阿力木江·阿不來提，李　渤，張　莉，陳　洋，徐海蓉

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亞臨床甲狀腺功能減退與冠心病相關(guān)性

阿力木江·阿不來提1，李渤2，張莉1，陳洋1，徐海蓉1

目的探索亞臨床甲狀腺功能減退與冠心病相關(guān)性。方法選擇2013-07至2015-04在我科住院，擬診冠心病并接受選擇性冠狀動(dòng)脈造影患者136例，按甲狀腺功能分為甲狀腺功能正常組(正常組)和亞臨床甲狀腺功能減退組(subclinical hypothyroidism, SCH)(減退組)。再根據(jù)冠狀動(dòng)脈造影結(jié)果分別列入冠狀動(dòng)脈造影陰性組，冠狀動(dòng)脈1支病變、2支病變、3支病變或左主干病變組。比較各組患者的基本資料、生化指標(biāo)、紅細(xì)胞總數(shù)、紅細(xì)胞分布寬度、冠狀動(dòng)脈病變數(shù)量和Gensini評(píng)分，以及超聲心動(dòng)圖等資料。結(jié)果減退組TC、肌酐水平高于正常組，TG水平低于正常組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)，而血壓、LDL-C、HDL-C、尿素氮、胱抑素、尿酸、FT3、FT4、紅細(xì)胞總數(shù)、紅細(xì)胞分布寬度等指標(biāo)間差異無統(tǒng)計(jì)學(xué)意義。減退組冠心病患者比例與正常組相同，但冠狀動(dòng)脈Gensini評(píng)分(18.90±26.07)高于正常組(11.66±15.34)，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。兩組超聲指標(biāo)間未發(fā)現(xiàn)差異。結(jié)論SCH可能影響冠狀動(dòng)脈病變嚴(yán)重程度。

甲狀腺功能減退；亞臨床；冠心病

臨床上將促甲狀腺激素(thyroid stimulating hormone,TSH)水平增高，但游離T3(FT3)、游離T4(FT4)水平正常，且無明顯相關(guān)癥狀稱為亞臨床甲狀腺功能減退癥(subclinical hypothyroidism, SCH)。SCH在人群中的患病率可達(dá)到5%～15%，且隨著年齡的增長逐漸上升，在60歲以上女性可達(dá)到20%[1，2]。橫斷面研究證實(shí)SCH患者有較高的動(dòng)脈粥樣硬化風(fēng)險(xiǎn)[3]。本研究通過分析SCH和甲狀腺功能正常患者的臨床資料、冠狀動(dòng)脈造影結(jié)果及超聲心動(dòng)圖特點(diǎn)，旨在發(fā)現(xiàn)冠心病與SCH之間的相關(guān)性。

1　對(duì)象與方法

1.1對(duì)象選擇2013-07至2015-04在武警新疆總隊(duì)醫(yī)院心內(nèi)科初診為冠心病并接受選擇性冠狀動(dòng)脈造影患者136例，根據(jù)甲狀腺功能分為甲狀腺功能正常組(正常組)和亞臨床甲狀腺功能減退組(減退組)。正常組71例，男27例，女44例，其中高血壓病35例；減退組65例，男34例，女31例，其中高血壓29例。在完善基礎(chǔ)臨床資料后均接受選擇性冠狀動(dòng)脈造影，并根據(jù)冠狀動(dòng)脈造影結(jié)果分別列入冠狀動(dòng)脈造影陰性組，1支病變、2支病變和3支或左主干病變組并計(jì)算Gensini評(píng)分。入選標(biāo)準(zhǔn)：(1)年齡大于50歲；(2)排除甲狀腺功能減退癥(甲減)、糖尿病、痛風(fēng)等影響糖脂代謝的代謝性疾病；(3)排除了急性冠脈綜合征、急性腦卒中等急性心血管疾病和肥厚性心肌病、擴(kuò)張性心肌病、心臟瓣膜病、先天性心臟病等其他結(jié)構(gòu)性心血管系統(tǒng)疾病。兩組患者一般情況對(duì)比，差異無統(tǒng)計(jì)學(xué)意義，除減退組TSH水平高于正常組(P<0.05)，其余甲狀腺功能指標(biāo)間無差異，符合分組條件。見表1。

