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Reevaluation of cardiovascular risk factors for thrombotic events in 580 Japanese patients with essential thrombocythemia

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Abstract

Risk-adapted therapy is recommended to prevent thrombosis in essential thrombocythemia (ET) patients. An advanced age, a history of thrombosis, and the presence of the JAK2V617F mutation are well-defined risk factors for thrombosis in ET; however, the impact of cardiovascular risk (CVR) factors on thrombosis in ET remains elusive. Therefore, we herein investigated the impact of CVR factors on thrombosis in 580 ET patients who met the 2017 World Health Organization Classification diagnostic criteria. A univariate analysis identified hypertriglyceridemia and multiple CVR factors as strong risk factors for thrombosis (hazard ratio [HR] 3.530, 95% confidence interval [CI] 1.630–7.643, P = 0.001 and HR 3.368, 95% CI 1.284–8.833, P = 0.014, respectively) and hyper-LDL cholesterolemia as a potential risk factor (HR 2.191, 95% CI 0.966–4.971, P = 0.061). A multivariate analysis revealed that hypertriglyceridemia was an independent risk factor for thrombosis (HR 3.364, 95% CI 1.541–7.346, P = 0.002). Furthermore, poor thrombosis-free survival was observed in patients with a serum triglyceride level ≥ 1.2 mmol/L (HR = 2.592, P = 0.026 vs. < 1.2 mmol/L) or two or more CVR factors (P = 0.011 vs. no CVR factors and P = 0.005 vs. one CVR factor). These results revealed the impact of CVR factors on thrombosis in ET. Since CVR factors are manageable, lifestyle interventions, such as the control of serum triglyceride levels, may effectively prevent thrombosis in ET patients.

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Acknowledgements

We thank all members of the Department of Hematology, Department of Advanced Hematology, and Laboratory for the Development of Therapies against MPN at Juntendo University Graduate School of Medicine for sample collection and technical assistance. We sincerely thank all the institutions that participated in this study: Juntendo University Shizuoka Hospital; Juntendo University Urayasu Hospital; Sapporo Hokuyu Hospital; Juntendo University Nerima Hospital; Saiseikai Yokohama-shi Nanbu Hospital; Japanese Red Cross Narita Hospital; Chiba Aoba Municipal Hospital; Kansai Medical University Hospital; Nihon University Itabashi Hospital; Toyama City Hospital; Toyama Red Cross Hospital; Tokai University Hachioji Hospital; Aichi Medical University Hospital; Japanese Red Cross Society Nagano Hospital; Eiju General Hospital; Iwate Prefectural Central Hospital; Meirikai Chuo General Hospital; National Hospital Organization Disaster Medical Center; Tokyo Metropolitan Tama Medical Center; Teine Keijinkai Hospital; Tenshi Hospital; Toyama University Hospital; Jichi Medical University Saitama Medical Center; Atami Tokoro Memorial Hospital; Wakayama Medical University Hospital; Fukui Prefectural Hospital; Kochi Medical School Hospital; Toyama Prefectural Central Hospital; Chofu Touzan Hospital; Kawasaki Saiwai Clinic; Saga University Hospital; Kameda Medical Center; Japanese Red Cross Kyoto Daiichi Hospital; Japanese Red Cross Medical Center; Shinmatsudo Central General Hospital; Aizu Medical Center; Fukui-ken Saiseikai Hospital; Fukushima Medical University Hospital; Jichi Medical University Hospital; Kuwana City Medical Center; Matsuyama Red Cross Hospital; Saiseikai Fukushima General Hospital; and Sapporo Medical University Hospital.

Funding

JSPS KAKENHI Grant No. #20H03715. Research grants from FUJIFILM Wako Pure Chemical Corporation, Fuso Pharmaceutical, Pfizer, Pharma Essentia, Shire International GmbH, Perseus Proteomics, Meiji Seika Pharma, Nippon Shinyaku, and Astellas, and scholarship donations from Otsuka, Chugai, Kyowa Kirin, Takeda, Novartis, Sumitomo Pharma, and Bristol-Myers Squibb.

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  1. Department of Hematology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Chiho Furuya, Tadaaki Inano, Tomonori Ochiai, Shuichi Shirane, Yoko Edahiro, Miki Ando & Norio Komatsu

  2. Department of Hematology, Tottori Prefectural Central Hospital, 730 Ezu, Tottori City, Tottori, 680-0901, Japan

    Yoshinori Hashimoto

  3. Department of Advanced Hematology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Yoshinori Hashimoto, Soji Morishita, Tomonori Ochiai, Shuichi Shirane, Yoko Edahiro, Marito Araki & Norio Komatsu

  4. Laboratory for the Development of Therapies Against MPN, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Soji Morishita, Tomonori Ochiai, Shuichi Shirane, Yoko Edahiro, Marito Araki & Norio Komatsu

  5. PharmaEssentia Japan KK, 1-3-13 Motoakasaka, Minato-ku, Tokyo, 107-0051, Japan

    Norio Komatsu

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Contributions

CF, YH, SM, and NK planned this study, CF, YH, SM, and NK performed research and wrote the manuscript, SS, TI, YE, TO, MA, and MA supervised the study and revised the manuscript.

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Correspondence to Norio Komatsu.

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Araki is an employee of Meiji Seika Pharma and Komatsu has received a salary from PharmaEssentia Japan where he is a board member. All other authors declare no conflicts of interest.

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This study was approved by the Ethics Committee of the School of Medicine, Juntendo University (IRB#M12-0895) and was conducted in accordance with the 1975 Helsinki Declaration.

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Furuya, C., Hashimoto, Y., Morishita, S. et al. Reevaluation of cardiovascular risk factors for thrombotic events in 580 Japanese patients with essential thrombocythemia. J Thromb Thrombolysis 55, 263–272 (2023). https://doi.org/10.1007/s11239-022-02751-0

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