血尿酸水平与阵发性心房颤动患者射频消融术后复发的关系

胡 晓，张 静，丁志坚



·论著·

血尿酸水平与阵发性心房颤动患者射频消融术后复发的关系

胡 晓，张 静，丁志坚

213000江苏省常州市，南京医科大学附属常州市第二人民医院心血管内科(胡晓，丁志坚)；江苏护理职业学院(张静)

【摘要】目的探讨血尿酸(SUA)水平与阵发性心房颤动患者射频消融术后复发的关系。方法选取2011年6月—2014年1月在南京医科大学附属常州市第二人民医院行射频消融术治疗的91例阵发性心房颤动患者为研究对象。术后3个月经心电图或24 h动态心电图检查确定有无心房颤动复发，将患者分为复发组(20例)和未复发组(71例)。详细记录患者的临床资料，分别于术前及术后1周、6个月抽取清晨空腹静脉血检测SUA、超敏C反应蛋白(hs-CRP)、白细胞计数(WBC)水平。结果复发组年龄、病程、左心房前后径(LAD)大于未复发组(P<0.05)。复发组术前、术后1周及术后6个月SUA、hs-CRP水平高于未复发组，复发组术前WBC水平高于未复发组(P<0.05)。复发组术后1周SUA、hs-CRP水平高于术前，术后6个月SUA、hs-CRP水平低于术后1周(P<0.05)。未复发组术后1周SUA水平高于术前，术后6个月SUA水平低于术前和术后1周(P<0.05)；术后1周hs-CRP水平高于术前，术后6个月hs-CRP水平低于术后1周(P<0.05)。多因素Logistic回归分析结果显示，LAD〔OR=1.945,95%CI(1.047，3.612)〕及术前SUA〔OR=1.024,95%CI(1.009，1.038)〕、hs-CRP〔OR=4.762,95%CI(1.359，16.685)〕水平是阵发性心房颤动患者射频消融术后复发的独立危险因素(P<0.05)。结论术前高SUA水平是阵发性心房颤动患者射频消融术后复发的独立预测因子，降低SUA水平可能会改善心房颤动患者的预后，降低射频消融术后的复发率。

【关键词】心房颤动；尿酸；导管消融术；复发

胡晓，张静，丁志坚.血尿酸水平与阵发性心房颤动患者射频消融术后复发的关系[J].中国全科医学，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.

心房颤动是临床最常见的心律失常。在过去的20年中，射频消融术已成为对药物治疗无效心房颤动患者的重要治疗手段[1]，但术后仍存在复发的风险。越来越多的证据表明，炎症在心房颤动的发生和维持中发挥重要作用。心房颤动患者炎性标志物水平升高，如超敏C反应蛋白(hs-CRP)、白介素6、白介素8和白细胞计数(WBC)等[2-4]。升高的血尿酸(SUA)能够激活炎症和氧化应激途径，炎症和氧化应激相互作用，形成钙超载并降低钠通道的活性，进而导致电重构；与此同时，通过成纤维细胞的增殖、炎症和细胞凋亡形成结构重构[5]。高水平SUA是心房颤动发生与发展的重要危险因素[6]，但术前SUA水平能否预测心房颤动患者射频消融术后的复发仍不明确。笔者假设，通过引起电重构和结构重构，SUA水平在心房颤动的复发中起了重要作用。本研究旨在探讨术前SUA水平与阵发性心房颤动患者射频消融术后复发的关系以及其对复发的预测价值。

1对象与方法

1.1研究对象选取2011年6月—2014年1月在南京医科大学附属常州市第二人民医院行射频消融术治疗的91例阵发性心房颤动患者为研究对象。纳入标准：(1)有症状的阵发性心房颤动，阵发性心房颤动的定义为症状持续时间≤7 d；(2)术前使用至少1种抗心律失常药物治疗失败。排除标准：(1)中度至重度心脏瓣膜病，左心房血栓，心力衰竭，心肌梗死或3个月前行心脏手术，左心房前后径(LAD)大于55 mm，有抗凝禁忌证；(2)正在服用维生素制剂(包括维生素C、烟酸、叶酸)，利尿药物或降低尿酸的药物(别嘌呤醇)；(3)未控制的甲状腺功能异常，肾功能不全(血肌酐水平≥1.5 mg/dl)，肝病及溶血性疾病，肿瘤或任何其他全身性疾病；(4)妊娠。治疗方案经本院医学伦理委员会批准，患者签署知情同意书。

