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甲狀腺功能影響心血管疾病患者心肌損害和遠期預后的研究

發(fā)布時間:2018-09-09 16:46
【摘要】:甲狀腺功能影響急性心肌梗死患者心肌損害及遠期預后的研究背景:既往認為重癥疾病狀態(tài)下甲狀腺激素水平的下調(diào)是人體進行自我保護的反饋調(diào)節(jié)。對于急性心肌梗死(acute myocardial infarction, AMI)患者,尚沒有證據(jù)表明甲狀腺功能下調(diào)究竟是對心肌具有保護作用還是加重心肌損害。本研究旨在評估甲狀腺激素水平與AMI患者心肌損害、他汀藥物負荷后血脂水平的相關性,以及甲狀腺功能異常對AMI患者長期預后的影響。方法:本研究為前瞻性隊列研究研究,原始隊列入選2010年1月至2012年12月間以“急性心肌梗死”診斷入院的患者1757例,根據(jù)入選排除標準納入1112例患者進入分析集。心肌損害的程度以CKMB陽cTnI的最高值來評估,取對數(shù)值以獲得正態(tài)分布,分別表示為log-CKMB和1og-cTnI。將他汀治療強度分為低、中等、高三個不同等級,在不同強度他汀治療背景下探索甲狀腺激素水平與他汀負荷后血脂指標的相關性。主要研究終點為主要不良心臟事件(major adverse cardiac events, MACE)(包括院內(nèi)全因死亡、心肌梗死、住院期間的再次血運重建)。結果:1112例AMI患者根據(jù)其FT3水平分為5個組(1.79pg/mL; 1.80-2.42 pg/mL; 2.43-2.67 pg/mL; 2.68-2.95 pg/mL;2.96 pg/mL)共計有222例患者(20%)出現(xiàn)各種類型的甲狀腺功能異常,其中以單純FT3下降為表現(xiàn)的“低T3綜合征”是最為常見的類型(90人,8.1%),其次是以TSH下降而T3、T4正常為特征的“亞臨床甲狀腺功能亢進”(73人,6.6%),以TSH升高而T3、T4正常為特征的“亞臨床甲狀腺功能減退”(51人,4.6%)和臨床甲狀腺功能減退(8人,0.7%)。FT3與log-CKMB (r=-0.251, P0.001)和log-cTnI (r=-0.287, P0.001)存在明顯負相關。另外,FT3還與代表炎癥反應狀態(tài)的高敏C反應蛋白存在較強程度的相關性(r=-0.469,P0.001)。LVEF作為心功能指標,與FT3存在正相關(r=0.191,P0.001)。其他甲狀腺激素(FT4和TSH)則未發(fā)現(xiàn)與上述指標存在相關性。在中、高強度他汀治療背景下,FT3與總膽固醇(中等劑量:Liner Coeff=-0.105, P=0.031;高劑量:Liner Coeff=-0.172,P=0.029)及低密度脂蛋白膽固醇(中等劑量:Liner Coeff=-0.082, P=0.001;高劑量:Liner Coeff=-0.113, P=0.005)存在顯著相關性。在低強度他汀治療背景下,未發(fā)現(xiàn)甲狀腺激素與血脂指標的相關性。在兩年隨訪中,較低水平的FT3 (1.79pg/mL(?)1.80-2.42pg/mL兩組)是MACE獨立預測因子(HR:3.37,95%CI:1.66-6.85; HR: 2.28,95%CI:1.23-4.20)。根據(jù)TSH水平進行生存分析發(fā)現(xiàn),TSH升高組(TSH4.78 IU/L)的患者MACE風險顯著增加(HR:2.133,95%CI:1.22-3.72),而TSH下降組(TSH0.55IU/L)的患者死亡風險沒有統(tǒng)計學意義上的升高(HR:1.545,95%CI: 0.91-2.61)。結論:急性心肌梗死患者FT3水平與患者心肌損害標記物和炎癥標記物負相關,而與患者心功能呈正相關。在中、高強度他汀治療負荷后,急性心肌梗死患者FT3下降與總膽固醇和低密度脂蛋白膽固醇水平升高有關。在長期隨訪中,低FT3和高TSH均是心血管不良事件的獨立危險因素。甲狀腺功能對擴張型心肌病患者心功能及遠期預后的影響背景:心衰中常并存的甲狀腺激素水平異常受到廣泛關注。甲狀腺激素的水平隨著心衰程度的加重而更低,并且,甲狀腺激素水平低下的心衰患者的預后也更差,F(xiàn)有關于甲狀腺功能異常與心衰的臨床證據(jù)存在諸多局限性。首先,沒有對心衰病因進行細化,而心衰的不同病因是影響預后的重要混雜因素。另外,已有的研究多集中關注于某一項甲狀腺功能指標,而沒有對各種類型甲功異常的預后價值進行探討,從而使不同類型甲功異常在心衰中的預后意義存在爭議。方法:本研究為前瞻性隊列研究,原始隊列入選2010年1月至2011年10月就診于阜外醫(yī)院的532例擴張型心肌病患者,經(jīng)過入選排除標準篩選后,最終由458例患者進入隨訪分析。主要研究終點為全因死亡,定義為任何原因?qū)е碌淖匀凰劳。次要研究終點為心源性死亡,定義為猝死、心衰導致的死亡、惡性心律失常導致的死亡以及心梗引起的死亡。采用Kaplan-Meier圖、單因素和多因素Cox模型分析FT3水平、TSH水平及甲狀腺功能狀態(tài)對患者預后的影響。結果:根據(jù)患者的甲功水平,458例擴張型心肌病患者被分為6組,其中,臨床甲亢組因人數(shù)過少而剔除(n=3)。發(fā)生率最高的甲功異常為亞臨床甲減(n=41,占9%),其次為亞臨床甲亢(n=35,占7%)、低T3綜合征(n=17,占4%)及臨床甲減(n=12,占3%)。NYHA Ⅲ-Ⅳ的患者相對于NYHA Ⅰ-Ⅱ的患者fT3水平顯著降低(2.89+0.45vs 2.68±0.54,P=0.05)而log-TSH顯著升高(2.18±0.36 vs 2.30±0.45,P=0.02)。兩組間的fT4沒有顯著差異。log-TSH水平升高和FT3水平下降均是心功能惡化的獨立預測因子;采用Stepwise法篩選單因素分析中P值小于0.05者進入多因素分析,結果顯示,og-TSH (HR:2.189,95%CI:1.217-3.938)、fT3 (HR:0.483,95%CI: 0.301-0.775)以及腎功能不全(HR:2.045,95%CI:1.077-3.882)是心功能惡化的獨立預測因子。低FT3是全因死亡的顯著預測因子(HR 3.18,95%CI:1.96-5.16, P0.001;見表3)。TSH升高是死亡的強預測因子(HR:2.828,95%CI:1.902-4.206), TSH降低對全因死亡沒有顯著影響(HR:0.883,95%CI:0.426-1.827)。多因素分析中,全因死亡的最強的預測因子為臨床甲減(HR:4.189,95%CI:2.118-8.283),其余依次為低T3綜合征(HR:3.147,95%CI:1.558-6.355)和亞臨床甲減(HR: 2.869,95%CI:1.817-4.532).