血尿酸水平與陣發(fā)性心房顫動患者射頻消融術后復發(fā)的關系

胡 曉，張 靜，丁志堅

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·論著·

血尿酸水平與陣發(fā)性心房顫動患者射頻消融術后復發(fā)的關系

胡 曉，張 靜，丁志堅

213000江蘇省常州市，南京醫(yī)科大學附屬常州市第二人民醫(yī)院心血管內(nèi)科(胡曉，丁志堅)；江蘇護理職業(yè)學院(張靜)

【摘要】目的探討血尿酸(SUA)水平與陣發(fā)性心房顫動患者射頻消融術后復發(fā)的關系。方法選取2011年6月—2014年1月在南京醫(yī)科大學附屬常州市第二人民醫(yī)院行射頻消融術治療的91例陣發(fā)性心房顫動患者為研究對象。術后3個月經(jīng)心電圖或24 h動態(tài)心電圖檢查確定有無心房顫動復發(fā)，將患者分為復發(fā)組(20例)和未復發(fā)組(71例)。詳細記錄患者的臨床資料，分別于術前及術后1周、6個月抽取清晨空腹靜脈血檢測SUA、超敏C反應蛋白(hs-CRP)、白細胞計數(shù)(WBC)水平。結果復發(fā)組年齡、病程、左心房前后徑(LAD)大于未復發(fā)組(P<0.05)。復發(fā)組術前、術后1周及術后6個月SUA、hs-CRP水平高于未復發(fā)組，復發(fā)組術前WBC水平高于未復發(fā)組(P<0.05)。復發(fā)組術后1周SUA、hs-CRP水平高于術前，術后6個月SUA、hs-CRP水平低于術后1周(P<0.05)。未復發(fā)組術后1周SUA水平高于術前，術后6個月SUA水平低于術前和術后1周(P<0.05)；術后1周hs-CRP水平高于術前，術后6個月hs-CRP水平低于術后1周(P<0.05)。多因素Logistic回歸分析結果顯示，LAD〔OR=1.945,95%CI(1.047，3.612)〕及術前SUA〔OR=1.024,95%CI(1.009，1.038)〕、hs-CRP〔OR=4.762,95%CI(1.359，16.685)〕水平是陣發(fā)性心房顫動患者射頻消融術后復發(fā)的獨立危險因素(P<0.05)。結論術前高SUA水平是陣發(fā)性心房顫動患者射頻消融術后復發(fā)的獨立預測因子，降低SUA水平可能會改善心房顫動患者的預后，降低射頻消融術后的復發(fā)率。

【關鍵詞】心房顫動；尿酸；導管消融術；復發(fā)

胡曉，張靜，丁志堅.血尿酸水平與陣發(fā)性心房顫動患者射頻消融術后復發(fā)的關系[J].中國全科醫(yī)學，2016，19(19)：2275-2278.[www.chinagp.net]

HU X,ZHANG J，DING Z J.Relationship between serum uric acid level and recurrence of patients with paroxysmal atrial fibrillation after radiofrequency ablation[J].Chinese General Practice，2016，19(19)：2275-2278.

心房顫動是臨床最常見的心律失常。在過去的20年中，射頻消融術已成為對藥物治療無效心房顫動患者的重要治療手段[1]，但術后仍存在復發(fā)的風險。越來越多的證據(jù)表明，炎癥在心房顫動的發(fā)生和維持中發(fā)揮重要作用。心房顫動患者炎性標志物水平升高，如超敏C反應蛋白(hs-CRP)、白介素6、白介素8和白細胞計數(shù)(WBC)等[2-4]。升高的血尿酸(SUA)能夠激活炎癥和氧化應激途徑，炎癥和氧化應激相互作用，形成鈣超載并降低鈉通道的活性，進而導致電重構；與此同時，通過成纖維細胞的增殖、炎癥和細胞凋亡形成結構重構[5]。高水平SUA是心房顫動發(fā)生與發(fā)展的重要危險因素[6]，但術前SUA水平能否預測心房顫動患者射頻消融術后的復發(fā)仍不明確。筆者假設，通過引起電重構和結構重構，SUA水平在心房顫動的復發(fā)中起了重要作用。本研究旨在探討術前SUA水平與陣發(fā)性心房顫動患者射頻消融術后復發(fā)的關系以及其對復發(fā)的預測價值。

