中华流行病学杂志  2015, Vol. 36 Issue (1): 87-89   PDF    
http://dx.doi.org/10.3760/cma.j.issn.0254-6450.2015.01.020
中华医学会主办。
0

文章信息

范国辉, 张林峰. 2014.
Fan Guohui, Zhang Linfeng. 2014.
心源性猝死的流行病学研究进展
Sudden cardiac death:progress in epidemiological research
中华流行病学杂志, 2015, 36(1): 87-89
Chinese Journal of Epidemiology, 2015, 36(1): 87-89
http://dx.doi.org/10.3760/cma.j.issn.0254-6450.2015.01.020

文章历史

投稿日期:2014-08-21
心源性猝死的流行病学研究进展
范国辉, 张林峰     
102308 北京, 中国医学科学院阜外心血管病医院国家心血管中心社区防治部
关键词心脏性猝死     流行病学    
Sudden cardiac death:progress in epidemiological research
Fan Guohui, Zhang Linfeng     
Division of Prevention and Community Health, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Acadamy of Medical Sciences, Beijing 102308, China
Key words: Sudden cardiac death     Epidemiology    

心源性猝死(SCD)是一个多病因、多危险因素疾病,是65岁以下成年人最常见死因,对患者及家庭影响深远,成为重大公共健康问题[1]。SCD也为院外心血管病死因之首,所占比例为60%[2]。近年来随着医疗环境的改善,SCD预防和急救设备如埋藏式复律除颤器(implantable cardioverter defibrillators,ICD)和自动体外除颤器(automated external defibrillators,AED)等的使用,使SCD的预防和管理取得显著进展。然而,SCD仍是一个不可忽视的公共健康问题。一方面由于糖尿病、高血压和冠心病等疾病发病率和患病率迅速增长,使得人群中心脏病或潜在心脏病患者的比例扩大,SCD的发病风险大幅上升;另一方面由于发生SCD的患者大多为之前未被诊断过心脏疾病,也未达到高风险标准的“健康人”[3]。为此笔者回顾近年来SCD研究进展,重点探讨其流行现状、危险因素和预防措施。

1. SCD流行现状:

(1)定义:目前广为接受的SCD定义是指突发性的非预料死亡,表现为症状出现短期内发生的突发意识丧失及循环、呼吸骤停。“短期”所规定时限为,有目击者时<1h,无目击者时为24h[4],死因多为心律失常,包括由心肌梗死造成的猝死,但不含如卒中、肺栓塞、大动脉破裂和药物或酒精中毒等原因导致的猝死[4]

(2)发病率:各国对SCD的研究广受重视。据估计,在美国SCD每年可造成18万至40万的死亡[5,6],占冠心病死亡的一半[7],但各研究机构往往采取不同的数据源、SCD定义、病例估算以及确诊方法,导致研究结果波动较大[6],如基于死亡证明书的研究对SCD资料收集很敏感,但是此法特异度不够,有可能高估真实的发病率,而严格限定死亡时间在1h内其标准又可导致病例数损失[2]。在日本Tokashiki等[8]开展的一项对冲绳南部居民SCD回顾性研究中,除将发生时间<1h的事件纳入外,还包含急性发作至死亡间隔2d的病例,最终得到该地区的年发病粗率为37/10万。原因是考虑到死亡证明书上记录的时间可能有偏倚,急性发作至死亡所经历的真实时间可能<24h;此外,Tokashiki等[8]还将医院记录、法院医疗记录以及警察局记录等一并考虑在内,这样多渠道收集信息,以确保无遗漏SCD病例。中国医学科学院阜外心血管病医院Hua等[9]在国内建立了3级疾病上报和确诊体系进行SCD调查,结果显示我国SCD发病率(40/10万至50/10万)虽低于美国等西方国家(40/10万至90/10万),但由于人口基数大,SCD致死人数也多。

(3)年龄分布:成年人中SCD发病风险随年龄增加而增多,并在一定程度上反映CHD的发病率[5]。<35岁人群发病率较低,在英国伦敦地区和意大利Veneto地区分别为平均4.5/10万[10]和1.4/10万[11]。我国一项研究显示,中老年男性SCD发病率显著增加,且大多数病例发生在≥65岁人群[9]。80岁老年男性SCD年发病率约为40岁男性的7倍;女性SCD随年龄的分布则显得更为极端:>70岁女性的发病率是<45岁女性发病率的40倍以上[12]

(4)性别分布:国外研究显示,男性SCD的发病率是女性的2~3倍[13];我国Hua等[9]研究显示,农村地区男性发病率是城市男性的2倍,约为女性的3倍。我国男女性总体发病率分别为44.6/10万和39.0/10万,差异无统计学意义。青年人群中SCD即以男性为主,性别比为1.5~3.6∶ 1[14];中年男性SCD发病风险为同年龄段女性的4倍,但该差异随年龄的增加而减小,其原因可能是女性绝经后CHD的患病率逐渐增加,而CHD则是SCD首要危险因素[2]

