Among 8152 participants (4267 women, 4245 men) with questionnaire data on cigarette smoking, 90% (n = 7375) had cotinine assays. The analysis sample excluded (i) n = 251 (3%) ex-smokers who quit <5 years previously, (ii) 162 taking warfarin (iii) 1472 with a history (self-report or record in GP notes) of MI, diabetes or stroke, (iv) 733 active cigarette smokers. The analysis sample comprised 4757 non-smokers (of which 52% never smoked). For comparison, descriptive analyses included 272 smokers of 1–9 cigarettes/day. Of 4757 non-smokers, 38% had undetectable cotinine (≤0.05 ng/mL) and the remainder were divided into three groups ().
Association between serum cotinine in non and active smokers and demographic or behavioural factors [mean or %]a.
The characteristics of active smokers and non-smokers with different levels of SHS exposure are shown in . Geometric mean cotinine was much higher in smokers than non-smokers; 100.58 ng/mL vs 0.15 ng/mL, P < 0.001. Active smokers tended to be from manual social groups, resident in the north of the UK, and physically inactive. Non-smokers with higher compared with lower serum cotinine levels (greater SHS exposure), were also from manual social class groups, resident in the north of the UK, physically inactive and were younger, male, ex-smokers rather than never-smokers.
presents adjusted mean values of CVD risk markers for active smokers and non-smokers with different levels of SHS exposure, compared to the non-smokers with cotinine ≤0.05 ng/mL. Active smokers had lower BMI, fasting insulin and albumin compared with non-smokers with cotinine ≤0.05 ng/mL. Smokers had higher triglycerides, CRP, IL-6, white blood cell count, fibrin D-dimer, plasma and blood viscosity, fibrinogen, VWF, t-PA, platelet count, homocysteine, CD40 Ligand and MMP-9. The largest percentage differences in CVD risk factor between smokers and non-smokers with cotinine ≤0.05 ng/mL were for CRP (62%), IL-6 (41%), MMP-9 (27%) fibrin D-dimer (21%) and white blood cell count (18%). Active smoking was not appreciably associated with blood pressure, waist circumference, total and HDL cholesterol, glucose, mean platelet volume, factor VII, factor VIII, haematocrit, IL-18 or TNFα levels.
Association between serum cotinine in non-smokers and active smokers with cardiovascular risk factorsa.
Among non-smokers, higher cotinine levels were associated with higher BMI, waist circumference, fasting insulin, CRP, IL-6, blood and plasma viscosity, fibrinogen, factor VIII, VWF, t-PA and with lower albumin (, a–d). Modest associations with factor VII, triglycerides and platelet count did not reach conventional levels (5%) of statistical significance; there were no associations with BP, fasting lipids and glucose, white cell count, fibrin D-dimer, mean platelet volume, haematocrit, homocysteine, IL-18, CD40L, MMP-9 and TNFα. Among non-smokers the largest percentage changes in CVD risk factors in participants with cotinine >0.7 ng/mL compared with ≤0.05 ng/mL were for CRP (26%), IL-6 (12%) and t-PA (9%).
Associations between serum cotinine level in non-smokers, or active smokers of 1–9 cigarettes/day and (a) CRP (b) VWF (c) t-PA (d) Albumin.
presents associations in non-smokers between log2[cotinine] and each risk factor in models adjusted first for gender, age and region of residence, then additionally for social and behavioural confounders including smoking history and BMI. The coefficients represent the risk factor difference associated with a doubling in cotinine concentration. Among factors where associations with increasing SHS exposure were in the same direction as associations with active smoking in earlier analyses, on full adjustment, CRP, IL6, fibrinogen, factor VIII, VWF, t-PA and albumin were still associated with cotinine, although adjustments attenuated the strengths of associations by up to half (for CRP, IL-6 and t-PA) and up to a quarter (albumin and factor VIII). Adjusted associations between cotinine level and blood and plasma viscosity were attenuated to the null. Cotinine levels were not consistently associated with BP, lipids, insulin or glucose, white cell count, fibrin D-dimer, mean platelet volume, platelet count, haematocrit, homocysteine, IL-18, CD40 ligand, MMP-9 or TNFα, after adjustment for health behaviours, social class and BMI. Additional adjustments for lipids and BP did not materially affect results except for IL-6, which was attenuated to the null. Treating cotinine as a dichotomous variable, (>0.7 ng/ml compared to ≤0.05) yielded similar results.
Association between cardiovascular risk factors and serum cotinine in non-smokers. The figures represent the risk factor difference associated with a doubling in cotinine concentration.
Restricting analyses in to never-smokers (n = 2496) reduced precision; associations of cotinine with BMI, CRP, IL-6 and albumin were of similar magnitude to those reported above for all current non-smokers but confidence intervals were wide and included the null value. Associations with waist circumference and fibrinogen were not found in never-smokers. Other significant associations between cotinine and risk markers were not materially changed by restriction to never-smokers, or to non-smokers with cotinine ≤9.5 ng/mL. Variables which were robustly associated with cotinine (), showed similar associations in both sexes and did not vary by age in regression models with cotinine as a continuous or a dichotomous variable (all LR tests of interactions, P > 0.05). Sensitivity analyses using 0.025 and 0.075 rather than 0.05 ng/ml for undetectable cotinine gave a similar pattern of results.