AF Patients Under Age 65 Have High Risk Factor Burden, More Adverse Outcomes

Atrial fibrillation (AF) appears to be more of a threat among patients younger than 65 than previously appreciated, according to data from a large health system in Pennsylvania.

This cohort had high rates of risk factors and comorbidities, as well as increased long-term risks of mortality and hospitalization for heart failure, stroke, and MI compared with similarly aged peers without AF, researchers led by Aditya Bhonsale, MD (University of Pittsburgh Medical Center, PA), report in a study published online this week in Circulation: Arrhythmia and Electrophysiology.

Anecdotally, the number of patients with AF who are on the younger end of the age spectrum, in their 40s and 50s, seems to be on the rise, Bhonsale told TCTMD, noting that it had been thought that when the arrhythmia occurs at such a young age, it’s not necessarily tied to risk factors or structural issues. “I don’t think [that] is the case,” he said. “I think this data suggests that most of our patients, even if they are younger, have atrial fibrillation because they have risk factors . . . that act as triggers for atrial fibrillation.”

That highlights an opportunity to improve the risk profiles of younger patients with AF, Bhonsale said. “Our focus, or cardiologists’ focus, should be on risk factor mitigation in this population.”

All-Cause Mortality 42% Higher

For the study, the investigators started with a cohort of 67,221 adult patients with AF (mean age 72.4 years; 45% women) who were managed within the University of Pittsburgh Medical Center system, which includes more than 40 academic, community, and specialty hospitals throughout Pennsylvania, between 2010 and 2019. They used electronic health records and administrative data to assess risk factors, comorbidities, and hospitalizations and cardiac interventions during follow-up.

Overall, 5% of patients were younger than 50 and 21% were between the ages of 50 and 65. That indicates that AF before age 65 is “probably more prevalent” than estimated in earlier studies, Bhonsale said.

In this cohort younger than 65, there were high rates of cardiovascular risk factors and comorbidities, which included hypertension (55%), dyslipidemia (47%), a body mass index over 40 kg/m² (28%), diabetes (21%), heart failure (21%), coronary artery disease (19%), obstructive sleep apnea (18%), current smoking (16%), chronic obstructive pulmonary disease (11%), prior ischemic stroke (6%), and chronic kidney disease (1.3%).

Even in those younger than age 65, AF was associated with high rates of all-cause mortality through more than 5 years of follow-up—6.7% among those younger than 50 and 13% among those ages 50 to 65. Rates of hospitalization for AF, heart failure, and MI were 31.1%, 12.4%, and 2.7%, respectively, in patients younger than 50 and 37.6%, 19.4%, and 4.7%, respectively, in those ages 50 to 65.

Moreover, AF ablation was performed in 11% of patients younger than age 65 during follow-up, with another 5% undergoing atrioventricular junction ablation and 17% requiring cardioversion.

Compared with similarly aged individuals without AF, patients younger than age 65 who had the arrhythmia had a greater risk of dying:

• Men < 50 years (HR 1.5; 95% CI 1.2-1.8)
• Men ages 50 to 65 (HR 1.3; 95% CI 1.3-1.4)
• Women < 50 years (HR 2.4; 95% CI 1.8-3.2)
• Women ages 50 to 65 (HR 1.7; 95% CI 1.6-1.9)

The increased risk of all-cause mortality in the below-65 cohort altogether (HR 1.42; 95% CI 1.35-1.49) was similar to that seen in patients with AF of all ages (HR 1.38; 95% CI 1.35-1.40). The younger patients with AF also had elevated risks of hospitalization for heart failure (HR 2.93; 95% CI 2.79-3.08), stroke (HR 1.77; 95% CI 1.61-1.96), and MI (HR 1.19; 95% CI 1.09-1.29) compared with patients without AF.

Building a Consensus

Along with other analyses from Australia and Europe, these findings are building a consensus “that in younger patients [with AF], our emphasis should be on prevention and early treatment,” Bhonsale said. In a 50-year-old patient with “a little bit” of AF and untreated sleep apnea and hypertension, for example, “those are risk factors that we can mitigate, treat, and control to hopefully avoid interventions down the road,” he added, referring to the initiation of oral anticoagulation or antiarrhythmic drug therapy or the performance of catheter ablation.

The overall message from this study is that AF before age 65 “is a problem” and “is not as exotic as we thought it was going to be,” Bhonsale said.

Clinicians can respond to this information by being more aggressive when it comes to risk factor control in these patients, “which will improve mortality or should improve mortality,” he stressed.

Bhonsale added, too, that the concern is not just all-cause mortality. “There’s a significant morbidity burden that’s associated with patients developing atrial fibrillation at a young age,” he said, “where these cumulative heart failure or stroke or myocardial infarction hospitalizations are at a nonzero level when these patients are followed for over a decade.”