Effects of smokeless tobacco (Maras powder) use on carotid intima media thickness

Background

Tobacco use is still an important cause of morbidity and mortality over the world [1]. Smoking not only affects many organ systems, but also causes hypoxia in vascular structures and thus formation of atheromas in the intima and deterioration of existing atheromas. In addition, it increases low-density lipoprotein (LDL) cholesterol and VLDL cholesterol, while it decreases high-density lipoprotein (HDL) cholesterol. For these reasons, smoking is known to initiate and accelerate atherosclerotic process through many mechanisms [2,3].

Maras powder, or Nicotiana rustica Linn, is obtained by crushing leaves of a wild tobacco plant into powder and mixing it with ashes of oak, walnut, and vine stems in the ratio of one-half or one-third [4]. Nicotine concentrations in tobacco used to produce Maras powder are 8 to 10 times higher than those in tobacco used to produce cigarettes. Tobacco used to make Maras powder is smokeless and consumed by chewing and sucking. It is widely consumed in the eastern Mediterranean region of Turkey. In fact, the rate of Maras powder use has been reported to be 4% and 16.8% in 2 studies carried out in our country [5,6]. The way Maras powder is consumed is known to increase oxidative stress and thus quicken the atherosclerotic process [7,8].

Clinically evident atherosclerosis is preceded by preclinical changes in the arterial wall, specifically, intima-media complex thickening and plaque formation [9]. After the first report of intima-media thickness measurement by Pignoli et al, carotid intima-media thickness (CIMT) has begun to be used as a reliable and reproducible method in the diagnosis of atherosclerosis [10,11].

We aimed to determine the effects of Maras powder use on CIMT.

Material and Methods

STUDY POPULATION:

Thirty-two Maras powder users presenting to the family medicine outpatient clinic to seek help giving up smoking between January 2013 and March 2013 were selected. The control group comprised 30 age-matched healthy volunteers. Medical history was taken and detailed physical examinations were performed in all subjects. The inclusion criterion was using Mara powder for at least 3 years. A package of Maras powder was considered as sufficient to provide 20 uses of the powder.

Data about demographic characteristics, biochemical parameters, lipid values, and electrocardiograms of the study sample were obtained. Exclusion criteria were: patients with hypertension (systolic >140 mmHg/diastolic 90 mmHg), diabetes mellitus, chronic obstructive lung disease, coronary artery disease, chronic renal failure, obesity, and osteoporosis (diseases likely to affect CIMT), history of taking medications for the above-mentioned diseases, and history of smoking and alcohol consumption. There were similar blood lipid levels and BMI between in the study and control groups.

Written informed consent was obtained from each subject and the institutional ethics committee approved the study protocol. Data about socio-demographic features, Maras powder use, and history of diseases were collected with a questionnaire.

MEASUREMENTS:

Blood pressure was measured with sphygmomanometer on both right and left arms while the patients were sitting after 10 minutes of resting. Measurements were made 3 times and the median of 3 measurements was obtained. In the Maras Powder users group, we measured blood pressure values before using Maras powder and 30–60 minutes after using Maras powder. Body weight was measured to the nearest 0.5 kg in light clothing without shoes. Height was measured to the nearest 0.5 cm. Body mass index (BMI) was calculated as kilograms divided by square meters (kg/m²).

BIOCHEMICAL ANALYSES AND COMPLETE BLOOD COUNT:

After 12 hours of fasting, 8 ml blood was drawn from the antecubital vein with minimal tourniquet method from each patient. Total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and blood sugar concentrations were measured.

EVALUATION OF CIMT:

Duplex ultrasound scanning was performed by a single trained radiologist using a high-end ultrasound machine (Aplio XG machine, Toshiba Medical Systems, Co, Ltd., Otawara, Japan), with 7 MHz or 10 MHz linear-array transducers. Subjects were examined in the supine position with their neck extended and their head turned 45° to the left or right. Ultrasound scans of the right and left last distal centimeter of the common carotid arteries (CCAs), the bifurcation, and of the first proximal centimeter of the internal carotid arteries in 3 different projections (anterior, lateral, and posterior) were performed. All subjects had a CIMT measurement at the far wall of both distal segments of the CCAs, and the measurements were made at the time of scanning on frozen images of longitudinal scans by using an automated border-detection program of the instrument. Two carotid segments for each projection were examined and the maximal CIMT value of each segment was measured. The CIMT values for the 3 different projections and for the right and left carotid arteries were averaged to obtain the mean maximum CIMT.

STATISTICAL ANALYSES:

Statistical analyses were performed using SPSS software version 15. All continuous variables are expressed as mean ± standard deviation; categorical variables are defined as percentages. Mean values of continuous variables were compared between groups using the t test or Mann-Whitney U test, according to whether they were normally distributed or not, as tested by the Kolmogorov-Smirnov test. Pearson’s correlation coefficients were used to assess the strength of the relationship between continuous variables. Before and after using Maras powder, mean blood pressure values in the Maras powder users group were analyzed by paired t test. A p-value of less than 0.05 was considered to show a statistically significant result.

Results

The mean age of the patients included in the study was 46.3+11.6 years (min=22; max=64). The mean age of Maras powder users was 45.4±11.3 years (min=27; max=67). All patients included in the study were male. BMI was 27.1±3.0 in the control group and 26.5±6.3 in the Maras powder users, without a significant difference (p=0.657). The mean duration of Maras powder use was 27.3±11.6 years (min=3, max=48). The mean amount of Maras powder consumed a day was 1 package.

There was a significant difference in CIMT between the Maras powder users and the controls (p<0.001). It was higher in the Maras powder users (Table 1).

Before using Maras powder, the mean systolic blood pressure was 110.3±9.4 and the mean diastolic blood pressure was 62.8±8 in the Maras powder users. A comparison of blood pressures measured before and after using Maras powder in the Maras powder users is shown in Figure 1.

There were no significant differences in terms of BMI, LDL cholesterol, HDL cholesterol, triglycerides, total cholesterol, and fasting blood sugar levels between the controls and Maras powder users (p>0.05). However, systolic and diastolic blood pressures measured after using Maras powder in the Maras powder users significantly differed from those measured in the control group (p<0.001). Maras powder use was found to increase systolic and diastolic blood pressures after using Maras powder (Table 1).

Results of correlation analysis of variables likely to be associated with CIMT are presented in Table 2. CIMT was significantly correlated with systolic blood pressure (r=0.613, p<0.001) and diastolic blood pressure (r=0.612, p<0.001), (Figures 2 and 3). There was not a significant correlation between CIMT and duration of Maras powder use and amount of Maras powder consumed (r=0.212; p=0.253) (Table 2).

Discussion

LIMITATIONS OF THE STUDY:

The major limitation of this study is its cross-sectional design. Another important limitation is that the sample size of the study was small since the patients both smoking and using Maras powder, which constituted a large number of the patients, were not included in the study. Another important limitation of the study was that we did not investigate markers for oxidative stress likely to elucidate the association between Maras powder use and CIMT. Investigation of these markers may explain the mechanism whereby Maras powder increases CIMT.

Conclusions

We showed that Maras powder use increased CIMT, which is an indicator of subclinical atherosclerosis. Increased CIMT might be associated with an acute increase in blood pressure due to use of Maras powder. However, further studies with larger sample sizes are needed to clarify the association between Maras powder use and pathogenesis of atherosclerosis. In addition, development of public health policies is of great importance in terms of prevention of Maras powder use. In addition, long-term Maras powder users should be screened and early diagnosis and treatment of possible conditions should be performed. This issue should also be investigated through studies with larger samples.