心血管疾患発症予防を目的とした中性脂肪の治療目標値の推定

2021 Fiscal Year Annual Research Report

• Project/Area Number: 19K17599
• Research Institution: Hiroshima University
• Principal Investigator: 梶川 正人 広島大学, 病院(医), 助教 (80777293)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 中性脂肪 / 血管内皮機能

Outline of Annual Research Achievements

LDLコレステロールは心血管疾患発症の危険因子として確立しているが、LDLコレステロールに対する薬物治療を行っても心血管疾患発症リスクが残存する。昨年度までの研究で、中性脂肪が血管内皮機能障害の独立した規定因子であること、中性脂肪が150 mg/dLよりも低い106 mg/dL 以上の群で、すでに血管内皮機能が障害されていること、中性脂肪が正常高値 (100-150 mg/dL) の群は中性脂肪100 mg/dL未満の群と比較し複合心血管死(心血管死、心筋梗塞、脳梗塞、狭心症)が有意に多く認められたこと、年齢等の動脈硬化危険因子で補正を行っても中性脂肪が正常高値の群は複合心血管死の独立した危険因子であることを報告した。日本や外国における脂質異常症ガイドラインは、中性脂肪が150 mg/dL以下を正常と定義している。しかし、より低い中性脂肪の症例では血管内皮機能がどのようになっているのかが不明であった。そこで、FMD検査を行った7047例を中性脂肪の測定値で50 mg/dL未満、50-69 mg/dL、70-89 mg/dL、90-109 mg/dL、110-129 mg/dL、130-149 mg/dL、150-199 mg/dL 200 mg/dL以上に分けて中性脂肪と血管内皮機能との関係を検討した。結果、中性脂肪50 mg/dL未満の群が最も血管内皮機能が良好であった。
これらの成果より、中性脂肪はより低い値を目標に治療を行うことで心筋梗塞、脳梗塞などの血管合併症発症の抑制につながることが示唆された。

