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

Bradley Tun, MD

Bradley Tun, MD1, Rachel Ehrbar, MA2, Meghan Short, PhD3, Susan Cheng, MD4, Ramachandran S. Vasan, MD5,6,7, and Vanessa Xanthakis, PhD2,5,6.

  1. Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA.
  2. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  3. Glenn Biggs Institute for Alzheimer’s Disease & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.
  4. Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  5. National Heart, Blood and Lung Institute, Framingham Heart Study, Framingham, MA, USA.
  6. Sections of Preventive Medicine and Epidemiology and Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  7. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.

Abstract 

Background: Exhaled carbon monoxide (eCO) is directly associated with traditional cardiovascular disease (CVD) risk factors and incident CVD. However, its relations with the cardiovascular health (CVH) score and incidence of heart failure (HF) have 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 CVH 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 CVH scores were associated with lower eCO (β = -0.02, P<0.0001), even among non-smokers. 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 [HR] 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; HR per SD increment in eCO: 1.43, 95% CI: 1.15-1.77; P = 0.001).

Conclusion:

In our community-based sample, higher levels of eCO were associated with lower CVH scores, an adverse cardiovascular biomarker profile, and a higher risk of HF, specifically HFrEF. Our findings suggest that CO may identify a novel pathway to HF development.

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