Editorials
Smoking and Incident Hypertension ― Importance of Cotinine-Verified Smoking Status ―
2018 Volume 82 Issue 6 Pages 1510-1512
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2018 Volume 82 Issue 6 Pages 1510-1512
Tobacco smoke contains many toxic components and exposure to tobacco smoke, not only by active smoking but also passively, is a major risk factor for cardiovascular diseases. Nicotine is one of the toxic components in tobacco smoke and temporally raises blood pressure (BP) via activation of the sympathetic nervous system. However, the long-term effect of smoking on BP has not been clarified. The relationship between smoking and incident hypertension (HT) is controversial, although longitudinal surveys have been conducted (Table).1–9 Several mechanisms to lower increased BP caused by long-term smoking have been speculated. In animal experimental models, chronic nicotine exposure caused tolerance to the effect of nicotine on BP and decreased BP through vasodilating mediators and the relaxation of the vascular smooth muscle.10–12 Lower body weight of smokers is another reason for lower BP.
| Country/race | No. of subjects | Mean age±SD (years) |
Follow-up (years) |
Association between smoking and HT |
References |
|---|---|---|---|---|---|
| Japanese | 2,107 (men) | 45.8±3.7 | 5 | Negative | Okubo et al1 |
| American Indian | 4,549 (men and women) | 45–74 (range) | 4 | Negative | Wang et al2 |
| USA | 28,236 (women) | 53.7±6.6 | 9.8 (median) | Positive | Bowman et al3 |
| USA | 13,529 (men) | 52.4±8.9 | 14.5 (median) | Positive | Halperin et al4 |
| Japanese | 5,512 (men) for HT cohort | 35.2±10.3 | 14 | Positive | Dochi et al5 |
| Turkey | 1,278 (men), 1,149 (women) | 45.8±11.7 | 7.4 (mean) | Negative | Onat et al6 |
| Japanese | 228 (men), 1,069 (women) | 60.0 | 5 | Negative | Kaneko et al7 |
| Japanese | 12,020 (men) for derivation cohort |
38.9±8.9 | 4.0 (median) | Positive | Otsuka et al8 |
| India | 142 (men), 155 (women) | 36.1±13.7 | 7.1±0.2 (mean) | Positive | Sathish et al9 |
HT, hypertension; SD, standard deviation.
Article p 1659
Other issues that may affect the results of the interaction between smoking and incident HT are the misclassification of smoking status according to the estimation of smoking status by self-reported questionnaires and the exposure to environmental tobacco smoke. Measurement of nicotine metabolites is one of the methods to avoid misclassification of smoking status.
In this issue of the Journal, Kim et al13 report on a longitudinal study to perform a simultaneous assessment of cotinine-verified smoking status and self-reported smoking status and also to include the change in the smoking status at baseline and follow-up. They show that cotinine-verified current smoking at baseline significantly decreased the risk of incident HT; cotinine-verified new smoking and sustained smoking according to the change in cotinine-verified smoking status at baseline and follow-up were significantly associated with decreased risk of incident HT; and the effects of cotinine-verified smoking status on incident HT were different from those of self-reported smoking status. The most important point in this report is that this is the first and largest longitudinal study to perform an assessment of smoking status using a cotinine-verified and self-reported questionnaire and to include the change in smoking status from baseline to follow-up.
Cotinine-verified smoking status is more accurate than self-reported smoking status for the evaluation of smoking status. Nicotine is metabolized by the liver to a number of metabolites14 (Figure). The most important metabolite of nicotine is cotinine. Approximately 70–80% of nicotine is converted into cotinine in humans. Cotinine is metabolized via the cotinine pathway, and only 10–15% of nicotine appears in the urine as unchanged cotinine. CYP2A6 is the enzyme primarily responsible for the oxidation of nicotine and cotinine. Polymorphism of CYP2A6 has been reported, and this affects nicotine metabolism. There is considerable interindividual variability in nicotine and cotinine metabolism caused by the genetic variations, diet, medications, age, sex, renal function, and racial differences. A subcommittee of the Society for Research on Nicotine and Tobacco (SRNT) evaluated the utility of cotinine as a biomarker of tobacco use and cessation, and recommended their application in clinical trials.15 The SRNT advocated an optimal cut-off point of urinary cotinine of 50 ng/mL. Gorber et al reported that cut-off points used to determine whether an individual was classified as a smoker were highly variable, ranging from 50 to 500 ng/mL in the urine.16 A more recent review article showed that urinary cotinine cut-off levels for cotinine-verified current smoking ranged between 31.5 and 550 ng/mL.17 Kim and Jung obtained an optimum cut-off value of 164 ng/mL for urinary cotinine using the Korea National Health and Nutrition Examination Survey database in 2008–2010 (n=11,629) and application of this urinary cotinine cut-off value had a sensitivity of 93.2% and specificity of 95.7%.18 Kim et al13 used a urinary cotinine cut-off level of 50ng/mL for cotinine-verified current smoking. The sensitivity and specificity values of that cotinine cut-off level for distinguishing current smokers from never smokers were 84.8% and 98.2%, respectively. Finally, they concluded that this urinary cotinine level was reasonable because their cross-sectional study showed that the degree of agreement between self-reported and cotinine-verified smoking status was almost perfect.19
Nicotine metabolism pathway. Nicotine is metabolized to a number of metabolites, the most important being cotinine, which is metabolized via the cotinine pathway.
Exposure to environmental tobacco smoke can affect the urinary cotinine level. Kim et al13 defined unobserved smokers as cotinine-verified current smokers among the self-reported never smokers. Those who were exposed to environmental tobacco smoke were included with the unobserved smokers. Unobserved smoking at follow-up as well as baseline showed decreased risk for incident HT. Further studies are needed to confirm the effect of environmental tobacco smoke exposure on incident HT.
To conclude this editorial comment, it should be emphasized that it is important to quit smoking irrespective of the effect on incident HT because smoking increases the risk of cardiovascular diseases.
The author has no conflicts of interest regarding the context of this article.
