Nagasaki Toshiki, Inaba Masaaki, Kumeda Yasuro, Ueda Misako, Hiura Yoshikazu, Tahara Hideki, Ishimura Eiji, Onoda Naoyoshi, Ishikawa Tetsuro, Nishizawa Yoshiki
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Biomed Pharmacother. 2005 Jan-Feb;59(1-2):8-14. doi: 10.1016/j.biopha.2004.11.001. Epub 2004 Dec 24.
This study examined the effect of hypothyroidism on arterial stiffening and the effect of levothyroxine (l-T(4)) replacement. The arterial stiffness index beta (stiffness beta) and intima-media thickness (IMT), a parameter of arterial stiffening and thickening, respectively, were determined in common carotid artery (CCA) by ultrasonography in 30 hypothyroid patients before and after 1 year of normalization of thyroid function by l-T(4) replacement. Baseline CCA stiffness beta and IMT was significantly higher in the hypothyroid patients than in age- and sex-matched normal controls [9.46 +/- 0.93 vs. 8.02 +/- 0.91 (mean +/- SE); P < 0.05, 0.635 +/- 0.018 mm vs. 0.541 +/- 0.019 mm; P < 0.005, respectively]. In multivariate analysis, baseline stiffness beta was significantly associated with baseline levels of IMT (r = 0.457, P = 0.0311), FT(4) (r = -0.413, P = 0.0169), and a plasma vascular injury marker, von Willebrand factor (vWF) (r = 0.412, P = 0.0261). During 1 year of euthyroidism, 22 and 29 out of 30 patients showed significant decreases of stiffness beta and IMT to normal respective level, from 9.46 +/- 0.93 to 7.58 +/- 0.34 and from 0.635 +/- 0.018 to 0.552 +/- 0.015 mm, respectively. Change in stiffness beta during l-T(4) therapy correlated significantly in a negative manner with baseline levels of age (r = -0.465, P = 0.011) and IMT (r = -0.406, P = 0.029). Stiffness beta after but not before l-T(4) therapy showed a tendency towards a positive correlation with age. This study suggested that increases of arterial thickening, and plasma vWF, and a reduction in serum FT(4) might have an important role independently in the increased arterial stiffening in hypothyroid patients. Furthermore, it was demonstrated that sustained euthyroidism might have the potential to reverse arterial stiffening in addition to thickening in hypothyroid patients.
本研究探讨了甲状腺功能减退对动脉僵硬度的影响以及左甲状腺素(l-T4)替代治疗的效果。通过超声检查测定了30例甲状腺功能减退患者在接受l-T4替代治疗使甲状腺功能正常化1年前及1年后颈总动脉(CCA)的动脉僵硬度指数β(僵硬度β)和内膜中层厚度(IMT),后者分别是动脉僵硬度和增厚的一个参数。甲状腺功能减退患者的基线CCA僵硬度β和IMT显著高于年龄及性别匹配的正常对照者[分别为9.46±0.93与8.02±0.91(均值±标准误);P<0.05,0.635±0.018mm与0.541±0.019mm;P<0.005]。多因素分析显示,基线僵硬度β与基线IMT水平(r=0.457,P=0.0311)、游离甲状腺素(FT4)(r=-0.413,P=0.0169)以及血浆血管损伤标志物血管性血友病因子(vWF)(r=0.412,P=0.0261)显著相关。在甲状腺功能正常的1年期间,30例患者中有22例和29例的僵硬度β和IMT分别显著下降至正常水平,即从9.46±0.93降至7.58±0.34,从0.635±0.018降至0.552±0.015mm。l-T4治疗期间僵硬度β的变化与年龄(r=-0.465,P=0.011)和IMT的基线水平(r=-0.406,P=0.029)呈显著负相关。l-T4治疗后而非治疗前的僵硬度β显示出与年龄呈正相关的趋势。本研究提示,动脉增厚、血浆vWF升高以及血清FT4降低可能在甲状腺功能减退患者动脉僵硬度增加中各自发挥重要作用。此外,研究表明持续的甲状腺功能正常状态除了可逆转甲状腺功能减退患者的动脉增厚外,还可能逆转动脉僵硬度。