Shiina Kazuki, Tomiyama Hirofumi, Tanaka Atsushi, Yoshida Hisako, Eguchi Kazuo, Kario Kazuomi, Kato Toru, Teragawa Hiroki, Toyoda Shigeru, Ohishi Mitsuru, Fukumoto Yoshihiro, Takase Bonpei, Ishizu Tomoko, Node Koichi
Department of Cardiology, Tokyo Medical University, Tokyo, Japan.
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
Hypertens Res. 2022 Apr;45(4):602-611. doi: 10.1038/s41440-022-00857-9. Epub 2022 Feb 15.
Atherosclerosis and arterial stiffness are phenotypes of atherosclerotic vascular damage. Atherosclerosis originates from endothelial vascular damage and forms focal morphological lesions; arterial stiffness originates from diffuse medial-layer damage in the arterial tree. Thus, the two phenomena reflect different facets of atherosclerotic vascular damage, and they both gradually progress. We conducted a subanalysis to compare the long-term effects of febuxostat on atherosclerosis and arterial stiffness in the PRIZE study (a multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial to examine the effect of febuxostat on carotid atherosclerosis). Among 514 study participants, arterial stiffness parameters (brachial-ankle pulse wave velocity or cardio-ankle vascular index) were obtained at baseline, 12 months, and 24 months in 100 subjects. Among them, 48 subjects were allocated to the control group (i.e., nonpharmacological lifestyle modification for hyperuricemia), and 52 subjects were allocated to the febuxostat treatment group. While the decrease in serum uric acid was greater in the febuxostat group than in the control group, the adjusted percentage decrease in arterial stiffness parameters at month 24 was greater in the febuxostat group than in the control group, with a mean between-group difference (febuxostat - control) of -5.099% (95% confidence interval (CI) -10.009% to -0.188%, p = 0.042). Thus, long-term treatment with febuxostat may exert beneficial effects on arterial stiffness without improving carotid atherosclerosis. A long-term study to examine the effect of febuxostat on cardiovascular outcomes related to increased arterial stiffness is warranted.
动脉粥样硬化和动脉僵硬度是动脉粥样硬化性血管损伤的表型。动脉粥样硬化起源于内皮血管损伤并形成局灶性形态学病变；动脉僵硬度起源于动脉树的弥漫性中层损伤。因此，这两种现象反映了动脉粥样硬化性血管损伤的不同方面，并且它们都逐渐进展。我们在PRIZE研究（一项多中心、前瞻性、随机、开放标签、盲终点临床试验，旨在研究非布司他对颈动脉粥样硬化的影响）中进行了一项亚分析，以比较非布司他对动脉粥样硬化和动脉僵硬度的长期影响。在514名研究参与者中，100名受试者在基线、12个月和24个月时获得了动脉僵硬度参数（臂踝脉搏波速度或心踝血管指数）。其中，48名受试者被分配到对照组（即对高尿酸血症进行非药物生活方式干预），52名受试者被分配到非布司他治疗组。虽然非布司他组血清尿酸的降低幅度大于对照组，但在第24个月时，非布司他组动脉僵硬度参数的调整后降低百分比大于对照组，组间平均差异（非布司他组-对照组）为-5.099%（95%置信区间（CI）为-10.009%至-0.188%，p = 0.042）。因此，长期使用非布司他治疗可能对动脉僵硬度产生有益影响，而不会改善颈动脉粥样硬化。有必要进行一项长期研究，以考察非布司他对与动脉僵硬度增加相关的心血管结局的影响。