2.病因及危险因素:

(1)传统危险因素:SCD病因复杂且难以预测,是约50%的心脏病首发症状[15]。80%的SCD由冠状动脉性心脏病(CHD)引起[16]。已证实的SCD传统危险因素包括年龄增加、男性、吸烟、高血压、糖尿病、高脂血症、肥胖和CHD家族史等[17],但这些因素特异性差。有文献指出左室射血分数(LVEF)可作为缺血性或非缺血性心脏病导致猝死的较强独立预测因子[18],但仅凭单个危险因素预测有很大的局限[19]。对此国外有研究提出,综合考虑年龄、心功能等级、心衰病史、不稳定性心律失常、LVEF等因素[20,21],可达到准确预测目的。

(2)心肌梗死:是SCD一个重要的危险因素。研究显示,急性ST段抬高性心肌梗死与心律失常和心脏停搏有关联,而后两者与心肌梗死后瘢痕性室性心动过速往往导致SCD[22]。心肌梗死后30d内SCD发病风险最高,并随着时间推移发病风险逐渐下降[23]

(3)心衰:是诱发SCD另一个重要的危险因素。我国一项大型流行病学调查显示,当前35~74岁人群中有超过40万例心衰患者,其中35~44岁人群的发病率为0.4%,>55岁者为1.3%,表明心衰发病率风险随年龄增加而增加[24]。心衰将导致SCD发病风险增加5倍,死于心衰的患者中,约30%~50%是由于SCD[25]。在心衰症状轻微的患者中,有66%发生SCD,而症状严重者中,只有33%发生SCD[26],说明心衰症状的轻重不足以成为SCD判断的条件,其具体判别机制仍需探讨。

(4)异常心电图:一般人群QT间隙延长可与SCD相关[27]。校正QT间隙长度>440ms者,其SCD发病风险是小于该长度者的2.3倍,且该因素独立于年龄、性别、心率和药物使用[28]。此外,运动心电图记录的异常心律、延迟电位、T波交替以及缺血性J波均提示与SCD有关联[29]

3. 预防和治疗:SCD由于缺乏特异性的判别因素,因此将个体的有效措施用于人群防治可能收效甚微[30],但由于SCD与心脏病尤其是CHD相关,因此降低一般心脏病危险因素的措施,亦可降低人群SCD的发病率。主要包括健康查体、健康咨询、纠正危险生活方式等,对有家族史、心肌梗死及心律失常的高危个体给以特别关注,做好三级预防。

(1)心脏磁共振成像(cardiac magnetic resonance imaging,CMR):是一种新型无辐射且效果优良的检测方法,对防治SCD有重要意义。CMR可准确评估心左室和右室功能,提供梗死面积及其组织特征等有价值信息[31]。不断有证据显示,CMR测量梗死面积在两方面优于LVEF,其中识别电生理诱发实验(EPS)可诱导室速患者[32],此外还可预测死亡或适用ICD疗法的患者[33]。但CMR应用前景仍需进一步证实其分类和检测作用[34]

(2)ICD置入:该方法可显著降低SCD幸存者及器质性心脏病患者的猝死风险,是目前高危患者预防和治疗SCD的主要手段[35]。ICD是通过在心脏内给以较低的能量,短时间内终止室速、室颤,达到预防猝死的目的,但由于目前使用ICD的护理费用昂贵,在一定程度上限制了其使用[36]

(3)使用AED:个体在发生SCD后保障存活最重要的条件是及时除颤。在无心肺复苏(CPR)和进行CPR下SCD患者的生还率分别为每分钟减少7%~10%和3%~4%[37];如10min内未进行除颤,95%的患者会死亡。我国的急救反应时间平均为16.5min,有些地区甚至>30min,与西方国家差距较大。有研究显示,AED的操作简便易学[38]。如在公共场所放置AED,当发生SCD可及时得到CPR和除颤,患者存活概率将大大提高。

(4)药物预防和治疗:目前药物可作为ICD的辅助治疗,其中有效抑制交感神经兴奋的β受体阻滞剂成为预防室速和室颤的一线药物[18]。研究显示,在长QT综合征患者中使用β受体阻滞剂,可60%减少各类心脏事件发生风险[39]

