Details of a Researcher - Okamura, Tomonori

Papers - Okamura, Tomonori

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Relationship between blood pressure category and incidence of stroke and myocardial infarction in an Urban Japanese population with and without chronic kidney disease

Kokubo Yoshihiro, Nakamura Satoko, Okamura Tomonori, Yoshimasa Yasunao, Makino Hisashi, Watanabe Makoto, Higashiyama Aya, Kamide Kei, Kawanishi Katsuyuki, Okayama Akira, Kawano Yuhei

Stroke 40 ( 8 ) 2674 - 2679 2009.08

ISSN 0039-2499

BACKGROUND AND PURPOSE-: Chronic kidney disease (CKD) is increasingly recognized as an independent risk factor for stroke and myocardial infarction (MI). Few studies, however, have examined the relationship between blood pressure (BP) category and these diseases in subjects with and without CKD. METHODS-: We studied 5494 Japanese individuals (ages 30 to 79, without stroke or MI at baseline) who completed a baseline survey and received follow-up through December 2005. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease study equation modified by the Japanese coefficient. CKD was defined as an estimated GFR <60 mL/min/1.73m. BP categories were defined by the European Society of Hypertension and European Society of Cardiology 2007 criteria. RESULTS-: In 64 395 person-years of follow-up, we documented 346 incidences of cardiovascular diseases (CVD; 213 strokes and 133 MI events). Compared with the GFR (≥90 mL/min/1.73m) group, the hazard ratios (95% confidential intervals) for stroke were 1.9 (1.3 to 3.0) in the GFR 50 to 59 mL/min/1.73m group and 2.2 (1.2 to 4.1) in the GFR <50 mL/min/1.73m group. Results for cerebral infarction were similar. Compared with the optimal BP subjects without CKD, the normal BP, high-normal BP, and hypertensive subjects without CKD showed increased risks of CVD and stroke; however the impact of each BP category on CVD (P for interaction: 0.04 in men, 0.49 in women) and stroke (0.03 in men, 0.90 in women) was more evident in men with CKD. CONCLUSIONS-: CKD may increase the association of BP and CVD in a Japanese urban population. © 2009 American Heart Association, Inc.

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Association of serum n-6 and n-3 polyunsaturated fatty acids with lipids in 3 populations of middle-aged men

Motoyama Kenneth R., Curb J. David, Kadowaki Takashi, El-Saed Aiman, Abbott Robert D., Okamura Tomonori, Evans Rhobert W., Nakamura Yasuyuki, Sutton-Tyrrell Kim, Rodriquez Beatriz L., Kadota Aya, Edmundowicz Daniel, Willcox Bradley J., Choo Jina, Katsumi Nakata, Otake Teruo, Kadowaki Sayaka, Kuller Lewis H., Ueshima Hirotusgu, Sekikawa Akira

American Journal of Clinical Nutrition 90 ( 1 ) 49 - 55 2009.07

ISSN 0002-9165

Background: The association of serum polyunsaturated fatty acids (PUFAs) with lipids in different populations is not known. Objective: Our aim was to examine the association of serum n-6 (omega-6) or n-3 (omega-3) PUFAs with triglycerides or HDL-cholesterol concentrations in 261 white, 285 Japanese, and 212 Japanese American men aged 40-49 y. Design: We used a population-based cross-sectional study. Of the original sample (n = 926), those taking lipid-lowering medications or who had diabetes (n = 168) were excluded. Serum fatty acids were analyzed by capillary gas-liquid chromatography. Multiple regression models as a function of tertile groups of each PUFA were used. Results: Serum n = 6 PUFAs were significantly inversely associated with triglycerides across populations after adjustment for age, body mass index, pack-years of smoking, and ethanol consumption [β = -0.39 (P < 0.001), -0.38 (P < 0.001), and -0.33 (P < 0.001) in whites, Japanese, and Japanese Americans, respectively]. Marine n-3 PUFAs were significantly inversely associated with triglycerides across populations [β = -0.15 (P < 0.001), -0.22 (P < 0.001), and -0.13 (P < 0.001) in whites, Japanese, and Japanese Americans, respectively]. n-6 PUFAs were significantly positively associated with HDL cholesterol in whites (β = 4.49, P < 0.001) and Japanese (β = 3.73, P < 0.01). Marine n-3 PUFAs were significantly positively associated with HDL cholesterol in Japanese (β = 2.15, P < 0.05), and eicosapentaenoic acid was significantly positively associated with HDL cholesterol in whites (β = 2.68, P < 0.01). Conclusion: Serum n-6 and n-3 PUFAs are inversely associated with triglycerides across populations. © 2009 American Society for Nutrition.