1.2方法

1.2.1术前准备患者均行超声心动图排除心脏结构异常，经食管超声排除左心房血栓。术前3 d停止服用华法林，并予低分子肝素抗凝。

1.2.2手术方法在左心房三维重建标测下行环肺静脉隔离消融。根据术中患者情况行肺静脉隔离(PVI)或PVI+线性消融与左心房复杂碎裂电位消融。术后给予持续24 h心电监护，6 h后予华法林和低分子肝素抗凝，维持凝血酶原国际标准化比值(INR)2～3。患者术后3个月内继续服用术前所服用的抗心律失常药物。3个月后根据患者CHADS2评分决定是否继续服用华法林[7]。分别于术后3、6、12个月进行随访，此后每6个月进行随访。随访内容包括心电图及24 h动态心电图检查。如若患者出现心悸等不适则及时至医院行心电图及24 h动态心电图检查。

1.2.3复发判断标准术后3个月经心电图或24 h动态心电图证实出现超过30 s的房性心律失常，包括心房颤动、心房扑动和房性心动过速。据此，将患者分为复发组(20例)和未复发组(71例)。

1.3观察指标详细记录患者的临床资料，包括性别、年龄、病程、BMI，有无高血压、血脂异常，钙离子拮抗剂(CCB)、血管紧张素转换酶抑制剂/血管紧张素受体拮抗剂(ACEI/ARB)使用情况以及超声心动图等相关信息。分别于术前及术后1周、6个月抽取清晨空腹静脉血检测SUA、hs-CRP、WBC水平。

2结果

2.1两组患者临床特征比较两组性别、BMI，高血压、高血脂检出率，CCB、ACEI/ARB使用比例比较，差异均无统计学意义(P>0.05)。复发组年龄、病程、LAD大于未复发组，差异均有统计学意义(P<0.05，见表1)。

2.2两组炎性因子水平比较复发组术前、术后1周及术后6个月SUA、hs-CRP水平高于未复发组，复发组术前WBC水平高于未复发组，差异均有统计学意义(P<0.05)。复发组术后1周SUA、hs-CRP水平高于术前，术后6个月SUA、hs-CRP水平低于术后1周，差异均有统计学意义(P<0.05)。未复发组术后1周SUA水平高于术前，术后6个月SUA水平低于术前和术后1周；术后1周hs-CRP水平高于术前，术后6个月hs-CRP水平低于术后1周，差异均有统计学意义(P<0.05，见表2)。

2.3多因素Logistic回归分析以射频消融术后复发(赋值：是=1，否=0)为因变量，以年龄、病程、LAD及术前SUA、hs-CRP、WBC水平为自变量行多因素Logistic回归分析。结果显示，LAD及术前SUA、hs-CRP水平是阵发性心房颤动患者射频消融术后复发的影响因素(P<0.05，见表3)。

3讨论

本研究对91例阵发性心房颤动患者射频消融术后进行(17.2±5.7)个月的随访，20例(22.0%)出现复发。术后1周患者SUA、hs-CRP水平较术前明显升高，考虑与射频消融过程中引起心肌损伤，进而诱导机体继发无菌性炎性反应有关[8]。未复发组患者在术后6个月SUA水平恢复至比术前更低水平，说明心房颤动在转复和维持窦性心律后，消除了炎症触发心房肌致使心房颤动的机制，进而降低了炎性反应水平，使得术后炎性因子水平下降[9]。而复发组患者术后6个月SUA水平与术前相比并无明显变化，复发组患者术后SUA水平与未复发组患者同期进行比较有差异，提示复发组患者SUA仍处于较高水平，机体仍相对存在炎性反应。多因素Logistic回归分析发现，术前SUA水平可作为独立的预测心房颤动射频术后复发的危险因素〔OR=1.024，95%CI(1.009,1.038)，P=0.001〕，高水平SUA患者在术后有更高的复发风险。