表1　兩組患者基本情況比較

1.2方法

1.2.1采樣患者清晨空腹抽取靜脈血9 ml，分裝3個(gè)試管。分別進(jìn)行：(1)采用全自動(dòng)免疫分析系統(tǒng)檢測(cè)游離三碘甲狀腺原氨酸(FT3)、游離甲狀腺素(FT4)、促甲狀腺激素(TSH)，參考值范圍，F(xiàn)T33.06～6.73 pmol/L、FT411.99～21.91 pmol/L、TSH 0.27～4.2 mU/L；(2)血脂分析，包括三酰甘油(TG)、總膽固醇(TC)、低密度脂蛋白膽固醇(LDL-C)、高密度脂蛋白膽固醇(HDL-C))、血糖、肌酐、尿素氮、尿酸等指標(biāo)檢測(cè)；(3)進(jìn)行血常規(guī)檢測(cè)，比較紅細(xì)胞總數(shù)、紅細(xì)胞分布寬度等指標(biāo)。

1.2.2選擇性冠狀動(dòng)脈造影采用荷蘭Philip 公司生產(chǎn)的血管造影機(jī)，經(jīng)橈動(dòng)脈途徑用TIG多功能造影導(dǎo)管選擇多體位行左、右冠狀動(dòng)脈造影。造影結(jié)果由2名介入醫(yī)師獨(dú)立診斷。根據(jù)1984年美國心臟病協(xié)會(huì)規(guī)定的冠狀動(dòng)脈血管圖像分段評(píng)價(jià)標(biāo)準(zhǔn)和Gensini評(píng)分系統(tǒng)對(duì)每支血管狹窄程度進(jìn)行定量評(píng)價(jià)：狹窄程度<50% 或顯示正常者為陰性，≥50% 者列入冠心病組。根據(jù)狹窄累及血管數(shù)量分為1支、2支和3支或左主干病變。Gensini評(píng)分系統(tǒng)：狹窄程度﹤25%為1分，26%～50%為2分，51%～75%為4分，76%～90%為8分，91%～99%為16分，100%閉塞為32分。不同節(jié)段冠狀動(dòng)脈評(píng)分系數(shù)：左主干病變計(jì)分×5，左前降支近段×2.5，中段×1.5，遠(yuǎn)段×1，第一對(duì)角支×1，第二對(duì)角支×0.5，左回旋支近段×2.5，遠(yuǎn)段×1，右冠狀動(dòng)脈近段，中段，遠(yuǎn)段均×1，后降支×1，后側(cè)支×0.5。將各分支積分相加得出冠狀動(dòng)脈病變程度的Gensini評(píng)分。所用對(duì)比劑均為非離子型對(duì)比劑(碘帕醇)。

1.2.3超聲心動(dòng)圖檢查采用西門子Acuson Sequoia 512彩色多普勒超聲心動(dòng)圖儀，探頭頻率3～8 MHz，對(duì)136例患者進(jìn)行常規(guī)超聲心動(dòng)圖檢查。由一名技師負(fù)責(zé)操作，以減少操作者誤差。

2　結(jié)　　果

2.1生化指標(biāo)及Gensini評(píng)分由表2可見，減退組TC高于正常組，TG水平低于正常組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)，LDL-C和HDL-C水平差異無統(tǒng)計(jì)學(xué)意義，提示減退組血脂異常。減退組肌酐水平高于正常組(P<0.05)，提示減退組腎功能損害比較明顯。減退組Gensini評(píng)分高于正常組(P<0.05)，提示減退組冠狀動(dòng)脈病變嚴(yán)重程度高于正常組。

表2　兩組冠心病患者生化指標(biāo)及Gensini評(píng)分比較　±s)

2.2冠狀動(dòng)脈造影結(jié)果比較甲狀腺功能正常組和減退組患者冠狀動(dòng)脈造影結(jié)果，無論是1支、2支、3支還是左主干病變，兩組患者比例相同，差異無統(tǒng)計(jì)學(xué)意義(表3)。

表3　兩組冠心病患者冠狀動(dòng)脈造影結(jié)果比較　(例)

2.3超聲心動(dòng)圖指標(biāo)兩組患者超聲資料，無論是心臟結(jié)構(gòu)參數(shù)還是心臟功能參數(shù)之間無統(tǒng)計(jì)學(xué)差異(表4)。

表4　兩組冠心病患者超聲心動(dòng)圖指標(biāo)比較　±s)