亞臨床甲亢對全因死亡沒有顯著影響(HR:0.973, 95%CI:0.469-2.018)。結論:在原發(fā)性擴張型心肌病患者中,FT3水平降低和TSH水平升高均與患者心功能惡化存在相關性。甲狀腺功能異常(低T3綜合征、亞臨床甲減、臨床甲減)是原發(fā)性擴張型心肌病患者全因死亡和心源性死亡的獨立危險因素。甲狀腺功能對原發(fā)性擴張型心肌病患者肌纖維化和心肌灌注/代謝損害的影響背景:甲狀腺激素水平與心衰患者心功能有顯著相關性,同時也是遠期不良預后的重要危險因素。目前關于甲功異常影響擴張型心肌病進展的機制研究僅停留在動物實驗水平,人體層面的證據(jù)尚不充足,從而導致臨床上對于該類患者是否需要補充甲狀腺素治療無法達成共識。目前的臨床實踐中,已經(jīng)可以應用心臟核磁共振(Cardiac magnetic resonance imaging, cardiac MRI)來檢測心肌纖維化程度,應用單光子發(fā)射計算機斷層成像術(Single-Photon Emission Computed Tomography, SPECT)和正電子發(fā)射斷層成像術(Positron Emission Tomography, PET)評估心肌灌注/代謝的方法也已逐步在臨床推廣。本研究利用心臟核磁共振和心肌核素顯像手段,探討甲狀腺激素水平與心肌纖維化和灌注/代謝異常的相關性。方法:入選2010年1月至2011年10月就診于阜外醫(yī)院的71例原發(fā)性擴張型心肌病患者。采用心臟磁共振延遲強化(late gadolinium enhancement, LGE)評估心肌纖維化,采用99mTc-MIBI SPECT顯像評估心肌灌注,采用18F-FDG PET顯像評估心肌代謝。磁共振及核素影像利用17節(jié)段模型進行半定量分析,將心肌分為6個基底段、6個中段和5個心尖節(jié)段。根據(jù)灌注/代謝圖像的不同特點將心肌節(jié)段分為4組:正常灌注/代謝,灌注/代謝不匹配,灌注/代謝輕中度匹配,灌注/代謝完全匹配。LGE類型分為三組:無延遲強化、壁間強化(延遲強化位于心肌壁內(nèi),呈線狀或斑片狀,未累及心肌全層)和透壁強化(延遲強化累及心肌全層)。主要研究終點為全因死亡,次要研究終點為心源性死亡。結果:將所有患者按照FT3四分位劃分為以下四組:Quartile1組(2.53pg/mL,n=20); Quartile2組(2.53 pg/mL-2.76 pg/mL, n=16); Quartile3組(2.77 pg/mL-3.19 pg/mL, n=18); Quartile4組(≥3.19 pg/mL, n=17)。從Quartile1到Quartile4,隨著FT3水平的升高,LGE節(jié)段的比例出現(xiàn)顯著的下降趨勢(23.53%,16.54%,5.22%,3.11%;P0.001),灌注異常節(jié)段的比例也存在下降趨勢(20.88%,16.54%,14.05%,9.69%;P0.001)。對于代謝異常節(jié)段而言,Quartile3的發(fā)生比例顯著低于Quartile1和Quartile2(8.82%,7.35%vs 1.63%;P=0.032)。Quartile4的代謝異常節(jié)段相對于Quartile3略有升高,但沒有統(tǒng)計學意義(4.84%vs 1.63%;P=0.83)。Logistic回歸分析中,FT3是患者出現(xiàn)LGE強化的唯一的危險因素(OR:0.180,95%CI:0.059-0.550)。對于心肌灌注異常,FT3在單因素模型中的OR值為0.38(95%CI:0.146-0.991),多因素模型中為0.172(95%CI:0.040-0.738)。對于心肌代謝異常,FT3是多因素模型中唯一有意義的預測因素(OR:0.338,95%CI:0.126-0.910)生存分析中,根據(jù)患者是否存在LGE強化以及FT3水平(中位數(shù)2.77 pg/mL),將或按著分為以下四組:LGE陰性+FT3≥2.77,LGE陰性+FT32.77,LGE強化+FT3≥2.77,LGE強化+FT32.77。LGE強化+FT3≥2.77(HR:4.966,1.851-8.658)和LGE強化+FT32.77(HR:8.623,95%CI:3.626-16.438)是死亡的獨立危險因素。結論:在原發(fā)性擴張型心肌病患者中,FT3水平下降與心室心肌節(jié)段纖維化和心肌灌注/代謝異常的比例存在顯著相關。低FT3和LGE陽性均是原發(fā)性擴張型心肌病患者遠期死亡率的危險因素,兩者聯(lián)合可更好的預測死亡風險
[Abstract]:Background: Thyroid function affects myocardial damage and long-term prognosis in patients with acute myocardial infarction (AMI). It has been previously thought that the reduction of thyroid hormone levels in patients with severe illness is a feedback regulation of human self-protection. There is no evidence of thyroid function in patients with acute myocardial infarction (AMI). The purpose of this study was to assess the relationship between thyroid hormone levels and myocardial damage in patients with AMI, serum lipid levels after statin loading, and the effect of thyroid dysfunction on long-term prognosis in patients with AMI. From January 2010 to December 2012, 1 757 patients with acute myocardial infarction were enrolled in the study. 