Covid-19 is a key driver of heart attacks and strokes, says study

Covid-19 is a key driver of heart attacks and strokes, a Swedish study has found. 

The study conducted by researchers from the Umeå University in Sweden provides strong evidence to date that Covid-19 is an independent risk factor for acute myocardial infarction (MI) and ischemic stroke. The study findings were published in The Lancet. 

According to the research team led by Dr Ioannis Katsoularis from the department of Public Health and Clinical Medicine, Umeå University, the risk for acute MI and ischemic stroke increased by roughly eight-fold and six-fold, 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 myocardial infarction and ischemic stroke. Our study findings 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,"  said senior author of the study Dr Anne-Marie Fors Connolly.

Numerous past studies that have suggested that Covid-19 is a "probable" risk factor for acute cardiovascular complications involved relatively few hospitalised patients.

However this study can be considered to be the largest study to date to investigate this association.

The study team 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 1 February and 14 September, 2020, and 348,481 matched control patients. The team then used two methods to assess the association of Covid-19 with risk for acute MI and stroke.
 
They first involved 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 second approach 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.
 
As the date of infection was unknown, the researchers identified the closest date possible and denoted it as day 0 (exposure date). The study reported that there was a large peak in cases of both acute MI and ischemic stroke recorded on day 0.

In the self-controlled case series (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. However 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. Again 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.

Importantly the matched cohort analysis provided similar results; this time expressed as odds ratios (ORs).

The study findings showed that 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. However 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.

Dr Connolly further commented, and explained "The day 0 has been a cause of discussion between clinicians and statisticians during this study. The study team argued that all events should be included, since we believe it is part of the clinical disease presentation."

However Professor Emeritus Paddy Farrington, PhD, a statistician of the Open University Milton Keynes-United Kingdom, and a key collaboration partner in the study team argued that "day 0 should be excluded because it represents a bias ie seeking healthcare likely precipitates testing for SARS-CoV-2 infection and therefore introduces a test bias that potentially inflates the observed risk."