Effects of Smoking on the Pulse Wave Velocity and Ankle Brachial Index in Adolescents

Original ORIGINAL Article ARTICLE Korean Circulation J 2007;37:414-418 ISSN 1738-5520 c 2007, The Korean Society of Circulation Effects of Smoking on the Pulse Wave Velocity and Ankle Brachial Index in Adolescents Hee Sun Koo, MD 1, Tae Young Gil, MD 1, Hee Woo Lee, MD 2, Keun Lee, MD 1 and Young Mi Hong, MD 1 1 Department of Pediatrics, School of Medicine, Ewha Womans University, Seoul, 2 School Health Promotion Center, Seoul, Korea ABSTRACT Background and Objectives:Smoking is known to increase arterial stiffness in adults. The pulse wave velocity (PWV) is known as an established index of arterial stiffness. The effects of smoking on the PWV in adolescents have not yet been established. We measured the PWV and ankle-brachial index (ABI) in adolescents to determine the effects of smoking on adolescents. Subjects and Methods:Four hundred twenty-seven adolescents between 14 to 16 years of age were enrolled from three high schools in Seoul, Korea. The study group was comprised of 48 smokers (38 males and 10 females) and 379 nonsmokers (254 males and 125 females). Measurements of the height, weight and body mass index (BMI) were performed. The blood pressures of the extremities, and the PWV, the ABI, the ejection time and the pre-ejection period were measured using an automatic device (VP-1000). Among the smoking group, we investigated the association between the duration of smoking, the age at which smoking started and the total number of cigarettes smoked with the PWV and ABI. Results:The brachial-ankle PWV (bapwv) in the smoking group was higher than that of the non-smoking group, but the difference was not statistically significant. There was no significant difference between the ABI of the two groups. Among the smokers, the heart-brachial PWV (hbpwv) was significantly associated with the duration of smoking and the total number of cigarettes smoked. Conclusion:Our study showed no significant difference in the PWV between the two groups. A longitudinal, long-term investigation is needed to more accurately determine the effects of smoking on adolescents. (Korean Circulation J 2007;37:414-418) KEY WORDS:Smoking;Adolescent;Pulse. Introduction Received:June 13, 2007 Revision Received:August 1, 2007 Accepted:August 14, 2007 Correspondence:Young Mi Hong, MD, Department of Pediatrics, School of Medicine, Ewha Womans University, #70 Jongno 6-ga, Jongno-gu, Seoul 110-126, Korea Tel: 82-2-760-5427, Fax: 82-2-745-9545 E-mail: hongym@chollian.net Smoking is known to be a major independent risk factor for cardiovascular morbidity and mortality in adults. 1-3) However, smoking by adolescents has increased over the past few decades and this continues to be a serious problem for the health of adolescents worldwide. Various mechanisms have been proposed for the hazardous effects of smoking that lead to cardiovascular morbidity. 4)5) These include changes in the hemostatic factors, the endothelial function and the blood lipids, as well as alterations in the dynamic properties of the arterial wall. 4)5) There has been a number of studies evaluating the changes in the dynamic properties of the arterial wall after smoking. 1)4)6)7-9) The PWV is known to be an established index of arterial stiffness in adults. 10-12) Increased arterial stiffness itself is an independent predictor of the cardiovascular disease risk and morbidity. 13) Measurements of PWV are being used in many clinical investigations as a simple and easy method to assess the cardiovascular risk of individuals. Acute cigarette smoking has been shown to increase the PWV, suggesting there is increased arterial stiffness in adult smokers, 6)9) but the effects of smoking on the PWV in adolescents has not yet been established. The purpose of this study was to measure the PWV and ABI to determine the effects of smoking on adolescents. Subjects and Methods Subjects Four hundred twenty-seven adolescents(233 males and 414

