Overlapping airway diseases and risk of major adverse cardiovascular events: a UK biobank prospective cohort study.

BACKGROUND

Asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis frequently coexist, but the cardiovascular implications of their overlap phenotypes have not been systematically quantified in large prospective cohorts.

METHODS

Among 407,127 UK Biobank participants free of cardiovascular disease at baseline, we classified asthma, COPD, and bronchiectasis into eight mutually exclusive phenotypes and used Cox proportional hazards regression to assess their associations with the first occurrence of major adverse cardiovascular events (MACE, comprising myocardial infarction, stroke, and cardiovascular death). We further tested for a dose-response relationship and effect modification by sex.

RESULTS

Over a median follow-up of 14 years, 19,660 MACE occurred. All overlap phenotypes carried elevated MACE risk, with asthma-bronchiectasis showing the highest risk (hazard ratio [HR] 3.23, 95% confidence interval [CI] 1.94-5.36); this association remained stable across sequential confounder adjustments, indicating that the risk was independent of traditional cardiovascular factors. MACE risk rose stepwise with the number of concurrent airway diseases (HRs of 1.00, 1.15, and 1.79 for 0, 1, and 2 diseases; P-trend = 1.45 × 10-23). Sex significantly modified this association (P-interaction = 0.0015), with consistently stronger risk elevations in women than in men across all principal phenotypes.

CONCLUSIONS

Overlapping airway diseases substantially elevate MACE risk in a dose-dependent manner, with risk most pronounced in women. Asthma-bronchiectasis emerged as a previously under-recognised high-risk combination. These findings support integrating airway comorbidity into cardiovascular risk stratification.