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[AHA2008] 一种炎症性疾病?——国际循环顾问委员Joseph S. Alpert谈房颤
Atrial Fibrillation- an Inflammatory Disease
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作者:JosephS.Alpert 编辑:国际循环网 时间:2008/11/7 10:19:00 关键字:房颤 炎症 细胞因子  

Joseph S. Alpert, M.D.     
  Professor of Medicine, University
of Arizona Health Sciences Center
Tucson, Arizona; Editor-in-Chief, American Journal of Medicine

美国亚利桑那医学中心医学教授
《American Journal of Medicine》杂志主编

心房颤动(房颤)是北美及欧洲患者最常见的持续性心律失常。显然,房颤在亚洲患者中不像西方那么常见1。在美国,大概有220万成人患有房颤,平均年龄在75岁。值得注意的是,80岁以上的人群中将近10%出现房颤,发病率随年龄的增长呈上升的趋势1,2。在20世纪末,Framingham心脏研究人群证实,房颤在65~74岁男性中的患病率7.8%,而在75~84岁男性达11.7%。随着工业化国家的老龄化,房颤的患病率也不断增长1-3。然而,经过年龄校正后,房颤的患病率近年来也不断上升,这提示年龄并不是房颤患病率上升的惟一原因3。  


 
    有趣地是,房颤在男性的发病率大概是女性的1.5倍。例如,Framingham心脏研究显示,无心肌梗死的男性患者房颤的发病率是8.7%,相似年龄组的女性患者房颤发病率仅为5.2%。尽管发病率存在性别差异,但由于女性的平均寿命长于男性,因此女性房颤患者总数超过男性患者。所以,在美国房颤住院患者最常见的是老年女性。

     绝大多数房颤患者伴有某种心血管疾病。常见的诱发房颤的心血管疾病包括高血压、瓣膜心脏疾病(特别是二尖瓣疾病)、伴有或不伴有心肌梗死病史的动脉粥样性心脏病以及充血性心力衰竭。诱发房颤的非心血管疾病包括糖尿病、甲状腺功能亢进、急性和慢性酒精中毒以及一系列肺部疾病,如慢性阻塞性肺病、肺炎、脓胸和肺栓塞。最后,房颤的潜在医源性因素包括心脏和非心脏手术,还有一系列药物,如扩张支气管的β受体激动剂、各种非处方感冒药、抗组胺药、局部麻醉药和含咖啡因的饮料4。最近的调查表明动脉炎症可能在房颤的发生、 持续和永久存在中发挥重要作用。确实,炎症标记物如白介素6和C反应蛋白在房颤患者中升高,特别是慢性房颤患者5

    下面是一些关于房颤的有趣的但并非众所周知的事实:

⑴地高辛治疗不能防止房颤再发,但β受体阻滞剂可以发回这个作用2,6

⑵特发的或“孤立性”房颤并不像以前认为的那样良性。Jouven 及其同事发现在患有孤立性房颤的中年法国人中,心血管死亡率升高4倍,总死亡率升高2倍7。明尼苏达州Omstead 县的最近一项研究和欧洲心力衰竭调查证实伴有或不伴有心力衰竭的新发房颤患者死亡率高,住院时间长,特别是诊断房颤后的最初4个月8,9。更值得关注的是,最近报道指出在无卒中的患者中,房颤和记忆缺陷、痴呆和海马萎缩有关10,11

⑶慢性房颤患者的生活质量和运动耐量下降。当窦性心律恢复,生活质量和运动耐量都提高12

⑷阵发性房颤患者大概40%有促发事件,如纵酒、重劳顿感和(或)情绪失常13。最常见的促发事件是运动,几乎占19%,其次是饮食,占8%,饮用含咖啡因的饮品仅占2.4%。

⑸越来越多证据表明房颤发生的遗传易感性14,常染色体显性遗传的房颤家族已有报道15

    在很多情况下,房颤会增加患者的致残率和致死率。所以,和房颤有关的迅速心室反应可以导致心肌缺血,在有潜在冠状动脉疾病的患者中引发不稳定性心绞痛或心肌梗死。关于房颤是否导致急性心肌梗死或新发心力衰竭患者预后恶化已有广泛争议。有趣地是,一些研究报道房颤是导致心力衰竭或心肌梗死患者的预后恶化的独立因素,而其他研究则发现房颤对预后无影响16-22

