Ischemic Stroke, TIA Risk in COVID-19 Lower Than Previously Seen

The risk of ischemic stroke in patients hospitalized with COVID-19 may not be as high as initial reports, mostly from single centers, suggested, according to data from COVID-19 CVD Registry launched just weeks into the pandemic by the American Heart Association (AHA).

In the largest analysis to date, ischemic stroke/TIA was seen in 0.75% of patients in the registry. “This is lower than reported previously but still higher than that reported after other infectious conditions like influenza,” lead investigator Saate Shakil, MD (University of Washington, Seattle), said during the virtual International Stroke Conference 2021 last week. Prior studies have suggested rates ranging from 0.9% to 2.8%.

Overall, COVID-19 patients with versus without ischemic stroke/TIA had more than double the risk of dying in the hospital and twice the length of stay, along with greater requirements for mechanical ventilation and intensive care.

Of note, not all racial/ethnic groups were equally affected. Ischemic stroke/TIA risk was higher  in non-Hispanic Black patients and lower in Hispanic patients compared with their white counterparts.

Shakil stressed during a media briefing, however, that the findings were not adjusted for baseline demographic factors or comorbidities, “so we will plan to do further analysis to understand the drivers of these disparities.”

Stroke Concerns During the Pandemic

As was seen for other acute conditions, admissions for stroke dipped during the initial COVID-19 surge, raising concerns of hospital avoidance amid other potential explanations. But there were also concerning reports of strokes caused by large-vessel occlusions as a presenting feature of COVID-19 in younger patients. Other evidence suggested that stroke risk was higher in COVID-19 than in influenza.

Worries about the potential impact of COVID-19 on cardiovascular conditions early on in the pandemic prompted the AHA to launch its COVID-19 CVD Registry built on the existing Get With The Guidelines infrastructure. From March 2020 to January 2021, the registry enrolled 31,659 patients hospitalized with COVID-19 at 160 participating centers.

For the current analysis, Shakil and her colleagues looked at data on 21,073 patients enrolled between March and November 2020. In this cohort, the risk of any stroke was 1.4%. About half of the 289 events identified (52.6%) were ischemic strokes and another 2.8% were TIAs.

The patients with versus without ischemic stroke/TIA were older on average (65.2 vs 61.1 years), were more likely to be men (63.1% vs 53.9%), and—not surprisingly—had higher rates of various established stroke risk factors, including hypertension, atrial fibrillation, diabetes, and cerebrovascular disease. Overall, 8.8% of the patients with stroke were treated with thrombolysis and 10.6% underwent thrombectomy.

Outcomes were substantially worse in the group with ischemic stroke/TIA, with higher rates of ICU admission (about 68% vs 30%), mechanical ventilation (about 57% vs 19%), new renal replacement therapy (about 15% vs 3%), and in-hospital death (about 37% vs 14%). Median length of stay was 20 days in the patients with stroke, compared with 10 in the others.

The rate of ischemic stroke/TIA in non-Hispanic white patients matched the overall rate seen in the study (0.75%). Risk was greater in non-Hispanic Black patients (0.91%) and lower in Hispanic patients (0.52%). Further research will be needed to tease out the reasons, Shakil said.

Keeping an Eye on Long-term Consequences

Commenting for TCTMD, Louise McCullough, MD, PhD (University of Texas Health Science Center at Houston), chair of this year’s meeting, said the ischemic stroke/TIA risk observed in this study “doesn’t seem as high as one would think,” noting that any infection can provoke stroke through inflammatory processes. “So I’m actually kind of surprised it wasn’t higher,” she commented

How COVID-19 compares with other infections in terms of increasing the risk of stroke requires further study, McCullough said. She pointed out that the issue might be confounded by the phenomenon of patients not coming to the hospital during the early stages of the pandemic. “There’s a lot of different factors that we have to kind of really account for before we can solidly say that COVID itself is worse than any other infection,” she said. “We do know that COVID can cause endothelial damage and clotting. Is that more than in other infections? Probably, but I think time will tell.”

It will be critical to take a longer-term view when assessing the impact of COVID-19 on stroke risk, because “now we have millions and millions of recovered patients with COVID,” she said. “How will this infection end up affecting their future brain health, both the endothelium and the brain itself? That’s going to be a major public health issue if we find COVID has a long-haul syndrome that affects the brain or vasculature.”

Marion Buckwalter, MD, PhD (Stanford University, CA), highlighted that major area of interest in a separate talk during the meeting. Although motor/functional impairments immediately come to mind as long-term effects of stroke, other issues—like depression, fatigue, seizures, and dementia—are common as well.

Clinical stroke doubles the risk of developing dementia over the next decade, she noted, partly due to disruptions of the immune system. “What we think is that stroke, in addition to damaging tissue acutely, is also starting a chronic immune response in the brain that acts against brain tissue to slowly cause neurodegeneration and dementia,” Buckwalter explained. A depressed immune system after stroke can open the door for infection, which in turn can amplify these “autoaggressive” immune responses, she said.

What all of this means for stroke in the context of COVID-19 is unclear, but studies of severe sepsis show that a high proportion of patients have acute neurological changes and ischemic brain lesions and that the condition comes with an increased risk of moderate or severe cognitive impairment in the future.

“It’s highly likely that sepsis, and probably COVID, are causing an amplification of these autoaggressive immune responses that lead to dementia,” Buckwalter said. But there is a need, she stressed, for long-term studies to better understand the interplay of COVID-19, stroke, and cognitive outcomes.