1112 patients were enrolled in the analysis set according to the exclusion criteria. The degree of myocardial damage was assessed by the highest value of CKMB positive cTnI, and logarithmic value was used to obtain normal distribution, which was expressed as log-CKMB and og-cTnI respectively. The primary endpoint was major adverse cardiac events (MACE) (including in-hospital all-cause death, myocardial infarction, and revascularization weight during hospitalization). Results: 1112 patients with AMI were divided into 5 groups according to their FT3 levels (1.79 pg/mL; 1.80-2.42 pg/mL; 2.43-2.67 pg/mL; 2.68-2.95 pg/mL; 2.96 pg/mL). A total of 222 patients (20%) had various types of thyroid dysfunction, and the most common type was low T3 syndrome (90 cases, 8.1%). Subclinical hyperthyroidism (73 cases, 6.6%) characterized by decreased TSH but normal T3 and T4, subclinical hypothyroidism (51 cases, 4.6%) and clinical hypothyroidism (8 cases, 0.7%) characterized by elevated TSH and normal T3 and T4, FT3 and log-CKMB (r =-0.251, P 0.001) and log-cTnI (r =-0.287, P 0.001) were significantly negatively correlated. In addition, there was a strong correlation between FT3 and high-sensitivity C-reactive protein (r = - 0.469, P 0.001). LVEF, as a cardiac function index, was positively correlated with FT3 (r = 0.191, P 0.001). Other thyroid hormones (FT4 and TSH) were not found to be correlated with the above indicators. There was a significant correlation between total cholesterol (moderate dose: Liner Coeff = - 0.105, P = 0.031; high dose: Liner Coeff = - 0.172, P = 0.029) and low density lipoprotein cholesterol (moderate dose: Liner Coeff = - 0.082, P = 0.001; high dose: Liner Coeff = - 0.113, P = 0.005). During the two-year follow-up, lower levels of FT3 (1.79 pg/mL (?) 1.80-2.42 pg/mL) were independent predictors of MACE (HR: 3.37, 95% CI: 1.66-6.85; HR: 2.28, 95% CI: 1.23-4.20). There was no statistically significant increase in the risk of death in patients with decreased SH (TSH 0.55IU/L) (HR: 1.545, 95% CI: 0.91-2.61). Conclusion: FT3 levels in patients with AMI were negatively correlated with myocardial damage markers and inflammatory markers, but positively correlated with cardiac function. Low FT3 and high TSH were independent risk factors for cardiovascular adverse events during long-term follow-up. The impact of thyroid function on cardiac function and long-term prognosis in patients with dilated cardiomyopathy Background: Abnormal thyroid hormone levels, which are common in heart failure, are affected. Extensive attention. Thyroid hormone levels are lower as heart failure progresses, and the prognosis of heart failure patients with low thyroid hormone levels is worse. In addition, previous studies focused on a certain thyroid function index, but did not explore the prognostic value of various types of thyroid dysfunction, so that different types of thyroid dysfunction in heart failure prognostic significance is controversial. Methods: This study was a prospective cohort study, the original cohort included in 2010. 