono Yuu, Miyamoto Yoshihiro, Furukawa Yoko, Kamide Kei, Kawanishi Katsuyuki, Okayama Akira, Yoshimasa Yasunao

Hypertension Research 33 ( 12 ) 1238 - 1243 2010.12

Research paper (scientific journal), ISSN 0916-9636

Few prospective studies have examined the combined impact of blood pressure (BP) categories and glucose abnormalities on the incidence of cardiovascular disease (CVD) in the general Asian population. This study aimed to examine the effect of the combined risks of these factors on the incidence of CVD in a general Japanese population. We studied 5321 Japanese individuals (aged 30-79 years), without CVD at baseline, who received follow-up for an average of 11.7 years. Serum fasting glucose categories were defined according to the 2003 American Diabetes Association recommendations. BP categories were defined by the 2009 Japanese Society of Hypertension Guidelines for the Management of Hypertension. The Cox proportional hazard ratios (HRs) for CVD according to the serum glucose and BP categories were calculated. In 62 036 person-years of follow-up, we documented 364 CVD events (198 stroke and 166 coronary heart disease (CHD)). Compared with normoglycemic subjects, the multivariable HRs (95% confidence intervals (CIs)) for CVD, CHD and stroke were 1.25 (1.00-1.58), 1.46 (1.04-2.04) and 1.11 (0.81-1.52), respectively, in individuals with impaired fasting glucose (IFG), whereas these values were 2.13 (1.50-3.03), 2.28 (1.34-3.88) and 2.08 (1.29-3.35), respectively, in individuals with diabetes mellitus (DM). Compared with normoglycemic and optimal blood pressure (BP) subjects, increased risks of CVD were observed in the normoglycemic subjects with high-normal BP or hypertension, the IFG subjects with normal or higher BP, and the DM subjects regardless of BP category (P-value for interaction0.046). In conclusion, the high-normal BP subjects in all glucose categories and the normal BP subjects with IFG showed increased risk of CVD in this Japanese population. Further investigation of larger cohorts of DM subjects should be conducted to better understand this phenomenon. © 2010 The Japanese Society of Hypertension All rights reserved.

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Common variants in the ATP2B1 gene are associated with susceptibility to hypertension

Tabara Yasuharu, Kohara Katsuhiko, Kita Yoshikuni, Hirawa Nobuhito, Katsuya Tomohiro, Ohkubo Takayoshi, Hiura Yumiko, Tajima Atsushi, Morisaki Takayuki, Miyata Toshiyuki, Nakayama Tomohiro, Takashima Naoyuki, Nakura Jun, Kawamoto Ryuichi, Takahashi Norio, Hata Akira, Soma Masayoshi, Imai Yutaka, Kokubo Yoshihiro, Okamura Tomonori, Tomoike Hitonobu, Iwai Naoharu, Ogihara Toshio, Inoue Itsuro, Tokunaga Katsushi, Johnson Toby, Caulfield Mark, Munroe Patricia, Umemura Satoshi, Ueshima Hirotsugu, Miki Tetsuro

Hypertension 56 ( 5 ) 973 - 980 2010.11

Research paper (scientific journal), ISSN 0194-911X

Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension (P=5.3×10; allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P=4.1×10). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P=5.9×10). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (P=1.4×10). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1, rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P=4.6×10) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1, as well as FGF5, CYP17A1, and CSK, to be associated with blood pressure levels and risk of hypertension. © 2010 American Heart Association, Inc.

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Lifetime risk of acute myocardial infarction in Japan

Turin Tanvir Chowdhury, Kokubo Yoshihiro, Murakami Yoshitaka, Higashiyama Aya, Rumana Nahid, Watanabe Makoto, Okamura Tomonori

Circulation: Cardiovascular Quality and Outcomes 3 ( 6 ) 701 - 703 2010.11

Research paper (scientific journal), ISSN 1941-7713

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A genome-wide association study of hypertension-related phenotypes in a Japanese population

Hiura Yumiko, Tabara Yasuharu, Kokubo Yoshihiro, Okamura Tomonori, Miki Tetsuro, Tomoike Hitonobu, Iwai Naoharu

