The international collaborative pharmacoepidemiological study on drugs for the treatment of lifestyle-related diseases.

• Project/Area Number: 18K06759
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Keio University (2019-2022); Showa Pharmaceutical University (2018)
• Principal Investigator: Hashimoto Azusa 慶應義塾大学, 薬学部(芝共立), 准教授 (20740426)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 生活習慣病 / 大規模医療情報データベース / 高血圧 / 高脂血症 / 糖尿病 / 薬剤疫学 / 降圧薬 / 糖尿病治療薬 / 脂質異常症治療薬

Outline of Final Research Achievements

This study was the international collaborative pharmacoepidemiological study on drugs for the treatment of lifestyle-related diseases.
First, we assessed antihypertensive drug effects according to the pretreatment self-measured home blood pressure using data from the HOMED-BP study. Second, we identified lifestyle behaviors that were associated with the initiation of renal replacement therapy among chronic kidney disease patients using a large-scale medical database. We also applied machine learning to large-scale medical data to try to predict the safety of drugs for the treatment of the lifestyle-related diseases.
Although research activities in Europe were not possible due to the COVID-19 pandemic, I performed several international collaborative activities, including a presentation about the joint research at an international conference and the publication of a review paper written together with international collaborators.

Academic Significance and Societal Importance of the Research Achievements

薬剤疫学研究の手法を用いて、生活習慣病薬の効果および副作用発現やそれらに関わる遺伝子多型を検討することで、生活習慣病薬の安全性および有効性に関するエビデンスを創出することができ、個人の特性にあった最適な個別化医療の実現へ貢献するものと期待される。
本研究で用いたHOMED-BP研究は、家庭血圧データを含む、精度の高い詳細な情報を有した類まれなデータベースを構築しており、本データに基づいて解析した結果は、非常に妥当性・信頼性の高いエビデンスとなることが期待できる。また、大規模診療報酬請求データを用いることで、発生数が少ない有害事象についての検討や機械学習の手法を用いた検討を行うことが可能となった。

