《美國(guó)醫(yī)學(xué)會(huì)雜志》（JAMA）11月4日在線發(fā)表的一項(xiàng)對(duì)REG**S研究數(shù)據(jù)的二次分析顯示，房顫（AF）***于冠狀動(dòng)脈危險(xiǎn)因素和潛在混雜因素與偶發(fā)性心肌梗死（MI）強(qiáng)烈相關(guān)（JAMA Intern. Med. 2013 Nov. 4 [doi: 10.1001/jamainternmed.2013.11912]）。

    已知MI是AF的危險(xiǎn)因素，近期研究表明反過(guò)來(lái)可能也成立，即AF是MI的危險(xiǎn)因素，但目前為止尚缺乏來(lái)自人群研究的證據(jù)支持這一觀點(diǎn)。為了探討這一問(wèn)題，維克森林大學(xué)流行病學(xué)心臟病血研究中心的Elsayed Z. Soliman醫(yī)生及其同事對(duì)REG**S研究的數(shù)據(jù)進(jìn)行了二次分析。REG**S是一項(xiàng)探討卒中死亡率的地區(qū)和種族差異的原因的大型、雙種族、人群隊(duì)列研究，在7年密切隨訪（中位4.5年）中對(duì)美國(guó)東南部“卒中帶”居住的超過(guò)30,000名成人的心血管風(fēng)險(xiǎn)進(jìn)行了仔細(xì)研究并對(duì)偶發(fā)性MI進(jìn)行嚴(yán)格判定。

    在二次分析中，Soliman醫(yī)生及其同事研究了23,928例基線時(shí)無(wú)冠心?。–HD）且AF狀態(tài)已知的受試者的記錄。1,631例受試者已被診斷AF或基線心電圖（ECG）檢出AF.隨訪期間共發(fā)生648起MI.

    在有和無(wú)AF的受試者中，校正年齡的MI發(fā)生率分別為12例/1,000人和6例/1,000人。校正多個(gè)社會(huì)人口學(xué)因素進(jìn)一步分析發(fā)現(xiàn)，與無(wú)AF相比，AF與MI風(fēng)險(xiǎn)增加96%相關(guān)。進(jìn)一步校正CHD危險(xiǎn)因素和多個(gè)潛在混雜因素后，仍觀察到AF與偶發(fā)性MI相關(guān)。研究者表示，這些結(jié)果表明，AF與MI存在雙向關(guān)聯(lián)，即一方可導(dǎo)致另一方。既往研究發(fā)現(xiàn)AF與慢性腎病之間及AF與心力衰竭之間也存在相似的雙向關(guān)聯(lián)。

    在亞組分析中，這一關(guān)聯(lián)仍具有魯棒性，不管受試者年齡如何，并且在老年成人（65歲或75歲以上）和年輕成人之間無(wú)差異。然而，該關(guān)聯(lián)依受試者性別和種族而存在差異：其在黑人男性中最強(qiáng)烈，在白人女性中強(qiáng)度次之但仍具有顯著性，在黑人女性中強(qiáng)度又次之但仍具有顯著性，在白人男性中無(wú)顯著性。

    此外，在使用華法林的受試者中觀察到的AF與偶發(fā)性MI的關(guān)聯(lián)顯著弱于未使用華法林的受試者中觀察到的關(guān)聯(lián)。這與既往研究觀察到的華法林可預(yù)防急性冠狀動(dòng)脈綜合征后MI的結(jié)果和在使用抗凝劑預(yù)防卒中的AF患者中觀察到的結(jié)果一致。

    雖然該研究的目的并不在于確定為什么AF可增加偶發(fā)性MI風(fēng)險(xiǎn)，但研究結(jié)果可通過(guò)以下幾點(diǎn)加以解釋。第一，AF和MI具有相似的危險(xiǎn)因素，因此兩者可能具有相同的病理生理過(guò)程。即在易感個(gè)體中，AF和MI兩者最終均可發(fā)生，問(wèn)題只在于哪個(gè)先發(fā)生。第二，亞臨床CHD可能與AF和MI兩者的高風(fēng)險(xiǎn)相關(guān)。因此，AF可能不是偶發(fā)性MI的危險(xiǎn)因素，而可能是流行性CHD的標(biāo)志物，其反過(guò)來(lái)增加了個(gè)體發(fā)生MI事件的風(fēng)險(xiǎn)。第三種可能性是AF建立和維持了一個(gè)炎癥性和促血栓形成的環(huán)境，包括全身血小板活化、凝血酶生成、內(nèi)皮功能障礙和炎癥，這反過(guò)來(lái)增加了MI的風(fēng)險(xiǎn)。最后，既往研究表明冠狀動(dòng)脈栓塞所致MI的發(fā)生率實(shí)際上高于預(yù)想，并且研究發(fā)現(xiàn)AF是此類(lèi)栓子的潛在原因。因此，冠狀動(dòng)脈栓塞或許是可解釋研究結(jié)果的機(jī)制之一。

    REG**S研究獲美國(guó)**衛(wèi)生研究院支持。Soliman醫(yī)生及其同事聲明無(wú)經(jīng)濟(jì)利益沖突。

    隨刊述評(píng)：探討與其他疾病的關(guān)聯(lián)

    加州大學(xué)舊金山分校心臟病科和電生理科的Jonathan W. Dukes醫(yī)生和Gregory M. Marcus醫(yī)生表示，該研究結(jié)果進(jìn)一步表明AF與其他心血管合并癥存在重要的雙向關(guān)聯(lián)。既往發(fā)現(xiàn)AF可導(dǎo)致腎病、心力衰竭，現(xiàn)在又發(fā)現(xiàn)AF可導(dǎo)致MI.研究結(jié)果并未表明當(dāng)代的AF治療發(fā)生改變，相反地，治療上的改變可能最適用于MI患者。例如，我們目前知道顯著比例的卒中是由亞臨床AF引起。這或許是否同樣適用于MI呢？我們的常規(guī)臨床實(shí)踐必須從詢問(wèn)“為什么這例患者患有AF”這一常見(jiàn)問(wèn)題變成詢問(wèn)“這一當(dāng)前問(wèn)題的發(fā)生是否是由AF引起？”兩位評(píng)論專(zhuān)家均聲明無(wú)經(jīng)濟(jì)利益沖突（JAMA Intern. Med. 2013 Nov. 4 [doi: 10.1001/jamainternmed.2013.11392]）。

    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 **ysis of data from the REG**S study published online Nov. 4 in JAMA.

    In a cohort study involving nearly 24,000 **s 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 **ysis of data from the REG**S （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. REG**S assessed more than 30,000 **s 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 **ysis, 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 **ysis 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 **yses, this association remained robust regardless of subject age, and was no different between older **s （those over age 65 or 75） and younger **s. 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 REG**S study was supported by the National Institutes of Health. Dr. Soliman and his associates reported no financial conflicts of interest.

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    Look for links with other conditions

    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]）。