Stress-related disorders and anxiety are associated with a higher risk of out-of-hospital cardiac arrest (OHCA), a new case-control study suggests.
Investigators compared more than 35,000 OHCA case patients with a similar number of matched control persons and found an almost 1.5 times higher hazard of long-term stress conditions among OHCA case patients in comparison with control persons, with a similar hazard for anxiety. Posttraumatic stress disorder (PTSD) was associated with an almost twofold higher risk of OHCA.
The findings applied equally to men and women and was independent of the presence of cardiovascular disease (CVD).
“This study raises awareness of the higher risks of OHCA and early risk monitoring to prevent OHCA in patients with stress-related disorders and anxiety,” write Talip Eroglu, of the Department of Cardiology, Copenhagen University Hospital, Denmark, and colleagues.
The study was published online May 10 in BMJ’s Open Heart.
Stress Disorders and Anxiety Overrepresented
OHCA “predominantly arises from lethal cardiac arrhythmias…that occur most frequently in the setting of coronary heart disease,” the authors write. However, increasing evidence suggests that rates of OHCA may also be increased in association with noncardiac diseases.
Individuals with stress-related disorders and anxiety are “overrepresented” among victims of cardiac arrest as well as those with multiple CVDs. But previous studies of OHCA have been limited by small numbers of cardiac arrests. In addition, those studies involved only data from selected populations or used in-hospital diagnosis to identify cardiac arrest, thereby potentially omitting OHCA patients who died prior to hospital admission.
The researchers therefore turned to data from Danish health registries that include a large, unselected cohort of patients with OHCA to investigate whether long-term stress conditions (ie, PTSD and adjustment disorder) or anxiety disorder was associated with OHCA.
They stratified the cohort according to sex, age, and CVD to identify which risk factor confers the highest risk of OHCA in patients with long-term stress conditions or anxiety, and they conducted sensitivity analyses of potential confounders, such as depression.
The design was a nested-case control model in which records at an individual patient level across registries were cross-linked to data from other national registries and were compared to matched control persons from the general population (35,195 OHCAs and 351,950 matched control persons; median [IQR] age, 72 [62 – 81] years; 66.82% men).
The prevalence of comorbidities and use of cardiovascular drugs were higher among OHCA case patients than among non-OHCA control persons.
Keep Aware of Stress and Anxiety as Risk Factors
Among OHCA and non-OHCA participants, long-term stress conditions were diagnosed in 0.92% and 0.45%, respectively. Anxiety was diagnosed in 0.85% of OHCA case patients and in 0.37% of non-OHCA control persons.
These conditions were associated with a higher rate of OHCA after adjustment for common OHCA risk factors.
Table. Risk of OHCA by Stress-Related Disorders and Anxiety
| Disorder | Hazard ratio (95% CI) |
|---|---|
| Long-term stress conditions overall | 1.44 (1.27 – 1.64) |
| PTSD | 1.80 (1.13 – 2.86) |
| Adjustment disorders | 1.42 (1.24 – 1.63) |
| Anxiety | 1.56 (1.37 – 1.79) |
There were no significant differences in results when the researchers adjusted for the use of anxiolytics and antidepressants.
When they examined the prevalence of concomitant medication use or comorbidities, they found that depression was more frequent among patients with long-term stress and anxiety, compared to individuals with neither of those diagnoses. Additionally, patients with long-term stress and anxiety more often used anxiolytics, antidepressants, and QT-prolonging drugs.
Stratification of the analyses according to sex revealed that the OHCA rate was increased in both women and men with long-term stress and anxiety. There were no significant differences between the sexes. There were also no significant differences between the association among different age groups, nor between patients with and those without CVD, ischemic heart disease, or heart failure.
Previous research has shown associations of stress-related disorders or anxiety with cardiovascular outcomes, including myocardial infarction, heart failure, and cerebrovascular disease. These disorders might be “biological mediators in the causal pathway of OHCA” and contribute to the increased OHCA rate associated with stress-related disorders and anxiety, the authors suggest.
Nevertheless, they note, stress-related disorders and anxiety remained significantly associated with OHCA after controlling for these variables, “suggesting that it is unlikely that traditional risk factors of OHCA alone explain this relationship.”
They suggest several potential mechanisms. One is that the relationship is likely mediated by the activity of the sympathetic autonomic nervous system, which “leads to an increase in heart rate, release of neurotransmitters into the circulation, and local release of neurotransmitters in the heart.”
Each of these factors “may potentially influence cardiac electrophysiology and facilitate ventricular arrhythmias and OHCA.”
In addition to a biological mechanism, behavioral and psychosocial factors may also contribute to OHCA risk, since stress-related disorders and anxiety “often lead to unhealthy lifestyle, such as smoking and lower physical activity, which in turn may increase the risk of OHCA.” Given the absence of data on these features in the registries the investigators used, they were unable to account for them.
However, “it is unlikely that knowledge of these factors would have altered our conclusions considering that we have adjusted for all the relevant cardiovascular comorbidities.”
Similarly, other psychiatric disorders, such as depression, can contribute to OHCA risk, but they adjusted for depression in their multivariable analyses.
“Awareness of the higher risks of OHCA in patients with stress-related disorders and anxiety is important when treating these patients,” they conclude.
Detrimental to the Heart, Not Just the Psyche
Commenting for theheart.org | Medscape Cardiology, Glenn Levine, MD, master clinician and professor of medicine, Baylor College of Medicine, Houston, Texas, called it an “important study in that it is a large, nationwide cohort study and thus provides important information to complement much smaller, focused studies.”
Like those other studies, “it finds that negative psychological health, specifically, long-term stress (as well as anxiety), is associated with a significantly increased risk of out-of-hospital cardiac arrest,” continued Levine, who is the chief of the cardiology section at Michael E. DeBakey VA Medical Center and was not involved with the study.
Levine thinks the study “does a good job, as best one can for such a study, in trying to control for other factors, and zeroing in specifically on stress (and anxiety), trying to assess their independent contributions to the risk of developing cardiac arrest.”
The take-home message for clinicians and patients “is that negative psychological stress factors, such as stress and anxiety, are not only detrimental to one’s psychological health but likely increase one’s risk for adverse cardiac events, such as cardiac arrest,” he stated.
No specific funding for the study was disclosed. Eroglu has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original article. Levine reports no relevant financial relationships.
Open Heart. Published online May 10, 2023. Abstract
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