急性冠脉综合征合并低促甲状腺素血症患者治疗及预后的研究

发布时间：2018-08-26 12:12

【摘要】：一.研究背景心血管相关危险因素的认识和干预对冠心病的发生发展及预后至关重要,因其存在引发潜在甚至加重原发心血管疾病的风险,在引发和加剧了潜在的心血管疾病的其他介质的作用日益得到承认。传统观点认为,冠心病的常见危险因素有年龄、性别、吸烟、高血压、糖尿病、血脂异常、缺少体力活动、早发心血管家族史等。近年来,大量临床回顾性分析显示,在影响心血管疾病发生和进展的因素中,甲状腺功能异常和冠心病有一定的关联性,甲状腺激素水平与冠心病病变的关系也被日益受到重视。促甲状腺素(thyroid stimulating hormone,TSH)能敏感地反映甲状腺功能,同时反映甲状腺激素水平,并对亚临床型甲状腺疾病的发展有预测作用。甲状腺激素的变化往往在TSH的变化之后,即使在血液中检测到甲状腺激素水平是正常的,TSH浓度的异常,也会对血脂代谢、骨骼、心脏甚至神经系统造成危害。随着甲状腺功能检测的普遍性,人们对甲状腺功能及其与心血管疾病认识的深入,发现甲亢患者冠脉事件的发生率显著增加。有多项研究发现,游离三碘甲状腺原氨酸(free triiodothyronine,FT3)升高是急性心肌缺血的独立危险因素,可引起急性心绞痛甚至是心肌梗死。2014年李梦等人对甲亢合并急性冠脉综合征(acute coronary syndrome,ACS)患者的临床特征及冠脉病变特点进行研究总结,推测其发生心肌缺血的可能机制为:心肌氧供需失衡、一过性血栓性血管闭塞、冠脉痉挛、内皮功能不全等。迄今为止,临床医师已经发现甲状腺激素对心血管疾病发生发展及转归有重大影响。对于ACS合并甲亢患者而言,抗甲状腺药物(anti-thyroid drug,ATD)的应用至关重要。在2015年欧洲甲状腺协会对内源性亚临床甲亢的诊断和治疗指南中明确指出,对大于65岁的合并有心脏病、糖尿病、肾衰、卒中或短暂性脑缺血发作、心脏瓣膜病、冠脉或外周血管病等的患者,有典型甲状腺毒症的临床表现,应积极治疗;而对于年龄在65岁以下、TSH明显下降且有症状的亚临床甲亢患者,因为有进展为临床甲亢的风险,尤其是在有症状和(或)潜在的风险因素或伴随疾病的患者也可以治疗[24,25,57],对于无甲状腺毒症的非Graves病所致的的低TSH血症患者,并不推荐使用ATD治疗。ATD的应用对于ACS合并无甲状腺毒症的非Graves病所致的低TSH血症患者是否可改善预后,尚需要进一步探讨。二.研究目的本课题通过前瞻性研究分析,探讨ATD的应用对于ACS合并无甲状腺毒症的非Graves病所致的的低TSH血症患者,是否可改善其预后,为解决临床实践中存在的困惑提供新的思路和更多依据。三.研究对象和方法选取2012年1月至2015年12月在南方医科大学第三附属医院心内科住院,同意参加本研究并签署知情同意书的ACS合并无甲状腺毒症的低TSH血症患者共27例。按照是否经过ATD的治疗分为治疗组和对照组。所有入选患者需排除以下情况:1)甲状腺功能亢进患者;2)有甲状腺毒症的低TSH血症患者;3)近半年内有用过影响甲状腺功能的药物的患者:左旋甲状腺素钠片、甲巯咪唑、丙基硫氧嘧啶、胺碘酮、放射性碘131、糖皮质激素、雌激素、碳酸锂、免疫调节剂等;4)由于垂体疾病所致的TSH降低患者;5)肺动脉栓塞患者;6)瓣膜性心脏病患者;7)自身免疫系统疾病患者;8)存在严重的全身性疾病(肝硬化失代偿期、肾替代治疗、恶性肿瘤或预期寿命小于半年)患者;9)严重心衰患者:NYHA心功能分级111级,Killip分级11级。对所有患者均采集年龄、性别、吸烟史等人口统计学特征、既往病史、入院时血压、血糖、肌酐等基线资料,记录患者在出院后1个月、3个月、6个月门诊或住院期间检测的血清TSH浓度,并通过电话或门诊随访的方式,仔细询问和记录患者发生主要不良心脏事件、再发心绞痛、再发心肌梗死、新发心力衰竭的时间、处理方式及病情转归,对比ATD的应用与否对ACS合并非Graves病、无甲状腺毒症的低TSH血症患者的治疗效果及预后是否有差别。所有入组患者均规律使用冠心病二级预防药物治疗,药物及行为干预遵循临床实践指南治疗原则,由临床医生决定。所有数据采用SPSS22.0统计学软件进行统计分析,采用P0.05认为差异有统计学意义。剔除随访期间停止ATD治疗、冠心病二级预防药物治疗者。最终27例患者纳入分析。根据有无给予ATD者,将研究对象分为两组:治疗组、对照组,采用多因素Logistic回归分析ATD对预后的影响。四.研究结果在纳入的所有27例ACS合并无甲状腺毒症的非Graves病所致的低TSH血症患者中,无死亡患者,发生主要不良心脏事件13例(治疗组12.5%vs对照组63.2%);非致命性再发心肌梗死发生1例(治疗组0vs对照组5.3%),再发心绞痛9例(治疗组Ovs对照组47.3%),心力衰竭3例(治疗组12.5%vs对照组10.5%),对照组主要不良心脏事件显著增加。通过多因素Logistic回归分析对治疗组与对照组间基线有显著性差异的变量及其他既往文献报道可能对主要不良心脏事件的发生存在潜在影响的变量进行校正后,对照组MACE的累计发生风险均显著增加。在随访期间两组患者再发心绞痛、MACE再发生率方面(OR=12.0,P=0.034)差异有统计学意义。五.研究结论ATD对ACS合并无甲状腺毒症的非Graves病所致的低TSH血症患者可以显著减少MACE、心绞痛再发生率。
[Abstract]:Background. Recognition and intervention of cardiovascular risk factors are essential for the occurrence, development and prognosis of coronary heart disease. The role of other mediators in triggering and exacerbating potential cardiovascular diseases is increasingly recognized because of their potential to trigger or even exacerbate the risk of primary cardiovascular disease. The risk factors were age, sex, smoking, hypertension, diabetes mellitus, dyslipidemia, lack of physical activity, and family history of early-onset cardiovascular disease. Thyroid stimulating hormone (TSH) can sensitively reflect thyroid function, as well as thyroid hormone levels, and can predict the development of subclinical thyroid diseases. Changes in thyroid hormone are often detected in the blood after changes in TSH. Thyroid hormone levels are normal, and abnormal TSH concentrations can also cause damage to lipid metabolism, bone, heart and even nervous system. With the prevalence of thyroid function testing, people have a deeper understanding of thyroid function and its relationship with cardiovascular disease, and found that the incidence of coronary events in hyperthyroidism patients has increased significantly. Elevated free triiodothyronine (FT3) is an independent risk factor for acute myocardial ischemia, which can lead to acute angina pectoris and even myocardial infarction. In 2014, Li Meng et al. summarized the clinical features and coronary lesion characteristics of hyperthyroidism complicated with acute coronary syndrome (ACS). So far, clinicians have found that thyroid hormones have a significant impact on the development and prognosis of cardiovascular diseases. For ACS patients with hyperthyroidism, anti-thyroid