Details of a Researcher - Miyagawa, Naoko

Papers - Miyagawa, Naoko

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肥満、非肥満別の各種循環器疾患危険因子による循環器疾患死亡の集団寄与危険割合　NIPPON DATA80の29年追跡結果より

宮澤伊都子, 三浦克之, 宮本恵宏, 岡村智教, 東山綾, 辰巳友佳子, 門田文, 高嶋直敬, 宮川尚子, 近藤慶子, 佐藤敦, 有馬久富, 岡山明, 上島弘嗣, NIPPON DATA80研究グループ

日本循環器病予防学会誌 ((一社)日本循環器病予防学会) 52 ( 3 ) 269 - 278 2017.12

Research paper (scientific journal), ISSN 1346-6267

【背景】我が国では、2008年より特定健診が開始され、肥満を必須とするメタボリックシンドローム該当者に対する保健指導介入が行われている。残る非肥満に対する有効な介入方法が模索されているが、肥満、非肥満別に循環器疾患危険因子による循環器疾患死亡の集団寄与危険割合を検討した報告は少ない。【目的】循環器疾患危険因子(血圧、血糖、喫煙)による循環器疾患死亡の集団寄与危険割合(Population Attributable Fraction:PAF)を非肥満群、肥満群に分けて検討する。【方法】対象は1980年に実施された循環器疾患基礎調査の受検者を29年間追跡したNIPPON DATA80対象者のうち、40歳〜74歳の男女計6,662人である。肥満の有無と循環器疾患危険因子のカテゴリーを組み合わせて対象者を分類し、"非肥満かつ循環器疾患危険因子正常群"に対する、各群の多変量調整ハザード比とPAFを算出した。PAFはより現在に近い2010年の危険因子の分布でも算出し、1980年との比較を行った。【結果】循環器疾患死亡に対する多変量調整ハザード比(95%信頼区間)は、血圧は正常、正常高値、高血圧1度、高血圧2度以上と上昇するに従い、非肥満群、肥満群ともに上昇を認めた(非肥満かつ高血圧2度以上群:2.10(1.64-2.70)、肥満かつ高血圧2度以上群:2.72(1.95-3.80)。血糖は正常(随時血糖140mg/dl未満)、境界型(140-200mg/dl)、糖尿病域(200mg/dl以上)と上昇するに従い、非肥満群、肥満群ともに上昇を認めた(非肥満かつ糖尿病域群:2.01(1.33-3.03)、肥満かつ糖尿病域群5.08(2.98-8.66)。喫煙は非喫煙、過去喫煙、現在喫煙(≦20本/日、≦21本/日)の順に上昇を認めた(非肥満かつ現在喫煙≦21本/日群:1.94(1.47-2.55)、肥満かつ現在喫煙≧21本/日群:1.98(1.24-3.15)。2010年の危険因子分布を用いた血圧のPAF合計は非肥満群37.2%、肥満群21.7%、血糖のPAF合計は非肥満群14.4%、肥満群16.3%、喫煙のPAF合計は非肥満群7.0%、肥満群0.9%と、いずれにおいても非肥満群のPAFは肥満群と同等もしくは高値を示した。【結論】各種循環器疾患危険因子は非肥満群、肥満群のどちらにおいても循環器疾患死亡リスクと関連していた。PAFは非肥満群の方が肥満群よりも大きい傾向であり、非肥満者に対しても循環器疾患危険因子に対する介入が重要であることが示唆された。(著者抄録)

Food sources of dietary sodium in the Japanese adult population: the international study of macro-/micronutrients and blood pressure (INTERMAP)

Nagako Okuda, Akira Okayama, Katsuyuki Miura, Katsushi Yoshita, Shigeyuki Saito, Hideaki Nakagawa, Kiyomi Sakata, Naoko Miyagawa, Queenie Chan, Paul Elliott, Hirotsugu Ueshima, Jeremiah Stamler

EUROPEAN JOURNAL OF NUTRITION (SPRINGER HEIDELBERG) 56 ( 3 ) 1269 - 1280 2017.04

Research paper (scientific journal), Accepted, ISSN 1436-6207

Purpose It is often reported that Na intake levels are higher in Japan than in western countries. Detailed analysis of food intake and its association with Na intake are necessary for supporting further decreases in Na consumption in Japan. We investigated the association between Na and food intake by food group using data from the Japanese participants of the INTERMAP Study.
Method Results from the Japanese participants of the INTERMAP Study who did not use antihypertensive medication and/or consume a reduced Na diet were used (531 men and 518 women, aged 40-59 years), obtained from four 24-h dietary recalls and two 24-h urine collections from each participant. We developed a classification system with 46 food group classifications; food consumption and Na intake from these groups were compared across quartiles of participants determined by 24-h urinary Na excretion per unit of body weight (UNa/BW).
Results Average daily Na intake from Japanese high-Na foods was 2552 mg/day. Participants with a higher UNa/BW consumed a significantly greater amount of high-Na Japanese foods, such as salted fish (P= 0.001) and miso soup (P < 0.001). They also had greater amount of rice (P = 0.001). Participants with lower UNa/BW consumed a significantly greater amount of western foods, such as bread (P < 0.001) and milk and dairy products (P < 0.001).
Conclusions Detailed analyses of various Japanese and western food intakes in addition to Na intake were performed. These results can be used to help draw up effective programs for the reduction in Na intake and prevention of prehypertension/hypertension in the Japanese population.

