Cardiovascular and mortality risks following COVID-19-related vs. non-COVID-19 COPD exacerbations

RATIONALE: COPD exacerbations, often triggered by viral infections like COVID-19, are associated with increased cardiovascular risk. We hypothesized that COVID-19-related exacerbations carry higher short-term cardiovascular and mortality risks than non-COVID-19-related exacerbations. OBJECTIVES: To compare 28-day risk of stroke, pulmonary embolism (PE), acute myocardial infarction (AMI), major adverse cardiovascular events (MACE) and all-cause mortality following COVID-19-related vs. non-COVID-19-related COPD exacerbations and assess variation across the pandemic. METHODS: Using Swedish national registers, we identified COPD with moderate (treated with oral corticosteroids with/without antibiotics) or severe (hospitalized) exacerbations from March 2020 to June 2023. Exacerbations with infection, hospitalization or intensive care admission for COVID-19 were defined as COVID-19-related. A target trial was emulated and adjusted hazard ratios (aHRs) with 95% confidence intervals (CI) estimated for each outcome, stratified by exacerbation severity and COVID-19 variants. MEASUREMENTS AND MAIN RESULTS: Among 266,273 exacerbations (87.2% moderate, 12.8% severe), 5,425 (2%) were COVID-19-related. COVID-19-related vs. non-COVID-19-related moderate exacerbations were associated with risk of PE (aHR 2.26, 95%CI 1.49-3.42), overall cardiovascular (1.94, 1.47-2.56), MACE (1.88, 1.28-2.76), and mortality (4.58, 4.06-5.17), but not significantly with AMI and stroke. Severe COVID-19-related exacerbations were only associated with higher mortality (1.46, 1.28-1.66). Cardiovascular risks were highest during pre-Alpha and Delta for moderate exacerbations. Mortality remained elevated for both moderate and severe exacerbations, particularly during the same periods. CONCLUSIONS: COVID-19-related exacerbations increased MACE, short-term cardiovascular and mortality risks, mainly for moderate exacerbations, with attenuation during Alpha and Omicron, highlighting the need for proactive cardiovascular care during respiratory outbreaks.