The Relationship between New Stroke Onset and Serum Thiocyanate as an Indicator to Cigarette Smoking

Smoking habits has been identified as a risk factor for stroke in several studies 1-3). Wolf et al. 3) reported that cigarette smoking was a significant risk factor for stroke, especially cerebral infarction, and that there was a dose-response relationship between the number of cigarettes smoked per day and the relative risk of stroke. However, these results were not confirmed in other studies 4-6). The potential of misclassification in assessing the smoking status with self-assessment reports may be one of the factors leading to these different results. Therefore, it is difficult to evaluate smoking status by using self-administered questionnaire only, and the objective method should be used to assess smoking status. Serum thiocyanate concentration is one of the objective indicators for assessing smoking habits. The validity of serum thiocyanate as an indicator of cigarette smoking has been studied by several investigators 7,8) The relatively long half-life (about 1-2 weeks) of serum thiocyanate makes its measurement particularly suitable for evaluating habitual smoking. There were few investigations on the direct relationship between serum thiocyanate level and stroke onset. We investigated the relation of serum thiocyanate with references to other associated risk factors of stroke using a nested case-control design in a community-based cohort study.


INTRODUCTION
Smoking habits has been identified as a risk factor for stroke in several studies 1-3).Wolf et al. 3) reported that cigarette smoking was a significant risk factor for stroke, especially cerebral infarction, and that there was a dose-response relationship between the number of cigarettes smoked per day and the relative risk of stroke.However, these results were not confirmed in other studies [4][5][6].The potential of misclassification in assessing the smoking status with self-assessment reports may be one of the factors leading to these different results.Therefore, it is difficult to evaluate smoking status by using self-administered questionnaire only, and the objective method should be used to assess smoking status.
Serum thiocyanate concentration is one of the objective indicators for assessing smoking habits.The validity of serum thio-cyanate as an indicator of cigarette smoking has been studied by several investigators 7,8) The relatively long half-life (about 1-2 weeks) of serum thiocyanate makes its measurement particularly suitable for evaluating habitual smoking.
There were few investigations on the direct relationship between serum thiocyanate level and stroke onset.We investigated the relation of serum thiocyanate with references to other associated risk factors of stroke using a nested case-control design in a community-based cohort study.

MATERIALS AND METHODS
A nested case-control study was designed and carried out based on the data from the Oyabe Community-based Stroke Registry, which was started from 1966.The hospitals and ambulance stations in and around the Oyabe district, Toyama Prefecture, Japan had been required to provide information on an indicator of smoking status.However, the misclassification due to these methods is inevitable, because, for example, individuals who sometimes mistake their cigarette consumption and smokers who have failed and/or want to stop smoking are apt to underreport.In addition to actual cigarette consumption, smoking status varies with depth of inhalation, frequency of puffing and proportion of each cigarette consumed.Therefore, it is important that we make an effort to gain an objective marker of smoking status.
To assess smoking status objectively, carbon monoxide in expired air, blood carboxyhemoglobin (COHb), cotinine or thiocyanate has been measured 11).Among these indicators, expired carbon monoxide can be easily measured and blood carboxyhemoglobin measurement has been substituted by expired air carbon monoxide measurements.Because of short half-life of expired carbon monoxide (about four hours) 12), it can't be used to assess smoking habit correctly.Cotinine, metabolite of nicotine, is specific to cigarette smoking and is one of the best indicators to distinguish smokers from nonsmokers, but it also has a short half-life (30 hours).
Thiocyanate is a metabolite of serum hydrogen cyanide the distribution in the total population.In this report, we observed that serum thiocyanate level in stroke patient was significantly higher than that in controls.The results were identical for all stroke patients and for cerebral infarction patients.
Cigarette smoking has been established as a risk factor for ischaemic heart diseases for many years but only in the past decade has its role as a risk factor for stroke and its pathological subtypes been delineated 1).Because stroke is pathologically and aetiologically heterogeneous, it is likely that the association between smoking and stroke risk is even stronger for certain pathological and aetiological subtypes of stroke, and weaker for others.For the relatively small sample size in this study, we have to focus on analyzing the data of subtype of cerebral infarction.The results showed very different statistical relationship between smoking and the risk of stroke, with selfreported number of cigarette smoked per day or measured serum thiocyanate used as the indicator of smoking status respectively.The risk of cerebral infarction elevated significantly with increment in the logarithmically transformed concentration of serum thiocyanate.On the other hand, with selfreported number of cigarettes instead of the serum thiocyanate in the same multiple logistic regression model, there is no statistical significant effect of smoking on the risk of cerebral infarction any more.Some points have been proposed to explain this kind of discrepancy.Studies using biochemical markers of smoking to check volunteered information suggest that self-reporting may be unreliable 16).Self-reports of smok-ing have showed a marked degree of digit preference, with the vast majority of smokers reporting in multiples of 10 cigarettes per day.Then, self-reports of number of cigarettes per day may be biased towards round numbers, rather than the exact number of cigarettes smoked per day 17).The results reported by Daly RJ, et al 18) indicated that use of serum thiocyanate levels revealed a considerably high level of smoking denial by smokers in ischaemic heart diseases (55%) and in peripheral vascular diseases (28%).It is almost impossible to estimate the effect of cigarette smoking on health correctly with such high proportion of smoking denial by using the method of self-reporting.The questionnaire information including the item of smoking and others has been rechecked, but the actual cigarette smoking behavior of individual subjects in this study cannot be reconfirmed at present.It seems plausible that the stroke risk of cigarettes smoking may be estimated much more precisely with serum thiocyanate than with self-reported number of cigarettes smoked per day as the indicator of smoking status, considering the small sample size in this study and relative weaker stroke risk to smoking.High blood pressure is the most important of the known risk factors for all stroke subtypes 19,20), although we did not determined it in our study since it was limited as one of the match factors for selecting control subjects.In our study, high serum total cholesterol increased the risk of cerebral about 3-fold, and was consistent with the result of other studies [21][22][23][24], although the relationship between serum total cholesterol and the risk for stroke attack is not so clear.Two recently published papers in the same issue of a neurological journal gave completely inconsistent answers 25,26).However, there is also mounting evidence that serum total cholesterol concentration is inversely associated with the risk of hemorrhagic stroke, and, in contrast, high serum total cholesterol concentration seems to increase the risk of cerebral infarction [21][22][23].Heavy alcohol consumption might result in an increased stroke risk.However, in a recent study by Sacco et al. 27), earlier observations of a protective effect of moderate alcohol consumption on ischaemic stroke risk have been confirmed, and this kind of effect was independent of gender, race, current smoking, hypertension and other disease status.We also observed the similar effect of alcohol consumption on cerebral infarction.
Finally, it is considered that the measurement of serum thiocyanate as indicator of smoking status may be more precisely and useful to assess the risk of stroke attack than the selfreported number of cigarettes smoked per day.In this study, we could not analyze the data of intracerebral hemorrhage and other types of stroke patients because of the small sample sizes.Well-designed study should be conducted to determine the reason why there is so big different result between the selfreported smoking status and measured serum thiocyanate used as the indicator of smoking habit, and find the way to solve the problem in the future.

Table 1 .
General characteristics of stroke patients and controls.
BMI, body mass index ; MBP, mean blood pressure ; T-Chol, serum total cholesterol ; The paired t-test was conducted between cases and controls with logarithmically transformed values of serum thiocyanate, and then the results changed back ; * P<0 .05,patients vs controls

Table 3 .
Analysis of the risk of cerebral infarction using multiple