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Significant inverse association of equol-producer status with coronary artery calcification but not dietary isoflavones in healthy Japanese men

Vasudha Ahuja, Katsuyuki Miura, Abhishek Vishnu, Akira Fujiyoshi, Rhobert Evans, Maryam Zaid, Naoko Miyagawa, Takashi Hisamatsu, Aya Kadota, Tomonori Okamura, Hirotsugu Ueshima, Akira Sekikawa

BRITISH JOURNAL OF NUTRITION (CAMBRIDGE UNIV PRESS) 117 ( 2 ) 260 - 266 2017.01

Research paper (scientific journal), Accepted, ISSN 0007-1145

Equol, a metabolite of the dietary isoflavone daidzein, is produced by the action of gut bacteria in some individuals who are termed as equol-producers. It is proposed to have stronger atheroprotective properties than dietary isoflavones. We examined a cross-sectional association of dietary isoflavones and equol-producer status with coronary artery calcification (CAC), a biomarker of coronary atherosclerosis, among men in Japan. A population-based sample of 272 Japanese men aged 40-49 years recruited from 2004 to 2007 was examined for serum isoflavones, serum equol, CAC and other factors. Equol-producers were classified as individuals having a serum level of equol >83 nm. The presence of CAC was defined as a coronary Ca score 10 Agatston units. The associations of dietary isoflavones and equol-producers with CAC were analysed using multiple logistic regression. The median of dietary isoflavones, equol and CAC were 5127 (interquartile range (IQR) 1941, 11700), 91 (IQR 010, 331) and 00 (IQR 00, 10) nm, respectively. Prevalence of CAC and equol-producers was 96 and 160 %, respectively. Dietary isoflavones were not significantly associated with CAC. After multivariable adjustment, the OR for the presence of CAC in equol-producers compared with equol non-producers was 010 (95 % CI 001, 090, P<004). Equol-producers had significantly lower CAC than equol non-producers, but there was no significant association between dietary isoflavones and CAC, suggesting that equol may be a key factor for atheroprotective properties of isoflavones in Japanese men. This finding must be confirmed in larger studies or clinical trials of equol that is now available as a dietary supplement.

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Overall nutrient and total fat intake among Japanese people: The INTERLIPID Study Japan

Tatsuya Koyama, Katsushi Yoshita, Nagako Okuda, Shigeyuki Saitoh, Kiyomi Sakata, Akira Okayama, Hideaki Nakagawa, Naoko Miyagawa, Katsuyuki Miura, Queenie Chan, Paul Elliott, Jeremiah Stamler, Hirotsugu Ueshima

ASIA PACIFIC JOURNAL OF CLINICAL NUTRITION (H E C PRESS, HEALTHY EATING CLUB PTY LTD) 26 ( 5 ) 837 - 848 2017

Research paper (scientific journal), Accepted, ISSN 0964-7058

Background and Objectives: Total fat intake is linked to the intake of other nutrients. Little data are available on the extent to which total fat affects diet quality in Japanese people. We investigated the relationship between total fat intake and other nutrient intake using INTERLIPID/INTERMAP data on Japanese people living in Japan. Methods and Study Design: The participants included 371 men and 401 women with a healthy body mass index and between the ages of 40 and 59 from 4 population samples in Japan. Nutrient intake data were based on four in-depth 24-hour dietary recalls per person. Results: Analysis of covariance adjusted for age revealed that total fat intake was positively related to intakes of calcium, thiamine, riboflavin, meat, eggs, and milks and dairy products for both sexes. Total fat intake was inversely associated with carbohydrate and cereals intake for both sexes. On average, men with total fat intake between 25.0 and 27.4% of total energy had saturated fatty acids above 7%, which is the upper limit recommended for preventing lifestyle-related diseases. Men with total fat intake less than 20% of total energy had a higher risk of not meeting the Dietary Reference Intakes for Japanese (2015) for some nutrients. Conclusions: Total fat intake was positively associated with calcium, thiamine, and riboflavin intakes and inversely associated with carbohydrate intake. Our results suggest that in 40-59-year-old men with a healthy body mass index, total fat intake between 20 and 27% of total energy may best support adequate intake of other nutrients.

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Lifetime cigarette smoking is associated with abdominal obesity in a community-based sample of Japanese men: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).

