INTERSTROKE: Anger, Heavy Physical Exertion May Trigger Strokes

People who are angry or upset, or who are physically exerting themselves, appear to be at increased risk for stroke, according to an analysis of the large INTERSTROKE study.

Anger/emotional upset was associated increased odds of any kind of stroke, including both ischemic events and intracerebral hemorrhage (ICH), whereas heavy physical exertion was tied to a greater likelihood of ICH, lead author Andrew Smyth, MBBCh, PhD (NUI Galway, Ireland, and Population Health Research Institute, McMaster University, Hamilton, Canada), and colleagues report.

Although much is known about the impact of chronic cardiovascular risk factors like hypertension, diabetes, and smoking—including from a prior analysis of INTERSTROKE, encompassing a cohort of patients with first strokes treated across 142 centers in 32 countries—there are fewer data addressing potential short-term triggers of adverse outcomes, Smyth told TCTMD.

His research group previously explored the impact of anger/emotional upset and heavy physical exertion as they relate to risk of acute MI in the INTERHEART study. For the current paper, published online December 1, 2021, ahead of print in the European Heart Journal, they used similarly methodology to look into associations with acute stroke in INTERSTROKE.

This line of research is important “because not everybody who has a lot of risk factors will actually have a stroke,” Smyth said, “and there are some people who don’t have those chronic risk factors and they may have a stroke.”

The analysis included 13,462 patients with acute stroke (mean age 62.2 years; 59.6% men). The patients and/or proxies completed questionnaires that included questions about exposures that could serve as potential triggers for the events. Using a case-crossover design, the investigators looked at the occurrence of anger/emotional upset or heavy physical exertion in the hour before the stroke (case period) and during the same hour the previous day (control period).

Overall, 9.2% of patients reported feeling angry or emotionally upset shortly before their stroke, with 5.3% saying that they were physically exerting themselves.

Anger/emotional upset was associated with greater odds of all strokes (OR 1.37; 99% CI 1.15-1.64), ischemic stroke (OR 1.22; 99% CI 1.00-1.49), and ICH (OR 2.05; 99% CI 1.40-2.99). Heavy physical exertion, on the other hand, was linked only to ICH (OR 1.62; 99% CI 1.03-2.55).

The associations were not modified by geographical region, prior CVD, common CV risk factors, CV medications, or time/day of symptom onset. Of note, however, the relationship between anger/emotional upset and stroke was stronger in people without a history of depression.

“I would wonder if those findings are seen because people who have a history of depression have had ongoing emotional changes and their body is probably more accustomed to the cardiovascular effects, perhaps, compared to somebody who has not had any significant mental health issues,” Smyth said.

The observational study cannot establish causal relationships between these potential triggers and the acute stroke events, but the investigators note that both anger/emotional upset and heavy physical exertion are accompanied by physiological changes—ie, sympathetic activation, catecholamine secretion, vasoconstriction, and increased heart rate and blood pressure—that provide a plausible mechanistic explanation.

Thus, there is the potential to incorporate these findings into discussions with patients about ways to reduce their stroke risks, Smyth indicated.

“What I would say to most patients is that we know from studies like this and other studies of cardiovascular disease that extremes of heavy physical exertion or extremes of anger or emotional upset may not be the healthiest things for people,” he said, pointing to the accompanying physiological changes. “So we would be . . . advising people as much as possible to avoid or minimize those sorts of exposures.”

And because these types of emotions or activities are sometimes unavoidable, Smyth said, people can take measures to minimize the physiological reaction to them and remain calm by focusing on things like mindfulness and breathing techniques.

In an accompanying editorial, Susanne Wegener, MD (University Hospital Zurich, Switzerland), points to some of the same potential mechanisms cited by the investigators to explain the findings observed in INTERSTROKE.

Though the analysis cannot establish causal relationships, some messages can be taken away, she suggests.

“Definitely, anger and emotional upset should be avoided, and physical exertion should not exceed the limits of individual capacity,” Wegener writes. “Although INTERSTROKE was conducted in patients with first-ever ischemic stroke, it is likely that this advice is even more important for secondary stroke prevention, which will have to be addressed in future studies.

“Furthermore, the study provides strong support for the recent concept of negative emotions and stress in the pathophysiology of cardiovascular disease,” she continues, adding that stroke survivors could be told that their event was possibly brought on by emotional stress. “Future research, possibly supported by stress indicators from wearable devices, will identify more potential triggers of stroke and delineate who is at particular risk.”