(5)其他方法:心室同步化起搏-电复律除颤器(cardiacresynchronization therapy with a defibrillator,CRT-D)是近年来心衰和SCD治疗的重大进展之一,适用于LVEF≤0.35、心衰和心电图显示QRS期延长性心律失常患者[40]。研究证实,与ICD相比,CRT-D可显著减少死亡率与再住院率,但可增加设备相关感染率[41]。另外随着自主神经活动与SCD的关系逐渐被阐明,肾动脉神经消融(renal artery denervation,RDN)预防SCD、治疗室性心动过速(ventricular tachycardia,VT)的价值也在凸显,国外已有RDN方法成功治疗VT的案例[42],但其进一步应用仍需探索。

4. 展望:目前在SCD的发病机制、危险因素、预防治疗及患者管理上,国内外均取得显著成果,但SCD仍是一个世界性的重大健康问题。当前对SCD定义还有争议,各地区研究者资料收集方法也不尽相同,对各地区实际发病情况的了解带来一定困难。SCD的危险因素也缺乏特异性指标,需要探索出更多的多变量协同模式以进行预测控制及识别高危人群。预防和治疗SCD还需要全社会共同努力并配备和培训使用AED。总之,控制SCD,减少其对社会的危害,还有很长一段路要走。

参考文献
[1] Gillum RF. Sudden coronary death in the United States:1980- 1985[J]. Circulation, 1989, 79(4):756-765.
[2] Adabag AS, Luepker RV, Roger VL, et al. Sudden cardiac death:epidemiology and risk factors[J]. Nature Rev Cardiol, 2010, 7(4):216-225.
[3] Myerburg RJ, Reddy V, Castellanos A. Indications for implantable cardioverter-defibrillators based on evidence and judgment[J]. J Am Coll Cardiol, 2009, 54(9):747-763.
[4] Chugh SS, Reinier K, Teodorescu C, et al. Epidemiology of sudden cardiac death:clinical and research implications[J]. Prog Cardiovasc Dis, 2008, 51(3):213-228.
[5] Chugh SS, Jui J, Gunson K, et al. Current burden of sudden cardiac death:multiple source surveillance versus retrospective death certificate-based review in a large U.S. community[J]. J Am Coll Cardiol, 2004, 44(6):1268-1275.
[6] Kong MH, Fonarow GC, Peterson ED, et al. Systematic review of the incidence of sudden cardiac death in the United States[J]. J Am Coll Cardiol, 2011, 57(7):794-801.
[7] Myerburg RJ, Kessler KM, Castellanos A. Sudden cardiac death:epidemiology, transient risk, and intervention assessment[J]. Ann Int Med, 1993, 119(12):1187-1197.
[8] Tokashiki T, Muratani A, Kimura Y, et al. Sudden death in the general population in Okinawa:incidence and causes of death[J].Japan Circul J, 1999, 63(1):37-42.
[9] Hua W, Zhang LF, Wu YF, et al. Incidence of sudden cardiac death in China:analysis of 4 regional populations[J]. J Am Coll Cardiol, 2009, 54(12):1110-1118.
[10] Donohoe RT, Innes J, Gadd S, et al. Out-of-hospital cardiac arrest in patients aged 35 years and under:a 4-year study of frequency and survival in London[J]. Resuscitation, 2010, 81(1):36-41.
[11] Corrado D, Basso C, Rizzoli G, et al. Does sports activity enhance the risk of sudden death in adolescents and young adults?[J]. J Am Coll Cardiol, 2003, 42(11):1959-1963.
[12] Tung P, Albert CM. Causes and prevention of sudden cardiac death in the elderly[J]. Nature Rev Cardiol, 2013, 10(3):135- 142.
[13] Obias-Manno D, Wijetunga M. Risk stratification and primary prevention of sudden cardiac death:sudden death prevention[J].AACN Clin Issu, 2004, 15(3):404-418.
[14] Holst AG, Winkel BG, Theilade J, et al. Incidence and etiology of sports-related sudden cardiac death in Denmark—implications for preparticipation screening[J]. Heart Rhythm, 2010, 7(10):1365-1371.
[15] de Vreede-Swagemakers JJ, Gorgels AP, Dubois-Arbouw WI, et al. Out-of-hospital cardiac arrest in the 1990's:a population- based study in the Maastricht area on incidence, characteristics and survival[J]. J Am Coll Cardiol, 1997, 30(6):1500-1505.
[16] Zipes DP. Epidemiology and mechanisms of sudden cardiac death[J]. Can J Cardiol, 2005, 21 Suppl A:37A-40A.
[17] Jouven X, Desnos M, Guerot C, et al. Predicting sudden death in the population:the Paris Prospective Study Ⅰ[J]. Circulation, 1999, 99(15):1978-1983.
[18] John RM, Tedrow UB, Koplan BA, et al. Ventricular arrhythmias and sudden cardiac death[J]. Lancet, 2012, 380(9852):1520- 1529.
[19] Lam CS, Anand I, Zhang S, et al. Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry[J]. Eur J Heart Fail, 2013, 15(8):928-936.
[20] Buxton AE, Lee KL, Hafley GE, et al. Limitations of ejection fraction for prediction of sudden death risk in patients with coronary artery disease:lessons from the MUSTT study[J]. J Am Coll Cardiol, 2007, 50(12):1150-1157.
[21] Buxton AE. Risk stratification for sudden death in patients with coronary artery disease[J]. Heart Rhythm, 2009, 6(6):836-847.