Circulation Journal 74 ( 11 ) 2353 - 2359 2010.11

Research paper (scientific journal), ISSN 1346-9843

Background: Large-scale genome-wide association studies (GWAS) have been successful in identifying genes that contribute to common diseases and phenotypes. A GWAS of hypertension-related phenotypes in a Japanese population was conducted in the current study. Methods and Results: A total of 936 participants were recruited from the Suita Study and a GWAS with 538,732 single nucleotide polymorphisms (SNP) was performed. The phenotypes included were systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI), waist-to-hip ratio (WHR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma brain natriuretic peptide (BNP) concentration and alcohol consumption (AC). The SNP exceeding the genome-wide significance level were subjected to subsequent association studies using samples available from the Suita Study and Nomura Study. There is no master gene in the Japanese population that profoundly affects SBP, DBP, BMI, WHR, PRA and PAC. AC was influenced by the functional polymorphism in ALDH2, which affected BP levels in men. The BNP concentration was influenced by a polymorphism in the 3' region of the gene encoding for BNP. However, this polymorphism did not influence blood pressure (BP). Six SNP were identified to be associated with hypertension in both the Suita and Nomura studies. Conclusions: Although several candidate SNP relevant to hypertension and those influencing AC and BNP were identified, our middle-sized GWAS indicated that there is no master gene in Japanese people that profoundly affects BP-related phenotypes.

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Comparison of low-density lipoprotein cholesterol concentrations measured by a direct homogeneous assay and by the Friedewald formula in a large community population

Tanno Kozo, Okamura Tomonori, Ohsawa Masaki, Onoda Toshiyuki, Itai Kazuyoshi, Sakata Kiyomi, Nakamura Motoyuki, Ogawa Akira, Kawamura Kazuko, Okayama Akira

Clinica Chimica Acta 411 ( 21-22 ) 1774 - 1780 2010.11

Research paper (scientific journal), ISSN 0009-8981

Background: We compare the direct homogeneous low-density lipoprotein cholesterol (LDL-C) assay with the Friedewald formula (FF) for determination of LDL-C in a large community-dwelling population. Methods: A total of 21,194 apparently healthy subjects aged 40 to 79 years with triglyceride (TG) concentrations < 4.52 mmol/l were enrolled. LDL-C were directly measured by the enzymatic homogeneous assay (LDL-C (D)) and also estimated by the FF (LDL-C (F)). Paired t-test, Pearson's correlation coefficient and linear regression analysis were performed and the concordances of the National Cholesterol Education Program (NCEP) risk category were estimated. Results: Both in fasting (n. = 3270) and nonfasting samples (n. = 17,924), LDL-C (D) highly correlated with LDL-C (F): r= 0.971 and 0.955, respectively. Concordant results for NCEP categories were 84.8% for fasting samples and 80.1% for nonfasting samples. However, the bias between the 2 measurements increased in samples with TG concentrations > 1.69 mmol/l, especially in nonfasting samples. Conclusions: The results showing less variability of the direct LDL-C assay than that of the FF in nonfasting samples suggest that epidemiological studies can use LDL-C measured by the direct assay both in fasting and nonfasting samples. © 2010 Elsevier B.V.

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Association of carotid atherosclerosis with genetic polymorphisms of the klotho gene in patients with hypertension

Oguro Ryosuke, Kamide Kei, Kokubo Yoshihiro, Shimaoka Izumi, Congrains Ada, Horio Takeshi, Hanada Hironori, Ohishi Mitsuru, Katsuya Tomohiro, Okamura Tomonori, Miyata Toshiyuki, Kawano Yuhei, Rakugi Hiromi