心房颤动发生和维持的确切机制尚不清楚，但炎症和氧化应激在其中发挥了重要作用[10]。SUA是嘌呤的代谢产物，大量证据表明，SUA水平与多种心血管疾病有关，包括高血压、糖尿病、充血性心力衰竭、冠心病和卒中[11-12]。SUA水平升高是细胞窘迫的迹象，SUA从濒死细胞中释放，引起固有和后天适应性免疫应答。SUA刺激白介素6和肿瘤坏死因子表达，这些炎性细胞因子均与心房颤动有关[13]。前瞻性研究表明，SUA与氧化应激有关[14]，而氧化应激是心房颤动最重要的致病机制[15]。SUA通过黄嘌呤氧化酶的作用产生，黄嘌呤氧化酶通过氧分子致使自由基超氧阴离子形成[16]。有研究表明，黄嘌呤氧化酶在心房颤动患者左心耳的酶活性比健康对照组高4.4倍[17]。此外，氧化应激可能会加剧细胞损伤，进而促进心房重构[18]。因此，SUA作为一个氧化应激的标志物，在心房颤动的产生、发展和复发中发挥了重要作用。

表3阵发性心房颤动患者射频消融术后复发影响因素的多因素Logistic回归分析

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

自变量bSEWaldχ2值P值OR(95%CI)年龄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)术前SUA0.0230.00710.1450.0011.024(1.009,1.038)术前hs-CRP1.5610.6405.9500.0154.762(1.359,16.685)术前WBC0.1240.4640.0720.7891.132(0.456,2.812)

表1　两组临床特征比较

注：CCB=钙离子拮抗剂，ACEI/ARB=血管紧张素转换酶抑制剂/血管紧张素受体拮抗剂；LAD=左心房前后径；a为t值

表2　复发组与未复发组各时间炎性因子水平比较±s)

注：与同组术前比较，aP<0.05；与同组术后1周比较，bP<0.05；SUA=血尿酸,hs-CRP=超敏C反应蛋白,WBC=白细胞计数

本研究表明，术前高SUA、hs-CRP水平和增大的LAD是阵发性心房颤动患者射频消融术后复发的独立预测因子，提示了炎症和氧化应激对心房颤动射频消融术后的复发有明显的影响。降低SUA水平可能会改善心房颤动患者的预后，进一步降低射频消融术后的复发率。SUA作为一种经济、易检测的生物标志物，临床工作中应引起关注。然而，目前尚不清楚在射频消融术中SUA是治疗中需要干预的指标，或仅为简单的血清标志物[19]，进一步探讨心房颤动与炎性标志物的关系和机制可能对心房颤动的治疗产生指导。

志谢：感谢南京医科大学附属常州第二人民医院心血管内科全体医生对课题的实施、评估、资料收集提供的帮助与指导。

作者贡献：胡晓进行课题设计与实施、资料收集与整理、撰写论文、成文并对文章负责；张静负责课题设计及数据统计分析；丁志坚进行质量控制及审校。

本文无利益冲突。

参考文献

[1]任焱.射频消融术治疗阵发性室上性心动过速的临床疗效分析[J].实用心脑肺血管病杂志，2014,22(8):72-73.

REN Y.Effect of radiofrequency ablation on paroxysmal supraventricular tachycardia[J].PJCCPVD,2014,22(8):72-73.

[2]LIU T,LI G,LI L,et al.Association between C-reactive protein and recurrence of atrial fibrillation after successful electrical cardioversion:a meta-analysis[J].J Am Coll Cardiol,2007,49(15):1642-1648.DOI:10.1016/j.jacc.2006.12.042.

[3]LAMM G,AUER J,WEBER T,et al.Postoperative white blood cell count predicts atrial fibrillation after cardiac surgery[J].J Cardiothorac Vasc Anesth,2006,20(1):51-56.DOI:10.1053/j.jvca.2005.03.026.