Akira Fujiyoshi, Katsuyuki Miura, Sayaka Kadowaki, Koichiro Azuma, Sachiko Tanaka, Takashi Hisamatsu, Hisatomi Arima, Aya Kadota, Naoko Miyagawa, Naoyuki Takashima, Takayoshi Ohkubo, Yoshino Saitoh, Sayuki Torii, Itsuko Miyazawa, Hiroshi Maegawa, Kiyoshi Murata, Hirotsugu Ueshima

Preventive medicine reports 4 225 - 32 2016.12

Research paper (scientific journal), Accepted, ISSN 2211-3355

Studies from Western countries suggest that smokers tend to display greater abdominal obesity than non-smokers, despite showing lower weight. Whether this holds true in a leaner population requires clarification. Using indices of abdominal obesity including visceral adipose tissue, we examined whether lifetime cigarette smoking is associated with unfavorable fat distribution among Japanese men. From 2006 to 2008, we conducted a cross-sectional investigation of a community-based sample of Japanese men at 40-64 years old, free of cardiovascular diseases and cancer. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography. We divided participants into four groups: never-smokers; and tertiles of pack-years of smoking among ever-smokers. Using multivariable linear regression, we calculated adjusted means of obesity indices (VAT, SAT, VAT-SAT ratio [VSR], and waist-hip ratio [WHR]) for each group, and mean differences between consecutive groups. We analyzed 513 men (median age, 58.2 years; current smokers, 40.1%). Two-thirds showed body mass index (BMI) < 25 kg/m(2) (median, 23.5 kg/m(2)). Overall, greater lifetime smoking group was associated with greater WHR and VSR. On average, one higher smoking group was associated with 0.005 higher WHR (95% CI, 0.001-0.008; P = 0.005) and 0.041 greater VSR (95% CI, 0.009-0.073; P = 0.012) after adjustment for potential confounders, including BMI. In this sample of relatively lean Japanese men, greater lifetime smoking was associated with a metabolically more adverse fat distribution. Although smoking is commonly associated with lower BMI, minimizing the amount of lifetime smoking should be advocated.

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一般国民における循環器疾患危険因子の認知度および危険因子保有と認知度との関連 NIPPON DATA2010

永井雅人, 大久保孝義, 門田文, 宮川尚子, 村上義孝, 高嶋直敬, 奥田奈賀子, 東山綾, 早川岳人, 藤吉朗, 中村好一, 岡村智教, 上島弘嗣, 岡山明, 三浦克之

日本循環器病予防学会誌 ((一社)日本循環器病予防学会) 51 ( 3 ) 166 - 175 2016.11

Research paper (scientific journal), ISSN 1346-6267

【目的】循環器疾患危険因子の正しい知識を持つ者ほど、循環器疾患発症に予防的な健康行動をとることが報告されている。そこで本研究では本邦国民における循環器疾患危険因子の認知度を明らかにするとともに、危険因子保有と認知度との関連を検討した。【方法】平成22年国民健康・栄養調査に参加した全国300地区からの20歳以上の男女2,891名に対し、「心筋梗塞または脳卒中の原因として正しいと思うもの」を選択する質問調査を実施した。正答は高血圧、糖尿病、高コレステロール血症、喫煙、不整脈、HDLコレステロール低値である。ロジスティック回帰分析で、各危険因子の保有者をそれぞれの非保有者と比較し、危険因子を認知している年齢調整オッズ比を算出した。【結果】循環器疾患危険因子の認知度はそれぞれ、85.8%(高血圧)、72.6%(高コレステロール血症)、58.5%(喫煙)、49.8%(不整脈)、45.1%(糖尿病)、38.5%(HDLコレステロール低値)であった。男性では、各危険因子の非保有者を基準とした時、高血圧者の高血圧認知度、高コレステロール血症を有する者の高コレステロール血症認知度、過去の喫煙習慣を有する者で喫煙に関する認知度、糖尿病者の糖尿病認知度が有意に高かった(オッズ比1.33〜2.73)。女性では、高コレステロール血症を有する者の高コレステロール血症認知度、過去の喫煙習慣を有する者で喫煙に関する認知度、糖尿病者の糖尿病認知度が有意に高かった(オッズ比1.54〜1.80)。【結論】循環器疾患危険因子の認知度は、高血圧で8割を超える一方、不整脈、糖尿病、HDLコレステロール低値では5割に満たなかった。また、危険因子保有者は保有する危険因子が循環器疾患危険因子であることを認知している傾向が観察されたが、その他の危険因子の認知度は非保有者と同程度、または低い傾向であった。国民に対する循環器疾患危険因子の周知が必要である。(著者抄録)

Relationship between non-high-density lipoprotein cholesterol and the long-term mortality of cardiovascular diseases: NIPPON DATA 90

Takahiro Ito, Hisatomi Arima, Akira Fujiyoshi, Katsuyuki Miura, Naoyuki Takashima, Takayoshi Ohkubo, Aya Kadota, Takehito Hayakawa, Yoshikuni Kita, Naoko Miyagawa, Akira Okayama, Tomonori Okamura, Hirotugu Ueshima

