B22-11 A Reduction in Sputum Macrophages and Lung Function Is Associated With Increased Estimated Cardiovascular Risk in Adults With Obese, Uncontrolled Asthma

Abstract Rationale Moderate-to-severe asthma has been linked to an increased risk of cardiovascular disease (CVD). The mechanisms underlying this association remain unclear. Current cardiovascular risk estimators, such as the PREVENT-30 model, incorporate classical CVD risk factors but do not account for chronic inflammation or lung function impairment, factors linked to all-cause and cardiovascular mortality. We sought to determine the relationship between systemic inflammation, lung function, and predicted 30-year cardiovascular risk (PREVENT-30), to evaluate whether these factors are associated with higher estimated CVD in obesity-associated asthma. Methods A cross-sectional investigation was conducted in 71 obese (BMI ≥27 kg/m2) adults with uncontrolled moderate-to-severe asthma (ACQ≥1.5) despite treatment with at least medium-dose inhaled corticosteroids. Key exclusion criteria included COPD, diabetes, and use of biologics. Participants underwent spirometry, induced sputum collection and blood sampling for differential cell counts, blood sampling for glycated hemoglobin (HbA1c), total cholesterol, and HDL cholesterol levels. The PREVENT-30 calculator was used to estimate 30-year cardiovascular risk. Associations between PREVENT-30 scores, inflammatory markers, and lung function parameters were evaluated using Spearman correlation and linear regression models. Variables significantly associated with higher PREVENT-30 score in univariate analyses were entered into a multivariable regression to identify independent predictors. We further excluded variables with high multicollinearity. Data are expressed as mean ± SD for normal and median IQR for non-normally distributed variables. Results The asthma cohort was 80% female, with a mean age of 47.7 ± 13.7 years, median BMI of 37.20 32.4-39.7 kg/m2. The median PREVENT-30 score was 17.7 5.8-26.2 %. In univariate analysis, PREVENT-30 scores were positively correlated with blood eosinophils (rs = 0.28, p = 0.01), sputum eosinophils (rs = 0.35, p = 0.003), and sputum neutrophils (rs = 0.21, p = 0.08), and inversely correlated with sputum macrophages (rs = −0.37, p = 0.002), FEV₁% predicted (rs = −0.32, p = 0.006), FVC (rs = −0.40, p = 0.0004), and FEV₁/FVC (rs = −0.34, p = 0.003). In multivariable regression, lower sputum macrophage (b = −0.41, p 0.001) and reduced FEV₁% predicted (b = −0.26, p = 0.021) emerged as independent predictors of higher PREVENT-30 scores, together explaining 26% of variance (Figure 1). Conclusion In adults with obesity-associated, moderate-to-severe asthma, reduced sputum macrophage and lower FEV₁% predicted were independently associated with higher PREVENT-30 scores. These findings suggest that impaired airway macrophage balance and reduced lung function may reflect shared inflammatory pathways linking asthma and cardiometabolic disease. Our study suggests that incorporating measures of airway inflammation and pulmonary function into CVD risk assessment tools may improve risk stratification and prediction in this high-risk population. This abstract is funded by: U01 AI155299