Small airways obstruction predicts cardiovascular disease incidence: a longitudinal study of UK Biobank

ERJ Open Res. 2026 Jun 8;12(3):01190-2025. doi: 10.1183/23120541.01190-2025. eCollection 2026 May.

ABSTRACT

BACKGROUND: Isolated small airways obstruction (SAO) is common, a precursor of COPD and associated with increased cardiovascular disease (CVD) mortality. Whether isolated SAO predicts CVD incidence is unknown.

METHODS: Using longitudinal data on 139 568 UK Biobank participants (median age 58 years), we calculated CVD incidence in those with, versus without, isolated SAO defined as forced expiratory volume in 3 s (FEV₃)/forced expiratory volume in 6 s (FEV₆) 1)/FEV₆ ratio. A second analysis was performed where isolated SAO was defined as forced expiratory flow at 25-75% of forced vital capacity (FEF_25-75%) 1/FEV₆ ratio. Using mixed effects quasi-Poisson regression models, we assessed the association between isolated SAO and CVD, investigating differences in association by sex and smoking status.

RESULTS: At baseline, 10 480 participants (7.5%) had isolated SAO. During follow-up (median 9.2 years), CVD was diagnosed in 30 763 (22%) participants, more commonly among those with isolated SAO at baseline (risk ratio 1.05 (95% CI 1.01-1.09)). This association was not significant in males (risk ratio 1.03 (95% CI 0.98-1.08)) nor in never-smokers (risk ratio 1.02 (95% CI 0.97-1.09)). The risk of CVD was increased when isolated SAO was defined using FEF_25-75%.

CONCLUSIONS: Adults with isolated SAO have a modest increased risk of developing CVD. However, this association is potentially driven by smoking. Further research should explore underlying mechanisms for this increased risk and how best this can be mitigated.

PMID:42267371 | PMC:PMC13244214 | DOI:10.1183/23120541.01190-2025