COVID-19 an Independent Driver for Heart Attack and Stroke
August 2, 2021 (Medscape Cardiology) — New data from Sweden provide the strongest evidence to date that COVID-19 is an independent risk factor for acute myocardial infarction (MI) and ischemic stroke, the researchers say.
The risk for acute MI and ischemic stroke increased by roughly eightfold and sixfold, respectively, in the first week following 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 acute MI and stroke was increased by roughly threefold.
“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 acute MI 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 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 say.
Their study was published online July 29 in The Lancet.
Previous studies that have suggested that COVID-19 is a “probable” risk factor for acute cardiovascular 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 348,481 matched control patients.
They used two methods to assess the association of COVID-19 with risk for acute MI and stroke.
One was a self-controlled case series (SCCS) method, which was used to compare incidence rate ratios (IRRs) for first acute MI and stroke before and after patients were determined to have COVID-19.
The other was a matched cohort study, which determined the odds of acute MI 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 acute MI and ischemic stroke recorded on day 0, they report.
In the SCCS, when day 0 was included in the risk period, the IRR for acute MI 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 following COVID- 19.
When day 0 was excluded from the risk period, the IRR for acute MI remained significantly elevated in the first week (IRR 2.89; 95% CI, 1.51 – 5.55) and second week (2.53; 95% CI, 1.29 – 4.94) following COVID-19. The IRR was 1.60 (95% CI, 0.84 – 3.04) in weeks 3 and 4 following 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 following 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, 2.80 (95% CI, 1.60 – 4.88) in the second week, and 2.10 (95% CI, 1.33 – 3.32) in weeks 3 and 4 following COVID-19.
The matched cohort analysis provided similar results, this time expressed as odds ratios (ORs).
Including day 0, the odds ratio (OR) was 6.61 (95% CI, 3.56 – 12.20) for acute MI and 6.74 (95% CI, 3.71 – 12·20) for ischemic stroke in the 2 weeks following COVID-19.
Excluding day 0, the ORs were 3.41 (95% CI, 1.58 – 7.36) and 3.63 (95% CI, 1.69 – 7.80) for acute MI and stroke, respectively, in the 2 weeks following COVID-19.
The Day Zero Debate
“The day 0 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.
But 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 healthcare 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 acute MI and stroke remains elevated when day 0 is excluded shows that COVID-19 is an independent risk factor for acute MI and ischemic stroke, she emphasized.
Findings Reinforce Importance of Vaccination, but Absolute Risks Small
In the matched cohort study, for each weighted Charlson comorbidity index point, the odds of acute MI 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 cardiovascular events,” Connolly told theheart.org | Medscape Cardiology.
Acute MI 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 note that the transient increase in the risk for MI and stroke in association withinfluenza, 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,” write Marion Mafham, MD, and Colin Baigent, FMedSci, of the University of Oxford, Oxford, United Kingdom.
They note, however, that the absolute risks are “small.” They also write that further studies are needed to evaluate the time course of increased cardiovascular risk for patients with COVID-19 and to investigate possible mechanisms.
“However, it is important to keep in mind that the excess risks of myocardial infarction and stroke in a person with COVID- 19 are substantially smaller than those resulting from respiratory failure,” Mafham and Baigent say.
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.
Lancet. Published online July 29, 2021.