INTERNATIONAL JOURNAL OF CARDIOLOGY (ELSEVIER IRELAND LTD) 220 262 - 7 2016.10

Research paper (scientific journal), Accepted, ISSN 0167-5273

Background: Non-high-density lipoprotein (HDL) cholesterol level, generally less affected by fasting status or serum triglyceride levels, may be useful for predicting future cardiovascular events in daily clinical practice. This study aimed to investigate the role of non-HDL cholesterol in the development of fatal coronary events and stroke in the general Japanese population.
Methods and results: From the NIPPON DATA 90 prospective cohort study, 8383 participants were followed up for 20 years since 1990. After exclusion of 666 cases without lipid or covariates data, 561 cases who were 75 years old or older, 274 cases with history of cardiovascular disease, and 181 cases with lipid-lowering treatment, 6701 participants were included in this analysis. Non-HDL cholesterol was defined as total cholesterol minus HDL cholesterol. Outcomes were death from coronary heart disease and stroke. During the period, 69 participants died from coronary heart disease and 112 from stroke. Compared with participants with non-HDL cholesterol level b3.9 mmol/L, age- and sex-adjusted hazard ratios for mortality by coronary heart disease in those with non-HDL cholesterol levels of 3.9-4.3 mmol/L, 4.4-4.8 mmol/L and >= 4.9 mmol/L were 1.27 (95% confidence interval [CI] 0.65-2.49), 1.81 (95% CI 0.92-3.55) and 2.40 (95% CI 1.30-4.43), respectively (P trend = 0.010). This association remained significant even after adjusting for other cardiovascular risk factors (P trend = 0.010). There was no clear association between non-HDL cholesterol levels and mortality by stroke (P trend= 0.052).
Conclusions: Among the general Japanese population, non-HDL cholesterol levels were clearly associated with future mortality by coronary heart disease, but not by stroke. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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

Maryam Zaid, Katsuyuki Miura, Akira Fujiyoshi, Robert D. Abbott, Takashi Hisamatsu, Aya Kadota, Hisatomi Arima, Sayaka Kadowaki, Sayuki Torii, Naoko Miyagawa, Sentaro Suzuki, Naoyuki Takashima, Takayoshi Ohkubo, Akira Sekikawa, Hiroshi Maegawa, Minoru Horie, Yasuyuki Nakamura, Tomonori Okamura, Hirotsugu Ueshima

JOURNAL OF CLINICAL LIPIDOLOGY (ELSEVIER SCIENCE INC) 10 ( 5 ) 1195 - 1202.e1 2016.09

Research paper (scientific journal), Accepted, ISSN 1933-2874

BACKGROUND: Low-density lipoprotein particle (LDL-P) has recently been found to be a stronger predictor of cardiovascular disease (CVD) than LDL-cholesterol (LDL-C).
OBJECTIVES: Whether LDL-P is associated with subclinical atherosclerosis, independent of LDLC, as well as other lipid measures has not been fully examined. We aimed to analyze LDL-P associations with measures of subclinical atherosclerosis.
METHODS: We examined 870 Japanese men randomly selected from Kusatsu City, Shiga, Japan, aged 40-79 years from 2006-2008, free of clinical CVD and not using lipid-lowering medication. Cross-sectional associations of lipid measures with carotid intima-media thickness (cIMT) and coronary artery calcification (CAC; >0 Agatston score) were examined.
RESULTS: LDL-P was significantly positively associated with cIMT and maintained this association after adjustments for LDL-C and other lipid measures. Although these lipid measures were positively associated with cIMT, model adjustment for LDL-P removed any significant relationships. Higher LDL-P was associated with a significantly higher odds ratio of CAC and further adjustment for LDL-C did not affect this relationship. In contrast, the LDL-C association with CAC was no longer significant after adjustment for LDL-P. Other lipid measures attenuated associations of LDL-P with CAC. Likewise, associations of these measures with CAC were attenuated when model adjustments for LDL-P were made.
CONCLUSIONS: In a community-based sample of Japanese men, free of clinical CVD, LDL-P was a robust marker for subclinical atherosclerosis, independent of LDL-C and other lipid measures. Associations of LDL-C and other lipid measures with either cIMT or CAC were generally not independent of LDL-P. (C) 2016 National Lipid Association. All rights reserved.

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Smoking, Smoking Cessation, and Measures of Subclinical Atherosclerosis in Multiple Vascular Beds in Japanese Men

Takashi Hisamatsu, Katsuyuki Miura, Hisatomi Arima, Aya Kadota, Sayaka Kadowaki, Sayuki Torii, Sentaro Suzuki, Naoko Miyagawa, Atsushi Sato, Masahiro Yamazoe, Akira Fujiyoshi, Takayoshi Ohkubo, Takashi Yamamoto, Kiyoshi Murata, Robert D. Abbott, Akira Sekikawa, Minoru Horie, Hirotsugu Ueshima

JOURNAL OF THE AMERICAN HEART ASSOCIATION (WILEY-BLACKWELL) 5 ( 9 ) 2016.08

Research paper (scientific journal), Accepted, ISSN 2047-9980

Background-Smoking is an overwhelming, but preventable, risk factor for cardiovascular diseases (CVD), although smoking prevalence remains high in developed and developing countries in East Asia.
Methods and Results-In a population-based sample of 1019 Japanese men aged 40 to 79 years, without CVD, we examined cross-sectional associations of smoking status, cumulative pack-years, daily consumption, and time since cessation, with subclinical atherosclerosis at 4 anatomically distinct vascular beds, including coronary artery calcification, carotid intima-media thickness (CIMT) and plaque, aortic artery calcification (AoAC), and ankle-brachial index. Current, former, and never smoking were present in 32.3%, 50.0%, and 17.7%, respectively. Compared to never smokers, current smokers had significantly higher risks of subclinical atherosclerosis in all 4 circulations (eg, odds ratios for coronary artery calcification >0, 1.79 [95% CIs, 1.16-2.79]; CIMT >1.0 mm, 1.88 [1.02-3.47]; AoAC >0, 4.29 [2.30-7.97]; and ankle-brachial index <1.1, 1.78 [1.16-2.74]) and former smokers did in carotid and aortic circulations (CIMT >1.0 mm, 1.94 [1.13-3.34]; and AoAC >0, 2.55 [1.45-4.49]). Dose-response relationships of pack-years and daily consumption, particularly with CIMT, carotid plaque, AoAC, and ankle-brachial index, were observed among both current and former smokers, and even a small amount of pack-years or daily consumption among current smokers was associated with coronary artery calcification and AoAC, whereas time since cessation among former smokers was linearly associated with lower burdens of all atherosclerotic indices.
Conclusions-Cigarette smoking was strongly associated with subclinical atherosclerosis in multiple vascular beds in Japanese men, and these associations attenuated with time since cessation.