Hee Sun Koo, et al:effects of Smoking on the Pulse Wave Velocity 415 194 females) aged between 14 to 16 years were enrolled from three high schools in Seoul, Korea. The participants included healthy subjects who did not have any underlying medical diseases such as diabetes mellitus, hypertension or coronary artery disease. The characteristics of the study population are shown in Table 1. Information about the smoking status was based on the patients selfreports. Smokers in this study were defined as someone who had a history of smoking at least once in their lifetime. Of 427 total study subjects, 48 were smokers(38 males and 10 females) and 379 were non-smokers(254 males and 125 males). Study protocol All the subjects heights and weights were measured. BMI was calculated as weight(kg) divided by the square of height(m 2 ) and the value was rounded up to one digit below zero. After at least a 10 minute rest in the supine position, measurements of the blood pressure of both extremities, the heart rate, the ejection time, the preejection period, the PWV and ABI in all subjects were done by an automatic device. Smokers were asked about the duration of smoking in months, the number of cigarettes smoked per day and the age at which smoking was first started. Informed consent was obtained from all participants. Measurements of the pulse wave velocity and ankle brachial index The PWV and ABI were measured by a VP-1000(Colin Co. Ltd, Komaki, Japan). The PWV and ABI, the blood pressure of both extremities, an electrocardiogram and heart sounds were measured simultaneously. The electrocardiogram electrodes were attached to both wrists and a heart sound microphone was placed on the left sternal border. Cuffs were encircled around both arms and ankles, and the cuffs were attached to both a plethymographic sensor and an oscillometric sensor. The plethymographic sensor determined the volume pulse form, and the blood pressure was measured from the oscillometric pressure sensor. PWV(cm/s) was defined as the distance between two distinct points(cm) divided by the pulse wave transit time(s). In this study we calculated the PWV from the right brachial artery to each side of the ankle(bapwv) and the PWV from the right brachial artery to the heart(hbpwv). The heart-brachial pulse transit time was measured from the second heart sound to the dicrotic notch of the carotid pulse waves. The brachial-ankle pulse transit time was measured from the ascending point of the right brachial pulse volume record to the ascending point of each ankle pulse volume record. The distance of the heart-brachial segment and the brachial-ankle segment were calculated automatically, based on the height of the subjects. The ABI was defined as the ratio of the systolic blood pressure measured at the ankle to the systolic blood pressure measured at the brachial artery. All the measurements were made during regular sinus rhythm. Statistical analysis Statistical analysis was performed with the use of the SPSS/PC software package(spss version 11.0). Statistical differences among the groups for the continuous variable were evaluated using one-way ANOVA. Data are expressed as means±sds. p<0.05 was considered statistically significant. Results The anthropometric data of the study population is shown in Table 1. There was no significant difference in height, weight and BMI between the smokers and nonsmokers. The characteristics of the smoking group are illustrated in Table 2. Among the 48 smokers, the median number of cigarettes smoked per day was 5.9±6.0 cigarettes and the median duration of smoking was 12.2±8.2 months. In this study, we defined the total number of cigarettes smoked as the value calculated by the number of cigarettes smoked per day multiplied by the duration of smoking in days. The average total number of cigarettes smoked was 1613.2±3170.0 cigarettes, which is about 80 packs. The age at which smoking was started was 14.9±0.9 year on average. Among the smokers, the hbpwv was positively correlated with the total duration of smoking and the total number of cigarettes smoked. The longer the duration of smoking, the higher the hbpwv was among the smokers(fig. 1). The total number of cigarettes smoked was log-transformed and Fig. 2 shows the scatterplots of the transformed data. The greater the total number of cigarettes smoked, the higher the PWV was among the smokers. The age at which smoking was first started did not show any effect on Table 1. Anthropometric data of study group Anthropometric data Smoking group Control group Number 48 379 Male/female 3.8/1 1.2/1 Age (year) 15.3±0.5 15.2±0.5 Height (cm) 168.2±8.10 166.0±7.50 Weight (kg) 060.7±13.4 059.8±12.1 BMI (kg/m 2 ) 21.3±3.9 21.7±3.8 p>0.05. BMI: body mass index Table 2. Characteristics of the smoking group Number 48 No. of cigarettes smoked per day 5.9±6.0 (0.5-20) Duration of smoking (months) 12.2±8.2 (1-36) Total no. of cigarettes smoked 1613.2±3170.0 (6-14400) Starting age of smoking (year) 14.9±0.9 (11-16)

