Abstract
Background Isolated small airways obstruction (SAO) is common, a precursor of chronic obstructive pulmonary disease, and is 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 FEV 3 /FEV 6 <LLN with a normal FEV 1 /FEV 6 ratio. A second analysis was performed where isolated SAO was defined as FEF 25-75% <LLN with a normal FEV 1 /FEV 6 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 (RR=1.05, 95% CI 1.01-1.09). This association was not significant in males (RR=1.03, 95%CI 0.98-1.08) nor in never smokers (RR 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. </p>