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

Yasuyuki Nakamura, Hirotsugu Ueshima, Nagako Okuda, Katsuyuki Miura, Yoshikuni Kita, Naoko Miyagawa, Katsushi Yoshita, Hideaki Nakagawa, Kiyomi Sakata, Shigeyuki Saitoh, Tomonori Okamura, Akira Okayama, Sohel R. Choudhry, Beatriz Rodriguez, Kamal H. Masaki, Queenie Chan, Paul Elliott, Jeremiah Stamler

EUROPEAN JOURNAL OF NUTRITION (SPRINGER HEIDELBERG) 55 ( 4 ) 1515 - 24 2016.06

Research paper (scientific journal), Accepted, ISSN 1436-6207

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

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Lipoprotein-associated phospholipase A(2) is related to risk of subclinical atherosclerosis but is not supported by Mendelian randomization analysis in a general Japanese population

Hirotsugu Ueshima, Takashi Kadowaki, Takashi Hisamatsu, Akira Fujiyoshi, Katsuyuki Miura, Takayoshi Ohkubo, Akira Sekikawa, Aya Kadota, Sayaka Kadowaki, Yasuyuki Nakamura, Naoko Miyagawa, Tomonori Okamura, Yoshikuni Kita, Naoyuki Takashima, Atsunori Kashiwagi, Hiroshi Maegawa, Minoru Horie, Takashi Yamamoto, Takeshi Kimura, Toru Kita

ATHEROSCLEROSIS (ELSEVIER IRELAND LTD) 246 141 - 7 2016.03

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

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme predominantly bound to low-density lipoprotein (LDL). Lp-PLA2 is recognized as playing a key role in inflammatory processes and the development of atherosclerosis. This study aimed to investigate whether Lp-PLA2 is related to subclinical atherosclerosis, independently from traditional risk factors, in a general Japanese population by analyses of both the observational study and Mendelian randomization using V279F polymorphism.
Methods and results: We cross-sectionally examined community-based sample of 929 Japanese men aged 40-79 years, without statin treatment, who were randomly selected from the resident registration. Multiple regression analyses of Lp-PLA2 activity and concentration were undertaken separately for men aged 40-49 years and 50-79 years, to clarify interactions of age and Lp-PLA2. Lp-PLA2 activity for men aged 50-79 years was significantly and positively related to intima-media thickness (IMT) (P = 0.013) and plaque index (P = 0.008) independent of traditional risk factors including small LDL particles, but not to coronary artery calcification (CAC) score. Associations with Lp-PLA2 concentration were qualitatively similar to those of activity. Corresponding relationships were not observed in men aged 40e49 years. Mendelian randomization analyses based on V279F genotype did not show any significant associations with subclinical atherosclerosis, although the homozygote and heterozygote of V279F showed low LpPLA2 activity and concentration.
Conclusions: Lp-PLA2 activity in Japanese men aged 50-79 years was associated significantly and positively with IMT and plaque in the carotid artery but Mendelian randomization did not support that LpPLA2 is a causative factor for subclinical atherosclerosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

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Serum level of LOX-1 ligand containing ApoB is associated with increased carotid intima-media thickness in Japanese community-dwelling men, especially those with hypercholesterolemia LOX-1 ligand and IMT in Japanese

Tomonori Okamura, Katsuyuki Miura, Tatsuya Sawamura, Aya Kadota, Takashi Hisamatsu, Akira Fujiyoshi, Naomi Miyamatsu, Naoyuki Takashima, Naoko Miyagawa, Takashi Kadowaki, Takayoshi Ohkubo, Yoshitaka Murakami, Yasuyuki Nakamura, Hirotsugu Ueshima

