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Assessment of quality of lipid parameters as a novel risk factor for cardiovascular diseases in community-based epidemiologic studies.

Research Project

Project/Area Number 16H05249
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Epidemiology and preventive medicine
Research InstitutionKeio University

Principal Investigator

OKAMURA Tomonori  慶應義塾大学, 医学部(信濃町), 教授 (00324567)

Co-Investigator(Kenkyū-buntansha) 東山 綾  国立研究開発法人国立循環器病研究センター, 病院, 医長 (20533003)
沢村 達也  信州大学, 学術研究院医学系, 教授 (30243033)
武林 亨  慶應義塾大学, 医学部(信濃町), 教授 (30265780)
大久保 孝義  帝京大学, 医学部, 教授 (60344652)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
KeywordsHDLコレステロール / LDLコレステロール / 酸化・変性脂質 / sLOX-1 / 疫学研究 / LDLコレステロール / HDLコレステロール / sLOX-1 / sLOX-1
Outline of Final Research Achievements

We have developed a novel ELISA by using recombinant LOX-1 and anti-apoA1 antibody to measure the activity of modified HDL(LOX-1 ligand containing apoA1, LAA). We selected 910 community-dwelling Japanese men aged 40-79 years and the multivariable adjusted odds ratio (95% confidence interval) per 1SD (standard deviation) of LAA for CAC (coronary artery calcification) was 1.14 (0.96-1.36) for all participants. Multivariable adjusted odds ratios per 1SD of LAA were 1.34 (1.02-1.76) and 0.97 (0.77-1.23) in men aged under 65 and 65 years and greater, respectively. Furthermore, we conducted a nested case-control study from a rural cohort study including 52 new incidences of atherosclerotic cardiovascular disease and 156 by matching with baseline year, sex age, and health check-up facility. In multivariable analysis, the matched odd ratio for the highest vs. lowest quartiles of LAA was 2.50 (0.70-8.86) and that for 1SD increment of LAA was 2.16 (1.28-3.64).

Academic Significance and Societal Importance of the Research Achievements

本研究では変性HDLとして世界で初めてLOX-1 ligand containing apolipoprotein AI(LAA)を測定する手法を開発した。そしてCTによる冠動脈石灰化、脳・心血管疾患の発症という異なるアウトカムとLAAとの関連を明らかにした。しかし冠動脈石灰化との関連は高齢者では認められず、横断研究としての限界を示した。また脳・心血管疾患発症との関連についてもコホートの追跡期間が短いため発症者数が少ないことなどが課題と考えられた。今後、LAAに対する治療介入の手法が重要となるが、喫煙者の場合、禁煙はLAA低下のために有用な介入手段であることが示唆された。

Report

(5 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (10 results)

All 2020 2019 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] The relationship between serum levels of LOX-1 ligand containing ApoAI as a novel marker of dysfunctional HDL and coronary artery calcification in middle-aged Japanese men.2020

    • Author(s)
      Hirata A, Kakino A, Okamura T, Usami Y, Fujita Y, Kadota A, Fujiyoshi A, Hisamatsu T, Kondo K, Segawa H, Sawamura T, Miura K, Ueshima H; SESSA Research Group.
    • Journal Title

      Atherosclerosis

      Volume: 313 Pages: 20-25

    • DOI

      10.1016/j.atherosclerosis.2020.09.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Cell-Free, Non-Fluorescent Method to Measure LOX-1-Binding Activity Corresponding to The Functional Activity of HDL2019

    • Author(s)
      Kakino A, Usami Y, Horiuchi S, Fujita Y, Kotanie K, Chenf CH, Okamura T, Sawamura T.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 26 Issue: 11 Pages: 947-958

    • DOI

      10.5551/jat.47183

    • NAID

      130007740412

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2019-11-01
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 日本の中年男性においてLOX-1 ligand containing ApoAIは冠動脈疾患と関連する.2020

    • Author(s)
      平田あや、垣野明美、岡村智教、門田文、藤吉朗、久松隆史、沢村達也、三浦克之、上島弘嗣.
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 血清変性HDLと脳卒中発症との関連:鶴岡メタボロームコホート研究.2020

    • Author(s)
      佐田みずき,飯田美穂,垣野明美,原田成,平田あや,桑原和代,杉山大典,宇佐美陽子,藤田佳子,大木宏一,伊澤良兼,高橋愼一,武林亨,沢村達也,岡村智教.
    • Organizer
      第45回日本脳卒中学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Serum modified HDL was associated with cardiovascular disease in a Japanese community-based cohort.2019

    • Author(s)
      Okamura T, Sata M, Iida M, Kakino A, Harada S, Hirata A, Kuwabara K, Sugiyama D, Sawamura T, Takabayashi T.
    • Organizer
      12th European Public Health Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Which traditional risk factors are associated with new onset of cardiovascular disease in the near future amongst Japanese community?2019

    • Author(s)
      Sata M, Sugiyama D, Hirata A, Harada S, Iida M, Takebayashi T, Okamura T.
    • Organizer
      First Asia-Pacific Congress on Cardiovascular Disease Prevention 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Serum modified HDL levels assessed by a novel assay was associated with coronary artery calcification in an apparently healthy population.2018

    • Author(s)
      Okamura T, Kakino A, Miura K, Fujiyoshi A, Kadota A, Fujita Y, Zaid M, Usami Y, Hisamatsu T, Horiuchi S, Kunimura A, Sugiyama D, Kondo K, Sawamura T and Ueshima H. Serum modified HDL levels assessed by a novel assay was associated with coronary artery calcification in an apparently healthy population.
    • Organizer
      European Society of Cardiology Congress, Munich 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 一般住民における飲酒量とHDL-C・変性HDLの関連:神戸研究.2018

    • Author(s)
      平田 匠, 垣野 明美, 東山 綾, 杉山 大典, 久保田 芳美, 西田 陽, 久保 佐智美, 宮松 直美, 宮本 恵宏, 沢村 達也, 岡村 智教.
    • Organizer
      第50回日本動脈硬化学会総会・学術集会(大阪)
    • Related Report
      2018 Annual Research Report
  • [Presentation] The effect of alcohol drinking and smoking on modified atherogenic high density lipoprotein cholesterol levels in a Japanese general population.2017

    • Author(s)
      Okamura T, Sawamura T, Miura K, Fujiyoshi A, Miyagawa N, Miyamastu N, Ueshima H.
    • Organizer
      European Society for Biomedical Research on Alcoholism Congress 2017, Crete, Greece
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 融合タンパク質、及びそれを用いた高密度リポタンパク質の測定キット2018

    • Inventor(s)
      沢村達也、垣野明美
    • Industrial Property Rights Holder
      国立大学法人信州大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-024007
    • Filing Date
      2018
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2022-01-27  

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