Depression Tied to a Doubling of New-Onset Atrial Fibrillation Risk

Depression is associated with a significantly increased cumulative incidence of, and risk for, atrial fibrillation (AF), new research suggests.

In a cohort study of more than five million adults, the cumulative incidence of new-onset AF was doubled for those with depression vs those without ― at 4.37 vs 1.86 per 1000 person-years, respectively.

Adjusted analysis also showed depression was linked to a 25% increased risk for new-onset AF.

Overall, the results suggest "the need for adequate screening for AF in people with depression," Yun Gi Kim, MD, Division of Cardiology, Department of Internal Medicine, Korea University College of Medicine and Korea University of Anam Hospital, Seoul, Republic of Korean, and colleagues write. They add this is particularly important for younger individuals and women.

The findings were published online January 4 in JAMA Network Open.

Psychological Stress a Culprit?

Although AF can profoundly affect patients' quality of life and substantially increases the incidence of major cardiac events, little research attempted to identify risk factors, the researchers note.

Nevertheless, it's possible psychological stress aggravates or induces tachyarrhythmias through activation of sympathetic tone. In fact, prior research showed a link between depression and increased sympathetic activity.

In addition, although previous studies have established a link between depression and increased risk for cardiovascular events in patients with myocardial infarction, any potential association between depression and risk for new-onset AF has yet to be established, the investigators write.

"Depression is a disease that can be controlled; therefore, evaluation of the association between depression and atrial fibrillation is important from a public health care perspective," they add.

As part of the cohort study, the researchers searched the Korean National Health Insurance Service database for all individuals who underwent a nationwide health checkup in 2009. Patients were excluded if they were less than 20 years old or had a history of heart valve surgery, had a previous diagnosis of mitral stenosis, or had been diagnosed with AF from January 2002 through December 2008.

The investigators compared risk for new-onset AF, defined as AF that occurred between 2009 and 2018, in individuals who were and were not diagnosed with depression within a year of the 2009 checkup. For purposes of the study, the incidence of new-onset AF was calculated as the number of events per 1000 person-years of follow-up.

Twofold Increased Risk

The final analysis included 5,031,222 individuals (mean age, 47 years; 55.1% men). Of these, 148,882 (3%) had a diagnosis of depression in the year before the 2009 checkup.

Individuals with depression were older than their counterparts who did not have depression (56.7 vs 46.7 years) and were more likely to be women (64.8% vs 44.3%). Interestingly, hypertension, diabetes, dyslipidemia, and heart failure were all more common among participants with depression.

The cumulative incidence of new-onset AF was 4.37 per 1000 person-years among individuals with depression vs 1.86 per 1000 person-years in those without depression (hazard ratio [HR], 2.36; 95% CI, 2.3 – 2.4; P < .001).

A multivariate analysis adjusted for a host of confounders showed depression was associated with a 25.1% increased risk for new-onset AF (HR, 1.25; 95% CI, 1.22 – 1.29; P < .001).

Results also showed that 56,951 of the 148,882 individuals with depression had recurrent episodes. Among this subpopulation, the incidence of new-onset AF was 5.55 per 1000 person-years, significantly greater than among those without recurrent episodes of depression (3.44 per 1000 person-years) and those with no depression at all (1.86 per 1000 person-years).

A young age or being female also had significant interactions with depression, suggesting young people and women with depression may be at increased risk for developing new-onset AF, the investigators report.

They note the study results add to the growing body of evidence examining the association between depression and new-onset AF, though these efforts have yielded conflicting results.

Previous studies have shown that patients with AF are at increased risk for developing depression. However, "whether depression can provoke development of new-onset atrial fibrillation" had not been "elucidated" before.

In a prospective cohort study of 30,746 women without a history of cardiovascular disease, there was no significant association between global psychological distress and specific depressive symptoms and development of new-onset AF. The HUNT study, which included more than 35,000 adults in Norway, showed similar results.

On the other hand, a study of 6644 people from the United States showed a 34% increased risk for new-onset AF, and a nationwide Danish study concluded that use of antidepressants was associated with an increased risk for new-onset AF.

Generalizable, Bidirectional

Commenting on the findings for Medscape Medical News, Parveen K. Garg, MD, associate professor of clinical medicine, Keck School of Medicine, University of Southern California, Los Angeles, said the generalizability of the findings to a US population is less important than the fact they add a global flavor to the literature.

"I think one of the real strengths of this paper is not only that it included over five million South Korean people but that it actually shows a similar relationship to that found in prior studies predominantly focused in North American and Europe," said Garg, who was not involved with the research.

"Therefore, it demonstrates that previous findings are generalizable to other populations, not vice versa, which is very valuable," he added.

The findings also help cement the bidirectional relationship between depression and AF, Garg noted.

"It's very clear that atrial fibrillation can lead to the development of depressive symptoms or depression because of the profound impact it has on patients' quality of life," he said.

He added that previous research has shown that patients with depression also have elevated levels of stress catecholamines ― and those chronically elevated levels are thought to be involved in the pathophysiology of developing AF.

"There are now quite a few studies that are providing more evidence for the bidirectional relationship between depression and atrial fibrillation," Garg said.

However, more research is needed, particularly into identifying mechanisms that may be responsible for the link between depression and AF, he added.

"If we can identify and treat depression before patients develop arrhythmias, does that actually reduce the risk of developing atrial fibrillation later on? That is the key next steps to focus our efforts on if we want to continue to advance this issue," Garg concluded.

The study was supported by grants from Korea University, Korea University Anam Hospital, and the National Research Foundation of Korea. The investigators and Garg have disclosed no relevant financial relationships.

JAMA Netw Open. Published online January 4, 2022. Full article

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