1對象與方法

1.1研究對象選取2011年6月—2014年1月在南京醫(yī)科大學附屬常州市第二人民醫(yī)院行射頻消融術治療的91例陣發(fā)性心房顫動患者為研究對象。納入標準：(1)有癥狀的陣發(fā)性心房顫動，陣發(fā)性心房顫動的定義為癥狀持續(xù)時間≤7 d；(2)術前使用至少1種抗心律失常藥物治療失敗。排除標準：(1)中度至重度心臟瓣膜病，左心房血栓，心力衰竭，心肌梗死或3個月前行心臟手術，左心房前后徑(LAD)大于55 mm，有抗凝禁忌證；(2)正在服用維生素制劑(包括維生素C、煙酸、葉酸)，利尿藥物或降低尿酸的藥物(別嘌呤醇)；(3)未控制的甲狀腺功能異常，腎功能不全(血肌酐水平≥1.5 mg/dl)，肝病及溶血性疾病，腫瘤或任何其他全身性疾病；(4)妊娠。治療方案經(jīng)本院醫(yī)學倫理委員會批準，患者簽署知情同意書。

1.2方法

1.2.1術前準備患者均行超聲心動圖排除心臟結構異常，經(jīng)食管超聲排除左心房血栓。術前3 d停止服用華法林，并予低分子肝素抗凝。

1.2.2手術方法在左心房三維重建標測下行環(huán)肺靜脈隔離消融。根據(jù)術中患者情況行肺靜脈隔離(PVI)或PVI+線性消融與左心房復雜碎裂電位消融。術后給予持續(xù)24 h心電監(jiān)護，6 h后予華法林和低分子肝素抗凝，維持凝血酶原國際標準化比值(INR)2～3?；颊咝g后3個月內(nèi)繼續(xù)服用術前所服用的抗心律失常藥物。3個月后根據(jù)患者CHADS2評分決定是否繼續(xù)服用華法林[7]。分別于術后3、6、12個月進行隨訪，此后每6個月進行隨訪。隨訪內(nèi)容包括心電圖及24 h動態(tài)心電圖檢查。如若患者出現(xiàn)心悸等不適則及時至醫(yī)院行心電圖及24 h動態(tài)心電圖檢查。

1.2.3復發(fā)判斷標準術后3個月經(jīng)心電圖或24 h動態(tài)心電圖證實出現(xiàn)超過30 s的房性心律失常，包括心房顫動、心房撲動和房性心動過速。據(jù)此，將患者分為復發(fā)組(20例)和未復發(fā)組(71例)。

1.3觀察指標詳細記錄患者的臨床資料，包括性別、年齡、病程、BMI，有無高血壓、血脂異常，鈣離子拮抗劑(CCB)、血管緊張素轉(zhuǎn)換酶抑制劑/血管緊張素受體拮抗劑(ACEI/ARB)使用情況以及超聲心動圖等相關信息。分別于術前及術后1周、6個月抽取清晨空腹靜脈血檢測SUA、hs-CRP、WBC水平。

2結果

2.1兩組患者臨床特征比較兩組性別、BMI，高血壓、高血脂檢出率，CCB、ACEI/ARB使用比例比較，差異均無統(tǒng)計學意義(P>0.05)。復發(fā)組年齡、病程、LAD大于未復發(fā)組，差異均有統(tǒng)計學意義(P<0.05，見表1)。

2.2兩組炎性因子水平比較復發(fā)組術前、術后1周及術后6個月SUA、hs-CRP水平高于未復發(fā)組，復發(fā)組術前WBC水平高于未復發(fā)組，差異均有統(tǒng)計學意義(P<0.05)。復發(fā)組術后1周SUA、hs-CRP水平高于術前，術后6個月SUA、hs-CRP水平低于術后1周，差異均有統(tǒng)計學意義(P<0.05)。未復發(fā)組術后1周SUA水平高于術前，術后6個月SUA水平低于術前和術后1周；術后1周hs-CRP水平高于術前，術后6個月hs-CRP水平低于術后1周，差異均有統(tǒng)計學意義(P<0.05，見表2)。