3　討　　論

心血管系統(tǒng)是甲狀腺激素的特定靶器官之一。SCH與冠心病相關(guān)性研究報(bào)道存在矛盾[4-7]。Rotterdam[3]發(fā)現(xiàn)，SCH是老年女性發(fā)生動(dòng)脈粥樣硬化和心肌梗死的獨(dú)立危險(xiǎn)因素。Kvetny等[5]提出，SCH可以預(yù)測(cè)50歲以下男性心血管疾病發(fā)病風(fēng)險(xiǎn)。但Hyland等[6]隨訪5888例年齡≥65歲的SCH患者，10年后發(fā)現(xiàn)由冠心病、心力衰竭和心血管疾病引起的死亡并沒有增加。Pearce等[7]甚至提出，SCH患者全因病死率低于甲狀腺功能正常者。雖然存在爭(zhēng)議，但更多的學(xué)者認(rèn)為SCH與冠心病有一定相關(guān)性。SCH通過多種途徑增加冠心病發(fā)病危險(xiǎn)。SCH患者膽固醇、低密度脂蛋白水平、血壓、胰島素抵抗程度等高于甲狀腺功能正常者[8-10]。Tseng等[10]發(fā)現(xiàn)，TSH水平在5.0～9.9 mU/L的SCH患者心血管病死亡風(fēng)險(xiǎn)明顯增加，特別是在老年患者中這種關(guān)聯(lián)更強(qiáng)。血脂異常、舒張壓升高、周圍血管阻力增加、內(nèi)皮依賴性血管舒張因子減少、凝血功能異常、高C反應(yīng)蛋白和高同型半胱氨酸水平等因素可能與SCH增加心血管疾病風(fēng)險(xiǎn)有關(guān)[11]。本研究采用了診斷冠心病金標(biāo)準(zhǔn)的冠狀動(dòng)脈造影檢查，嚴(yán)格入選標(biāo)準(zhǔn)，特別排除了可能成為混雜因素的臨床甲減和糖尿病等患者，平衡了性別、年齡等指標(biāo)，結(jié)果提示SCH患者冠狀動(dòng)脈狹窄程度較甲狀腺功能正常者明顯，與以上研究一致。血脂異常是公認(rèn)的冠心病危險(xiǎn)因素。與甲狀腺功能正?；颊呦啾?，SCH患者血脂水平高于正常者[9，12]，但是具體哪些血脂指標(biāo)之間有差別報(bào)道不一。Liu等[9]薈萃分析發(fā)現(xiàn)，SCH患者TG、TC、LDL-C水平高，但HDL-C水平無差別。本研究發(fā)現(xiàn)，減退組TC水平(3.90±1.63)mmol/L高于甲狀腺功能正常組(2.50±1.63)mmol/L，TG水平低于正常組，HDL-C和LDL-C水平無差異。研究方法和研究人群的不同可能是出現(xiàn)這種差異的原因。理論上認(rèn)為，甲狀腺功能減退引起的主動(dòng)脈硬化、外周血管阻力增大，可能導(dǎo)致高血壓，特別是舒張壓的升高，但實(shí)際上這方面的研究結(jié)果存在矛盾[13，14]。本研究未發(fā)現(xiàn)兩組患者血壓水平存在差異，但不除外患者均已服用降壓藥物等因素的可能。

減退組患者肌酐水平高于甲狀腺功能正?；颊?。慢性腎臟病患者中大約18%有SCH，且SCH與eGFR進(jìn)行性下降獨(dú)立相關(guān)[15]。慢性腎功能不全往往與高齡、高血壓、糖尿病等冠心病危險(xiǎn)因素伴發(fā)，同時(shí)存在炎性反應(yīng)、內(nèi)皮功能異常、凝血因子激活等冠狀動(dòng)脈粥樣硬化的共同機(jī)制。腎功能不全也是冠心病的獨(dú)立危險(xiǎn)因素之一[16,17]。甲狀腺功能減退時(shí)血液黏稠度增加，血流速度減慢、腎臟血流減少都有可能影響腎功能。SCH不僅與冠心病發(fā)生相關(guān)，而且與嚴(yán)重程度也有關(guān)。冠心病高危患者如果合并SCH則冠狀動(dòng)脈狹窄更嚴(yán)重[18]，冠狀動(dòng)脈鈣化積分更高[19]。Silva等[20]發(fā)現(xiàn)，F(xiàn)ramingham危險(xiǎn)評(píng)分≥10%的人群中SCH者冠狀動(dòng)脈鈣化積分高于甲狀腺功能正常者。本研究發(fā)現(xiàn)，減退組患者冠狀動(dòng)脈Gensini評(píng)分(18.90±26.07)分明顯高于甲狀腺功能正常組(11.66±15.34)分，提示SCH與冠心病嚴(yán)重程度有關(guān)。

