Longitudinal Impact of Smoking and Smoking Cessation on Inflammatory Markers of Cardiovascular Disease Risk

King CC, Piper ME, Gepner AD, et al.
Arterioscler Thromb Vasc Biol 2017;37:published online ahead of print

Background

Tobacco smoking increases the CVD risk by activating inflammatory pathways, lipid oxidation, hypercoagulability, and vascular dysfunction [1,2]. There are data showing that smokers have higher levels of CVD risk-associated inflammatory markers, however, the effects of smoking cessation on such inflammatory markers have not been evaluated [3,4].

In this study, the cross-sectional and longitudinal relationships between smoking burden, smoking cessation and six inflammatory markers were assessed, in a large cohort of smokers.
The inflammatory markers, which are predictive of CVD events, included: c-reactive protein (CRP), D-dimer, fibrinogen, urinary F2 isoprostane:creatinine [F2:Cr] ratio, myeloperoxidase, and WBC count. These were compared with smoking heaviness markers exhaled carbon monoxide (CO), cigarettes per day, and packyears.

Main results

• Smokers were on average 49.6 years old, smoked 16.8 cigarettes/day, and had a smoking burden of 27.3 pack-years with CO levels of 14.4 ppm.
• The mean BMI was 29.4 kg/m², 18% of participants were on lipid-lowering therapy and 8.7% of participants were receiving antidiabetic medications.  
• There were strong, independent associations between smoking heaviness markers and the F2:Cr ratio, WBC counts, and myeloperoxidase.
• There were no statistically significant associations between CRP, D-dimers, and fibrinogen levels and any smoking heaviness marker.
• Out of the 888 participants who made an aided quit attempt and completed the year 1 assessments, 344 (29.7%) participants had biochemically confirmed 7-day point-prevalence abstinence at 1 year.
• Eventual abstainers smoked fewer cigarettes/day (t=2.95; P=0.003) and had lower CO levels (t=4.17; P<0.001) at baseline compared with continuing smokers.
• Abstainers gained more weight compared with continued smokers (4.0 kg vs. 0.4 kg; P<0.001) and had greater increases in homeostasis model of insulin resistance scores (15.4 U versus 7.2 U; P=0.02).
• There were statistically significant correlations between changes in CO with changes in urinary F2:Cr ratio (P=0.002) and WBC counts (P<0.001), but no significant correlations with the other inflammatory biomarkers after 1 year.

Conclusion

In a large cohort, smoking heaviness was independently associated with urinary F2:Cr ratio, myeloperoxidase and WBC count, which are three inflammatory markers related to CVD risk. However, no association was observed with CRP, fibrinogen or D-dimer. In addition, cessation reduced urinary F2:Cr ratios and WBC counts. As F2:CR ratio and myeloperoxidase reflect oxidative stress, these results suggest that oxidant stress may mediate increased inflammation and CVD risk in smokers.

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References

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