416 Korean Circulation J 2007;37:414-418 Heart-brachial PWV (cm/sec) Heart-brachial PWV (cm/sec) 800 600 400 200 000 800 700 600 500 400 300 200 y=47.440χ+325.385 r=0.428, p<0.05 Y=10.544χ+318.141 r=0.442, p<0.05-200 0 10 20 30 40 Duration of smoking (months) Fig. 1. Linear correlation between the duration of smoking and the hbpwv in the smoking group. hbpwv: heart-brachial pulse wave velocity. 1.00 2.00 3.00 4.00 Log total no.of cigarettes Fig. 2. Linear correlation between log-transformed total number of cigarettes smoked and the hbpwv in the smoking group. hbpwv: heart-brachial pulse wave velocity. the PWV among the smokers. The systolic, diastolic and mean arterial blood pressures were not significantly different between the two groups(table 3). The heart rate, ejection time and preejection period were not significantly different between the two groups(table 4). The right bapwv was 1000.6±102.7 cm/sec in the smoking group and 973.4±160.7 cm/sec in the nonsmoking group. The left bapwv in the non-smoking group was higher than that of the smoking group (980.5±162.6 cm/sec in the smoking group versus 1012.6±103.6 cm/sec in the non-smoking group), but the difference was not statistically significant(table 5). The ABI was not significantly different between the two groups(table 5). Table 3. Comparison of blood pressure in the smoking group vs the control group (mmhg) Blood pressure Smoking group Control group RB Systolic BP 115.7±8.30 117.0±12.5 MAP 082.1±7.70 083.3±12.9 Diastolic BP 061.9±6.20 063.2±10.1 LB Systolic BP 114.8±80.0 116.4±12.8 MAP 082.1±8.60 083.3±11.5 Diastolic BP 061.0±6.9* 063.3±9.00 RA Systolic BP 124.5±11.8 124.5±14.9 MAP 081.3±8.70 082.3±9.40 Diastolic BP 061.0±7.60 062.1±8.60 LA Systolic BP 124.8±13.0 123.5±15.2 MAP 082.3±9.00 082.4±9.90 Diastolic BP 062.3±7.70 062.1±8.30 *: p<0.05 significantly different from control group. BP: blood pressure, MAP: mean arterial pressure, RB: right brachial, LB: left brachial, RA: right ankle, LA: left ankle Table 4. Comparison of the heart rate, ejection time and pre-ejection period in the smoking group vs the control group Smoking group Table 5. Comparison of pulse wave velocities and ankle-brachial index in the smoking group vs the control group Smoking group Discussion Control group Heart rate (bpm) 070.3±9.50 076.4±10.7 Ejection time 276.7±60.9 259.4±74.1 Pre-ejection period 079.3±22.3 075.6±26.0 p>0.05 Control group RhbPWV (cm/sec) 0398.4±156.1 372.1±148.4 RbaPWV (cm/sec) 1000.6±102.7 973.4±160.7 LbaPWV (cm/sec) 1012.6±103.6 980.5±162.6 Rt. ABI 0106.8±8.100 105.1±7.800 Lt. ABI 0106.9±7.700 104.3±7.900 p>0.05. RhbPWV: right heart brachial pulse wave velocity, RbaPWV: right brachial-ankle pulse wave velocity, LbaPWV: left brachial-ankle pulse wave velocity, ABI: ankle brachial index Smoking is known to increase arterial stiffness in adults. 4-6)14-17) Several mechanisms are proposed for the acute increases in blood pressure and arterial stiffness that are seen immediately after smoking. 6) During smoking, the adrenergic mechanism is activated as the nicotine contained in tobacco stimulates the sympathetic nerve terminals, which results in smooth muscle contraction and thus a reduction in arterial distensibility. 6)7)18) Impaired nitric oxide production and endothelial dysfunction have also been known to play major roles in altering the mechanical properties of large arteries. 6)7)18) PWV is known as an established index of arterial sti-

Hee Sun Koo, et al:effects of Smoking on the Pulse Wave Velocity 417 ffness in adults. 10)11) An automatic non-invasive device has recently been developed that measures the bapwv by using a simple, oscillometric technique. It has been revealed in previous studies 19)20) that measurements of the bapwv significantly correlate with the conventional carotid-femoral PWV. In this study, we investigated the effects of smoking on the cardiovascular risk in adolescents by measuring the PWV and ABI by using this simple automatic oscillometric technique. Since there are currently no established normal cut-off values for PWV in children, we compared the PWV of smokers with that of the non-smoking controls of the same age. Our study showed no significant difference in the bapwv and hbpwv between adolescent smokers and non-smokers. This suggests there was no significant difference in arterial stiffness between the two groups. Changes in the dynamic properties of arterial wall, including an increase in arterial stiffness, have been suggested as one of the contributing factors for the progression of cardiovascular diseases in smoking adults. 1)4)6-8)17) There have been several previous studies to support this hypothesis in adults. A significant decrease in aortic distensibility was seen after acute smoking in habitual smokers. 