Cardiovascular disease risk associated with asthma and respiratory morbidity might be mediated by short-acting β₂-agonists

Background: Studies examining the asthma-related risks of cardiovascular disease (CVD) events have generally used selected samples or did not control for the effects of β₂-agonist use, itself associated with CVD events. Objectives: We assessed the relationship between incident CVD/stroke and asthma and the effect of atopy while controlling for β₂-agonist use in a representative adult population cohort free of CVD at baseline. Methods: The North West Adelaide Health Study (stage 1, n = 3812; stage 2, n = 3113) assessed spirometry, anthropometry, atopy, blood pressure, and lipid levels. Questionnaires assessed doctor-diagnosed asthma and CVD (myocardial infarction and angina)/stroke, smoking status, and demographics. Asthma was defined by self-report or FEV₁ reversibility. Current short- and long-acting β₂-agonist use was identified at follow-up. Results: Results are expressed as odds ratios (ORs) and 95% CIs. By using multivariable logistic regression, after adjustment for risk factors, in female subjects incident CVD/stroke events were associated with asthma (OR, 3.24; 95% CI, 1.55-6.78), with no effect modification by atopy (P for interaction = .61), and with as-required short-acting β₂-agonist use (OR, 2.66; 95% CI, 1.06-6.61). In male subjects events were associated with daily cough/sputum (OR, 1.92; 95% CI, 1.05-3.50) and FEV₁ of less than 80% of predicted value but an FEV₁/forced vital capacity ratio of greater than 0.70 (OR, 2.15; 95% CI, 0.91-5.09; P = .08). Although few CVD/stroke events occurred in male subjects with asthma, a significant interaction with atopic status was found (P = .05). Conclusions: Studies are required to elucidate how asthma exposes older women to excess macrovascular risk and prospectively determine the short-acting β₂-agonist-related risk in persons without existing CVD. CVD risk in relation to atopic status of asthma also requires further investigation.