drugs (anti-thyroid drugs) The European Thyroid Association's Guidelines for the Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism in 2015 clearly indicate that patients older than 65 years of age with heart disease, diabetes, renal failure, stroke or transient ischemic attack, heart valvular disease, coronary or peripheral vascular disease, etc., have typical thyroid toxicity. The clinical manifestations of the disease should be actively treated; for subclinical hyperthyroidism patients under 65 years of age with marked decrease in TSH and symptoms, there is a risk of progression to clinical hyperthyroidism, especially in patients with symptoms and/or potential risk factors or accompanying diseases [24,25,57], and for non-Graves'disease without thyroid toxicity ATD is not recommended for patients with hypoTSH caused by ACS and non-Graves'disease without thyroid toxicity. Further study is needed to determine whether the use of ATD can improve the prognosis of patients with hypoTSH caused by ACS and non-Graves' disease without thyroid toxicity. Whether non-Graves'disease patients with hypoTSH can improve their prognosis and provide new ideas and more evidence for solving the puzzles in clinical practice. 3. The subjects and methods were selected to be hospitalized in the Department of Cardiology of the Third Affiliated Hospital of Southern Medical University from January 2012 to December 2015. Twenty-seven patients with hypothyroidism complicated by ACS without thyroid toxicity were divided into treatment group and control group according to whether they had been treated with ATD or not. Thyroxine sodium tablets, methimazole, propylthiouracil, amiodarone, radioactive iodine 131, glucocorticoid, estrogen, lithium carbonate, immunomodulators, etc.; 4) patients with reduced TSH due to pituitary disease; 5) patients with pulmonary embolism; 6) patients with valvular heart disease; 7) patients with autoimmune system disease; 8) patients with serious systemic disease (liver disease) Sclerosis decompensation, renal replacement therapy, malignant tumor or life expectancy less than half a year) patients; 9) severe heart failure patients: NYHA cardiac function classification 111, Killip classification 11. After 1 month, 3 months, 6 months of outpatient or hospitalized serum TSH concentration, and through telephone or outpatient follow-up, carefully inquired and recorded patients with major adverse cardiac events, angina pectoris, myocardial infarction, new heart failure time, treatment and prognosis, compared with the application of ATD to ACS merger. All patients were treated regularly with secondary preventive drug therapy for coronary heart disease. Drug and behavioral interventions were guided by clinical practice and were determined by clinicians. All data were analyzed by SPSS22.0 statistical software. The results were included in the analysis. According to whether or not ATD was given, the subjects were divided into two groups: the treatment group and the control group. Multivariate logistic regression was used to analyze the effect of ATD on prognosis. Of all 27 patients with ACS without thyroid toxicity, 13 had major adverse cardiac events (12.5% vs 63.2% in the treatment group), 1 had non-fatal recurrent myocardial infarction (5.3% in the 0vs control group), 9 had recurrent angina pectoris (47.3% in the Ovs control group), and heart failure. There were 3 cases (12.5% vs 10.5% in the treatment group) and the major adverse cardiac events were significantly increased in the control group. The cumulative risk of MACE increased significantly. During the follow-up period, there was a significant difference in the recurrence rate of angina pectoris and MACE between the two groups (OR = 12.0, P = 0.034). 5. Conclusion ATD can significantly reduce MACE and the recurrence rate of angina pectoris in ACS patients with hypoTSH caused by non-Graves'disease without thyroid toxicity.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.4;R581

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