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Elevated serum creatine kinase predicts first-ever myocardial infarction

Watanabe Makoto, Okamura Tomonori, Kokubo Yoshihiro, Higashiyama Aya, Okayama Akira

International Journal of Epidemiology 38 ( 6 ) 1571 - 1579 2009.06

ISSN 0300-5771

Background: In myocardial infarction (MI), it is well known that serum creatine kinase (s-CK) increases after onset, but it is unclear whether s-CK elevates before MI onset. The present analysis examined whether elevated s-CK levels predicted first-ever MI or stroke. Methods: This study was a population-based cohort study in a Japanese urban area. Study subjects were comprised of 5026 initially healthy Japanese (2370 men and 2656 women, mean age: 54.5 years) without a history of MI or stroke. They were followed-up for 11.8 years on average, and 103 MIs (definite: 45; probable: 58) and 168 strokes (definite: 126; probable: 42) were observed. There was no subject who developed MI just at baseline (the follow-up period among those with definite MI was, at earliest, 0.20 years). Results: The adjusted hazard ratio for definite MI was 4.18 (95% confidence interval 1.66-10.53) with s-CK levels of ≥200 IU/l, compared with the reference category (s-CK levels of ≤99 IU/l), whereas no relationship was observed between s-CK levels and the risk for stroke. With regard to definite MI, an interaction between s-CK levels and dyslipidaemia was observed. Among subjects with hypercholesterolaemia, the hazard ratio linearly elevated with increased s-CK levels. On the other hand, no linear elevation was observed among subjects without hypercholesterolaemia (P for interaction = 0.011). Conclusions: The present study suggested that screening for elevated s-CK levels in initially healthy Japanese subjects was useful to predict first-ever MI in the future, especially in subjects with dyslipidaemia. Published by Oxford University Press on behalf of the International Epidemiological Association. © The Author 2009.

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Identification of genetic markers associated with high-density lipoprotein-cholesterol by genome-wide screening in a Japanese population - The Suita study

Hiura Yumiko, Shen Chun Shen, Kokubo Yoshihiro, Okamura Tomonori, Morisaki Takayuki, Tomoike Hitonobu, Yoshida Teruhiko, Sakamoto Hiromi, Goto Yoichi, Nonogi Hiroshi, Iwai Naoharu

Circulation Journal 73 ( 6 ) 1119 - 1126 2009.06

ISSN 1346-9843

Background: Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels. Given the difference in allele frequencies and linkage disequilibrium patterns across the populations, a GWAS was conducted using the Illumina 550K in a Japanese population (n=900) in search of population-specific genetic variations associated with high-density lipoprotein (HDL)-cholesterol. Methods and Results: Among the 368,274 single nucleotide polymorphisms (SNPs) with a minor allele frequency of at least 0.1, 43 SNPs exceeded the arbitrary threshold of -log₁₀P >4.0. The most significant SNP was rs3764261, located 5′upstream of CETP, exhibiting a -log₁₀P value of 6.17. Increasing the sample size by genotyping in the additional Suita sample (n=1,810) further improved the level of significance, with each additional copy of the minor allele being associated with an increase in HDL-cholesterol by 6.2 mg/dl (P=3.4×10^-12). Interestingly, the minor allele was more prevalent in cases with myocardial infarction than in controls (0.221 vs 0.196, nominal P=0.02). Conclusions: The association between genetic variants at CETP and HDL-cholesterol was replicated in our sample. None of the genetic variants exerted a greater influence on HDL levels than those at CETP. Associations for the top-ranked SNPs need to be tested for further replication in an independent sample.

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Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol and the incidence of cardiovascular disease in an urban Japanese cohort study

Okamura Tomonori, Kokubo Yoshihiro, Watanabe Makoto, Higashiyama Aya, Miyamoto Yoshihiro, Yoshimasa Yasunao, Okayama Akira

