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The goal of this activity is to assess the risk for acute myocardial infarction (AMI) and stroke associated with infection with COVID-19.
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Acute respiratory infections promote systemic inflammation, the type of inflammation that promotes a higher risk for acute myocardial infarction (AMI) and stroke. Barnes and colleagues assessed this issue in a systematic review and meta-analysis of case-control studies of influenza and myocardial infarction (MI). The results of their study were published in the November 2015 issue of Heart.[1]
The review involved 16 studies, including 8 studies that evaluated the role of influenza vaccination in protecting against MI. Recent influenza infection or influenza-like illness was associated with a 2-fold increase in the risk for AMI. Meanwhile, influenza vaccination was associated with a pooled odds ratio (OR) of 0.71 (95% CI: 0.56, 0.91) for AMI.
COVID-19 is associated with an even more robust inflammatory response compared with influenza. Is the SARS-CoV-2 virus associated with a higher risk for AMI and stroke? The current study by Katsoularis and colleagues assesses this issue.
New data from Sweden provide the strongest evidence to date that COVID-19 is an independent risk factor for AMI and ischemic stroke, the researchers said.
The risk for acute MI and ischemic stroke increased by roughly 8-fold and 6-fold, respectively, in the first week after onset of COVID-19 when day 0 (exposure day) was included in the analysis. Even when day 0 was excluded (reducing the risk for bias), the risk for AMI and stroke was increased by roughly 3-fold.
"The fact that the risk is still increased even when day 0 is excluded indicates that COVID-19 is indeed an independent risk factor for [AMI] and ischemic stroke," senior author Anne-Marie Fors Connolly, MD, PhD, with Umeå University, Umeå, Sweden, told theheart.org | Medscape Cardiology.
"Our results indicate that acute cardiovascular [(CV)] complications might represent an essential clinical manifestation of COVID-19 and the long-term effects might be a challenge for the future," she and her colleagues said.
Their study was published online July 29 in The Lancet.[2]
Digging DeeperPrevious studies that have suggested that COVID-19 is a "probable" risk factor for acute CV complications involved relatively few hospitalized patients.
In what is believed to be the largest study to date to investigate this association, Swedish researchers linked data from national registers for outpatient and inpatient clinics and the cause of death register for all 86,742 patients (median age, 48 years; 43% male) with COVID-19 between February 1 and September 14, 2020, and 348,841 matched control patients.
They used 2 methods to assess the association of COVID-19 with risk for AMI and stroke.
One was a self-controlled case series (SCCS) method, which was used to compare incidence rate ratios (IRRs) for first AMI and stroke before and after patients were determined to have COVID-19.
The other was a matched cohort study, which determined the odds of AMI or stroke in the 14 days after COVID-19 onset in comparison with control individuals who had not been diagnosed with COVID-19.
Because the date of infection was unknown, the researchers identified the closest date possible and denoted it as day 0 (exposure date).
There was a large peak in cases of both AMI and ischemic stroke recorded on day 0, they reported.
In the SCCS, when day 0 was included in the risk period, the IRR for AMI was 8.44 (95% CI: 5.45, 13.08) in the first week; 2.56 (95% CI: 1.31, 5.01) in the second week; and 1.62 (95% CI: 0.85, 3.09) in weeks 3 and 4 after COVID-19.
When day 0 was excluded from the risk period, the IRR for AMI remained significantly elevated in the first week (IRR = 2.89 [95% CI: 1.51, 5.55) and second week (IRR = 2.53 [95% CI: 1.29, 4.94) after COVID-19. The IRR was 1.6 (95% CI: 0.84, 3.04) in weeks 3 and 4 after COVID-19.
The corresponding IRRs for ischemic stroke when day 0 was included in the risk period were 6.18 (95% CI: 4.06, 9.42) in the first week; 2.85 (95% CI: 1.64, 4.97) in the second week; and 2.14 (95% CI: 1.36, 3.38) in weeks 3 and 4 after COVID-19.
When day 0 was excluded from the risk period, the corresponding IRRs for stroke were 2.97 (95% CI: 1.71, 5.15) in the first week; 2.8 (95% CI: 1.6, 4.88) in the second week; and 2.1 (95% CI: 1.33, 3.32) in weeks 3 and 4 after COVID-19.
The matched cohort analysis provided similar results: this time expressed as odds ratios (ORs).
The Day Zero Debate"The day [zero] has been a cause of discussion between clinicians and statisticians during this study," Connolly told theheart.org | Medscape Cardiology.
"The clinicians (myself included) argued that all events should be included, since we believe it is part of the clinical disease presentation," she explained.
Still, Paddy Farrington, PhD, professor emeritus and statistician of The Open University, Milton Keynes, in Milton Keynes, United Kingdom, and "an important collaboration partner on our study," argued that day 0 should be excluded because it represents a bias. Seeking health care likely precipitates testing for SARS-CoV-2 infection and therefore introduces a test bias that potentially inflates the observed risk, Connolly explained.
The observation that the risk for AMI and stroke remains elevated when day 0 is excluded shows that COVID-19 is an independent risk factor for AMI and ischemic stroke, she emphasized.
Findings Reinforce Importance of Vaccination, but Absolute Risks Are SmallIn the matched cohort study, for each weighted Charlson comorbidity index point, the odds for AMI and ischemic stroke increased approximately 40%.
Hence, the findings reinforce the importance of getting vaccinated against COVID-19, particularly for elderly people with comorbid conditions, "to avoid potential acute [CV] events," Connolly told theheart.org | Medscape Cardiology.
Acute myocardial infarction and stroke "could be an extrapulmonary manifestation of COVID-19; therefore, this is good to keep in mind for clinicians who see these types of patients," she added.
The authors of an accompanying comment[2] noted that the transient increase in the risk for MI and stroke in association with influenza, pneumonia, acute bronchitis, and other chest infections has been known for decades.
"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," wrote Marion Mafham, MD, and Colin Baigent, FMedSci, of the University of Oxford, Oxford, United Kingdom.
They noted, however, that the absolute risks are "small." They also wrote that further studies are needed to evaluate the time course of increased CV risk for patients with COVID-19 and to investigate possible mechanisms.
"However, it is important to keep in mind that the excess risks of [MI] and stroke in a person with COVID-19 are substantially smaller than those resulting from respiratory failure," Mafham and Baigent said.
Funding for the study was provided by Central ALF-Funding and Base Unit ALF-Funding, Region Västerbotten, Sweden; strategic funding during 2020 from the department of clinical microbiology, Umeå University, Sweden; stroke research in Northern Sweden; and the Laboratory for Molecular Infection Medicine Sweden. The authors and editorialists have disclosed no relevant financial relationships.