The cardiovascular impact of antimicrobial resistance: insights from patients with bronchiectasis

Abstract Background Bronchiectasis is a clinical condition characterized by a chronic pro-inflammatory state, which is associated with an increased risk of cardiovascular events. In this context, prolonged antibiotic therapy is often required but can lead to antimicrobial resistance (AMR), further exacerbating the pro-inflammatory state. However, the impact of the inflammatory component of AMR on the risk of cardiovascular events in these patients remains unknown. Purpose To assess the impact of AMR on major adverse cardiovascular event (MACE) risk in patients with bronchiectasis. Methods This retrospective study utilized data from the TriNetX research network, analysing patients with bronchiectasis categorized by the presence or absence of AMR. Primary outcomes included the risk of MACE (myocardial infarction, stroke and systemic thromboembolism, and cardiac arrest) and all-cause death. Event rates were expressed as annual incidences. Cox regression analysis with 1:1 propensity score matching (PSM) was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the primary outcomes. Sensitivity analysis was performed to calculate the risk of a first MACE (excluding those who experienced any MACE before the index event. Lastly, subgroup analyses were conducted to validate results of the main analysis in clinically relevant subgroups. Results Prior to PSM, patients with AMR (n=6,543, 61.0±22.0 years, 55.8% female) were younger, more often male, and had a higher prevalence of cardiovascular risk factors compared to those without AMR (n=154,685, 67.3±16.0 years, 59.4% female). After a median follow-up of 730 days (interquartile range: 409), patients with AMR had a significantly higher annual incidence of MACE (4.9% vs. 10.2%, P0.001), all-cause death (8.1% vs. 17.6%, P0.001), acute myocardial infarction (2.3% vs. 5.0%, P0.001), stroke and systemic thromboembolism (2.5% vs. 4.6%, P0.001), and cardiac arrest (0.6% vs. 2.1%, P0.001) compared to those without AMR. After PSM, no significant differences were observed between groups. However, AMR patients remained at higher risk for MACE (HR 1.29, 95% CI 1.17–1.41), all-cause death (HR 1.49, 95% CI 1.38–1.61), and all individual MACE components compared to non-AMR patients (Table 1). The MACE risk was particularly elevated among AMR patients without prior cardiovascular events (HR 1.56, 95% CI 1.34–1.81) (Table 1). Similar MACE risks were observed in cystic fibrosis (HR 1.24, 95% CI 0.86–1.78) and non-cystic fibrosis subgroups (HR 1.28, 95% CI 1.16–1.41), with consistent findings across sex, age groups (≥65 vs. 65 years), and the presence or absence of key cardiovascular risk factors. The increased risk of primary outcomes was observed across all AMR subtypes (Figure 1). Conclusions In patients with bronchiectasis, AMR is associated with an increased risk of MACE and all-cause death. controlling AMR spread may confer broader health benefits, particularly in reducing cardiovascular risk