Atherosclerosis 203 ( 2 ) 587 - 592 2009.04

ISSN 0021-9150

Objective: Only a small number of population-based cohort studies have directly compared the predictive value of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDLC) for coronary artery disease in Asian populations, such as Japan. Methods: We performed an 11.9-year cohort study of 4694 men and women, aged 30-74 years, selected randomly from an urban general population in Japan. Baseline LDL-C levels were estimated using the Friedewald formula. The predictive values of LDL-C and non-HDLC for myocardial infarction (MI) and stroke were compared. Results and conclusion: During the follow-up period, there were 80 incident cases of MI and 139 of stoke, comprised of 23 intracerebral hemorrhages, 85 cerebral infarctions and 31 other types of stroke. The Hazard ratio (HR) for MI was highest in the top quintile of LDL-C (HR: 3.03, 95% CI, 1.32-6.96) when male and female data were combined. The HR for MI was also highest in the top quintile of non-HDLC (HR: 2.97, 95% CI, 1.26-6.97). Analysis of trends showed a significant positive relationship between MI incidence and serum LDL-C and non-HDLC levels (both P = 0.02). However, there was no relationship between the incidence of any subtype of stroke and either LDL-C or non-HDLC. The predictive value of LDL-C and non-HDLC for MI, assessed by calculating the differences in the -2 logarithm likelihood (-2 ln [L]) and area under the curve (AUC), were almost similar. © 2008 Elsevier Ireland Ltd. All rights reserved.

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Effects of habitual alcohol intake on ambulatory blood pressure, heart rate, and its variability among japanese men

Ohira Tetsuya, Tanigawa Takeshi, Tabata Minako, Imano Hironori, Kitamura Akihiko, Kiyama Masahiko, Sato Shinichi, Okamura Tomonori, Cui Renzhe, Koike Kazuko A., Shimamoto Takashi, Iso Hiroyasu

Hypertension 53 ( 1 ) 13 - 19 2009.01

ISSN 0194-911X

We sought to examine effects of habitual alcohol intake on ambulatory blood pressure (BP), heart rate (HR), and HR variability among Japanese men. Subjects were 539 men aged 35 to 65 years from rural and urban communities. Ambulatory BP and HR were monitored with an automated, portable, noninvasive multibiomedical recorder. Power spectral analysis of the RR intervals on the ECG was performed every 5 minutes. Compared with nondrinkers, moderate drinkers (alcohol intake 23 to 45 g/d) and heavy drinkers (alcohol intake ≥46 g/d) showed higher age- and field-adjusted mean values of systolic and diastolic BPs during the morning and while awake, but there were no differences in BPs over 24-hour periods and while asleep among the alcohol intake categories. Alcohol intake was positively associated with mean values of sleep-morning differences and daytime variability in BPs, HRs while awake and asleep, and low frequency: high frequency ratio while asleep. The results were virtually unchanged after adjustment for body mass index, smoking, and diabetes mellitus. Compared with the nondrinkers, age- and field-adjusted odds ratios of the morning BP surge (excess elevation of BP in the morning: morning systolic BP minus sleep systolic BP ≥37 mm Hg) for light (alcohol intake 0 to 22 g/d), moderate, and heavy drinkers were 0.96 (95% CI: 0.34 to 2.78), 1.68 (95% CI: 0.64 to 4.38), and 2.73 (95% CI: 1.12 to 6.67), respectively. Habitual alcohol intake was associated with increased BP in the morning, HR while awake and asleep, and sympathetic activity while asleep, which may explain some of the mechanisms of the relationship between heavy alcohol intake and risk of cardiovascular diseases. © American Heart Association, Inc.

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Association of Asn221Ser mutation in tissue factor pathway inhibitor-β with plasma total tissue factor pathway inhibitor level

Ishikawa Junko, Okada Hiromi, Kato Hisao, Takeshita Satoshi, Honda Shigenori, Kawasaki Tomio, Suehisa Etsuji, Tsuji Hajime, Madoiwa Seiji, Sakata Yoichi, Kojima Tetsuhito, Murata Mitsuru, Ikeda Yasuo, Kokubo Yoshihiro, Okamura Tomonori, Tomoike Hitonobu, Miyata Toshiyuki

Blood Coagulation and Fibrinolysis 20 ( 1 ) 22 - 26 2009.01

ISSN 0957-5235

Tissue factor pathway inhibitor (TFPI) is an anticoagulant protease inhibitor that inhibits the tissue factor-initiated blood coagulation cascade reactions. Based on these anticoagulant functions of TFPI, we hypothesized that genetic variations in TFPI may alter the TFPI expression or impair the anticoagulant function and could predispose persons to deep vein thrombosis (DVT). This study was undertaken to examine whether the genetic polymorphisms in TFPI are associated with the plasma TFPI levels and risk for DVT. We sequenced the entire coding regions of TFPI in 175 Japanese DVT patients and identified 12 genetic variants, including one missense mutation, Asn221Ser. The missense mutation occurred at the site presumably attached to the glycosylphosphatidylinositol anchor in the TFPI-p form. The allele frequency of the mutant Ser-coding allele of the Asn221Ser mutation was 8% in the Japanese general population consisting of 1684 individuals. The Asn221Ser mutation was significantly associated with the total TFPI levels (Asn/Asn, n = 108, total TFPI = 56.57 ± 0.88 ng/ml (mean ± SD) vs. Asn/Ser + Ser/Ser, n = 16, total TFPI = 63.44 ±.28 ng/ml, P= 0.0058). The genotype was not associated with the free TFPI level. This Asn221Ser mutation was not associated with DVT. Thus, the Asn221Ser mutation occurring in the TFPI-p form was associated with the total TFPI level, but not a risk for DVT. The absence of the putative glycosylphosphatidylinositol anchor in TFPI-β under pathological conditions remains to be studied. Blood Coagul Fibrinolysis 20:22-26 © 2009 Wolters Kluwer Health Lippincott Williams & Wilkins.

