Cardiovascular and mortality risks following COVID-19–related versus non-COVID-19–related chronic obstructive pulmonary disease exacerbations

Abstract Rationale Chronic obstructive pulmonary disease (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 (CIs) were estimated for each outcome, stratified by exacerbation severity and COVID-19 variants. Results Among 266 273 exacerbations (87.2% moderate, 12.8% severe), 5425 (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 events (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.