房颤与偶发性心肌梗死相关

《美国医学会杂志》(JAMA)11月4日在线发表的一项对REGARDS研究数据的二次分析显示，房颤(AF)独立于冠状动脉危险因素和潜在混杂因素与偶发性心肌梗死(MI)强烈相关(JAMA Intern. Med. 2013 Nov. 4 [doi: 10.1001/jamainternmed.2013.11912])。

已知MI是AF的危险因素，近期研究表明反过来可能也成立，即AF是MI的危险因素，但目前为止尚缺乏来自人群研究的证据支持这一观点。为了探讨这一问题，维克森林大学流行病学心脏病血研究中心的Elsayed Z. Soliman医生及其同事对REGARDS研究的数据进行了二次分析。REGARDS是一项探讨卒中死亡率的地区和种族差异的原因的大型、双种族、人群队列研究，在7年密切随访(中位4.5年)中对美国东南部“卒中带”居住的超过30,000名成人的心血管风险进行了仔细研究并对偶发性MI进行严格判定。

在二次分析中，Soliman医生及其同事研究了23,928例基线时无冠心病(CHD)且AF状态已知的受试者的记录。1,631例受试者已被诊断AF或基线心电图(ECG)检出AF。随访期间共发生648起MI。

在有和无AF的受试者中，校正年龄的MI发生率分别为12例/1,000人和6例/1,000人。校正多个社会人口学因素进一步分析发现，与无AF相比，AF与MI风险增加96%相关。进一步校正CHD危险因素和多个潜在混杂因素后，仍观察到AF与偶发性MI相关。研究者表示，这些结果表明，AF与MI存在双向关联，即一方可导致另一方。既往研究发现AF与慢性肾病之间及AF与心力衰竭之间也存在相似的双向关联。

在亚组分析中，这一关联仍具有鲁棒性，不管受试者年龄如何，并且在老年成人(65岁或75岁以上)和年轻成人之间无差异。然而，该关联依受试者性别和种族而存在差异：其在黑人男性中最强烈，在白人女性中强度次之但仍具有显著性，在黑人女性中强度又次之但仍具有显著性，在白人男性中无显著性。

此外，在使用华法林的受试者中观察到的AF与偶发性MI的关联显著弱于未使用华法林的受试者中观察到的关联。这与既往研究观察到的华法林可预防急性冠状动脉综合征后MI的结果和在使用抗凝剂预防卒中的AF患者中观察到的结果一致。

虽然该研究的目的并不在于确定为什么AF可增加偶发性MI风险，但研究结果可通过以下几点加以解释。第一，AF和MI具有相似的危险因素，因此两者可能具有相同的病理生理过程。即在易感个体中，AF和MI两者最终均可发生，问题只在于哪个先发生。第二，亚临床CHD可能与AF和MI两者的高风险相关。因此，AF可能不是偶发性MI的危险因素，而可能是流行性CHD的标志物，其反过来增加了个体发生MI事件的风险。第三种可能性是AF建立和维持了一个炎症性和促血栓形成的环境，包括全身血小板活化、凝血酶生成、内皮功能障碍和炎症，这反过来增加了MI的风险。最后，既往研究表明冠状动脉栓塞所致MI的发生率实际上高于预想，并且研究发现AF是此类栓子的潜在原因。因此，冠状动脉栓塞或许是可解释研究结果的机制之一。

REGARDS研究获美国国立卫生研究院支持。Soliman医生及其同事声明无经济利益冲突。

随刊述评：探讨与其他疾病的关联

加州大学旧金山分校心脏病科和电生理科的Jonathan W. Dukes医生和Gregory M. Marcus医生表示，该研究结果进一步表明AF与其他心血管合并症存在重要的双向关联。既往发现AF可导致肾病、心力衰竭，现在又发现AF可导致MI。研究结果并未表明当代的AF治疗发生改变，相反地，治疗上的改变可能最适用于MI患者。例如，我们目前知道显著比例的卒中是由亚临床AF引起。这或许是否同样适用于MI呢？我们的常规临床实践必须从询问“为什么这例患者患有AF”这一常见问题变成询问“这一当前问题的发生是否是由AF引起？”两位评论专家均声明无经济利益冲突(JAMA Intern. Med. 2013 Nov. 4 [doi: 10.1001/jamainternmed.2013.11392])。

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By: MARY ANN MOON, Cardiology News Digital Network

Atrial fibrillation is strongly associated with incident myocardial infarction, independently of coronary risk factors and potential confounders, according to an analysis of data from the REGARDS study published online Nov. 4 in JAMA.