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Risk of smoking and metabolic syndrome for incidence of cardiovascular disease - Comparison of relative contribution in urban Japanese population

Higashiyama Aya, Okamura Tomonori, Ono Yuu, Watanabe Makoto, Kokubo Yoshihiro, Okayama Akira

Circulation Journal 73 ( 12 ) 2258 - 2263 2009

ISSN 1346-9843

Background: Risk factor clustering, the so-called metabolic syndrome (MetS), is an important risk factor for cardiovascular disease (CVD). Smoking is also an important CVD risk factor with still a high prevalence. However, few previous studies have compared the risk for CVD or the population-attributable fraction (PAF) of smoking, MetS, and both. Methods and Results: The present study was an 11.9-year cohort study of 1,822 men and 2,089 women, aged 40-74 years, selected randomly from an urban general population in Japan. MetS was defined according to the National Cholesterol Education Program on Adult Treatment Panel III (NCEP-ATPIII) guideline modified by the Asian criteria for waist circumference. The prevalence of smoking was 49.5% in men and 11.1% in women, and that of MetS was 19.8% and 23.5%, respectively. In men, the multivariate-adjusted hazard ratio for CVD incidence, compared with non-smoking participants without MetS, was 2.07 (1.26-3.40) in those who smoked, 2.09 (1.08-4.04) in those with MetS, and 3.56 (1.89-6.72) in those with both. In men the PAF for CVD incidence was 21.8% because of smoking, 7.5% because of MetS, and 11.9% because of both. Conclusions: Although countermeasures for MetS are important, smoking should continue to be considered an important public health problem and antismoking campaigns should be promoted, especially for men, to prevent CVD.

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Gender-specific associations of vision and hearing impairments with adverse health outcomes in older Japanese

Michikawa Takehiro, Nishiwaki Yuji, Kikuchi Yuriko, Nakano Makiko, Iwasawa Satoko, Asakura Keiko, Milojevic Ai, Mizutari Kunio, Saito Hideyuki, Ishida Susumu, Okamura Tomonori, Takebayashi Toru

BMC Geriatrics 9 ( 1 ) 2009

ISSN 1471-2318

Background. Several epidemiological studies have shown that self-reported vision and hearing impairments are associated with adverse health outcomes (AHOs) in older populations; however, few studies have used objective sensory measurements or investigated the role of gender in this association. Therefore, we examined the association of vision and hearing impairments (as measured by objective methods) with AHOs (dependence in activities of daily living or death), and whether this association differed by gender. Methods. From 2005 to 2006, a total of 801 residents (337 men and 464 women) aged 65 years or older of Kurabuchi Town, Gunma, Japan, participated in a baseline examination that included vision and hearing assessments; they were followed up through September 2008. Vision impairment was defined as a corrected visual acuity of worse than 0.5 (logMAR = 0.3) in the better eye, and hearing impairment was defined as a failure to hear a 30 dB hearing level signal at 1 kHz in the better ear. Information on outcomes was obtained from the town hall and through face-to-face home visit interviews. We calculated the risk ratios (RRs) of AHOs for vision and hearing impairments according to gender. Results. During a mean follow-up period of 3 years, 34 men (10.1%) and 52 women (11.3%) had AHOs. In both genders, vision impairment was related to an elevated risk of AHOs (multi-adjusted RR for men and women together = 1.60, 95% CI = 1.05-2.44), with no statistically significant interaction between the genders. In contrast, a significant association between hearing impairment and AHOs (multi-adjusted RR = 3.10, 95% CI = 1.43-6.72) was found only in the men. Conclusion. In this older Japanese population, sensory impairments were clearly associated with AHOs, and the association appeared to vary according to gender. Gender-specific associations between sensory impairments and AHOs warrant further investigation. © 2009 Michikawa et al; licensee BioMed Central Ltd.

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High blood pressure in middle age is associated with a future decline in activities of daily living. NIPPON DATA80

Hozawa A., Okamura T., Murakami Y., Kadowaki T., Okuda N., Takashima N., Hayakawa T., Kita Y., Miura K., Nakamura Y., Okayama A., Ueshima H.

