By Cara Pellegrini, MD
Assistant Professor of Medicine, UCSF, Cardiology Division, Electrophysiology Section, San Francisco VA Medical Center
Dr. Pellegrini reports no financial relationships relevant to this field of study.
SOURCE: Soliman EZ, et al. Atrial fibrillation and risk of ST-segment elevation versus non-ST segment elevation myocardial infarction: The atherosclerosis risk in communities (ARIC) study. Circulation 2015 Apr 27. pii: CIRCULATIONAHA.114.014145. [Epub ahead of print].
Atrial fibrillation (AF), a condition that affects more than 5 million people in the United States alone, has long been recognized to have implications beyond its obvious effect on heart rhythm. A diagnosis of AF quickly triggers discussions of appropriate stroke prevention, given the associated five-fold risk of stroke in persons with AF. It has also been found to portend other poor outcomes, such as a three-fold risk of heart failure, and a doubling of risk of dementia and death. Most recently, the relationship of AF and myocardial infarction (MI) has been a focus of study, with large cohorts finding prevalent AF to be associated with increased risk of incident MI.
Soliman and colleagues sought to confirm that association and, more interestingly, shed some light on a potential mechanism in utilizing the atherosclerosis risk in communities (ARIC) cohort of 14,462 participants without coronary heart disease at baseline. The ARIC study investigated the variation in cardiovascular risk factors, medical care, and disease by race and sex; more than half the study population was female and a quarter were African American. Only 31 patients had known AF at baseline. Incident AF came from intermittent electrocardiograms and review of discharge records, and MI data came from hospitalization records. AF was investigated as a time-varying variable with overall incident MI and by type of MI, ST elevation MI (STEMI) or non-ST elevation MI (NSTEMI). AF events occurring after an MI were not included.
Over a median follow-up of 21.6 years, 1374 MI events occurred, 80% of which were NSTEMIs. AF was associated with a 63% increased risk of MI after adjustment for potential confounders (hazard ratio [HR] 1.63; 95% confidence interval [CI], 1.32-2.02). Notably, AF was only associated with NSTEMI risk, (HR, 1.80; 95% CI, 1.39-2.31), and not STEMI risk. With adjustment for age, those with AF had an almost three-fold incidence of MI as compared to those without an AF diagnosis. Among women and blacks, the risk of MI in the setting of AF was disproportionately high, with women incurring an almost four-fold risk of MI with a diagnosis of AF (incidence rate ratio 3.75; 95% CI, 3.14-4.47) and blacks a more than three-fold risk (incidence rate ratio 3.26; 95% CI, 2.57-4.14).
The relationship between AF and MI is complex. AF may predispose to MI due to an increase in oxygen demand with higher heart rates and sympathetic activation. Alternatively, the mechanism may be less direct, occurring in part due to the endothelial dysfunction, pro-inflammatory state, and prothrombotic effects of AF. The lack of association between AF and STEMIs, typically vaso-occlusive events, suggests that direct coronary thromboembolism is a less likely mechanism. Coronary artery disease is also known to increase AF risk, but those with coronary heart disease were excluded at baseline.
The elevated risk in women and African Americans may be due to genetic differences or differences in AF-associated morbidities. As previous data have shown, these groups are less likely to be treated with anticoagulation or even be aware of their AF; under-treatment may play a role. Though adjustment for warfarin use did not do much to narrow the gap between women and men or whites and blacks in this study, the absolute number of those treated with anticoagulation, how tight their INR control was, and the effect of novel anticoagulants were not studied.
Given the mounting evidence suggesting that stroke, MI, and AF have pathophysiologic mechanisms in common, the presence of any one should at a minimum heighten suspicion for the others. Other data have suggested that CHADS-Vasc scores predict stroke incidence outside the context of AF, though with a lower absolute risk. Particularly with the options provided by the novel anticoagulants, I suspect that our threshold for anticoagulation of a cohort deemed to be at risk for cardiovascular disease in general will continue to drop. Special attention to seeking and treating AF in women and blacks should be encouraged, as the complications of this rhythm appears higher for them.