JOURNAL OF CLINICAL LIPIDOLOGY (ELSEVIER SCIENCE INC) 10 ( 1 ) 172 - 80.e1 2016.01

Research paper (scientific journal), Accepted, ISSN 1933-2874

BACKGROUND: The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than usual lipid parameters; however, the relationship between LAB and carotid intima-media thickness (IMT) was not clear even in Asian populations.
METHODS: A total of 992 community-dwelling Japanese men, aged 40 to 79 years, were enrolled in the present study. Serum LAB levels were measured by enzyme-linked immunosorbent assays (ELISAs) with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody.
RESULTS: Serum LAB levels (median [interquartile range], mu g cs/L) were 5341 mu g cs/L (4093-7125). The mean average IMT of the common carotid artery was highest in the fourth LAB quartile (842 mu m) compared with the first quartile (797 mu m) after adjustment for age, high-density lipoprotein cholesterol, triglyceride, body mass index, hypertension, diabetes, high sensitivity C-reactive protein, smoking, and alcohol drinking. However, this statistically significant difference was lost after further adjustment for total cholesterol (TC). After stratification using the combination of median LAB and hypercholesterolemia (serum TC >= 6.21 mmol/L and/or lipid-lowering medication), the adjusted mean average IMT (standard error) in the high LAB/hypercholesterolemia group was 886 mu m (12.7), 856 mu m (16.7) in the low LAB/hypercholesterolemia group, and 833 mu m (8.4) in the low LAB/normal cholesterol group (P = .004). After further adjustment for TC, mean average IMT in the high LAB group was significantly higher than that measured in the low LAB group in hypercholesterolemic participants not taking lipid-lowering medication.
CONCLUSION: Serum LAB was associated with an increased carotid IMT in Japanese men, especially those with hypercholesterolemia. (C) 2016 National Lipid Association. All rights reserved.

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Association of Total Energy Intake with 29-Year Mortality in the Japanese: NIPPON DATA80

Masato Nagai, Takayoshi Ohkubo, Katsuyuki Miura, Akira Fujiyoshi, Nagako Okuda, Takehito Hayakawa, Katsushi Yoshita, Yusuke Arai, Hideaki Nakagawa, Koshi Nakamura, Naoko Miyagawa, Naoyuki Takashima, Aya Kadota, Yoshitaka Murakami, Yasuyuki Nakamura, Robert D. Abbott, Tomonori Okamura, Akira Okayama, Hirotsugu Ueshima

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS (JAPAN ATHEROSCLEROSIS SOC) 23 ( 3 ) 339 - 54 2016

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

Aim: In animals, dietary energy restriction is reported to increase longevity, whereas in humans, all cohort studies from Western countries have not shown an association between the low energy intake and longevity. We examined the association between total energy intake and longevity in Japan where dietary pattern is different from that in the West.
Methods: A total of 7,704 Japanese aged 30-69 years were followed from 1980 to 2009. Participants were divided into the quintiles of total energy (kcal/day) based on data collected from the National Nutrition Survey. Hazard ratios and 95% confidence intervals (CIs) were derived through the use of Cox proportional hazards models to compare the risk of death across and between the quintiles.
Results: There was a significant association between increased energy intake and all-cause mortality risk in only men (P for linear trend 0.008). In cause-specific analysis, compared with the lowest quintile, there was rise in coronary heart disease (CHD) mortality among men (HR; 2.63, 95% CI; 0.95-7.28, P for linear trend 0.016) and women (HR; 2.91, 95% CI; 1.02-8.29, P for linear trend 0.032) and cancer mortality among men (HR; 1.50, 95% CI; 0.999-2.24, P for linear trend 0.038) in the top quintile.
Conclusion: We observed significant associations of high energy intake with all-cause and cancer mortality among men and with CHD mortality among men and women. Further studies are needed to confirm the benefits of caloric restriction.

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

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

Hypertension research : official journal of the Japanese Society of Hypertension 38 ( 11 ) 790 - 5 2015.11

Research paper (scientific journal), ISSN 0916-9636

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

Maryam Zaid, Akira Fujiyoshi, Katsuyuki Miura, Robert D. Abbott, Tomonori Okamura, Naoyuki Takashima, Sayuki Torii, Yoshino Saito, Takashi Hisamatsu, Naoko Miyagawa, Takayoshi Ohkubo, Aya Kadota, Akira Sekikawa, Hiroshi Maegawa, Yasuyuki Nakamura, Kenichi Mitsunami, Hirotsugu Ueshima

ATHEROSCLEROSIS (ELSEVIER IRELAND LTD) 239 ( 2 ) 444 - 50 2015.04

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

Objective: The association of high-density lipoprotein particle (HDL-P) with atherosclerosis may be stronger than that of HDL-cholesterol (HDL-C) and independent of conventional cardiovascular risk factors. Whether associations persist in populations at low risk of coronary heart disease (CHD) remains unclear. This study examines the associations of HDL-P and HDL-C with carotid intima-media thickness (cIMT) and plaque counts among Japanese men, who characteristically have higher HDL-C levels and a lower CHD burden than those in men of Western populations.
Methods: We cross-sectionally examined a community-based sample of 870 Japanese men aged 40-79 years, free of known clinical cardiovascular disease (CVD) and not on lipid-lowering medication. Participants were randomly selected among Japanese living in Kusatsu City in Shiga, Japan.
Results: Both HDL-P and HDL-C were inversely and independently associated with cIMT in models adjusted for conventional CHD risk factors, including low-density lipoprotein cholesterol (LDL-C) and diabetes. HDL-P maintained an association with cIMT after further adjustment for HDL-C (P < 0.01), whereas the association of HDL-C with cIMT was noticeably absent after inclusion of HDL-P in the model. In plaque counts of the carotid arteries, HDL-P was significantly associated with a reduction in plaque count, whereas HDL-C was not.
Conclusion: HDL-P, in comparison to HDL-C, is more strongly associated with measures of carotid atherosclerosis in a cross-sectional study of Japanese men. Findings demonstrate that, HDL-P is a strong correlate of subclinical atherosclerosis even in a population at low risk for CHD. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