Journal of Human Hypertension 23 ( 8 ) 546 - 552 2009

ISSN 0950-9240

Although several studies have reported on the relation between high blood pressure (BP) and impaired activities of daily living (ADL), only a few studies have reported on the relation of high BP in middle-aged subjects with future impaired ADL. Furthermore, no studies reported an excess impaired ADL due to non-normal BP. Using ADL 1999 data, we compared data from NIPPON DATA80 survivors without impaired ADL (N = 1816) with those with impaired ADL (N = 75) using baseline BP information collected in 1980. We analysed participants who were aged 47-59 years at baseline. Multiple adjusted logistic regression analyses were used to estimate the risk of impaired ADL, according to baseline BP categories using Joint National Committee 7 guidelines (normal BP, prehypertension, stage 1 hypertension (HT) and stage 2 HT). Subjects who used antihypertensive medications were classified as having stage 2 HT. We calculated excess impaired ADL due to non-normal BP. Compared with normal BP categories, the adjusted odds ratio (OR) and 95% confidence interval (CI) of having impaired ADL was higher in subjects with prehypertension (OR = 1.50, 95% CI: 0.55-4.09), stage 1 HT (OR = 1.56, 95% CI: 0.56-4.32) and stage 2 HT (OR = 2.96, 95% CI: 1.09-8.05). Non-normal BP explained 45% (33.7/75) of impaired ADL. A positive relation of BP categories with the composite end point of mortality and impaired ADL was also observed. In conclusion, controlling BP in middle age may prevent deaths and future ADL decline.

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Prognostic value of Q wave for cardiovascular death in a 19-year prospective study of the Japanese general population

Higashiyama Aya, Hozawa Atsushi, Murakami Yoshitaka, Okamura Tomonori, Watanabe Makoto, Nakamura Yasuyuki, Hayakawa Takehito, Kadowaki Takashi, Kita Yoshikuni, Okayama Akira, Ueshima Hirotsugu, Iimura Osamu, Omae Teruo, Ueda Kazuo, Horibe Hiroshi, Kodama Kazunori, Kasagi Fumiyoshi, Tanihara Shinichi, Saitoh Shigeyuki, Sakata Kiyomi, Nakamura Yosikazu, Kakuno Fumihiko, Takeuchi Toshihiro, Hasebe Mitsuru, Kusano Fumitsugu, Kawamoto Takahisa, Minowa Masumi, Kawaminami Katsuhiko, Choudhury Sohel R., Kiyohara Yutaka, Iida Minoru, Hashimoto Tsutomu, Terao Atsushi, Sawai Koryo, Shibata Shigeo

Journal of Atherosclerosis and Thrombosis 16 ( 1 ) 40 - 50 2009

ISSN 1340-3478

Aim: Little is known about the prognostic value of q wave abnormality for cardiovascular disease (CVD) on a resting electrocardiogram (ECG) of the Japanese general population with an extremely low incidence of myocardial infarction. Methods: We followed 8,339 participants without a past and present history of CVD for 19 years. The multivariate-adjusted hazard ratio (HR) of q wave abnormality for CVD mortality was estimated by the Cox proportional hazards model. Results: The multivariate-adjusted HR of composite findings of moderate or severe q wave abnormality was 1.75 (95% confidence interval (CI): 0.97-3.17) for mortality due to CVD and 2.97 (95%CI: 1.43-6.16) due to heart diseases. The multivariate-adjusted HR of mild abnormality for mortality from heart diseases was 1.95 (95%CI: 1.00-3.81). The relationship between moderate or severe abnormalities and mortality from CVD was unchanged when participants with ST-T changes and high amplitude R waves were excluded and when participants were divided by the presence of major CVD risk factors such as hypertension. Q wave abnormality was not associated with the risk of stroke. Conclusion: Moderate or severe q wave abnormalities are prominent and important predictors of mortality due to CVD and heart disease in the Japanese general population without CVD history.