532 patients with dilated cardiomyopathy hospitalized in Fuwai Hospital from January 2001 to October 2011 were screened by exclusion criteria, and 458 patients were followed up. The primary endpoint was all-cause death, defined as natural death from any cause. The secondary endpoint was cardiac death, defined as sudden death and death from heart failure. Death, death from malignant arrhythmias, and death from myocardial infarction. Kaplan-Meier diagram, univariate and multivariate Cox model were used to analyze the effect of FT3, TSH and thyroid function on prognosis. Results: According to thyroid function, 458 patients with dilated cardiomyopathy were divided into 6 groups, including hyperthyroidism. The highest incidence of thyroid dysfunction was subclinical hypothyroidism (n = 41, 9%), followed by subclinical hyperthyroidism (n = 35, 7%), hypothyroidism (n = 17, 4%) and clinical hypothyroidism (n = 12, 3%). There was no significant difference in fT4 between the two groups. The increase of log-TSH and the decrease of FT3 were independent predictors of deterioration of cardiac function. Stepwise method was used to screen those whose P value was less than 0.05 in univariate analysis and entered multivariate analysis. The results showed that og-TSH (HR: 2.189, 95% CI: 1.217-3.938), fT3 (HR: 0.483, 95% CI: 1.217-3.938), and fT3 (HR: 0.483, F3). 95% CI: 0.301-0.775) and renal insufficiency (HR: 2.045, 95% CI: 1.077-3.882) were independent predictors of deterioration of cardiac function. Low FT3 was a significant predictor of all-cause mortality (HR 3.18, 95% CI: 1.96-5.16, P 0.001; see Table 3). Elevated TSH was a strong predictor of death (HR: 2.828, 95% CI: 1.902-4.206), and decreased TSH had no significant effect on all-cause mortality. In multivariate analysis, the strongest predictors of all-cause mortality were clinical hypothyroidism (HR: 4.189, 95% CI: 2.118-8.283), followed by low T3 syndrome (HR: 3.147, 95% CI: 1.558-6.355) and subclinical hypothyroidism (HR: 2.869, 95% CI: 1.817-4.532). I:0.469-2.018). Conclusion: In patients with primary dilated cardiomyopathy, the decrease of FT3 and the increase of TSH levels are associated with the deterioration of cardiac function. Abnormal thyroid function (hypothyroidism, subclinical hypothyroidism, clinical hypothyroidism) is an independent risk factor for all-cause and cardiac death in patients with primary dilated cardiomyopathy. Background: Thyroid hormone levels are significantly associated with cardiac function in patients with heart failure, and are also an important risk factor for long-term adverse prognosis. At the animal level, there is insufficient evidence at the human level, leading to clinical consensus on the need for thyroid hormone therapy in these patients. The methods of single-photon emission computed tomography (SPECT) and positron emission tomography (PET) for evaluating myocardial perfusion/metabolism have also been widely used in clinic. Methods: 