Research Products

• [Int'l Joint Research] Erasmus Medical Centre(オランダ)
• [Int'l Joint Research] University of Leuven(ベルギー)
• [Int'l Joint Research] Erasmus Medical Centre(オランダ)
• [Int'l Joint Research] University of Leuven(ベルギー)
• [Int'l Joint Research] Erasumus Medical Centre(オランダ)
• [Int'l Joint Research] University of Leuven(ベルギー)
• [Int'l Joint Research] Erasumus Medical Centre(オランダ)
• [Int'l Joint Research] University of Leuven(ベルギー)
• [Int'l Joint Research] エラスムスメディカルセンター(オランダ)
• [Int'l Joint Research] ルーヴェン大学(ベルギー)
• [Journal Article] Female Reproductive Events and Subclinical Atherosclerosis of the Brain and Carotid Arteriopathy: the Ohasama Study (2023)
  • Author(s): Sato Wakana、Nomura Kyoko、Satoh Michihiro、Hara Azusa、Tsubota-Utsugi Megumi、Murakami Takahisa、Asayama Kei、Tatsumi Yukako、Kobayashi Yuki、Hirose Takuo、Inoue Ryusuke、Totsune Tomoko、Kikuya Masahiro、Hozawa Atsushi、Metoki Hirohito、Imai Yutaka、Watanabe Hiroyuki、Ohkubo Takayoshi
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 30 Issue: 8 Pages: 956-978
  • DOI: 10.5551/jat.63592
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2023-08-01
  • Peer Reviewed / Open Access
• [Journal Article] The long-term reproducibility of the white-coat effect on blood pressure as a continuous variable from the Ohasama Study (2023)
  • Author(s): Satoh Michihiro、Yoshida Tomoya、Metoki Hirohito、Murakami Takahisa、Tatsumi Yukako、Hirose Takuo、Takabatake Kyosuke、Tsubota-Utsugi Megumi、Hara Azusa、Nomura Kyoko、Asayama Kei、Kikuya Masahiro、Hozawa Atsushi、Imai Yutaka、Ohkubo Takayoshi
  • Journal Title: Scientific Reports Volume: 13 Issue: 1 Pages: 4985-4985
  • DOI: 10.1038/s41598-023-31861-9
  • Peer Reviewed / Open Access
• [Journal Article] Public and occupational health risks related to lead exposure updated according to present-day blood lead levels (2022)
  • Author(s): Yu Yu-Ling、Yang Wen-Yi、Hara Azusa、Asayama Kei、Roels Harry A.、Nawrot Tim S.、Staessen Jan A.
  • Journal Title: Hypertension Research Volume: 46 Issue: 2 Pages: 395-407
  • DOI: 10.1038/s41440-022-01069-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regular dental visits, periodontitis, tooth loss, and atherosclerosis: The Ohasama study (2022)
  • Author(s): Sho Yamada,Takamasa Komiyama,Takashi Ohi,Takahisa Murakami,Yoshitada Miyoshi,Kosei Endo,Takako Hiratsuka,Azusa Hara,Michihiro Satoh,Yukako Tatsumi,Ryusuke Inoue,Kei Asayama,Masahiro Kikuya,Atsushi Hozawa,Hirohito Metoki,Yutaka Imai,Takayoshi Ohkubo,Yoshinori Hattori
  • Journal Title: J Periodontal Res. Volume: in press Issue: 3 Pages: 1-8
  • DOI: 10.1111/jre.12990
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between urinary sodium-to-potassium ratio and home blood pressure and ambulatory blood pressure: the Ohasama study (2022)
  • Author(s): Muroya Tomoko、Satoh Michihiro、Murakami Takahisa、Nakayama Shingo、Asayama Kei、Hirose Takuo、Tatsumi Yukako、Inoue Ryusuke、Tsubota-Utsugi Megumi、Hara Azusa、Kogure Mana、Nakaya Naoki、Nomura Kyoko、Kikuya Masahiro、Metoki Hirohito、Imai Yutaka、Hozawa Atsushi、Ohkubo Takayoshi
  • Journal Title: Journal of Hypertension Volume: 40 Issue: 5 Pages: 862-869
  • DOI: 10.1097/hjh.0000000000003087
  • Peer Reviewed / Open Access
• [Journal Article] Association of home and office systolic and diastolic hypertension with glucose metabolism in a general population: the Ohasama study (2022)
  • Author(s): Tatsumi Yukako、Satoh Michihiro、Asayama Kei、Murakami Takahisa、Hirose Takuo、Hara Azusa、Tsubota-Utsugi Megumi、Inoue Ryusuke、Kikuya Masahiro、Nomura Kyoko、Metoki Hirohito、Hozawa Atsushi、Katagiri Hideki、Imai Yutaka、Ohkubo Takayoshi
  • Journal Title: Journal of Hypertension Volume: 40 Issue: 7 Pages: 1336-1343
  • DOI: 10.1097/hjh.0000000000003145
  • Peer Reviewed
• [Journal Article] Lifestyle Behaviors Associated with the Initiation of Renal Replacement Therapy in Japanese Patients with Chronic Kidney Disease: A Retrospective Cohort Study Using a Claims Database Linked with Specific Health Checkup Results (2021)
  • Author(s): Hara A, Hirata T, Okamura T, Kimura S, Urushihara H.
  • Journal Title: Environ Health Prev Med. Volume: 26 Issue: 1 Pages: 102-102
  • DOI: 10.1186/s12199-021-01022-3
  • Peer Reviewed / Open Access
• [Journal Article] Lifetime risk of stroke stratified by chronic kidney disease and hypertension in the general Asian population: the Ohasama study (2021)
  • Author(s): Nakayama Shingo、Satoh Michihiro、Metoki Hirohito、Murakami Takahisa、Asayama Kei、Hara Azusa、Hirose Takuo、Kanno Atsuhiro、Inoue Ryusuke、Tsubota-Utsugi Megumi、Kikuya Masahiro、Mori Takefumi、Hozawa Atsushi、Imai Yutaka、Ohkubo Takayoshi