A Japanese diet and 19-year mortality

Nakamura Yasuyuki, Ueshima Hirotsugu, Okamura Tomonori, Kadowaki Takashi, Hayakawa Takehito, Kita Yoshikuni, Abbott Robert D., Okayama Akira

British Journal of Nutrition 101 ( 11 ) 1696 - 1705 2009

ISSN 0007-1145

Few studies have examined the association between Japanese diet and mortality outcomes. We analysed the relationship between a healthy Japanese diet and all-cause and cause-specific mortality using the database from the National Integrated Project for Prospective Observation of Non-Communicable Diseases and its Trends in the Aged, 1980. At baseline in 1980, data were collected on study participants aged ≧30 years from randomly selected areas in Japan. We defined a measure of a healthy reduced-salt Japanese diet based on seven components from FFQ. The total score ranged from 0 to 7, with 0 being least healthy and 7 being most healthy. Participants were divided into approximate tertiles of dietary scores (0-2, 3 and 4-7 scores). After excluding participants with co-morbidities, we followed 9086 participants (44% men) for 19 years. There were 1823 all-cause and 654 cardiovascular deaths during the follow-up. With the dietary score group 0-2 serving as a reference, the Cox multivariate-adjusted hazard ratios for groups with scores 3 and 4-7 were 0.92 (95% CI 0.83, 1.04) and 0.78 (95% CI 0.70, 0.88) for all-cause mortality (trend P<0.0001), and 0.91 (95% CI 0.75, 1.10) and 0.80 (95% CI 0.66, 0.97) for cardiovascular mortality (trend P = 0.022). Adherence to a healthy reduced-salt Japanese diet was associated with an approximate 20% lower rate of all-cause and cardiovascular mortality.

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Effect of chronic kidney disease on individual and population medical expenditures in the Japanese population

Higashiyama Aya, Okamura Tomonori, Watanabe Makoto, Murakami Yoshitaka, Otsuki Hidemi, Adachi Noriko, Kaneko Chiaki, Uehara Emi, Okayama Akira, Ueshima Hirotsugu

Hypertension Research 32 ( 6 ) 450 - 454 2009

ISSN 0916-9636

Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD), and may also lead to an increase in medical expenditures. The effect of CKD on individual and population medical expenditures was examined in a Japanese cohort study. The participants included 4026 Japanese National Health Insurance beneficiaries aged 40-74 years living in one city, who had no history of major CVD. They were classified into three categories according to their glomerular filtration rate (GFR) at the baseline survey, and their total medical expenditures were followed-up for 3 years. The arithmetic and geometric means of the cumulative medical expenditures were calculated for each category. The geometric mean was also expressed after adjusting for several confounding factors using analysis of covariance. The CKD-related medical expenditures attributable to the participants with mild (60 ≤ GFR<90) or moderate (30 ≤ GFR<60) kidney dysfunction were compared with those of participants with normal (GFR < 90) kidney function. There was a negative correlation between the GFR category and the arithmetic and geometric means of personal medical expenditures (adjusted geometric mean: GFR < 90, 167879 yen; 60 ≤GFR <90, 210660 yen; and 30 ≤ GFR<60, 330050 yen). The CKD-related medical expenditures accounted for 11.5 and 6.5% of the total medical expenditures for the participants with mild and moderate kidney dysfunction, respectively. The prevention of mild CKD is very important for containing medical expenditures. Appropriate strategies, such as regular creatinine measurement, are needed for early detection of CKD.

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The taste of salt measured by a simple test and blood pressure in Japanese women and men

Michikawa Takehiro, Nishiwaki Yuji, Okamura Tomonor, Asakura Keiko, Nakano Makiko, Takebayashi Toru

Hypertension Research 32 ( 5 ) 399 - 403 2009

ISSN 0916-9636

Salt intake is an important risk factor for hypertension. Because it has been reported that increased salt intake dulls the taste of salt, measuring the sense of taste might be a good way of identifying individuals who consume excessive salt. Using a recently developed simple salt taste test, we investigated the relationship between the taste of salt and blood pressure. The subjects in this cross-sectional study were 823 Japanese adults (479 women and 344 men) 40 years old or older. Following a taste test with salt-impregnated taste strips, the subjects were divided into two groups: normal (recognition threshold of salt at <1.0% concentration) and taste impaired (≥1.0%). We determined hypertension from the measured blood pressure. In women, the multi-adjusted odds ratio (95% CI) of hypertension in the impaired group was 2.47 (1.53-3.99) compared with the normal group, whereas no significant difference was observed between the two male groups. When we excluded subjects with moderate and severe hypertension, similar findings were observed. A sub-analysis of couples living alone showed a higher prevalence of hypertension among men whose wives were in the impairment group (58.8%) than in the normal group (36.7%, P=0.10). In conclusion, the taste of salt is associated with blood pressure in Japanese women, but not in men. Because most family meals in Japan are prepared by women, educating women about salt reduction may contribute to the prevention of hypertension, not only among women but also among their husbands and family members.