2.3多因素Logistic回歸分析以射頻消融術后復發(fā)(賦值：是=1，否=0)為因變量，以年齡、病程、LAD及術前SUA、hs-CRP、WBC水平為自變量行多因素Logistic回歸分析。結果顯示，LAD及術前SUA、hs-CRP水平是陣發(fā)性心房顫動患者射頻消融術后復發(fā)的影響因素(P<0.05，見表3)。

3討論

本研究對91例陣發(fā)性心房顫動患者射頻消融術后進行(17.2±5.7)個月的隨訪，20例(22.0%)出現(xiàn)復發(fā)。術后1周患者SUA、hs-CRP水平較術前明顯升高，考慮與射頻消融過程中引起心肌損傷，進而誘導機體繼發(fā)無菌性炎性反應有關[8]。未復發(fā)組患者在術后6個月SUA水平恢復至比術前更低水平，說明心房顫動在轉(zhuǎn)復和維持竇性心律后，消除了炎癥觸發(fā)心房肌致使心房顫動的機制，進而降低了炎性反應水平，使得術后炎性因子水平下降[9]。而復發(fā)組患者術后6個月SUA水平與術前相比并無明顯變化，復發(fā)組患者術后SUA水平與未復發(fā)組患者同期進行比較有差異，提示復發(fā)組患者SUA仍處于較高水平，機體仍相對存在炎性反應。多因素Logistic回歸分析發(fā)現(xiàn)，術前SUA水平可作為獨立的預測心房顫動射頻術后復發(fā)的危險因素〔OR=1.024，95%CI(1.009,1.038)，P=0.001〕，高水平SUA患者在術后有更高的復發(fā)風險。

心房顫動發(fā)生和維持的確切機制尚不清楚，但炎癥和氧化應激在其中發(fā)揮了重要作用[10]。SUA是嘌呤的代謝產(chǎn)物，大量證據(jù)表明，SUA水平與多種心血管疾病有關，包括高血壓、糖尿病、充血性心力衰竭、冠心病和卒中[11-12]。SUA水平升高是細胞窘迫的跡象，SUA從瀕死細胞中釋放，引起固有和后天適應性免疫應答。SUA刺激白介素6和腫瘤壞死因子表達，這些炎性細胞因子均與心房顫動有關[13]。前瞻性研究表明，SUA與氧化應激有關[14]，而氧化應激是心房顫動最重要的致病機制[15]。SUA通過黃嘌呤氧化酶的作用產(chǎn)生，黃嘌呤氧化酶通過氧分子致使自由基超氧陰離子形成[16]。有研究表明，黃嘌呤氧化酶在心房顫動患者左心耳的酶活性比健康對照組高4.4倍[17]。此外，氧化應激可能會加劇細胞損傷，進而促進心房重構[18]。因此，SUA作為一個氧化應激的標志物，在心房顫動的產(chǎn)生、發(fā)展和復發(fā)中發(fā)揮了重要作用。

表3陣發(fā)性心房顫動患者射頻消融術后復發(fā)影響因素的多因素Logistic回歸分析

Table 3Multivariate Logistic regression analysis on influencing factors for the recurrence of paroxysmal atrial fibrillation after radiofrequency ablation

自變量bSEWaldχ2值P值OR(95%CI)年齡0.0600.0680.7790.3771.062(0.930,1.212)病程0.5360.3192.8350.0921.710(0.916,3.192)LAD0.6650.3164.4370.0351.945(1.047,3.612)術前SUA0.0230.00710.1450.0011.024(1.009,1.038)術前hs-CRP1.5610.6405.9500.0154.762(1.359,16.685)術前WBC0.1240.4640.0720.7891.132(0.456,2.812)

表1　兩組臨床特征比較

注：CCB=鈣離子拮抗劑，ACEI/ARB=血管緊張素轉(zhuǎn)換酶抑制劑/血管緊張素受體拮抗劑；LAD=左心房前后徑；a為t值

表2　復發(fā)組與未復發(fā)組各時間炎性因子水平比較±s)

注：與同組術前比較，aP<0.05；與同組術后1周比較，bP<0.05；SUA=血尿酸,hs-CRP=超敏C反應蛋白,WBC=白細胞計數(shù)

