血管生成素样蛋白3、4和8与接受左甲状腺素治疗的未经治疗的亚临床和显性甲状腺功能减退患者的心血管功能有关。
Angiopoietin-like proteins 3, 4 and 8 are linked to cardiovascular function in naïve sub-clinical and overt hypothyroid patients receiving levothyroxine therapy.
作者信息
El Hini Sahar Hossam, Mahmoud Yehia Zakaria, Saedii Ahmed Abdelfadel, Mahmoud Sayed Shehata, Amin Mohamed Ahmed, Mahmoud Shereen Riad, Matta Ragaa Abdelshaheed
机构信息
Diabetes and Endocrinology Unit, Department of Internal Medicine, Faculty of Medicine, Minia University, Minia, Egypt.
Department of Internal Medicine, Faculty of Medicine, Minia University, Minia, Egypt.
出版信息
Endocr Connect. 2021 Nov 29;10(12):1570-1583. doi: 10.1530/EC-21-0398.
OBJECTIVE
Angiopoietin-like proteins (ANGPTL) 3, 4 and 8 are upcoming cardiovascular biomarkers. Experimental studies showed that thyroid hormones altered their levels. We assessed ANGPTL3, 4 and 8 as predictors of cardiovascular functions among naïve subclinical and naïve overt hypothyroidism (SCH and OH) and altered ANGPTL levels with levothyroxine replacement (LT4) and their association with improved cardiovascular risk factors and cardiovascular function.
DESIGN AND METHODS
The study was a prospective follow-up study that assessed ANGPTL3, 4 and 8 levels, vascular status (flow-mediated dilation% of brachial artery (FMD%), carotid intima-media thickness (CIMT), aortic stiffness index (ASI)), left ventricle (LV) parameters (ejection fraction (EF), myocardial performance index (MPI), and LV mass), well-known cardiovascular risk factors and homeostatic model for the assessment of insulin resistance, at two time points, that is, among naïve SCH, naïve OH, and healthy subjects groups; and at 6 months after achieving the euthyroid state with LT4 by calculating their increased or decreased delta changes (∆↑ or ∆↓) in longitudinal arm among LT4-hypothyroid groups.
RESULTS
Significantly elevated levels of ANGPTL3, 4 and 8 among hypothyroid groups than the healthy subjects were reduced with LT4. Multivariate analysis revealed ANGPTLs as independent predictors of cardiovascular functions and the contributors for ANGPTL level included ANGPTL3 and 4 for impaired FMD%, and ANGPTL8 for LV mass among naïve SCH; ANGPTL3 for EF% and ANGPTL8 for CIMT in naïve OH; ∆↓ANGPTL3 for ∆↓ASI meanwhile ∆↑freeT4 for ∆↓ANGPTL3, ∆↓fasting glucose, ∆↓triglyceride, and ∆↓thyroid peroxidase antibody for ∆↓ANGPTL4 among LT4-SCH. ∆↓ANGPTL4 for ∆↓MPI and ∆↓LV mass, meanwhile ∆↓TSH and ∆↓triglyceride for ∆↓ANGPTL3, ∆↑free T3 and ∆↓HOMA-IR for ∆↓ANGPTL4, and systolic blood pressure and waist circumference for ∆↓ANGPTL8 among LT4-OH.
CONCLUSION
Elevated ANGPTL3, 4 and 8 levels are differentially independent predictors of endothelial and cardiac function and are reduced with LT4 in SCH and OH.
目的
血管生成素样蛋白（ANGPTL）3、4和8是新兴的心血管生物标志物。实验研究表明甲状腺激素会改变它们的水平。我们评估了ANGPTL3、4和8作为初发亚临床甲状腺功能减退和初发显性甲状腺功能减退（SCH和OH）中心血管功能预测指标的情况，以及左甲状腺素替代治疗（LT4）对ANGPTL水平的影响及其与心血管危险因素改善和心血管功能的关联。
设计与方法
本研究为前瞻性随访研究，在两个时间点评估ANGPTL3、4和8水平、血管状态（肱动脉血流介导的扩张百分比（FMD%）、颈动脉内膜中层厚度（CIMT）、主动脉僵硬度指数（ASI））、左心室（LV）参数（射血分数（EF）、心肌性能指数（MPI）和LV质量）、知名心血管危险因素以及评估胰岛素抵抗的稳态模型，即初发SCH组、初发OH组和健康受试者组；以及在LT4治疗甲状腺功能减退组达到甲状腺功能正常状态6个月后，通过计算纵向臂中它们增加或减少的变化量（∆↑或∆↓）来评估。
结果
甲状腺功能减退组中ANGPTL3、4和8水平显著高于健康受试者，LT4治疗后降低。多变量分析显示ANGPTL是心血管功能的独立预测指标，在初发SCH中，ANGPTL水平的影响因素包括FMD%受损时的ANGPTL3和4以及LV质量时的ANGPTL8；在初发OH中，EF%时的ANGPTL3和CIMT时的ANGPTL8；在LT4 - SCH中，∆↓ASI时的∆↓ANGPTL3，同时∆↓ANGPTL3时的∆↑游离T4、∆↓空腹血糖、∆↓甘油三酯和∆↓甲状腺过氧化物酶抗体时的∆↓ANGPTL4。在LT4 - OH中，∆↓MPI和∆↓LV质量时的∆↓ANGPTL4，同时∆↓ANGPTL3时的∆↓TSH和∆↓甘油三酯，∆↓ANGPTL4时的∆↑游离T3和∆↓HOMA - IR，以及∆↓ANGPTL8时的收缩压和腰围。
结论
ANGPTL3、4和8水平升高是内皮功能和心脏功能的不同独立预测指标，在SCH和OH中LT4治疗后降低。
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