Spirometric Impairment and Incident Cardiovascular Disease: Beyond Airflow Limitation

Impaired spirometry is associated with cardiovascular disease (CVD), but it is unclear whether this risk is driven by airflow limitation or other spirometric dimensions. We compared spirometric phenotypes and lung-function measures in relation to incident CVD.

We included 3,660 Sleep Heart Health Study participants (mean age, 64.2 ± 10.5 years) without prespecified baseline CVD. Phenotypes were normal spirometry, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 1, preserved ratio impaired spirometry (PRISm), and GOLD grades 2-4. Measures were forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), and FEV₁/FVC. Cox models adjusted for demographic, smoking, socioeconomic, and cardiovascular covariates.

During a median 11.4 years of follow-up, 730 incident CVD events occurred. Lower FEV₁ and lower FVC were associated with CVD, whereas FEV₁/FVC was not. In joint FVC-FEV₁ models, FVC remained associated with CVD (hazard ratio per 10-percentage-point lower FVC percent predicted, 1.124; 95% confidence interval, 1.035-1.221), whereas FEV₁ did not. In the principal model including fixed-ratio airflow limitation, lower FVC remained associated with CVD (hazard ratio, 1.091; 95% confidence interval, 1.048-1.136), whereas airflow limitation was not independently associated. The association persisted without airflow limitation and across sensitivity analyses. FVC improved model fit beyond spirometric phenotypes, with modest discrimination gain.

CVD risk associated with impaired spirometry was more consistently related to lower FVC than to airflow limitation. FVC may capture cardiovascular risk not reflected by airflow limitation alone.