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

Abstract

Objectives To evaluate longitudinal changes in six inflammatory markers that predict cardiovascular disease events among smokers making a quit attempt and to characterize their cross-sectional associations between smoking and smoking heaviness. Approach and Results In a longitudinal cohort study of contemporary smokers (N=1652), we evaluated (i) independent associations of smoking heaviness markers (exhaled carbon monoxide, cigarettes/day, pack-years) with inflammatory markers (C-reactive protein [CRP], D-dimer, fibrinogen, urinary F2 isoprostane:creatinine [F2:Cr] ratio, white blood cell count [WBC], myeloperoxidase [MPO]), and (ii) the effects of smoking cessation and continued smoking on these inflammatory markers after one year, among the 888 smokers who made an aided quit attempt as part of a randomized comparative effectiveness trial or standard care. There were strong, independent associations between smoking heaviness markers and the F2:Cr ratio, WBC, and MPO (all padj<0.001), but not hsCRP, D-dimer, or fibrinogen. Participants were mean (standard deviation) 49.6 (11.6) years old, 54% female, 34% non-White, and smoked 16.8 (8.5) cigarettes /day for 27.3 (18.6) pack-years. After 1 year, the 344 successful abstainers gained more weight (4.0 [6.0] vs. 0.4 [5.7] pounds, p<0.001) and had larger increases in insulin resistance scores (p=0.02) than continuing smokers. Despite these increases, abstainers had significant decreases in F2:Cr ratio (p<0.001) and WBC counts (p<0.001). Changes in other markers were not related to quitting. Conclusions Smoking heaviness is associated with increased F2:Cr ratio, MPO, and WBC counts. Cessation improves the F2:Cr ratio and WBC counts independent of weight change, suggesting reduced inflammation related to less oxidant stress.

The association between cigarette smoking and inflammation: The Genetic Epidemiology Network of Arteriopathy (GENOA) study

“…Our results are consistent with prior findings that show a relationship between cigarette smoking and vascular inflammation [ 9 – 11 , 13 , 38 , 39 ]. Smoking has been shown to modulate inflammation by activating the NF- K B pathway thereby inducing the transcription of genes involved in the innate immune response [ 40 , 41 ].…”

Review of biomarkers to assess the effects of switching from cigarettes to modified risk tobacco products

“…On the other hand, a more recent, albeit smaller study, found no significant difference (p ¼ 0.09) (Bazzano et al 2003). In another study, there was no reduction in FBG levels in subjects who refrained from smoking for 1 year (King et al 2017) One study found no significant difference between smokers who continued to smoke conventional cigarettes compared to those who switched to an RRP (p ¼ 0.88) (Nordskog et al 2015). It is important to note that many studies have shown that the functionality of FBG as an acute phase protein in response to inflammatory conditions is better reflected in changes in CRP than in corresponding changes of FBG levels (Al Rifai et al 2017).…”

Peripheral immune biomarkers and neurodegenerative diseases: A prospective cohort study with 20 years of follow‐up

“…18,19 Furthermore, smoking has also been suggested to influence the levels of different inflammatory markers including white blood cells. 20 Therefore, in another sensitivity analysis, we further adjusted for smoking status. Information on smoking was gathered from different sources in the AMORIS cohort, including a number of cohort studies and the Swedish Medical Birth Register.…”

“…Smoking has a known inverse relationship with PD and has recently been suggested to be causally related to the risk of ALS . Furthermore, smoking has also been suggested to influence the levels of different inflammatory markers including white blood cells . Therefore, in another sensitivity analysis, we further adjusted for smoking status.…”