急性冠脈綜合征合并低促甲狀腺素血癥患者治療及預(yù)后的研究
發(fā)布時(shí)間：2018-08-26 12:12
【摘要】：一.研究背景心血管相關(guān)危險(xiǎn)因素的認(rèn)識(shí)和干預(yù)對(duì)冠心病的發(fā)生發(fā)展及預(yù)后至關(guān)重要,因其存在引發(fā)潛在甚至加重原發(fā)心血管疾病的風(fēng)險(xiǎn),在引發(fā)和加劇了潛在的心血管疾病的其他介質(zhì)的作用日益得到承認(rèn)。傳統(tǒng)觀點(diǎn)認(rèn)為,冠心病的常見危險(xiǎn)因素有年齡、性別、吸煙、高血壓、糖尿病、血脂異常、缺少體力活動(dòng)、早發(fā)心血管家族史等。近年來,大量臨床回顧性分析顯示,在影響心血管疾病發(fā)生和進(jìn)展的因素中,甲狀腺功能異常和冠心病有一定的關(guān)聯(lián)性,甲狀腺激素水平與冠心病病變的關(guān)系也被日益受到重視。促甲狀腺素(thyroid stimulating hormone,TSH)能敏感地反映甲狀腺功能,同時(shí)反映甲狀腺激素水平,并對(duì)亞臨床型甲狀腺疾病的發(fā)展有預(yù)測作用。甲狀腺激素的變化往往在TSH的變化之后,即使在血液中檢測到甲狀腺激素水平是正常的,TSH濃度的異常,也會(huì)對(duì)血脂代謝、骨骼、心臟甚至神經(jīng)系統(tǒng)造成危害。隨著甲狀腺功能檢測的普遍性,人們對(duì)甲狀腺功能及其與心血管疾病認(rèn)識(shí)的深入,發(fā)現(xiàn)甲亢患者冠脈事件的發(fā)生率顯著增加。有多項(xiàng)研究發(fā)現(xiàn),游離三碘甲狀腺原氨酸(free triiodothyronine,FT3)升高是急性心肌缺血的獨(dú)立危險(xiǎn)因素,可引起急性心絞痛甚至是心肌梗死。2014年李夢等人對(duì)甲亢合并急性冠脈綜合征(acute coronary syndrome,ACS)患者的臨床特征及冠脈病變特點(diǎn)進(jìn)行研究總結(jié),推測其發(fā)生心肌缺血的可能機(jī)制為:心肌氧供需失衡、一過性血栓性血管閉塞、冠脈痙攣、內(nèi)皮功能不全等。迄今為止,臨床醫(yī)師已經(jīng)發(fā)現(xiàn)甲狀腺激素對(duì)心血管疾病發(fā)生發(fā)展及轉(zhuǎn)歸有重大影響。對(duì)于ACS合并甲亢患者而言,抗甲狀腺藥物(anti-thyroid drug,ATD)的應(yīng)用至關(guān)重要。在2015年歐洲甲狀腺協(xié)會(huì)對(duì)內(nèi)源性亞臨床甲亢的診斷和治療指南中明確指出,對(duì)大于65歲的合并有心臟病、糖尿病、腎衰、卒中或短暫性腦缺血發(fā)作、心臟瓣膜病、冠脈或外周血管病等的患者,有典型甲狀腺毒癥的臨床表現(xiàn),應(yīng)積極治療;而對(duì)于年齡在65歲以下、TSH明顯下降且有癥狀的亞臨床甲亢患者,因?yàn)橛羞M(jìn)展為臨床甲亢的風(fēng)險(xiǎn),尤其是在有癥狀和(或)潛在的風(fēng)險(xiǎn)因素或伴隨疾病的患者也可以治療[24,25,57],對(duì)于無甲狀腺毒癥的非Graves病所致的的低TSH血癥患者,并不推薦使用ATD治療。ATD的應(yīng)用對(duì)于ACS合并無甲狀腺毒癥的非Graves病所致的低TSH血癥患者是否可改善預(yù)后,尚需要進(jìn)一步探討。二.研究目的本課題通過前瞻性研究分析,探討ATD的應(yīng)用對(duì)于ACS合并無甲狀腺毒癥的非Graves病所致的的低TSH血癥患者,是否可改善其預(yù)后,為解決臨床實(shí)踐中存在的困惑提供新的思路和更多依據(jù)。三.研究對(duì)象和方法選取2012年1月至2015年12月在南方醫(yī)科大學(xué)第三附屬醫(yī)院心內(nèi)科住院,同意參加本研究并簽署知情同意書的ACS合并無甲狀腺毒癥的低TSH血癥患者共27例。按照是否經(jīng)過ATD的治療分為治療組和對(duì)照組。