Research Products

• [Journal Article] Self-reported total sitting time on a non-working day is associated with blunted flow-mediated vasodilation and blunted nitroglycerine-induced vasodilation (2022)
  • Author(s): Yamaji T, Harada T, Hashimoto Y, Nakano Y, Kajikawa M, Yoshimura K, Chayama K, Goto C, Han Y, Mizobuchi A, Yusoff FM, Kishimoto S, Maruhashi T, Nakashima A, Higashi Y.
  • Journal Title: Sci Rep Volume: 12(1) Pages: 6366
  • DOI: 10.1038/s41598-022-10242-8.
  • Peer Reviewed / Open Access
• [Journal Article] Implantation of Hypoxia-Induced Mesenchymal Stem Cell Advances Therapeutic Angiogenesis (2022)
  • Author(s): Yusoff FM, Nakashima A, Kawano KI, Kajikawa M, Kishimoto S, Maruhashi T, Ishiuchi N, Abdul Wahid SFS, Higashi Y.
  • Journal Title: Stem Cells Int Volume: - Pages: 6795274
  • DOI: 10.1155/2022/6795274.
  • Peer Reviewed / Open Access
• [Journal Article] Poor tooth brushing behavior is associated with high risk of cardiovascular events: A prospective observational study (2022)
  • Author(s): Matsui S, Maruhashi T, Kishimoto S, Kajikawa M, Yusoff FM, Nakashima A, Taguchi A, Higashi Y.
  • Journal Title: Int J Cardiol . Volume: 350 Pages: 111-117
  • DOI: 10.1016/j.ijcard.2021.12.056.
  • Peer Reviewed
• [Journal Article] Isolated diastolic hypertension is not associated with endothelial dysfunction (2022)
  • Author(s): Han Y, Maruhashi T, Kajikawa M, Kishimoto S, Yamaji T, Harada T, Hashimoto Y, Yusoff FM, Nakano Y, Chayama K, Nakashima A, Goto C, Yoshimura K, Higashi Y.
  • Journal Title: Hypertens ResInt Volume: 45(4) Pages: 698-707
  • DOI: 10.1038/s41440-022-00854-y.
  • Peer Reviewed
• [Journal Article] Vascular Dysfunction Predicts Future Deterioration of Left Ventricular Ejection Fraction in Patients with Heart Failure with Mildly Reduced Ejection Fraction (2022)
  • Author(s): Kishimoto S, Maruhashi T, Kajikawa M, Harada T, Yamaji T, Han Y, Mizobuchi A, Hashimoto Y, Yoshimura K, Nakano Y, Chayama K, Goto C, Yusoff FM, Nakashima A, Higashi Y.
  • Journal Title: J Clin Med Volume: 10(24) Pages: 5980
  • DOI: 10.3390/jcm10245980.
  • Peer Reviewed / Open Access
• [Journal Article] Serum Potassium Levels of 4.5 to Less Than 5.0 mmol/L Are Associated with Better Vascular Function (2022)
  • Author(s): Maruhashi T, Kajikawa M, Kishimoto S, Takaeko Y, Yamaji T, Harada T, Hashimoto Y, Han Y, Aibara Y, Yusoff FM, Nakano Y, Chayama K, Nakashima A, Goto C, Yoshimura K, Higashi Y.
  • Journal Title: J Atheroscler Thromb Volume: - Pages: in press
  • DOI: 10.5551/jat.63285.
  • Peer Reviewed
• [Journal Article] Short stature is associated with low flow-mediated vasodilation in Japanese men (2022)
  • Author(s): Harada T, Kajikawa M, Maruhashi T, Kishimoto S, Yamaji T, Han Y, Mizobuchi A, Hashimoto Y, Yoshimura K, Nakano Y, Chayama K, Goto C, Yusoff FM, Nakashima A, Higashi Y.
  • Journal Title: Hypertens Res Volume: 45(2) Pages: 308-314
  • DOI: 10.1038/s41440-021-00785-0.
  • Peer Reviewed
• [Journal Article] Relationship between hemoglobin A1c level and flow-mediated vasodilation in patients with type 2 diabetes mellitus receiving antidiabetic drugs (2022)
  • Author(s): Yamaji T, Harada T, Hashimoto Y, Nakano Y, Kajikawa M, Yoshimura K, Aoki G, Chayama K, Goto C, Mizobuchi A, Han Y, Yusoff FM, Kishimoto S, Maruhashi T, Nakashima A, Higashi Y.
  • Journal Title: J Diabetes Investig Volume: 13(4) Pages: 677-686
  • DOI: 10.1111/jdi.13705.
  • Peer Reviewed
• [Journal Article] Falsely normalized ankle-brachial index despite the presence of lower-extremity peripheral artery disease: two case reports (2021)
  • Author(s): Maruhashi T, Matsui S, Yusoff FM, Kishimoto S, Kajikawa M, Higashi Y.
  • Journal Title: J Med Case Rep Volume: 15(1) Pages: 622
  • DOI: 10.1186/s13256-021-03155-z.
  • Peer Reviewed / Open Access
• [Journal Article] A body shape index is associated with endothelial dysfunction in both men and women (2021)
  • Author(s): Kajikawa M, Maruhashi T, Kishimoto S, Yamaji T, Harada T, Hashimoto Y, Han Y, Mizobuchi A, Aoki G, Yoshimura K, Chayama K, Goto C, Yusoff FM, Nakashima A, Higashi Y.
  • Journal Title: Sci Rep Volume: 11(1) Pages: 17873
  • DOI: 10.1038/s41598-021-97325-0.
  • Peer Reviewed / Open Access
• [Journal Article] Upstroke time as a marker of atherosclerosis in patients with diabetes mellitus who have a normal ankle-brachial index (2021)
  • Author(s): Maruhashi T, Kajikawa M, Kishimoto S, Takaeko Y, Yamaji T, Harada T, Hashimoto Y, Han Y, Yusoff FM, Nakano Y, Chayama K, Nakashima A, Goto C, Yoshimura K, Higashi Y.
  • Journal Title: J Diabetes Complications Volume: 35(11) Pages: 108044
  • DOI: 10.1016/j.jdiacomp.2021.108044.
  • Peer Reviewed