1)8) The aortic(carotid-femoral) PWV showed a significant increase after short-term smoking in other reports. 6)17) Kool et al. 4) reported that smoking caused a short-term increase in arterial wall stiffness of both the elastic common carotid and the muscular brachial arteries. Both the radial artery and carotid artery distensibility were shown to be remarkably reduced after smoking. 7) Our study was a cross-sectional study that was conducted to compare the baseline brachial-ankle and heart-brachial PWV of smokers and non-smokers. In our study, the PWV was higher in smokers than nonsmokers, but the difference was not statistically significant. Comparison of the PWV between smokers and non-smokers has been used as a method to evaluate the chronic effects of smoking in other previous studies, but the results have been inconsistent. There has been a few studies reporting no significant differences of the baseline PWV in chronic smokers compared to nonsmokers, 5)15)21) whereas an increased baseline PWV was observed in healthy smokers compared with non-smokers. 14) Jatoi et al. 16) showed a significant linear relationship between the smoking status and the PWV in a group of patients with untreated essential hypertension. They reported a significantly higher baseline PWV in the smokers compared with the non-smokers. That report strongly suggests chronic smoking increases arterial stiffness and it may be one of the underlying mechanisms for the increased cardiovascular events observed in hypertensive patients. 16) One of the main reasons our study failed to show this association between smoking and an increase in PWV could be that our subjects were adolescents who had an average smoking duration of only 12.2 months. Although the exact duration or intensity of smoking that cause chronic changes in the arterial wall properties are unknown, adolescents generally have a relatively short exposure to smoking, which is probably too short to cause a significant difference in arterial stiffness. However, in our study, although these were not significant, both the right and left bapwv and the hbpwv of the smokers were higher than those of the non-smoking adolescents, and this shows a tendency toward a higher PWV in smoking adolescents. From this finding, it is possible to make the assumption that smoking in adolescents could affect arterial stiffening in a cumulative manner, which may at some point induce significant changes in arterial stiffness. This hypothesis is supported by Li et al., 22) where the cumulative burdens of the systolic blood pressure and the duration of smoking since childhood were independent predictors of the bapwv in young adults. A longer follow-up would be necessary to elucidate our hypothesis. Among the smokers, the hbpwv was positively correlated with the total duration and the total number of cigarettes smoked. This finding might suggest a dosedependent relationship of smoking on the PWV in smoking adolescents, but further investigations will be necessary to clarify this relationship. Arterial stiffness increase with age 23) and with hypertension. 24) It is also enhanced in subjects with DM, 25) atherosclerosis, 26) end-stage renal disease 27)28) and obesity. 29) In our study these confounding factors could be thought to have been excluded as only healthy adolescents with no known underlying medical conditions and who had normal blood pressure were enrolled in this study. The ABI is a simple ratio of the systolic blood pressure over the ankle and arm, and this is a non-invasive method to assess individuals with peripheral arterial disease. 10)17) An ABI less than 0.9 is known to be associated with increased cardiovascular events in adults, 9) but there has not been many studies on ABI in children. The ABI showed no significant difference between smokers and non-smokers in our study. This is in contrast with a previous report, 18) in which smoking was shown to be independently related to a low ABI in a group of adults with known coronary artery disease. Previous studies have shown that acute cigarette smoking in healthy nonsmokers is associated with an increase in heart rate, but there was no difference in the baseline heart rate between chronic smokers and nonsmokers. 6)15) Our finding is consistent with these previous reports as no significant difference in the baseline heart rate, the ejection time and the pre-ejection period were observed between the two groups. There were several limitations in this study. As information about the smoking status was based on the pa-

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