有研究提示，SCH患者左室舒張功能、心室腔均受到影響[21，22]。但本研究比較兩組心臟超聲心動(dòng)圖，結(jié)果顯示減退組超聲指標(biāo)與甲狀腺功能正常組差異無統(tǒng)計(jì)學(xué)意義?？赡芘c本研究不同的測(cè)量指標(biāo)及樣本量較少等因素有關(guān)。紅細(xì)胞分布寬度是反映紅細(xì)胞大小差異性的一項(xiàng)指標(biāo)，反映紅細(xì)胞體積的離散程度，既往主要用于貧血的診斷和鑒別診斷，以及形態(tài)學(xué)分類。目前，RDW與冠心病特別是急性冠脈綜合征之間的相關(guān)性被廣泛關(guān)注[23，24]。本研究發(fā)現(xiàn)兩組患者紅細(xì)胞分布寬度之間差異無統(tǒng)計(jì)學(xué)意義，可能與本研究排除了急性冠脈綜合征的患者、樣本量少，以及橫斷面研究的缺陷等因素有關(guān)。

綜上所述，冠心病的發(fā)生、發(fā)展歸因于高血壓病、糖尿病、血脂異常及高尿酸血癥等綜合危險(xiǎn)因素的共同作用。SCH患者往往存在三種以上代謝綜合征危險(xiǎn)因素[25]，也有人認(rèn)為，SCH可能是代謝綜合征危險(xiǎn)因素之一[26]。本研究認(rèn)為，對(duì)有代謝綜合征或冠心病危險(xiǎn)因素的患者進(jìn)行甲狀腺功能篩查可能具有積極的治療和預(yù)后意義。目前，對(duì)SCH與冠心病相關(guān)性證據(jù)逐漸增多，但爭(zhēng)論依然未停息，特別是TSH水平低于10 mU/L的患者是否需要治療方面爭(zhēng)議頗大，仍需要大規(guī)模臨床試驗(yàn)來回答、證實(shí)。

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(2015-08-10收稿2015-12-18修回)

(責(zé)任編輯郭青)

Relationship between subclinical hypothyroidism and coronary artery disease

ABULAITI Alimujiang1, LI Bo2, ZHANG Li1, CHEN Yang1, and XU Hairong1.

1.Department of Cardiology, Xinjiang Uigur Autonomous Region Corps Hospital, Chinese People’s Armed Police Force, Urumqi 830091, China；2. Health Team, 5th Detachment of Xinjiang Uigur Autonomous Region, Chinese People’s Armed Police Force, Hetian 844000, China

ObjectiveTo evaluate the relationship between subclinical hypothyroidism(SCH) and coronary artery disease. Methods136 patients admitted from July 2013 to April 2015 were recruited for the study. Clinical data including age, gender, blood pressure, thyroid function, blood sugar, lipid profiles，red blood cell counts, and red cell distribution width(RDW) were analyzed. All patients received selective coronary angiography. Based on results of coronary angiography, they were categorized into one, two, three or left main artery stenosis groups and angiographic normal group. Clinical characteristics, coronary angiography, Gensini scores and echocardiographic parameters were compared. ResultsTC, serum creatine levels were higher and TG were lower in SCH group(P<0.05);blood pressure, LDL-C,HDL-C, urea, cystatin-C, uric acid, FT3,FT4,red blood cells,and RDW levels were not different between the groups. Number of coronary artery disease patients and number of coronary arteries involved were not different, but the Gensini scores were higher in SCH group(P<0.05). ConclusionsSubclinical hypothyroidism might affect severity of coronary artery stenosis.

hypotyroidism；subclinical；coronary artery disease

阿力木江·阿不來提，博士，副主任醫(yī)師。

1.830099烏魯木齊，武警新疆總隊(duì)醫(yī)院心內(nèi)科；2.844000烏魯木齊，武警新疆總隊(duì)第五支隊(duì)衛(wèi)生隊(duì)

R540.4