71 patients with primary dilated cardiomyopathy were enrolled in Fuwai Hospital from January 2010 to October 2011. Myocardial fibrosis was assessed by late gadolinium enhancement (LGE) and myocardium was assessed by 99mTc-MIBI SPECT. Myocardial perfusion was assessed by 18F-FDG PET imaging. Magnetic resonance imaging and radionuclide imaging were performed with 17-segment model. The myocardium was divided into 6 basal segments, 6 middle segments and 5 apical segments. LGE types were divided into three groups: no delayed enhancement, intermural enhancement (delayed enhancement in the myocardial wall, linear or patchy, not involving the whole myocardial layer) and transmural enhancement (delayed enhancement involving the whole myocardial layer). The primary endpoint was all-cause death, and the secondary endpoint was cardiac death. All patients were divided into four groups according to FT3 quadrant: Quartile 1 group (2.53 pg/mL, n=20); Quartile 2 group (2.53 pg/mL-2.76 pg/mL, n=16); Quartile 3 group (2.77 pg/mL-3.19 pg/mL, n=18); Quartile 4 group (> 3.19 pg/mL, n=17). From Quartile 1 to Quartile 4, the proportion of LGE segments decreased significantly with the increase of FT3 level. Potential (23.53%, 16.54%, 5.22%, 3.11%; P 0.001), the proportion of abnormal perfusion segments also showed a downward trend (20.88%, 16.54%, 14.05%, 9.69%; P 0.001). For abnormal metabolic segments, the incidence of Quartile 3 was significantly lower than that of Quartile 1 and Quartile 2 (8.82%, 7.35% vs 1.63%; P = 0.032). In logistic regression analysis, FT3 was the only risk factor for LGE enhancement (OR: 0.180, 95% CI: 0.059-0.550). For myocardial perfusion abnormalities, the OR value of FT3 in single-factor model was 0.38 (95% CI: 0.146-0.991) and in multivariate model was 0.172 (95% CI: 0.040-0.738). For myocardial metabolic abnormalities, FT3 was the only significant predictor in the multivariate model (OR: 0.338, 95% CI: 0.126-0.910). According to the presence of LGE enhancement and FT3 level (median 2.77 pg/mL), patients were divided into four groups: LGE negative + FT3 (> 2.77), LGE negative + FT32.77, LGE enhancement + FT3 (> 2.77), LGE enhancement + FT3 (> 2.77), LGE enhancement + FT3 (> 3.77), LGE enhancement + FT3 (%) 3 (> 2.77). 2.77. LGE enhancement + FT3 (> 2.77) (HR: 4.966, 1.851 - 8.658) and LGE enhancement + FT32.77 (HR: 8.623, 95% CI: 3.626 - 16.438) were independent risk factors for death. Conclusion: In patients with primary dilated cardiomyopathy, the decrease of FT3 level was significantly associated with the proportion of ventricular segmental fibrosis and abnormal myocardial perfusion / metabolism. Both are risk factors for long-term mortality in patients with primary dilated cardiomyopathy, and the combination of both can better predict the risk of death.
【學位授予單位】:北京協(xié)和醫(yī)學院
【學位級別】:博士
【學位授予年份】:2016
【分類號】:R542.22

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