COVID-19 Infection Boosts Acute MI, Stroke Risk in Early Weeks

The risk of acute MI or stroke was increased threefold in the first 2 weeks after COVID-19 infection among all Swedish residents who contracted the virus over more than a 7-month period, a large cohort study shows. Researchers say these acute CV complications may be a hallmark of initial clinical manifestation of COVID-19 and should be an added incentive for unvaccinated persons to get the jab, especially if they have chronic comorbid conditions.

While the vaccine does not confer complete immunity, “you’re less likely to get severe disease, which would also mean that you also have less of an inflammatory response, and that in turn would likely mean that you have less risk of AMI or stroke,” senior author Anne-Marie Fors Connolly, PhD (Umeå University, Sweden), told TCTMD.

When COVID-19 patients were compared with a matched cohort of noninfected patients, the odds ratio of acute MI in the 2 weeks following a COVID-19 diagnosis or onset of symptoms was 3.41 (95% CI 1.58-7.36), with a corresponding odds ratio for stroke of 3.63 (95% CI 1.69-7.80).

“It seems reasonable to infer that the persistence of risk for several weeks after SARS-CoV-2 infection is consistent with COVID-19 causing an increased risk of thrombo-occlusive disease, as has been reported for other respiratory infections,” write Marion Mafham, MD, and Colin Baigent, BM BCH (Nuffield Department of Population Health, Oxford, England), in an editorial accompanying the study.

While the “absolute risks are small,” they say, more research is needed to understand the timing of the increased CV risk in relation to COVID-19 infection, as well as the mechanisms that are involved.

“However, it is important to keep in mind,” they add, “that the excess risks of myocardial infarction and stroke in a person with COVID-19 are substantially smaller than those resulting from respiratory failure.”

Tracking the Cases

The Swedish study, with first author Ioannis Katsoularis, MD (Umeå University, Sweden), and published online ahead of print in the Lancet, included nationwide registry data from all Swedish patients diagnosed with COVID-19 (n = 86,742) between February and mid-September 2020, and 348,481 matched controls. The analysis included a self-controlled case series analysis to calculate the incidence of a first acute MI or ischemic stroke following COVID-19 compared with a control period. The matched cohort study calculated the increased risk of MI or stroke conferred by COVID-19 compared with noninfected controls.

In the self-controlled case series, there were 186 first acute MIs during the study period and 36 deaths, as well as 254 first ischemic stroke events. The absolute risk of acute MI or stroke was less than 1 per 1,000.

The analyses used “day of exposure” as a marker where day 0 represented either the date of COVID-19 symptom onset, date of test, or date of the clinic visit or hospital admission. When day of exposure was excluded from the risk period in the self-controlled case series, the incidence rate ratio (IRR) for acute MI was 2.89 (95% CI 1.51-5.55) in the first week after COVID-19, 2.53 (95% CI 1.29-4.94) in the second week, and 1.60 (95% CI 0.84-3.04) in weeks 3 and 4. Including day of exposure led to much higher corresponding numbers in the first week (IRR 8.44; 95% CI 5.45-13.08) but similar numbers thereafter.

Similarly, for ischemic stroke, the IRR was 2.97 (95% CI 1.71-5.15) in the first week, 2.80 (95% CI 1.60-4.88) in the second week, and 2.10 (95% CI 1.33-3.32) in weeks 3 and 4 when day 0 was excluded. Again, excluding day 0 resulted in higher risks in the first week, but the risks were similar after that point.  

In the editorial, Mafham and Baigent say excluding day 0 eliminates the potential that those high numbers reflect a testing bias, where patients without COVID-19 symptoms presenting with MI or stroke have a higher likelihood of being tested, “but might lead to an underestimate of the true risks of myocardial infarction and stroke secondary to COVID-19.”

Missing and Excess MIs

The findings of increased MI and stroke seem at odds with reports of pandemic-related “missing STEMIs” and plunging hospital admissions for MI in both the United States and Europe.

“If there is indeed a moderately increased risk of myocardial infarction and stroke secondary to COVID-19, then why was there a 30-40% fall in admissions for both acute coronary syndromes and stroke during the first wave of the pandemic?” ask Mafham and Baigent.

The answer may be “that any possible attributable excess due to COVID-19 was far smaller than the numbers of people who did not seek medical attention for symptoms of acute coronary syndrome or stroke during this period,” they propose. In the current study, the estimated excess attributable risk of MI or stroke was 0.02%. Extrapolating that to the population of the United Kingdom, they add, would mean that COVID-19 was responsible for about 76 additional MIs during the study period, far smaller than the estimated 5,000 patients thought to have not presented with MI during the first wave of the pandemic.

To TCTMD, Fors Connolly said while the absolute numbers may be small, implicating the virus as an independent risk factor is an important takeaway.

“Also, as a clinician it’s important to note that [acute MI or stroke] could be the first thing you see in a COVID-19 patient,” she added, a finding that’s been particularly conspicuous for stroke in the young. Fors Connolly said her group is planning additional research to see how rates of first acute MI and stroke compare in vaccinated individuals with breakthrough COVID-19 infections.