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

N. Okuda, K. Miura, A. Okayama, T. Okamura, R. D. Abbott, N. Nishi, A. Fujiyoshi, Y. Kita, Y. Nakamura, N. Miyagawa, T. Hayakawa, T. Ohkubo, Y. Kiyohara, H. Ueshima

EUROPEAN JOURNAL OF CLINICAL NUTRITION (NATURE PUBLISHING GROUP) 69 ( 4 ) 482 - 488 2015.04

Accepted, ISSN 0954-3007

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

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Association between Pulse Wave Velocity and Coronary Artery Calcification in Japanese men the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA)

Sayuki Torii, Hisatomi Arima, Takayoshi Ohkubo, Akira Fujiyoshi, Aya Kadota, Naoyuki Takashima, Sayaka Kadowaki, Takashi Hisamatsu, Yoshino Saito, Naoko Miyagawa, Maryam Zaid, Yoshitaka Murakami, Robert D. Abbott, Minoru Horie, Katsuyuki Miura, Hirotsugu Ueshima

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS (JAPAN ATHEROSCLEROSIS SOC) 22 ( 12 ) 1266 - 77 2015

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

Aim: Pulse wave velocity (PWV) is a simple and valid clinical method for assessing arterial stiffness. Coronary artery calcification (CAC) is an intermediate stage in the process leading to overt cardiovascular disease (CVD) and an established determinant of coronary artery disease. This study aimed to examine the association between PWV and CAC in a population-based sample of Japanese men.
Methods: This is a cross-sectional study of 986 randomly selected men aged 40-79 years from Shiga, Japan. CVD-free participants were examined from 2006 to 2008. Brachial-ankle PWV (baPWV) was measured using an automatic waveform analyzer. CAC was assessed using computed tomography. Agatston scores >= 10 were defined as the presence of CAC.
Results: Prevalence of CAC progressively increased with rising levels of baPWV: 20.6%, 41.7%, 56.3%, and 66.7% across baPWV quartiles < 1378, 1378-1563, 1564-1849, and > 1849 cm/s (P < 0.001 for trend). Associations remained significant after adjusting for age and other factors, including body mass index, systolic blood pressure, pulse rate, total and high-density lipoprotein cholesterol, hemoglobin A1c, drinking, smoking and exercise status, and the use of medication to treat hypertension, dyslipidemia and diabetes (P = 0.042 for trend). The optimal cutoff level of baPWV to detect CAC was 1612 cm/s using receiver operating characteristic curve analysis.
Conclusions: Arterial stiffness as defined by an elevated baPWV is associated with an increased prevalence of CAC in a general population-based setting among Japanese men.

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Lipoprotein particle profiles compared with standard lipids in association with coronary artery calcification in the general Japanese population

Takashi Hisamatsu, Akira Fujiyoshi, Katsuyuki Miura, Takayoshi Ohkubo, Aya Kadota, Sayaka Kadowaki, Takashi Kadowaki, Takashi Yamamoto, Naoko Miyagawa, Maryam Zaid, Sayuki Torii, Naoyuki Takashima, Yoshitaka Murakami, Tomonori Okamura, Minoru Horie, Hirotsugu Ueshima

ATHEROSCLEROSIS (ELSEVIER IRELAND LTD) 236 ( 2 ) 237 - 43 2014.10

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

Objective: The utility of lipoprotein particle profiles measured by nuclear magnetic resonance (NMR) spectroscopy beyond standard serum lipids remains inconclusive. Furthermore, few studies have compared NMR measurements with standard lipids in association with coronary artery calcification (CAC) in Japanese, where the coronary atherosclerotic burden is low. We examined whether NMR-based lipoprotein particle profiles are associated with CAC, and compared them with standard lipid and lipid ratios in the Japanese general population.
Methods and Results: We conducted a cross-sectional study in 851 men aged 40-79 years without cardiovascular diseases and lipid-lowering therapies. Adjusted odds ratios (ORs) (95% confidence intervals) for the top versus the bottom quartile of NMR-measured particle concentrations were 2.01 (1.24-3.23) for low-density lipoprotein (LDL-P), 1.04 (0.62-1.75) for high-density lipoprotein (HDL-P), 1.82 (1.13-2.95) for very-low-density lipoprotein (VLDL-P), and 1.92 (1.18-3.17) for LDL-P/HDL-P ratio. Similarly adjusted ORs of NMR-measured particle sizes were 0.59 (0.36-0.97) for LDL-P, 0.66 (0.40-1.10) for HDL-P, and 0.67 (0.40-1.12) for VLDL-P. The corresponding ORs were 1.82 (1.14-2.90) for total cholesterol (TC), 2.06 (1.28-3.30) for low-density lipoprotein cholesterol (LDL-C), 0.56 (0.34-0.91) for high-density lipoprotein cholesterol (HDL-C), 2.02 (1.24-3.29) for triglycerides, 2.08 (1.29-3.36) for non-high-density lipoprotein cholesterol (non-HDL-C), 2.27 (1.37-3.78) for TC/HDL-C ratio, and 1.73 (1.06-2.85) for LDL-C/HDL-C ratio. After mutual adjustment for total LDL-P concentration and TC/HDL-C ratio or non-HDL-C, LDL-P was no longer associated, whereas TC/HDL-C ratio remained significantly associated with CAC.
Conclusions: In community-based Japanese men, the overall association of CAC with NMR-measured lipoprotein indices is comparable, but not superior, to that with standard lipids. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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Low-carbohydrate diets and cardiovascular and total mortality in Japanese: a 29-year follow-up of NIPPON DATA80

