Anxiety a Marker of Exercise-Induced Ischemia in Women but Not Men

In women with no known history of CAD, having an anxiety disorder increases the probability of an abnormal exercise stress test. The relationship was not seen in men and suggests that symptoms of CAD often may be missed in women due to coexisting and sometimes overlapping anxiety symptoms, which may lead to treatment delays and worsened outcomes. 

The findings were somewhat surprising, study coauthor Simon Bacon, PhD, of Concordia University (Montreal, Canada), told TCTMD. 

Take Home: Anxiety a Marker of Exercise-Induced Ischemia in Women but Not Men

“Generally, we tend to see in most studies a strong impact of depression and anxiety [in] those people who have preexisting disease,” he said. “We didn’t actually see that in this particular study. What we saw was this signal was coming loud and clear in those that haven’t had a previous diagnosis [of CAD].”

As reported online February 23, 2016, ahead of print in Circulation: Cardiovascular Quality and Outcomes, the researchers, led by Nicola Paine, PhD, also of Concordia University, examined 1,582 men and 760 women referred for a SPECT exercise stress test and then screened for mood and anxiety with the Primary Care Evaluation of Mental Disorders (PRIME-MD) test.

Compared with women, men were more likely to have hyperlipidemia, diabetes, previous MI, a history of CAD, and previous CABG and to be current and previous smokers. Men also were more likely than women to have been prescribed vasodilators, beta-blockers, calcium-channel blockers, ACE inhibitors, aspirin, and lipid-lowering medications and less likely to have been prescribed diuretics.

Anxiety and Ischemia: A Troubling Duo

Mood and anxiety test results showed that compared with men, women were more likely to present with any psychiatric disorder, anxiety disorder, mood disorder, or comorbid anxiety and mood disorders, but less likely to have evidence of ischemia during stress testing.

Logistic regression analysis was used to explore the relationships between sex, psychiatric status, and the presence of ischemia during stress testing. In patients with no history of CAD, interactions were seen for anxiety (P = .015) and comorbid mood and anxiety disorders (P = .005). No such interactions were seen in patients with a history of CAD.

A post hoc analysis showed that among patients without a history of CAD, men with or without anxiety were more likely to exhibit ischemia during exercise testing compared with women without anxiety. Women with anxiety were more likely to have ischemia than were women without anxiety (OR 1.75; 95% CI 1.05-2.89), but a similar relationship was not observed among men.

Among the patients who had a history of CAD, on the other hand, an association between anxiety and ischemia was not seen in either women or men.

Mood was not a factor in any of the analyses looking at the presence of ischemia, a finding that “is surprising considering that depression has consistently been shown to be a key risk factor in predicting CAD events and outcomes,” the authors say.

The Chicken or the Egg?

Determining exactly when and how anxiety enters the picture is not easy and may never be known, Martha Gulati, MD, of the ‎University of Arizona College of Medicine (Phoenix, AZ), told TCTMD.

“They’ve shown an association between anxiety and an abnormal stress test. I don’t know which happened first,” Gulati said. “Does anxiety occur because you’re having symptoms of ischemia and you’re not sure what they are?” Or, is the chronic stress of anxiety adversely affecting the myocardium? she said. “Whatever the reason is, anxiety may be a good measure for us to be assessing.”

More importantly, she observed, is the need to quantify the ischemia as mild, moderate, or severe, which the study authors did not do. That lack of information, she said, makes it difficult to know what presumably happened or should have happened next in terms of further diagnostic testing.

Still, Gulati said the main message of the study is that women’s symptoms should not be dismissed.

“This was true ischemia that they could see using a nuclear stress test and they saw reduced blood flow to the heart,” she said. “That’s important to know and it’s important to recognize that women may be presenting differently than men.”

Bacon added that because of the similarity in bodily sensations between anxiety and CAD, “it may be unclear to the healthcare professionals whether this is heart disease, or whether it’s anxiety, and they may be… less concerned about it than they possibly should be, and that may influence the care pattern and trajectory of these women.

“Certainly, my message would be, if in doubt, put someone on the exercise stress test,” he said.

Gulati agreed that individualizing decision-making based on symptom presentation is the most important message. “We can see even from this study that women are referred [for exercise testing] far less than men even though we live longer… but sometimes I wonder if we’re missing people because we blow off their symptoms as anxiety and stress,” she said.

Paine NJ, Bacon SL, Pelletier R, et al. Do women with anxiety or depression have higher rates of myocardial ischemia during exercise testing than men? Circ Cardiovasc Qual Outcomes. 2016;Epub ahead of print. 


  • The study was supported by grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada. 
  • Bacon, Gulati, and Paine report no relevant conflicts of interest. 

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