Assessment of HDL functionality for the prevention of acute coronary syndrome in patients with coronary artery disease

• Project/Area Number: 17K09553
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Showa University
• Principal Investigator: Shinke Toshiro 昭和大学, 医学部, 教授 (60379419)
• Co-Investigator(Kenkyū-buntansha): 石田 達郎 神戸大学, 医学研究科, 特命教授 (00379413)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 動脈硬化 / 低比重リポ蛋白 / 高比重リポ蛋白特異的コレステロール取込み能 / 光干渉断層映像法 / 炎症 / 血糖変動 / HDL機能 / 循環器・高血圧 / 内科 / 糖尿病 / 脂質

Outline of Final Research Achievements

Cholesterol efflux from atherosclerotic lesion is a key function of high-density lipoprotein (HDL). We evaluated the clinical implication of HDL Cholesterol uptake capacity (CUC) in patients treated with coronary artery disease. CUC has shown to be correlated with plaque vulnerability and in-stent neoatherosclerosis assessed by optical coherence tomography. This study demonstrated intensive lipid-lowering therapy using statin and eicosapentaenoic acid has enabled to stabilize vulnerable plaques and suppress the progression of neoatherosclerosis.

Academic Significance and Societal Importance of the Research Achievements

冠動脈疾患の一次予防、二次予防において、脂質低下療法はその根幹をなすが、低比重リポ蛋白（LDL）低下のみでは不十分であり、精度高く残余リスクをコントロールすることが重要である。今回の研究から、高比重リポ蛋白(HDL)特異的コレステロール取込み能 (Cholesterol uptake capacity: CUC)が、LDLとは独立して冠動脈プラークの脆弱化やステント内新規動脈硬化の進展に関与することが証明され、至適な治療戦略を立てる上で重要な指標となることが示された。

Research Products

• [Journal Article] Small Dense Low-Density Lipoprotein Cholesterol: A Residual Risk for Rapid Progression of Non-Culprit Coronary Lesion in Patients with Acute Coronary Syndrome (2021)
  • Author(s): Sekimoto Teruo、Koba Shinji、Shinke Toshiro
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 28 Issue: 11 Pages: 1161-1174
  • DOI: 10.5551/jat.60152
  • NAID: 130008110105
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2021-11-01
  • Peer Reviewed / Open Access
• [Journal Article] The impact of vildagliptin on the daily glucose profile and coronary plaque stability in impaired glucose tolerance patients with coronary artery disease: VOGUE?A multicenter randomized controlled trial (2021)
  • Author(s): Yamamoto Hiroyuki、Konishi Akihide、Shinke Toshiro、Otake Hiromasa、Kuroda Masaru、Osue Tsuyoshi、Sawada Takahiro、Takaya Tomofumi、Kawai Hiroya、Hashimoto Naoko、Ohara Takeshi、Hirota Yushi、Sakaguchi Kazuhiko、Omori Takashi、Ogawa Wataru、Hirata Ken-ichi
  • Journal Title: BMC Cardiovascular Disorders Volume: 21 Issue: 1
  • DOI: 10.1186/s12872-021-01902-0
  • NAID: 120006993640
  • Peer Reviewed / Open Access
• [Journal Article] Association of cholesterol uptake capacity, a novel indicator for HDL functionality, and coronary plaque properties: An optical coherence tomography-based observational study (2020)
  • Author(s): Oshita T、Toh R、Nagano Y、Kuroda K、Nagasawa Y、Harada A、Murakami K、Kiriyama M、Yoshikawa K、Miwa K、Kubo T、Iino T、Nagao M、Irino Y、Hara T、Shinohara M、Otake H、Shinke T、Nakajima K、Ishida T、Hirata Ken-ichi
  • Journal Title: Clinica Chimica Acta Volume: 503 Pages: 136-144
  • DOI: 10.1016/j.cca.2020.01.001
  • NAID: 120006824021
  • Peer Reviewed
• [Journal Article] Impact of daily glucose fluctuations on cardiovascular outcomes after percutaneous coronary intervention for patients with stable coronary artery disease undergoing lipid‐lowering therapy (2020)
  • Author(s): Yamamoto Hiroyuki、Shinke Toshiro、Otake Hiromasa、Kawamori Hiroyuki、Toba Takayoshi、Kuroda Masaru、Hirota Yushi、Sakaguchi Kazuhiko、Ogawa Wataru、Hirata Ken‐ichi
  • Journal Title: Journal of Diabetes Investigation Volume: - Issue: 6 Pages: 1015-1024
  • DOI: 10.1111/jdi.13448
  • NAID: 120007097045
  • Peer Reviewed / Open Access
• [Journal Article] Impaired Cholesterol‐Uptake Capacity of HDL Might Promote Target‐Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation (2019)
  • Author(s): Nagano Y, Otake H, Toba T, Kuroda K, Shinkura Y, Tahara N, Tsukiyama Y, Yanaka K, Yamamoto H, Nagasawa A, Onishi H, Sugizaki Y, Takeshige R, Harada A, Murakami K, Kiriyama M, Oshita T, Irino Y, Kawamori H, Ishida T, Toh R, Shinke T, Hirata KI.
  • Journal Title: Journal of the American Heart Association Volume: 8 Issue: 9
  • DOI: 10.1161/jaha.119.011975
  • NAID: 120006733129
  • Peer Reviewed / Open Access
• [Journal Article] Effect of rosuvastatin and eicosapentaenoic acid on neoatherosclerosis: the LINK-IT Trial (2019)
  • Author(s): Kuroda K, Otake H, Shinohara M, Kuroda M, Tsuda S, Toba T, Nagano Y, Toh R, Ishida T, Shinke T, Hirata KI.
  • Journal Title: EuroIntervention Volume: 15 Issue: 12 Pages: e1099-e1106
  • DOI: 10.4244/eij-d-18-01073
  • Peer Reviewed / Open Access
• [Journal Article] Data on impact of monocytes and glucose fluctuation on plaque vulnerability in patients with coronary artery disease (2018)
  • Author(s): Yamamoto H, Yoshida N, Shinke T, Otake H, Kuroda M, Sakaguchi K, Hirota Y, Toba T, Takahashi H, Terashita D, Uzu K, Tahara N, Shinkura Y, Kuroda K, Nagasawa Y, Nagano Y, Tsukiyama Y, Yanaka KI, Emoto T, Sasaki N, Yamashita T, Ogawa W, Hirata KI1
  • Journal Title: Data Brief. Volume: 18 Pages: 172-175
  • DOI: 10.1016/j.dib.2018.03.022
  • NAID: 120006543326
  • Peer Reviewed / Open Access
• [Journal Article] Impact of CD14++CD16+ monocytes on coronary plaque vulnerability assessed by optical coherence tomography in coronary artery disease patients. (2018)
  • Author(s): Yamamoto H, Yoshida N, Shinke T, Otake H, Kuroda M, Sakaguchi K, Hirota Y, Toba T, Takahashi H, Terashita D, Uzu K, Tahara N, Shinkura Y, Kuroda K, Nagasawa Y, Nagano Y, Tsukiyama Y, Yanaka KI, Emoto T, Sasaki N, Yamashita T, Ogawa W, Hirata KI.
  • Journal Title: Atherosclerosis Volume: 269 Pages: 245-251
  • Peer Reviewed