Yasuyuki Nakamura, Nagako Okuda, Tomonori Okamura, Aya Kadota, Naoko Miyagawa, Takehito Hayakawa, Yoshikuni Kita, Akira Fujiyoshi, Masato Nagai, Naoyuki Takashima, Takayoshi Ohkubo, Katsuyuki Miura, Akira Okayama, Hirotsugu Ueshima

BRITISH JOURNAL OF NUTRITION (CAMBRIDGE UNIV PRESS) 112 ( 6 ) 916 - 24 2014.09

Research paper (scientific journal), ISSN 0007-1145

Long-term safety of consuming low-carbohydrate diets (LCD) in Asian populations, whose carbohydrate intake is relatively high, is not known. In the present study, the association of LCD with CVD and total mortality was assessed using data obtained in the NIPPON DATA80 (National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged 1980) during 29 years of follow-up. At baseline in 1980, data were collected from study participants aged >= 30 years from randomly selected areas in Japan. LCD scores were calculated based on the percentage of energy as carbohydrate, fat and protein, estimated by 3 d weighed food records. A total of 9200 participants (56% women, mean age 51 years) were followed up. During the follow-up, 1171 CVD deaths (52% in women) and 3443 total deaths (48% in women) occurred. The multivariable-adjusted hazard ratio (HR) for CVD mortality using the Cox model comparing the highest v. lowest deciles of LCD score was 0 60 (95% CI 0 38, 0 94; P-trend = 0 021) for women and 0 78 (95% CI 0 58, 1 05; P-trend = 0 079) for women and men combined; the HR for total mortality was 0 74 (95% CI 0 57, 0 95; P-trend = 0 029) for women and 0 87 (95% CI 0 74, 1 02; P-trend = 0 090) for women and men combined. None of the associations was statistically significant in men. No differential effects of animal-based and plant-fish-based LCD were observed. In conclusions, moderate diets lower in carbohydrate and higher in protein and fat are significantly inversely associated with CVD and total mortality in women.

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High long-chain n-3 fatty acid intake attenuates the effect of high resting heart rate on cardiovascular mortality risk: A 24-year follow-up of Japanese general population

Takashi Hisamatsu, Katsuyuki Miura, Takayoshi Ohkubo, Takashi Yamamoto, Akira Fujiyoshi, Naoko Miyagawa, Aya Kadota, Naoyuki Takashima, Nagako Okuda, Katsushi Yoshita, Yoshikuni Kita, Yoshitaka Murakami, Yasuyuki Nakamura, Tomonori Okamura, Minoru Horie, Akira Okayama, Hirotsugu Ueshima

JOURNAL OF CARDIOLOGY (ELSEVIER SCIENCE BV) 64 ( 3 ) 218 - 24 2014.09

Research paper (scientific journal), Accepted, ISSN 0914-5087

Background: Increased resting heart rate (RHR) independently predicts cardiovascular mortality. Meanwhile, long-chain n-3 fatty acids (LCn3FAs) have a cardioprotective effect. Our aim was to evaluate whether higher LCn3FAs intake attenuates the elevated risk of cardiovascular mortality associated with increased RHR.
Methods: We conducted a population-based 24-year prospective cohort study of Japanese, whose LCn3FAs intake is relatively high. Study participants included 8807 individuals aged 30-95 years from randomly selected areas across Japan without cardiovascular diseases and anti-hypertensive drugs at baseline. The primary endpoint was cardiovascular mortality, and the secondary endpoints were cardiac and stroke mortality during 24 years of follow-up. Individual dietary LCn3FAs intake was estimated from household-based 3-day weighed food records. RHR was obtained from 3 consecutive R-wave intervals on 12-lead electrocardiography. Cox models were used to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) adjusting for possible confounders.
Results: During the follow-up period, 617 cardiovascular deaths were observed. The median daily intake of LCn3FAs was 0.37% kcal (0.86 g/day). The interaction between dietary LCn3FAs intake and RHR in the risk of cardiovascular mortality was statistically significant (p = 0.033). The risk of cardiovascular mortality was significantly higher in the low-intake group (<0.37% kcal) with an RHR >85 beats/min (bpm) [hazard ratio (HR), 1.67; 95% confidence interval (CI), 1.15-2.43], but not in the high-intake group (>= 0.37% kcal) with an RHR >85 bpm (HR, 0.92; 95% CI, 0.61-1.38), compared with those in the high-intake group with an RHR <70 bpm. Similar results were observed with stroke mortality, but not with cardiac mortality.
Conclusions: The risk of cardiovascular mortality associated with increased RHR is elevated in participants with low dietary LCn3FAs intake, but not in participants with high dietary LCn3FAs intake in a representative Japanese general population. These results suggest that high dietary LCn3FAs intake may prevent cardiovascular mortality associated with increased RHR. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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