[4]LIUBA I,AHLMROTH H,JONASSON L.Source of inflammatory markers in patients with atrial fibrillation[J].Europace,2008,10(7):848-853.DOI:10.1093/europace/eun111.

[5]YOUN J Y,ZHANG J,ZHANG Y,et al.Oxidative stress in atrial fibrillation:an emerging role of NADPH oxidase[J].J Mol Cell Cardiol,2013,62:72-79.DOI:10.1016/j.yjmcc.2013.04.019.

[6]NYRNES A,IOGT I,NJLSTAD I,et al.Uric acid is associated with future atrial fibrillation:an 11-year follow-up of 6308 men and women-the Tromso Study[J].Europace,2014,16(3):320-326.DOI:10.1093/europace/eut260.

[7]GAGE B F,WATERMAN A D,SHANNON W,et al.Validation of clinical classification schemes for predicting stroke:results from the National Registry of Atrial Fibrillation[J].JAMA,2001,285(22):2864-2870.DOI:10.1001/jama.285.22.2864.

[8]PSYCHARI S N,APOSTOLOU T S,SINOS L,et al.Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation[J].Am J Cardiol,2005,95(6):764-767.DOI:10.1016/j.amjcard.2004.11.032.

[9]MARCUS G M,SMITH L M,ORDOVAS K,et al.Intracardiac and extracardiac markers of inflammation during atrial fibrillation[J].Heart Rhythm,2010,7(2):149-154.

[10]MIHM M J,YU F,CARNES C A,et al.Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation[J].Circulation,2001,104(2):174-180.DOI:10.1161/01.CIR.104.2.174.

[11]HEO S H,LEE S H.High levels of serum uric acid are associated with silent brain infarction[J].J Neurol Sci,2010,297(1/2):6-10.

[12]KIM T H,LEE S S,YOO J H,et al.The relationship between the regional abdominal adipose tissue distribution and the serum uric acid levels in people with type 2 diabetes mellitus[J].Diabetol Metab Syndr,2012,4(1):3.DOI:10.1186/1758-5996-4-3.

[13]YAMASHITA T,SEKIGUCHI A,IWASAKI Y K,et al.Recruitment of immune cells across atrial endocardium in human atrial fibrillation[J].Circ J,2010,74(2):262-270.DOI:10.1253/circj.CJ-09-0644.

[14]SUN C C,LUO F F,WEI L,et al.Association of serum uric acid levels with the progression of Parkinson′s disease in Chinese patients[J].Chin Med J:Engl,2012,125(4):583-587.DOI:10.3760/cma.j.issn.0366-6999.2012.04.005.

[15]KIM S M,LEE J H,KIM J R,et al.Female patients with atrial fibrillation have increased oxidized and glycated lipoprotein properties and lower apolipoprotein A-I expression in HDL[J].Int J Mol Med,2011,27(6):841-849.DOI:10.3892/ijmm.2011.646.

[16]WU S H,SHU X O,MILNE G,et al.Uric acid correlates to oxidation and inflammation in opposite directions in women[J].Biomarkers,2015,20(4):225-231.DOI:10.3109/1354750X.2015.1068852.

[17]DUDLEY S C,HOCH N E,MCCANN L A,et al.Atrial fibrillation increases production of superoxide by the left atrium and left atrial appendage:role of the NADPH and xanthine oxidases[J].Circulation,2005,112(9):1266-1273.DOI:10.1161/CIRCULATIONAHA.105.538108.

[18]VAN WAGONER D R.Oxidative stress and inflammation in atrial fibrillation:role in pathogenesis and potential as a therapeutic target[J].J Cardiovasc Pharmacol,2008,52(4):306-313.DOI:10.1097/FJC.0b013e31817f9398.

[19]KIRCHHOF P,BREITHARDT G,ALIOT E,et al.Personalized management of atrial fibrillation:proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference[J].Europace,2013,15(11):1540-1556.DOI:10.1093/europace/eut232.

(本文编辑：吴立波)

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：丁志坚，213000江苏省常州市，南京医科大学附属常州市第二人民医院心血管内科；

【中图分类号】R 541.75

【文献标识码】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