Milionis Haralampos J, Efstathiadou Zoe, Tselepis Alexandros D, Bairaktari Eleni T, Tsironis Loukas D, Tsatsoulis Agathocles, Elisaf Moses S
Department of Internal Medicine, Medical School of Ioannina, Ioannina, Greece.
Thyroid. 2003 Apr;13(4):365-9. doi: 10.1089/105072503321669857.
The increased risk for ischemic heart disease (IHD) associated with subclinical hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited information on the effect of SH on lipoprotein (a) [Lp(a)], which is considered a significant predictor of IHD. Serum Lp(a) levels are predominantly regulated by apolipoprotein [apo(a)] gene polymorphisms. The aim of our study was to evaluate the Lp(a) levels and apo(a) phenotypes in patients with SH compared to healthy controls as well as the influence of levothyroxine substitution therapy on Lp(a) values in relation to the apo(a) isoform size. Lp(a) levels were measured in 69 patients with SH before and after restoration of a euthyroid state and in 83 age- and gender-matched healthy controls. Apo(a) isoform size was determined by sodium dodecyl sulfate (SDS) agarose gel electrophoresis followed by immunoblotting and development via chemiluminescence. Patients with SH exhibited increased Lp(a) levels compared to controls (median value 10.6 mg/dL vs. 6.0 mg/dL, p = 0.003]), but this was not because of differences in the frequencies of apo(a) phenotypes. There was no association between thyrotropin (TSH) and Lp(a) levels in patients with SH. In subjects with either low (LMW; 25 patients and 28 controls) or high (HMW; 44 patients and 55 controls) molecular weight apo(a) isoforms, Lp(a) concentrations were higher in patients than in the control group (median values 26.9 mg/dL vs. 21.8 mg/dL, p = 0.02 for LMW, and 6.0 mg/dL versus 3.3 mg/dL, p < 0.001 for HMW). Levothyroxine treatment resulted in an overall reduction of Lp(a) levels (10.6 mg/dL baseline vs. 8.9 mg/dL posttreatment, p = 0.008]). This effect was mainly evident in patients with LMW apo(a) isoforms associated with high baseline Lp(a) concentrations (median values 26.9 mg/dL vs. 23.2 mg/dL pretreatment and posttreatment, respectively; p = 0.03). In conclusion, even though a causal effect of thyroid dysfunction on Lp(a) was not clearly demonstrated in patients with SH, levothyroxine treatment is beneficial, especially in patients with increased baseline Lp(a) levels and LMW apo(a) isoforms.
亚临床甲状腺功能减退（SH）与缺血性心脏病（IHD）风险增加有关，部分原因是血脂异常。关于SH对脂蛋白（a）[Lp（a）]的影响的信息有限，而Lp（a）被认为是IHD的重要预测指标。血清Lp（a）水平主要由载脂蛋白[apo（a）]基因多态性调节。我们研究的目的是评估SH患者与健康对照者的Lp（a）水平和apo（a）表型，以及左甲状腺素替代治疗对与apo（a）异构体大小相关的Lp（a）值的影响。在69例SH患者甲状腺功能恢复正常前后以及83例年龄和性别匹配的健康对照者中测量Lp（a）水平。通过十二烷基硫酸钠（SDS）琼脂糖凝胶电泳，然后进行免疫印迹和化学发光显影来确定apo（a）异构体大小。与对照组相比，SH患者的Lp（a）水平升高（中位数为10.6mg/dL对6.0mg/dL，p = 0.003），但这并非由于apo（a）表型频率的差异。SH患者的促甲状腺激素（TSH）与Lp（a）水平之间无关联。在低分子量（LMW；25例患者和28例对照）或高分子量（HMW；44例患者和55例对照）apo（a）异构体的受试者中，患者的Lp（a）浓度高于对照组（LMW的中位数为26.9mg/dL对21.8mg/dL，p = 0.02；HMW的中位数为6.0mg/dL对3.3mg/dL，p < 0.001）。左甲状腺素治疗导致Lp（a）水平总体降低（基线为10.6mg/dL，治疗后为8.9mg/dL，p = 〇〇〇8）。这种效应主要在基线Lp（a）浓度高的LMW apo（a）异构体患者中明显（预处理和治疗后的中位数分别为26.9mg/dL对23.2mg/dL；p = 0.03）。总之，尽管在SH患者中未明确证明甲状腺功能障碍对Lp（a）有因果效应，但左甲状腺素治疗是有益的，尤其是在基线Lp（a）水平升高和LMW apo（a）异构体的患者中。
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