Stroke Risk Highest Right After COVID Infection

Pauline Anderson

February 15, 2022

The risk for acute ischemic stroke (AIS) in patients with COVID-19 appears to be significantly elevated in the first 3 days after the infection, new research shows.

The study, among Medicare beneficiaries with COVID-19, also showed that stroke risk is higher for relatively young older adults, those aged 65 to 74 years, and those without a history of stroke.

Quanhe Yang PhD

The study highlights the impact COVID-19 has on the cardiovascular system, study author Quanhe Yang, PhD, senior scientist, Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, told | Medscape Cardiology.

"Clinicians and patients should understand that stroke might be one of the very important clinical consequences of COVID-19."

The study was presented during the International Stroke Conference (ISC) 2022 held in New Orleans, Louisiana, and online February 9 to 11.

Stroke is the fifth leading cause of death in the US. As an increasing number of people become infected with COVID-19, "it's important to determine if there's a relationship between COVID and the risk of stroke," said Yang.

Findings from prior research examining the link between stroke and COVID-19 have been inconsistent, he noted. Some studies found an association while others did not, and in still others the association was not as strong as expected.

Many factors may contribute to these inconsistent findings, said Yang, including differences in study design, inclusion criteria, comparison groups, sample sizes, and countries where the research was carried out.

Yang pointed out that many of these studies were done in the early stages of the pandemic or didn't include older adults, the population most at risk for stroke.

The current study included 19,553 Medicare beneficiaries aged 65 years and older diagnosed with COVID-19 and hospitalized with AIS. The median age at diagnosis of COVID-19 was 80.5 years, 57.5% were women, and more than 75% were non-Hispanic whites.

To ensure the stroke occurred after a COVID infection, researchers used a self-controlled case series study design, a "within person" comparison between the risk period and the control period.

They divided the study period (January 1, 2019, to February 28, 2021) into the exposure or stroke risk periods after the COVID diagnosis (0-3 days; 4-7 days; 8-15 days; and15-28 days) and control periods.

Strokes that occurred 7 days before or 28 days after a COVID diagnosis served as a control period. "Any stroke that occurred outside the risk window is in the control period," explained Yang.

He added the control period provides a baseline. "Without COVID-19, this is what I would expect" in terms of the number of strokes.

To estimate the incidence rate ratio (IRR), investigators compared the incidence of AIS in the various risk periods with control periods.

The IRR was 10.97 (95% CI, 10.30-11.68) at 0-3 days. The risk then quickly declined but stayed higher than the control period. The IRRs were: 1.59 (95% CI, 1.35-1.87) at 4-7 days; 1.23 (95% CI, 1.07-1.41) at 8-14 days, and 1.06 (95% CI, 0.95-1.18) at 15-28 days.

The temporary increase in stroke risk early after an infection isn't novel; the pattern has been observed with influenza, respiratory infections, and shingles, said Yang. "But COVID-19 appears to be particularly risky."

Although the mechanism driving the early increased stroke risk isn't fully understood, it's likely tied to an "exaggerated inflammatory response," said Yang.

This can trigger the cascade of events setting the stage for a stroke — a hypercoagulation state leading to the formation of blood clots that then block arteries to the brain, he said.

It's also possible the infection directly affects endothelial cells, leading to rupture of plaque, again blocking arteries and raising stroke risks, added Yang.

The association was stronger among younger beneficiaries, aged 65 to 74 years, compared to those 85 years and older, a finding Yang said was somewhat surprising.

But he noted other studies have found stroke patients with COVID are younger than stroke patients without COVID — by some 5 to 6 years.

"If COVID-19 disproportionately affects younger patients, that may explain the stronger association," said Yang. "Stroke risk increases tremendously with age, so if you're a younger age, your baseline stroke risk is lower."

The association was also stronger among beneficiaries without a history of stroke. Again, this could be related to the stronger association among younger patients who are less likely to have suffered a stroke.

The association was largely consistent across sex and race/ethnicities. 

Yang stressed the findings need to be confirmed with further studies.

The study was carried out before widespread use of vaccinations in the US. Once those data are available, Yang and his colleagues plan to determine if vaccinations modify the association between COVID-19 and stroke risk.

The new results contribute to the mounting evidence that a COVID-19 infection "can actually affect multiple human organs structurally or functionally in addition to the impact on [the] respiratory system," said Yang.

Some dates of COVID-19 diagnoses may be incorrect due to limited test availability, particularly early in the pandemic. Another limitation of the study was possible misclassification from the use of Medicare real-time preliminary claims.

Commenting in a provided statement, Louise D. McCullough, MD, PhD, chair of the ISC 2022, and professor and chair of neurology, McGovern Medical School, University of Texas Health Science Center at Houston, noted the study focused on older adults because it was examining Medicare beneficiaries.

"But everyone is likely at risk for stroke after COVID," she said. "Any infection is linked to stroke risk, probably because any infection will cause inflammation, and inflammation can cause clots or thrombus, which is the cause of stroke."

There was no outside funding for the study. No relevant conflicts of interest were disclosed.

International Stroke Conference 2022. Presentation TMP16. Presented February 10, 2022.

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