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Cardiovascular disease and risk factors in Asia

Ueshima Hirotsugu, Sekikawa Akira, Miura Katsuyuki, Turin Tanvir Chowdhury, Takashima Naoyuki, Kita Yoshikuni, Watanabe Makoto, Kadota Aya, Okuda Nagako, Kadowaki Takashi, Nakamura Yasuyuki, Okamura Tomonori

Circulation 118 ( 25 ) 2702 - 2709 2008.12

ISSN 0009-7322

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Risk Factor Effects and Total Mortality in Older Japanese Men in Japan and Hawaii

Abbott Robert D., Ueshima Hirotsugu, Hozawa Atsushi, Okamura Tomonori, Kadowaki Takashi, Miura Katsuyuki, Okuda Nagako, Nakamura Yasuyuki, Okayama Akira, Kita Yoshikuni, Rodriguez Beatriz L., Yano Katsuhiko, Curb J. David

Annals of Epidemiology 18 ( 12 ) 913 - 918 2008.12

ISSN 1047-2797

purpose: We sought to identify factors related to total mortality in older Japanese men in Japan and Hawaii. Methods: Baseline data were collected from 1980 to 1982 in 1379 men in Hawaii and 954 men in Japan. Ages ranged from 61 to 81 years, with mortality follow-up during a 19-year period. Results: Compared with Japan, men in Hawaii had a 2-fold excess of diabetes and a 4-fold excess of prevalent coronary heart disease (P < .001). Total cholesterol and body mass index were also greater in Hawaiian men (P < .001). In contrast, men in Japan had greater systolic blood pressure and were nearly 3 times more likely to smoke cigarettes (P < .001). Although each cohort had elements of a poor risk factor profile, there was a 1.4-fold excess in the risk of death in Japan (49.4 vs. 36.2/1,000 person-years, P < .001). Although mortality was similar after risk factor adjustment, only blood pressure and cigarette smoking accounted for the higher risk of death in Japan. Conclusions: Cigarette smoking and hypertension explain much of the excess mortality in Japan versus Hawaii. In this comparison of genetically similar cohorts, evidence further suggests that Japanese in Japan are equally susceptible to develop the same adverse risk factor conditions that exist in Hawaii. © 2008 Elsevier Inc. All rights reserved.

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Medical expenditure for diabetic patients

Nakamura K., Okamura T., Kanda H., Hayakawa T., Murakami Y., Okayama A., Ueshima H.

Public Health 122 ( 11 ) 1226 - 1228 2008.11

ISSN 0033-3506

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Impact of high-normal blood pressure on the risk of cardiovascular disease in a Japanese urban cohort

Kokubo Yoshihiro, Kamide Kei, Okamura Tomonori, Watanabe Makoto, Higashiyama Aya, Kawanishi Katsuyuki, Okayama Akira, Kawano Yuhei

Hypertension 52 ( 4 ) 652 - 659 2008.10

ISSN 0194-911X

Few prospective studies have examined the association between high-normal blood pressure and cardiovascular disease (CVD) in Asia. We examined the impact of high-normal blood pressure on the incidence of CVD in a general urban population cohort in Japan. We studied 5494 Japanese individuals (ages 30 to 79 years without CVD at baseline) after completing a baseline survey who received follow-up through December 2005. Blood pressure categories were defined on the basis of the ESH-ESC 2007 criteria. In 64 391 person-years of follow-up, we documented the incidence of 346 CVD events. The frequencies of high-normal blood pressure and hypertension Stage 1 and Stage ≥2 were 18.0%, 20.1%, and 10.1% for men and 15.9%, 15.6%, and 8.8% for women, respectively. Antihypertensive drug users were also classified into the baseline blood pressure categories. Compared with the optimal blood pressure group, the multivariable hazard ratios (95% confidence intervals) of CVD for normal and high-normal blood pressure and hypertension Stage 1 and Stage ≥2 were 2.04 (1.19 to 3.48), 2.46 (1.46 to 4.14), 2.62 (1.59 to 4.32), and 3.95 (2.37 to 6.58) in men and 1.12 (0.59 to 2.13), 1.54 (0.85 to 2.78), 1.35 (0.75 to 2.43), and 2.86 (1.60 to 5.12) in women, respectively. The risks of myocardial infarction and stroke for each blood pressure category were similar to those of CVD. Population-attributable fractions of high-normal blood pressure and hypertension for CVD were 12.2% and 35.3% in men and 7.1% and 23.4% in women, respectively. In conclusion, high-normal blood pressure is a risk factor for the incidence of stroke and myocardial infarction in a general urban population of Japanese men. © 2008 American Heart Association, Inc.

