Atrial Fibrillation Is a Risk Marker for Cancer: Women’s Health Study
BASEL, SWITZERLAND — A Women’s Health Study cohort analysis concludes that new-onset atrial fibrillation (AF) is an independent predictor of risk for future cancer.
It found that the risk of developing cancer is threefold higher in the first 3 months after an AF diagnosis (hazard ratio [HR] 3.54;P<0.001) and remains significantly higher beyond 1 year (HR 1.42; P<0.001), even after adjustment for potential confounders such as smoking, alcohol, and hormone-replacement therapy.
In contrast, the risk of developing AF in women with cancer was increased only within the first 3 months after their cancer diagnosis (HR 4.67; P<0.001) and not thereafter (HR 1.15;P=0.15).
“The most interesting part of this relationship is the long-term increasing risk of cancer after AF. This suggests that not only have cancers already been there, but there is a true association there,” principal investigator Dr David Conen (University Hospital, Basel, Switzerland) told heartwire from Medscape.
Detection bias could explain the findings because women with AF have more contact with the health system and thus a higher likelihood of having their cancer diagnosed. “However, if this were true, then we should also have an increased long-term risk of AF after cancer because these cancer patients also have much more contact with the healthcare system,” he said.
The literature contains several reports on cancer as a risk factor for AF, often attributed to the side effects of chemotherapy or cancer surgery, particularly thoracic, or to the direct invasion of cancer to the heart.
Very few data exist, however, on AF preceding a cancer diagnosis. Danish investigators recently reported a fivefold increased risk of cancer in the first 3 months after AF diagnosis, but the risk was small thereafter, and 57% of the cancers were metastatic, suggesting AF was unlikely to have been the cause.
Prospective Cohort Analysis
For the present study, published online May 25, 2016 in the JAMA Cardiology, 34,691 healthy women aged at least 45 years were prospectively followed within the Women’s Health Study, a randomized trial of aspirin and vitamin E for the prevention of cardiovascular disease and cancer. During a median follow-up of 19.1 years, new-onset AF was diagnosed in 1467 (4.2%) patients and malignant cancer in 5130 (14.8%).
Among those diagnosed with new-onset AF, 10% developed cancer during follow-up. The absolute risk of cancer observed in women with and without AF was modest at 1.4 and 0.8 events per 100 person-years of follow-up.
AF type did not play a significant role, with similar risk estimates reported for women who developed paroxysmal (HR 1.37;P=0.004) and nonparoxysmal (HR 1.50; P=0.003) AF, observed Conen, a cardiologist.
Women diagnosed with AF were at significantly higher risk of colon cancer (HR 2.11; P=0.002), but not breast or lung cancer. AF was not significantly associated with cancer mortality in multivariable-adjusted models (HR 1.32; P=0.07).
Research in mixed-sex cohorts is needed to confirm the findings, but it’s likely men with AF would also face an elevated risk of cancer, he said.
In an accompanying editorial, Drs Faisal Rahman, Darae Ko, and Emelia Benjamin (Boston University School of Medicine, Massachusetts) agree with the investigators that “AF most likely serves as a risk marker for future diagnoses of cancer” and say the study has several strengths, including its large sample size, few missing data, the ability to account for multiple potential confounders, and adjudication for cancer and AF diagnoses.
The editorialists note, however, “Several factors argue against routine screening” with a new AF diagnosis, including the low absolute risk of cancer, potential costs, and the burden of screening.
Conen agreed that the data are not yet sufficient to recommend screening AF patients differently for cancer but said these patients warrant close follow-up because they’re at risk for other diseases such as heart failure and stroke, not just cancer. “We should thoroughly treat their risk factors—smoking, obesity. This might help not only for cancer prevention, but also for risk of recurrence. Taking care of risk factors is probably the most important take-home message and looking closely at your patients.”
Shared Risk Factors
AF and cancer share several risk factors, including obesity, alcohol, smoking, hypertension, and diabetes, but emerging data also suggest that AF is not a localized left atrial disease but more of a systemic disease with an increase in thrombogenicity and inflammation, he said.
The editorialists point out that the reported relationships between AF and MI, heart failure, chronic kidney disease, and venous thromboembolism are more likely to be “truly causally bidirectional,” but that the underlying mechanisms explaining the association between AF and cancer “may be even more complicated, with a possible interlinking bidirectional relationship with a wide variety of factors.”
Both the editorialists and investigators call for further research on the complex interrelations between AF and cancer, particularly with an aging population with a higher burden of risk factors.