Geriatrics and Gerontology International 10 ( 4 ) 311 - 318 2010.10

Research paper (scientific journal), ISSN 1444-1586

Aim: Previous studies suggest that klotho gene polymorphisms may be associated with atherosclerosis, but did not assess the relationship between klotho gene polymorphisms and atherosclerosis parameters such as carotid artery intima-media thickness (IMT). Here, we studied whether klotho single nucleotide polymorphisms (SNP) were associated with carotid atherosclerosis. Methods: All subjects were Japanese. Eight-hundred and fifty-three patients with hypertension (465 men and 388 women) in the outpatient clinic and 1783 subjects from the general population (821 men and 962 women) attending health check-ups were analyzed in the present study. We measured mean IMT of the common carotid artery to evaluate carotid atherosclerosis. Four single nucleotide polymorphisms (SNP) (rs7323281; intron1, rs5644481; exon4, rs3752472; exon3, rs650439; intron4) of klotho were selected as representative SNP in haplotype blocks. Results: Multivariate logistic regression analysis adjusted by confounding factors showed a significant association of rs650439 with carotid atherosclerosis in hypertensive patients (TT vs TA vs AA, P < 0.01; TT + TA vs AA, P < 0.01). By ancova considering confounding factors, rs650439 was also significantly associated with mean IMT (TT + TA vs AA, P = 0.04) in the hypertensive population. However, there was no significant association between klotho SNP and carotid IMT in the general population. Compared to the general population, the subject group with hypertensive patients clearly had more atherosclerosis risk factors. Conclusion: Only in hypertensive patients was klotho rs650439 strongly associated with mean IMT thickening of the common carotid artery. Therefore, klotho SNP (rs650439) may influence on the progression of carotid atherosclerosis in patients with hypertension. © 2010 Japan Geriatrics Society.

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[Drinking/smoking habits and knowledge regarding heavy drinking/ smoking as a risk factor of stroke among Japanese general population].

Morimoto Akiko, Miyamatsu Naomi, Okamura Tomonori, Nakayama Hirohumi, Morinaga Miho, Toyota Akihiro, Suzuki Kazuo, Hata Takashi, Yamaguchi Takenori

Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 45 ( 5 ) 411 - 419 2010.10

Research paper (scientific journal), ISSN 1341-8963

We examined the knowledge regarding heavy drinking and smoking as risk factors of stroke according to drinking/smoking habits among randomly selected Japanese general population. The Japan Stroke Association and co-researchers have performed a large-scale educational intervention to improve knowledge concerning stroke from 2006 to 2008. Prior to above-mentioned intervention, we conducted mail-surveillance on knowledge about stroke in 11,306 randomly selected residents aged 40 to 74. We assessed the relationship between drinking/smoking habits and knowledge regarding heavy drinking and smoking as risk factors by using the chi-square test and multiple logistic regression analysis adjusting for age, sex, area, employment, living situation, history of stroke and other stroke related diseases, history of liver disease, family history of stroke and drinking (non-drinker / ex-drinker / occasional drinker / habitual drinker) / smoking habits (non-smoker / ex-smoker / current smoker). Total 5,540 subjects (49.0%) participated in this study. Ex-smokers and current smokers had better knowledge regarding smoking as a risk factor of stroke than non-smokers (odds ratio and 95% confidence intervals: 1.89, 1.55-2.31, 1.76, 1.45-2.12, respectively). There was no difference between habitual drinkers and non-drinkers in their knowledge, whereas current smokers had greater knowledge regarding smoking than nonsmokers. Accordingly, it is suggested that it will be necessary for habitual drinkers to be enlightened regarding heavy drinking as a risk factor of stroke and for current smokers to be provided with information regarding not only these risks but also the specific strategies for invoking behavioral changes.

Genetic link between obesity and MMP14-dependent adipogenic collagen turnover

Chun Tae Hwa, Inoue Mayumi, Morisaki Hiroko, Yamanaka Itaru, Miyamoto Yoshihiro, Okamura Tomonori, Sato-Kusubata Kaori, Weiss Stephen J.