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Marine-Derived n-3 Fatty Acids and Atherosclerosis in Japanese, Japanese-American, and White Men. A Cross-Sectional Study

Sekikawa Akira, Curb J. David, Ueshima Hirotsugu, El-Saed Aiman, Kadowaki Takashi, Abbott Robert D., Evans Rhobert W., Rodriguez Beatriz L., Okamura Tomonori, Sutton-Tyrrell Kim, Nakamura Yasuyuki, Masaki Kamal, Edmundowicz Daniel, Kashiwagi Atsunori, Willcox Bradley J., Takamiya Tomoko, Mitsunami Ken ichi, Seto Todd B., Murata Kiyoshi, White Roger L., Kuller Lewis H.

Journal of the American College of Cardiology 52 ( 6 ) 417 - 424 2008.08

ISSN 0735-1097

Objectives: We sought to examine whether marine-derived n-3 fatty acids are associated with less atherosclerosis in Japanese versus white populations in the U.S. Background: Marine-derived n-3 fatty acids at low levels are cardioprotective through their antiarrhythmic effect. Methods: A population-based cross-sectional study in 281 Japanese (defined as born and living in Japan), 306 white (defined as white men born and living in the U.S.), and 281 Japanese-American men (defined as Japanese men born and living in the U.S.) ages 40 to 49 years was conducted to assess intima-media thickness (IMT) of the carotid artery, coronary artery calcification (CAC), and serum fatty acids. Results: Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar levels. Japanese had 2-fold higher levels of marine-derived n-3 fatty acids than whites and Japanese Americans in the U.S. Japanese had significant and nonsignificant inverse associations of marine-derived n-3 fatty acids with IMT and CAC prevalence, respectively. The significant inverse association with IMT remained after adjusting for traditional cardiovascular risk factors. Neither whites nor Japanese Americans had such associations. Significant differences between Japanese and whites in multivariable-adjusted IMT (mean difference 39 μm, 95% confidence interval [CI]: 21 to 57μm, p < 0.001) and CAC prevalence (mean difference 10.7%, 95% CI: 2.9% to 18.4%, p = 0.007) became nonsignificant after we adjusted further for marine-derived n-3 fatty acids (22 μm, 95% CI: -1 to 46 μm, p = 0.065 and 5.0%, 95% CI: -5.3% to 15.4%, p = 0.341, respectively). Conclusions: Very high levels of marine-derived n-3 fatty acids have antiatherogenic properties that are independent of traditional cardiovascular risk factors and may contribute to lower the burden of atherosclerosis in Japanese, a lower burden that is unlikely the result of genetic factors. © 2008 American College of Cardiology Foundation.

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Relation of dietary and other lifestyle traits to difference in serum adiponectin concentration of Japanese in Japan and Hawaii

Nakamura Yasuyuki, Ueshima Hirotsugu, Okuda Nagako, Higashiyama Aya, Kita Yoshikuni, Kadowaki Takashi, Okamura Tomonori, Murakami Yoshitaka, Okayama Akira, Choudhury Sohel Reza, Rodriguez Beatriz, Curb J. David, Stamler Jeremiah

American Journal of Clinical Nutrition 88 ( 2 ) 424 - 430 2008.08

ISSN 0002-9165

Background: In initial analyses, we found significant differences between serum adiponectin in Japanese living in Japan and Hawaii. Objective: We investigated whether differences in dietary and other lifestyle factors explain higher serum adiponectin concentrations in Japanese in Japan compared with Japanese emigrants living a Western lifestyle in Hawaii. Design: Serum adiponectin and nutrient intakes were examined by standardized methods in men and women aged 40-59 y from 2 population samples, one Japanese American in Hawaii (99 men, 104 women), the other Japanese in central Japan (124 men, 125 women). Multiple linear regression models were used to assess the role of dietary and other lifestyle traits in accounting for serum adiponectin difference between Hawaii and Japan. Results: Mean adiponectin was significantly higher in Japan than in Hawaii (10.5 ± 5.5 μg/mL compared with 6.7 ± 3.2 μg/mL in men, P = 0.002; 12.9 ± 5.9 μg/mL compared with 9.4 ± 4.2 in women, P < 0.0001). In men, the difference in body mass index (BMI; in kg/m²) in the 2 populations explained ≈90% of the difference in serum adiponectin; in women, only 29%. In multiple linear regression analyses in women further adjustment for physical activity and 4 nutrients (nonvegetable protein, n-3 polyunsaturated fatty acid, arachidonic acid, dietary cholesterol) produced a further reduction in the coefficient for the difference (total 56%); P value for the difference became 0.074. Conclusions: The significantly higher mean serum adiponectin concentration in Japan than in Hawaii may be attributable largely to differences in BMI. Differences in nutrient intake in the 2 samples were associated with only modest relation to the adiponectin difference. © 2008 American Society for Nutrition.

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