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.

Atrial fib linked to incident myocardial infarction