New-onset atrial fibrillation (AF) was linked with increased cancer risk in an analysis of data from the Women's Health Study.
The risk of cancer was highest within 3 months of AF diagnosis (hazard ratio 3.54; 95% CI 2.05-6.10; P<0.001) but remained significant beyond 1 year (hazard ratio 1.42; 95% CI 1.18-1.71; P<0.001), reported Christine Albert, MD, of Brigham and Women's Hospital in Boston, and colleagues.
The study also found that new-onset cancer was associated with a slight but significantly increased risk for AF (HR 1.20; 95% CI 1.01-1.44; P=0.04), suggesting that the two diseases may share an underlying etiology, Albert and colleagues said in JAMA Cardiology.
"Our data may have clinical implications. Although the absolute increase in cancer risk among women with new-onset AF was modest in this low-risk cohort of initially healthy women, it may be higher in older populations with a higher burden of risk factors.
"These data further emphasize the importance of risk factor reduction in patients with AF to not only reduce recurrent AF episodes but also potentially decrease other adverse outcomes," the researchers said. "Additional analyses are needed to evaluate whether incorporating AF into cancer prediction models improves their performance."
Still, screening patients with AF for cancer is not warranted at this point, said Emelia Benjamin, MD, of Boston University, and colleagues in an accompanying editorial.
"This provocative work raises both clinical and research questions. Clinically, should a diagnosis of AF prompt a search for occult cancer? Several factors argue against routine screening, including the low absolute risk of cancer (1.4 versus 0.8 per 100 person-years of follow-up in individuals with versus without AF in the Women's Health Study) and the potential cost and burden of cancer screening.
"Similar to the literature regarding screening in cases of unprovoked venous thromboembolism, based on available data, cancer screening beyond standard routine health care is currently not merited with a new diagnosis of AF," Benjamin and colleagues advised.
The analysis by Albert et al included 34,691 women enrolled in the Women's Health Study, a completed clinical trial that examined the effects of low-dose aspirin and vitamin E in preventing cardiovascular disease and cancer. The participants were age 45 or older and free of AF, cardiovascular disease, and cancer at baseline.
The investigators prospectively followed these women from 1993 to 2013 for incident AF and malignant cancer. During a median 19 years of follow-up, 1,467 cases of new-onset AF and 5,130 cases of cancer were confirmed.
The incidence of cancer among women with new-onset AF was 1.4 events per 100 person-years of follow-up, versus 0.8 events in women without AF. In a multivariable adjusted analysis, AF was significantly associated with incident cancer (HR 1.48; 95% CI 1.25-1.75; P<0.001). Neither low-dose aspirin nor vitamin E affected the association.
The investigators reported a nonsignificant trend toward increased cancer mortality with new-onset atrial fibrillation (HR 1.32; 95% CI 0.98-1.79; P=0.7).
Among women with new-onset cancer, the relative risk of AF increased within the first 3 months after diagnosis (HR 4.67; 95% CI 2.85-7.64; P< 0.001) but not beyond 3 months (HR 1.15; 95% CI 0.95-1.39; P=0.15).
Potential Underlying Mechanisms
"The potential mechanisms underlying the increased long-term risk of cancer among individuals with AF are currently unknown," the researchers said. "Shared risk factors could be one explanation. The similar risk factor profiles among women with new-onset AF and new-onset cancer provide support to this concept. Alternatively, AF may be an early sign of occult cancer or an initial manifestation of a systemic process, which increases the risk for both diseases. Inflammation or oxidative stress could represent combined predisposing processes. Both disease processes are associated with prothrombotic states."
In addition, the team speculated, since apoptosis plays a potential role in the development of AF, resultant disruption of the counter-regulatory balance between pro-apoptotic and anti-apoptotic factors could contribute to carcinogenesis by reducing the degree of apoptosis in cancer cells.
"Clearly many research questions regarding the complex interrelations between AF and cancer remain and, with an aging population, represent important areas for future research," Benjamin and colleagues said in the editorial.
"Understanding the intermediate steps that link AF and cancer in the bidirectional associations reported by Conen et al may provide valuable mechanistic and therapeutic insights with regard to both conditions."
The study was funded by the National Institutes of Health and the Swiss National Science Foundation.
None of the study authors or editorialists reported any relationships with industry.
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