[22] Solomon SD, Zelenkofske S, McMurray JJ, et al. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both[J]. New Engl J Med, 2005, 352(25):2581-2588.
[23] Adabag AS, Therneau TM, Gersh BJ, et al. Sudden death after myocardial infarction[J]. JAMA, 2008, 300(17):2022-2029.
[24] Jiang H, Ge J. Epidemiology and clinical management of cardiomyopathies and heart failure in China[J]. Heart, 2009, 95(21):1727-1731.
[25] Kannel WB, Plehn JF, Cupples LA. Cardiac failure and sudden death in the Framingham Study[J]. Am Heart J, 1988, 115(4):869-875.
[26] Myerburg RJ. Scientific gaps in the prediction and prevention of sudden cardiac death[J]. J Cardiovascu Electrophysiol, 2002, 13(7):709-723.
[27] Chugh SS, Reinier K, Singh T, et al. Determinants of prolonged QT interval and their contribution to sudden death risk in coronary artery disease:the Oregon Sudden Unexpected Death Study[J]. Circulation, 2009, 119(5):663-670.
[28] Al Aloul B, Adabag AS, Houghland MA, et al. Brugada pattern electrocardiogram associated with supratherapeutic phenytoin levels and the risk of sudden death[J]. Pac Clin Electrophysiol, 2007, 30(5):713-715.
[29] Stein KM. Noninvasive risk stratification for sudden death:signal- averaged electrocardiography, nonsustained ventricular tachycardia, heart rate variability, baroreflex sensitivity, and QRS duration[J].Prog Cardiovasc Dis, 2008, 51(2):106-117.
[30] Chugh SS. Early identification of risk factors for sudden cardiac death[J]. Nature Rev Cardiol, 2010, 7(6):318-326.
[31] Yan AT, Shayne AJ, Brown KA, et al. Characterization of the peri- infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality[J]. Circulation, 2006, 114(1):32-39.
[32] Bello D, Fieno DS, Kim RJ, et al. Infarct morphology identifies patients with substrate for sustained ventricular tachycardia[J]. J Am Coll Cardiol, 2005, 45(7):1104-1108.
[33] Totzeck M, Hendgen-Cotta UB, Rammos C, et al. Assessment of the functional diversity of human myoglobin[J]. Nitric Oxide , 2012, 26(4):211-216.
[34] Zaman S, Kovoor P. Sudden cardiac death early after myocardial infarction:pathogenesis, risk stratification, and primary prevention[J]. Circulation, 2014, 129(23):2426-2435.
[35] Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death:a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines(writing committee to develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death):developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society[J]. Circulation, 2006, 114(10):e385-484.
[36] Josephson M, Wellens HJ. Implantable defibrillators and sudden cardiac death[J]. Circulation, 2004, 109(22):2685-2691.
[37] Hazinski MF, Idris AH, Kerber RE, et al. Lay rescuer automated external defibrillator ("public access defibrillation") programs:lessons learned from an international multicenter trial:advisory statement from the American Heart Association Emergency Cardiovascular Committee;the Council on Cardiopulmonary, Perioperative, and Critical Care;and the Council on Clinical Cardiology[J]. Circulation, 2005, 111(24):3336-3340.
[38] Gundry JW, Comess KA, DeRook FA, et al. Comparison of naive sixth-grade children with trained professionals in the use of an automated external defibrillator[J]. Circulation, 1999, 100(16):1703-1707.
[39] Sauer AJ, Moss AJ, McNitt S, et al. Long QT syndrome in adults[J]. J Am Coll Cardiol, 2007, 49(3):329-337.
[40] Tracy CM, Epstein AE, Darbar D, et al. 2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines[J]. Heart Rhythm, 2012, 9(10):1737-1753.
[41] Masoudi FA, Mi X, Curtis LH, et al. Comparative effectiveness of cardiac resynchronization therapy with an implantable cardioverter-defibrillator versus defibrillator therapy alone:a cohort study[J]. Ann Int Med, 2014, 160(9):603-611.
[42] Remo BF, Preminger M, Bradfield J, et al. Safety and efficacy of renal denervation as a novel treatment of ventricular tachycardia storm in patients with cardiomyopathy[J]. Heart Rhythm, 2014, 11(4):541-546.