本研究表明，術前高SUA、hs-CRP水平和增大的LAD是陣發(fā)性心房顫動患者射頻消融術后復發(fā)的獨立預測因子，提示了炎癥和氧化應激對心房顫動射頻消融術后的復發(fā)有明顯的影響。降低SUA水平可能會改善心房顫動患者的預后，進一步降低射頻消融術后的復發(fā)率。SUA作為一種經(jīng)濟、易檢測的生物標志物，臨床工作中應引起關注。然而，目前尚不清楚在射頻消融術中SUA是治療中需要干預的指標，或僅為簡單的血清標志物[19]，進一步探討心房顫動與炎性標志物的關系和機制可能對心房顫動的治療產(chǎn)生指導。

志謝：感謝南京醫(yī)科大學附屬常州第二人民醫(yī)院心血管內(nèi)科全體醫(yī)生對課題的實施、評估、資料收集提供的幫助與指導。

作者貢獻：胡曉進行課題設計與實施、資料收集與整理、撰寫論文、成文并對文章負責；張靜負責課題設計及數(shù)據(jù)統(tǒng)計分析；丁志堅進行質(zhì)量控制及審校。

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(本文編輯：吳立波)

Relationship Between Serum Uric Acid Level and Recurrence of Patients With Paroxysmal Atrial Fibrillation After Radiofrequency Ablation

HUXiao,ZHANGJing，DINGZhi-jian.

DepartmentofCardiovascularMedicine,ChangzhouSecondPeople′sHospitalAffiliatedtoNanjingMedicalUniversity,Changzhou213000,China

【Abstract】ObjectiveTo establish the relation between serum uric acid (SUA) level and the recurrence of patients with paroxysmal atrial fibrillation after radiofrequency ablation.MethodsFrom June 2011 to January 2014,we enrolled 91 paroxysmal atrial fibrillation patients who received radiofrequency ablation in Changzhou Second People′s Hospital Affiliated to Nanjing Medical University.Three months after the operation,electrocardiogram or 24 h dynamic electrocardiogram were conducted to determine whether atrial fibrillation recurred,and divided the patients into recurrence group (n=20) and non-recurrence group (n=71).The clinical data of patients were recorded in detail.Early-morning fasting venous blood was sampled before the operation,one week and 6 months after the operation to determine SUA,hs-CRP and WBC level.ResultsThe recurrence group had higher age,longer disease course and larger LAD than non-recurrence group(P<0.05).The recurrence group had higher SUA and hs-CRP level than the non-recurence group before the operation,one week and 6 months after the operation,and the recurrence group was higher than non-recurrence group in WBC level before the operation(P<0.05).The SUA and hs-CRP level of the recurrence group one week after the operation were higher than those before the operation,and the SUA and hs-CRP level of the recurrence group six months after the operation were lower than those one week after the operation(P<0.05).The SUA level of non-recurrence group one week after operation was higher than that before the operation,and the SUA level of non-recurrence group six months after operation was lower than that before the operation and one week after the operation(P<0.05).The hs-CRP level of the non-recurrence group one week after the operation was higher than that before the operation,and the hs-CRP level of the non-recurrence group six months after the operation were lower than those one week after the operation(P<0.05).Multivariate Logistic regression analysis showed that LAD〔OR=1.945,95%CI(1.047，3.612)〕,SUA〔OR=1.024,95%CI(1.009，1.038)〕 and hs-CRP〔OR=4.762,95%CI(1.359，16.685)〕 before the operation were independent risk factors for the recurrence of atrial fibrillation after radiofrequency ablation (P<0.05).ConclusionHigh SUA level before surgery is an independent predictive factor for the recurrence of atrial fibrillation after radiofrequency ablation.Lowering SUA level may improve the prognosis of patients with atrial fibrillation and lower the recurrence rate of atrial fibrillation after radiofrequency ablation.

【Key words】Atrial fibrillation；Uric acid；Catheter ablation ；Recurrence

通信作者：丁志堅，213000江蘇省常州市，南京醫(yī)科大學附屬常州市第二人民醫(yī)院心血管內(nèi)科；

【中圖分類號】R 541.75

【文獻標識碼】A

DOI:10.3969/j.issn.1007-9572.2016.19.010

(收稿日期：2015-09-23；修回日期：2016-03-29)

E-mail：dingzhijian@hotmail.com.cn