    虽然通常房颤使患者预后恶化,但在许多患者中,尽管房颤已持续数年甚至数十年,患者并无症状且状态良好。因此,患者的预后并不是恒定的。β受体阻滞剂、非二氢吡啶类钙离子阻断剂(地尔硫卓和维拉帕米)和(或)地高辛控制心室率联合抗凝治疗以及控制心血管危险因素可以维持房颤患者病情稳定多年,这当然是以控制良好的静息和运动心率以及防止血栓性卒中的抗凝治疗为前提。两项研究表明,与80年代相比,90年代房颤患者的预后显著改善22,23。在我自己的临床工作中,我和患者一起努力以达到静息和运动时良好的心率控制。有动脉栓塞高风险的患者也谨慎地给予华法林抗凝治疗。一些老年患者由于害怕发生出血而拒绝服用华法林,对于这类患者我改用阿司匹林,但提醒他们阿司匹林防止动脉血栓的效果没有华法林好。

Atrial fibrillation (AF) is the commonest sustained arrhythmia in North American and European patients.  Apparently, Asians are affected less commonly by AF than are patients in the West1.  In the United States, AF affects approximately 2.2 million adults whose median age is 75. It is remarkable that nearly 10% of individuals over the age of 80 manifest this arrhythmia with a clear increase in incidence and prevalence with age1,2. During the late 20th century, the Framingham Heart Study population demonstrated a 7.8% prevalence of AF in men aged 65-74 with a corresponding prevalence in men aged 75-84 of 11.7%.  As the population of older individual has increased in industrialized nations,  the prevalence of AF in these countries has also grown1-3.  However, even  age-adjusted prevalence of AF has increased in recent years suggesting that age alone does not account for all aspects of the increased frequency with which physicians are encountering patients with this arrhythmia3. 

It is of interest that atrial fibrillation occurs approximately 1.5 times more frequently in men than in women.  For example, in the Framingham Heart Study experience, the prevalence of AF in men without a prior myocardial infarction was 8.7%.  A similar cohort of women had a prevalence of AF of only 5.2%.  Despite the gender difference in prevalence, the overall number of  female patients with AF exceeds the number of men with this condition because of greater longevity in women.  Thus, the commonest hospitalized patient with AF in US hospitals is an elderly woman. 

The vast majority of patients with AF have some form of cardiovascular disease.  Common cardiovascular conditions predisposing to AF include hypertension, valvular heart disease (especially mitral valve disease), arteriosclerotic heart disease with and without a prior myocardial infarction, and congestive heart failure.  Non- cardiovascular diseases that also predispose to AF include diabetes mellitus, hyperthyroidism, acute and chronic alcohol abuse, and a variety of pulmonary diseases such as chronic obstructive lung disease, pneumonia, empyema, and pulmonary embolism. Finally, potential iatrogenic causes of AF include cardiac and non-cardiac surgery as well as therapy with a variety of medications such as bronchodilating beta agonists, various non-prescription cold remedies, antihistamines, local anesthetics, and caffeine containing beverages4.  Recent investigation has revealed that inflammation in the atria might play an important role in the initiation, maintenance, and perpetuation of AF.  Indeed, inflammatory markers such as interleukin-6 and C-reactive protein are elevated in patients with AF, particularly those individuals with chronic AF5.

Here are a number of  interesting but less well-known facts about AF: 

1) Therapy with digoxin does not prevent recurrent episodes of AF although beta blocker administration can accomplish this goal2,6. 

2) Idiopathic or “lone” AF is not as benign an entity as once thought.  Jouven and colleagues observed a 4 fold increase in cardiovascular mortality and a 2 fold increase in all cause mortality for middle-aged Frenchmen with lone AF7.  A recent community based study from Omstead County in Minnesota and the EuroHeart Failure Survey  demonstrated that patients with newly diagnosed AF with or without heart failure had a high mortality risk as well as prolonged hospitalization, especially within the first 4 months following diagnosis8,9.  Of further concern are recent reports that AF in patients w

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