In a cohort study involving nearly 24,000 adults in the general population, those who had AF at baseline were twice as likely to develop MI during the ensuing 7 years of follow-up as were those without AF. The increased risk conferred by AF was significantly stronger among women and blacks than among men and whites, reported Dr. Elsayed Z. Soliman of the Epidemiological Cardiology Research Center, Wake Forest University, Winston-Salem, N.C., and his associates.

"These findings add to the growing concerns of the seriousness of AF as a public health burden: In addition to being a well-known risk factor for stroke, it is also associated with increased risk of MI," they said.

This is the first report of such an association, the investigators noted.

MI is known to be a risk factor for AF, and recent research has suggested that the converse may also be true. But to date there has been little evidence from population studies to support this assertion.

Dr. Soliman and his colleagues examined the issue in a secondary analysis of data from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, a large biracial, population-based cohort study of the causes of regional and racial disparities in stroke mortality. REGARDS assessed more than 30,000 adults residing in the "stroke belt" of the southeastern United States, carefully characterizing their cardiovascular risk and rigorously adjudicating incident MIs during up to 7 years of close follow-up (median follow-up, 4.5 years).

For their analysis, Dr. Soliman and his associates studied the records of a subset of 23,928 participants who had no coronary heart disease (CHD) at baseline and whose atrial fibrillation status was known. There were 1,631 study subjects who had already been diagnosed as having AF or who were found to have AF on baseline ECG.

A total of 648 MIs occurred during follow-up.

The age-adjusted incidence of MI was 12 per 1,000 in participants who had AF, compared with 6 per 1,000 in participants who didn\'t have AF, the researchers reported (JAMA Intern. Med. 2013 Nov. 4 [doi: 10.1001/jamainternmed.2013.11912]).

In a further analysis that adjusted for numerous sociodemographic factors, AF was associated with a 96% increase in MI risk, compared with no AF.

The association between AF and incident MI remained strong after further adjustment for CHD risk factors and numerous potential confounders.

These results indicate a bidirectional relationship between AF and MI, "with each leading to the other. Similar bidirectional relationships between AF and chronic kidney disease and between AF and heart failure have been reported," the researchers said.

In subgroup analyses, this association remained robust regardless of subject age, and was no different between older adults (those over age 65 or 75) and younger adults. However, the association was different according to subject gender and race: It was strongest among black men, less strong but still significant among white women, even less strong but still significant among black women, and nonsignificant among white men.

In addition, the association between AF and incident MI was significantly weaker among participants who were taking warfarin than among those who were not. "This accords with previous reports showing that warfarin might provide a protective effect against MI after acute coronary syndromes and in patients with AF who are prescribed anticoagulation for stroke prevention," the investigators said.

Although this study was not designed to determine why AF appears to raise the risk of incident MI, there are several plausible explanations.

First, both conditions share similar risk factors, so common pathophysiologic processes might underlie both outcomes. "That is, in susceptible individuals, both AF and MI may eventually occur, and it is just a matter of which comes first," Dr. Soliman and his associates said.

Second, subclinical CHD may be associated with a high risk of both AF and MI. Thus, "AF may not be a risk factor for incident MI but rather a marker of prevalent CHD that in turn places individuals at higher risk for MI events," they said.

A third possibility is that AF "creates and sustains an inflammatory and prothrombotic environment," including systemic platelet activation, thrombin generation, endothelial dysfunction, and inflammation, which in turn increase the risk of MI.

Finally, reports have suggested that MI due to coronary embolism actually is more frequent than it is thought to be, and have identified AF as an underlying cause of such emboli. So "coronary embolization, which may not be as rare as we think, could be one of the mechanisms explaining our findings," the investigators said.

The REGARDS study was supported by the National Institutes of Health. Dr. Soliman and his associates reported no financial conflicts of interest.

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Jonathan W. Dukes, M.D., and Gregory M. Marcus, M.D., commented: These findings "add to the growing recognition of important bidirectional relationships between AF and other cardiovascular comorbidities," with AF appearing to lead to kidney disease, heart failure, and now MI, said Dr. Jonathan W. Dukes and Dr. Gregory M. Marcus.

They do not suggest a change in contemporary AF treatment, but rather a "change in management may be most applicable to patients with MI. For example, we now know that a large proportion of strokes are due to subclinical AF. Perhaps the same is true for MI?"

"Our regular clinical practice must extend beyond the common question, ‘Why does this patient have AF?’ to ‘Could this current problem have occurred due to AF?’ " they said.

Jonathan W. Dukes, M.D., and Gregory M. Marcus, M.D., are in the division of cardiology and section of electrophysiology at the University of California, San Francisco. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Soliman’s report (JAMA Intern. Med. 2013 Nov. 4 [doi: 10.1001/jamainternmed.2013.11392]).