Association of Exhaled Carbon Monoxide With Ideal Cardiovascular Health, Circulating Biomarkers, and Incidence of Heart Failure in the Framingham Offspring Study

BACKGROUND: Exhaled carbon monoxide (eCO) is directly associated with traditional cardiovascular disease risk factors and incident cardiovascular disease. However, its relation with the cardiovascular health score and incidence of heart failure (HF) has not been investigated. METHODS AND RESULTS: We measured eCO in 3521 Framingham Heart Study Offspring participants attending examination cycle 6 (mean age 59 years, 53% women). We related the cardiovascular health score (composite of blood pressure, fasting plasma glucose, total cholesterol, body mass index, smoking, diet, and physical activity) to eCO adjusting for age, sex, and smoking. Higher cardiovascular health scores were associated with lower eCO (β=−0.02, P<0.0001), even among nonsmokers. Additionally, C‐reactive protein, plasminogen activator inhibitor‐1, fibrinogen, growth differentiation factor‐15, homocysteine, and asymmetrical dimethylarginine were positively associated with eCO (P≤0.003 for all). The age‐ and sex‐adjusted and multivariable‐adjusted heritabilities of eCO were 49.5% and 31.4%, respectively. Over a median follow‐up of 18 years, 309 participants (45% women) developed HF. After multivariable adjustment, higher eCO was associated with higher risk of HF (hazards ratio per SD increment: 1.39; 95% CI, 1.19–1.62 [P<0.001]) and with higher risk of HF with reduced ejection fraction (N=144 events; hazard ratio per SD increment in eCO: 1.43; 95% CI, 1.15–1.77 [P=0.001]). CONCLUSIONS: In our community‐based sample, higher levels of eCO were associated with lower cardiovascular health scores, an adverse cardiovascular biomarker profile, and a higher risk of HF, specifically HF with reduced ejection fraction. Our findings suggest that carbon monoxide may identify a novel pathway to HF development.