• [Journal Article] Low-intensity pulsed ultrasound decreases major amputation in patients with critical limb ischemia: 5-year follow-up study (2021)
  • Author(s): Mohamad Yusoff F, Kajikawa M, Yamaji T, Takaeko Y, Hashimoto Y, Mizobuchi A, Han Y, Kishimoto S, Maruhashi T, Nakashima A, Higashi Y.
  • Journal Title: PLoS One Volume: 16(8) Pages: e0256504
  • DOI: 10.1371/journal.pone.0256504.
  • Peer Reviewed / Open Access
• [Journal Article] Stair climbing activity and vascular function in patients with hypertension (2021)
  • Author(s): Yamaji T, Harada T, Hashimoto Y, Nakano Y, Kajikawa M, Yoshimura K, Chayama K, Goto C, Han Y, Mizobuchi A, Yusoff FM, Kishimoto S, Maruhashi T, Nakashima A, Higashi Y.
  • Journal Title: Hypertens Res Volume: 44(10) Pages: 1274-1282
  • DOI: 10.1038/s41440-021-00697-z.
  • Peer Reviewed
• [Journal Article] Inconvenient relationship of haemoglobin A1c level with endothelial function in type 2 diabetes in a cross-sectional study (2021)
  • Author(s): Yamaji T, Harada T, Hashimoto Y, Takaeko Y, Kajikawa M, Han Y, Maruhashi T, Kishimoto S, Hashimoto H, Kihara Y, Hida E, Chayama K, Goto C, Yusoff FM, Nakashima A, Higashi Y.
  • Journal Title: BMJ Open Volume: 11(6) Pages: e045415
  • DOI: 10.1136/bmjopen-2020-045415.
  • Peer Reviewed
• [Journal Article] Lower triglyceride levels are associated with better endothelial function (2021)
  • Author(s): Takaeko Y, Maruhashi T, Kajikawa M, Kishimoto S, Yamaji T, Harada T, Hashimoto Y, Han Y, Kihara Y, Chayama K, Goto C, Yusoff FM, Yoshimura K, Nakashima A, Higashi Y.
  • Journal Title: J Clin Lipidol Volume: 15(3) Pages: 500-511
  • DOI: 10.1016/j.jacl.2021.04.004.
  • Peer Reviewed
• [Journal Article] Spontaneous renal hemorrhage in acquired cystic kidney disease (2021)
  • Author(s): Kajikawa M, Tanji H, Higashi Y.
  • Journal Title: J Gen Fam Med Volume: 22(2) Pages: 94-95
  • DOI: 10.1002/jgf2.400.
  • Peer Reviewed
• [Journal Article] Smoking status and endothelial function in Japanese men (2021)
  • Author(s): Hashimoto H, Maruhashi T, Yamaji T, Harada T, Han Y, Takaeko Y, Kihara Y, Chayama K, Goto C, Aibara Y, Yusoff FM, Kishimoto S, Kajikawa M, Nakashima A, Higashi Y.
  • Journal Title: Sci Rep Volume: 11(1) Pages: 95
  • DOI: 10.1038/s41598-020-80012-x.
  • Peer Reviewed / Open Access
• [Journal Article] Promising Assessment of Vascular Function for Future Cardiovascular Events (2021)
  • Author(s): Kajikawa M, Higashi Y.
  • Journal Title: J Atheroscler Thromb Volume: 28(11) Pages: 1123-1125
  • DOI: 10.5551/jat.ED154.
  • Peer Reviewed
• [Journal Article] Volume Elastic Modulus, Vascular Function, and Vascular Structure in Patients with Cardiovascular Risk Factors (2021)
  • Author(s): Maruhashi T, Kajikawa M, Kishimoto S, Takaeko Y, Yamaji T, Harada T, Hashimoto Y, Han Y, Aibara Y, Mohamad Yusoff F, Chayama K, Nakashima A, Goto C, Nakano Y, Higashi Y.
  • Journal Title: J Atheroscler Thromb Volume: 28(9) Pages: 963-973
  • DOI: 10.5551/jat.59261.
  • Peer Reviewed
• [Journal Article] Association of Body Mass Index with Endothelial Function in Asian Men (2021)
  • Author(s): Kajikawa M, Maruhashi T, Kishimoto S, Hashimoto H, Takaeko Y, Yamaji T, Harada T, Hashimoto Y, Han Y, Kihara Y, Hida E, Chayama K, Goto C, Yusoff FM, Nakashima A, Higashi Y.
  • Journal Title: Int J Cardiol Volume: 324 Pages: 186-192
  • DOI: 10.1016/j.ijcard.2020.09.029.
  • Peer Reviewed
• [Presentation] Relationship between a Body Shape Index and Endothelial Function: FMD-Japan Registry (2022)
  • Author(s): Masato Kajikawa, Tatsuya Maruhashi, Shinji Kishimoto, Takayuki Yamaji, Takahiro Harada, Yu Hashimoto, Yiming Han, Farina Mohamad Yusoff, Ayumu Nakashima, Yukihito Higashi
  • Organizer: 第86回日本循環器学会学術集会
  • Int'l Joint Research
• [Presentation] Body Mass Index (BMI)と血管内皮機能との関係 (2022)
  • Author(s): 梶川 正人、丸橋 達也、岸本 真治、山路 貴之、原田 崇弘、橋本 悠、Farina Mohamad Yusoff、Yiming Han、中島 歩、東 幸仁
  • Organizer: 第7回日本血管不全学会学術集会
• [Presentation] Relationship between body mass index and endothelial function in men: FMD-Japan registry (2021)
  • Author(s): Masato Kajikawa, Tatsuya Maruhashi, Shinji Kishimoto, Yuji Takaeko, Takayuki Yamaji, Takahiro Harada, Yu Hashimoto, Yiming Han, Farina Mohamad Yusoff, Ayumu Nakashima, Yukihito Higashi
  • Organizer: 第85回日本循環器学会学術集会
  • Int'l Joint Research
• [Presentation] 改良型ezFMDで評価した血管内皮機能による新規イベント発症リスクの層別化 (2021)
  • Author(s): 梶川 正人、森本 陽香、橋本 悠、山路 貴之、原田 崇弘、岸本 真治、丸橋 達也、Farina Mohamad Yusoff、Yiming Han、中島 歩、辻 敏夫、東 幸仁
  • Organizer: 第6回日本血管不全学会学術集会
• [Presentation] 骨折リスクと血管機能との関係 (2021)
  • Author(s): 梶川 正人、橋本 悠、高永甲 有司、山路 貴之、原田 崇弘、岸本 真治、丸橋 達也、Farina Mohamad Yusoff、Yiming Han、中島 歩東 幸仁
  • Organizer: 第74回日本酸化ストレス学会第21回日本NO学会合同学術集会