所有入選患者需排除以下情況:1)甲狀腺功能亢進(jìn)患者;2)有甲狀腺毒癥的低TSH血癥患者;3)近半年內(nèi)有用過影響甲狀腺功能的藥物的患者:左旋甲狀腺素鈉片、甲巰咪唑、丙基硫氧嘧啶、胺碘酮、放射性碘131、糖皮質(zhì)激素、雌激素、碳酸鋰、免疫調(diào)節(jié)劑等;4)由于垂體疾病所致的TSH降低患者;5)肺動(dòng)脈栓塞患者;6)瓣膜性心臟病患者;7)自身免疫系統(tǒng)疾病患者;8)存在嚴(yán)重的全身性疾病(肝硬化失代償期、腎替代治療、惡性腫瘤或預(yù)期壽命小于半年)患者;9)嚴(yán)重心衰患者:NYHA心功能分級(jí)111級(jí),Killip分級(jí)11級(jí)。對(duì)所有患者均采集年齡、性別、吸煙史等人口統(tǒng)計(jì)學(xué)特征、既往病史、入院時(shí)血壓、血糖、肌酐等基線資料,記錄患者在出院后1個(gè)月、3個(gè)月、6個(gè)月門診或住院期間檢測的血清TSH濃度,并通過電話或門診隨訪的方式,仔細(xì)詢問和記錄患者發(fā)生主要不良心臟事件、再發(fā)心絞痛、再發(fā)心肌梗死、新發(fā)心力衰竭的時(shí)間、處理方式及病情轉(zhuǎn)歸,對(duì)比ATD的應(yīng)用與否對(duì)ACS合并非Graves病、無甲狀腺毒癥的低TSH血癥患者的治療效果及預(yù)后是否有差別。所有入組患者均規(guī)律使用冠心病二級(jí)預(yù)防藥物治療,藥物及行為干預(yù)遵循臨床實(shí)踐指南治療原則,由臨床醫(yī)生決定。所有數(shù)據(jù)采用SPSS22.0統(tǒng)計(jì)學(xué)軟件進(jìn)行統(tǒng)計(jì)分析,采用P0.05認(rèn)為差異有統(tǒng)計(jì)學(xué)意義。剔除隨訪期間停止ATD治療、冠心病二級(jí)預(yù)防藥物治療者。最終27例患者納入分析。根據(jù)有無給予ATD者,將研究對(duì)象分為兩組:治療組、對(duì)照組,采用多因素Logistic回歸分析ATD對(duì)預(yù)后的影響。四.研究結(jié)果在納入的所有27例ACS合并無甲狀腺毒癥的非Graves病所致的低TSH血癥患者中,無死亡患者,發(fā)生主要不良心臟事件13例(治療組12.5%vs對(duì)照組63.2%);非致命性再發(fā)心肌梗死發(fā)生1例(治療組0vs對(duì)照組5.3%),再發(fā)心絞痛9例(治療組Ovs對(duì)照組47.3%),心力衰竭3例(治療組12.5%vs對(duì)照組10.5%),對(duì)照組主要不良心臟事件顯著增加。通過多因素Logistic回歸分析對(duì)治療組與對(duì)照組間基線有顯著性差異的變量及其他既往文獻(xiàn)報(bào)道可能對(duì)主要不良心臟事件的發(fā)生存在潛在影響的變量進(jìn)行校正后,對(duì)照組MACE的累計(jì)發(fā)生風(fēng)險(xiǎn)均顯著增加。在隨訪期間兩組患者再發(fā)心絞痛、MACE再發(fā)生率方面(OR=12.0,P=0.034)差異有統(tǒng)計(jì)學(xué)意義。五.研究結(jié)論ATD對(duì)ACS合并無甲狀腺毒癥的非Graves病所致的低TSH血癥患者可以顯著減少M(fèi)ACE、心絞痛再發(fā)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.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R541.4;R581
本文編號(hào)：2204834
[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.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R541.4;R581
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