Diabetes 59 ( 10 ) 2484 - 2494 2010.10

Research paper (scientific journal), ISSN 0012-1797

OBJECTIVE - In white adipose tissue, adipocytes and adipocyte precursor cells are enmeshed in a dense network of type I collagen fibrils. The fate of this pericellular collagenous web in diet-induced obesity, however, is unknown. This study seeks to identify the genetic underpinnings of proteolytic collagen turnover and their association with obesity progression in mice and humans. RESEARCH DESIGN AND METHODS - The hydrolysis and degradation of type I collagen at early stages of high-fat diet feeding was assessed in wild-type or MMP14 (MT1-MMP)-haploinsufficient mice using immunofluorescent staining and scanning electron microscopy. The impact of MMP14-dependent collagenolysis on adipose tissue function was interrogated by transcriptome profiling with cDNA microarrays. Genetic associations between MMP14 gene common variants and obesity or diabetes traits were examined in a Japanese cohort (n = 3,653). RESULTS - In adult mice, type I collagen fibers were cleaved rapidly in situ during a high-fat diet challenge. By contrast, in MMP14 haploinsufficient mice, animals placed on a high-fat diet were unable to remodel fat pad collagen architecture and display blunted weight gain. Moreover, transcriptional programs linking type I collagen turnover with adipogenesis or lipogenesis were disrupted by the associated decrease in collagen turnover. Consistent with a key role played by MMP14 in regulating high-fat diet-induced metabolic programs, human MMP14 gene polymorphisms located in proximity to the enzyme's catalytic domain were closely associated with human obesity and diabetes traits. CONCLUSIONS - Together, these findings demonstrate that the MMP14 gene, encoding the dominant pericellular collagenase operative in vivo, directs obesogenic collagen turnover and is linked to human obesity traits. © 2010 by the American Diabetes Association.

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Bundle branch block and other cardiovascular disease risk factors

Liu Longjian, Okamura Tomonori, Kadowaki Takashi, Murakami Yoshitaka, Hozawa Atsushi, Kita Yoshikuni, Takashima Naoyuki, Okuda Nagako, Okayama Akira, Ueshima Hirotsugu

International Journal of Cardiology 143 ( 3 ) 432 - 440 2010.09

Research paper (scientific journal), ISSN 0167-5273

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Risk factors for heart failure and coronary heart disease mortality over 24-year follow-up period in Japan

Nakamura Yasuyuki, Turin Tanvir C., Rumana Nahid, Miura Katsuyuki, Kita Yoshikuni, Takashima Naoyuki, Fujiyoshi Akira, Hayakawa Takehito, Okamura Tomonori, Ueshima Hirotsugu

CVD Prevention and Control 5 ( 3 ) 97 - 103 2010.09

ISSN 1875-4570

Background: Although prevention of heart failure (HF) is an urgent public health need with national and global implications, population-based studies are rare. Methods and results: We studied risk factors for HF and coronary heart disease (CHD) mortality using the NIPPON DATA80 database with a 24-year follow-up. At the baseline in 1980, data were collected on study participants aged 30 years and over from randomly selected areas in Japan. We followed 9300 participants (44% men, mean age 51). Over the 24-year follow-up, there were 189 deaths from HF (82 men and 107 women) and 188 (91 men and 97 women) from CHD. Cox analyses revealed common and specific risk factors for both mortalities. Common risk factors were: systolic blood pressure for male HF (hazard ratio: 1.28 per 1SD, P = 0.02) and for CHD in both (men: 1.20, P = 0.01; women: 1.27, P = 0.003), smoking for male CHD (1.31, P = 0.004) and for female HF (1.39, P = 0.01), blood sugar for HF and CHD in men (HF: 1.21 per 1SD, P = 0.009; CHD: 1.29, P < 0.0001); T wave abnormality in male HF (2.33, P = 0.003) and female CHD (1.84, P = 0.001). Specific risk factors were: serum creatinine for HF in both (men: 1.14 per 1SD, P < 0.0001, women: 1.09, P = 0.01); total cholesterol for CHD in men (1.38 per 1SD, P = 0.001), history of valvular heart disease (6.48, P = 0.002) or stroke (2.41, P = 0.048) in male HF, and history of angina in female CHD (3.59, P = 0.003). Conclusion: Common and specific measures need to be undertaken to prevent HF and CHD mortality. © 2010 Published by Elsevier Ltd. on behalf of World Heart Federation.

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