  • Journal Title: Hypertension Research Volume: 44 Issue: 7 Pages: 866-873
  • DOI: 10.1038/s41440-021-00635-z
  • Peer Reviewed
• [Journal Article] Antihypertensive drug effects according to the pretreatment self-measured home blood pressure: the HOMED-BP study. (2020)
  • Author(s): Sano H, Hara A, Asayama K, Miyazaki S, Kikuya M, Imai Y, Ohkubo T.
  • Journal Title: BMJ Open. Volume: 10 Issue: 12 Pages: e040524-e040524
  • DOI: 10.1136/bmjopen-2020-040524
  • Peer Reviewed / Open Access
• [Journal Article] 【日本高血圧学会みらい医療計画(JSH Future Plan)-良い血圧で健やか100年人生-】高血圧のPrecision Medicine(精密医療) AI・ビッグデータ解析の高血圧みらい医療への応用 (2019)
  • Author(s): 原 梓, 大久保 孝義
  • Journal Title: Progress in Medicine Volume: 39 Pages: 869-871
• [Journal Article] Association Between Amplitude of Seasonal Variation in Self‐Measured Home Blood Pressure and Cardiovascular Outcomes: HOMED‐BP (Hypertension Objective Treatment Based on Measurement By Electrical Devices of Blood Pressure) Study (2018)
  • Author(s): Tomohiro Hanazawa, Kei Asayama, Daisuke Watabe, Ayumi Tanabe, Michihiro Satoh, Ryusuke Inoue, Azusa Hara, Taku Obara, Masahiro Kikuya, Kyoko Nomura, Hirohito Metoki, Yutaka Imai, Takayoshi Ohkubo, the HOMED‐BP (Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure) Investigators
  • Journal Title: J Am Heart Assoc. Volume: 7 Issue: 10
  • DOI: 10.1161/jaha.117.008509
  • Peer Reviewed / Open Access
• [Presentation] SGLT2阻害剤の重要な潜在的リスクに関する評価 (2023)
  • Author(s): 前川拓也, 原 梓, 漆原 尚巳
  • Organizer: 第14回日本臨床試験学会学術集会総会
• [Presentation] Real-time Survey of Vaccine Safety of the mRNA-1273 SARS-CoV-2 Vaccine in Workplace Vaccination at Keio University (2022)
  • Author(s): Azusa Hara, Kaho Okumura, Isa Inada, Daisuke Sugiyama, Takahiro Hoshino, Takahiro Yakoh, Hirokatsu Yokoyama, Hisashi Urushihara
  • Organizer: ICPE 2022: 38th International Conference for Pharmacoepidemiology
  • Int'l Joint Research
• [Presentation] 腎臓や循環器疾患の臨床研究実施において押さえておくべきポイント (2022)
  • Author(s): 原梓
  • Organizer: 第32回日本医療薬学会年会
  • Invited
• [Presentation] The Kawasaki Aging and Wellbeing Project のデータを用いた生活習慣病に関する診療報酬請求データによる疾患定義の妥当性の検討 (2022)
  • Author(s): 猪澤一樹, 原梓, 佐々木貴史, 安藤崇之, 阿部由紀子, 色本涼, 新井康通, 漆原尚巳
  • Organizer: 第27回日本薬剤疫学会学術総会
• [Presentation] BERT を用いた糖尿病治療薬における有害事象間の潜在的関連性の探索 (2022)
  • Author(s): 八重樫昇吾, 石川智貴, 安藤崇之, 原梓, 大石尚央, 漆原尚巳
  • Organizer: 第27回日本薬剤疫学会学術総会
• [Presentation] 機械学習を用いた降圧剤・高脂血症用剤の安全性リスクの予測 (2022)
  • Author(s): 佐立 悠, 原 梓, 漆原 尚巳
  • Organizer: 第42回医療情報学連合大会（第23回日本医療情報学会学術大会）
• [Presentation] 機械学習を用いた降圧薬および高脂血症用剤における潜在的リスクの予測 (2022)
  • Author(s): 佐立 悠, 漆原 尚巳, 原 梓
  • Organizer: 日本薬学会第142年会
• [Presentation] Lifetime risk of stroke stratified by chronic kidney disease and hypertension in an Asian general population: the Ohasama study (2021)
  • Author(s): Shingo Nakayama, Michihiro Satoh, Hirohito Metoki, Takahisa Murakami, Kei Asayama, Azusa Hara, Takuo Hirose, Atsuhiro Kanno, Ryusuke Inoue, Megumi Tsubota-Utsugi, Masahiro Kikuya, Takefumi Mori, Atsushi Hozawa, Yutaka Imai, Takayoshi Ohkubo
  • Organizer: Joint Meeting of the European Society of Hypertension (ESH) and International Society of Hypertension (ISH)
  • Int'l Joint Research
• [Presentation] 家庭血圧に基づく高血圧発症10年予測モデル ―大迫研究― (2021)
  • Author(s): 佐藤 倫広, 目時 弘仁, 浅山 敬, 菊谷 昌浩, 村上 任尚, 辰巳 友佳子, 原 梓, 廣瀬 卓男, 井上 隆輔, 野村 恭子, 寳澤 篤, 今井 潤, 大久保 孝義
  • Organizer: 第43回日本高血圧学会学術総会
• [Presentation] Daily Lifestyle Behaviors associated with Initiating of Renal Replacement Therapy in Japanese Patients with Chronic Kidney Disease: A Descriptive Study Using a Claims Database Linked with Specific Health Checkup Results. (2020)
  • Author(s): Kazuaki Enomoto, Azusa Hara, Nanae Tanemura, Takumi Hirata, Tomonori Okamura, Hisashi Urushihara
  • Organizer: ICPE 2020 All Access (36th International Conference on Pharmacoepidemiology and Therapeutic Risk Management)
  • Int'l Joint Research
• [Presentation] HOMEDBP Study (2019)
  • Author(s): Azusa Hara
  • Organizer: IDACO/IDHOCO/IDCARS Consortium Meeting 2019
  • Int'l Joint Research
• [Presentation] Impact of chronological changes in propensity to be exposed a comparison validity in health insurance claim database (2019)
  • Author(s): Daisuke Kato, Azusa Hara, Nanae Tanemura, Hisashi Urushihara
  • Organizer: ISPE's 12th Asian Conference on Pharmacoepidemiology and 25th Japanese Conference on Pharmacoepidemiology joint meeting
  • Int'l Joint Research
• [Presentation] 家庭血圧に基づく降圧度に関する検討－HOMED-BP研究－ (2018)
  • Author(s): 佐野ひかり、浅山敬、原梓、飯尾悠平、北澤貴博、宮崎生子、菊谷昌浩、今井潤、大久保孝義
  • Organizer: 第30回血圧管理研究会