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Associations of smoking and smoking cessation with CT-measured visceral obesity in 4656 Korean men
Preventive Medicine 55 (2012) 183–187
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Associations of smoking and smoking cessation with CT-measured visceral obesity in 4656 Korean men Kiheon Lee a, Cheol Min Lee b,⁎, Hyuk Tae Kwon b, Seung-Won Oh b, Hochun Choi c, Jin Ho Park c, BeLong Cho c a b c
Department of Family Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, South Korea Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
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Available online 20 June 2012 Keywords: Smoking Smoking cessation Visceral obesity Visceral adipose tissue Subcutaneous adipose tissue Abdominal obesity
a b s t r a c t Objectives. Although obesity is shown to be less common among current smokers than never smokers, the association between visceral obesity and smoking remains uncertain. Methods. For this cross-sectional analysis, we recruited 4656 Korean men of 19 to 79 years who received a regular checkup at a health examination center between 2008 and 2010. Computed tomography was performed to measure the area of visceral and subcutaneous adipose tissue (VAT and SAT). We compared the mean VAT by multiple regression analysis across smoking status after adjusting for confounders. Results. Both current and former smokers had more mean VAT than never smokers. Current smokers who consumed more than 20 cigarettes per day had 11% higher mean VAT than never smokers (Pb 0.01). Longer smoking duration, higher daily cigarette consumption before quitting, and shorter abstinence duration among ex-smokers were associated with increasing mean VAT (all P for trendb 0.01). The mean VAT in former smokers was highest within 2 years of abstinence. There was no significant difference of mean VAT between ex-smokers with >20 years of abstinence duration and never smokers. Conclusion. Both current and former smoking is associated with increased VAT. The risk of visceral obesity is proportional to the degree of exposure to cigarette smoking. © 2012 Elsevier Inc. All rights reserved.
Introduction Both cigarette smoking and abdominal obesity are strong independent risk factors for cardiovascular disease (CVD). In particular, the combination of smoking and obesity or abdominal obesity is related to a much higher mortality (Chouraki et al., 2008; Despres et al., 2008; Hansson et al., 1999; Koster et al., 2008; Lakka et al., 2002; Manson et al., 1990). The majority of smokers who quit smoking gain weight and harmful changes in cardiovascular risk factors associated with smoking cessation may be mainly secondary to weight gain (Yoon et al., 2010). Smoking cessation also results in substantial increase in central fat, which might attenuate some of the beneficial effects of smoking cessation (Pisinger and Jorgensen, 2007). The association between smoking and abdominal obesity is not fully understood. There is increasing evidence that smoking is conducive to greater accumulation of visceral fat (Chiolero et al., 2008) and one
⁎ Corresponding author at: Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Gangnam Finance Center, 152 Teheran-ro, Gangnam-gu, Seoul 135-984, South Korea. Fax: + 82 2 2112 5636. E-mail address: [email protected] (C.M. Lee). 0091-7435/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.ypmed.2012.06.009
might speculate that the weight gain after smoking cessation mostly occurs in the subcutaneous region of the body (Filozof et al., 2004). The majority of these previous studies chose waist circumference as an alternative for abdominal obesity, which does not allow for the differentiation between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Visceral obesity, which provides a more precise assessment of CVD risk, is evaluated by computed tomography (CT) and VAT may be a pathogenic fat compartment (Pascot et al., 1999). To our knowledge, only four cross-sectional studies have explored the association between smoking status and visceral obesity by CT method, but considerable disagreement remains regarding the change of VAT and SAT according to smoking status (Komiya et al., 2006; Matsushita et al., 2011; Molenaar et al., 2009; Onat et al., 2009). Data from the Framingham heart study reported that both current and former smoking was associated with higher VAT than never smokers (Molenaar et al., 2009), but current smokers had the lowest VAT than former smokers in one Japanese study that comprised 5697 subjects (Matsushita et al., 2011). The change of SAT was also inconsistent in a few studies. Furthermore, they did not include the detailed smoking data of current and former smokers in their analyses. Here, we aimed to investigate the association between smoking habits in Korean men, obtained from the detailed smoking data, and visceral obesity determined by evaluating the VAT area with CT.
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Statistics
Methods Study population We used data from 7141 men aged over 18 years who voluntarily received a routine comprehensive health checkup including CT scan analyses of abdominal adipose tissue, between March 2008 and February 2010 at the Healthcare System Gangnam Center of Seoul National University Hospital in Korea. Subjects lacking a smoking history (n= 99), those who underwent repeated abdominal CT scans (n = 348) to avoid the inverse causality of the relationship between smoking cessation and obesity, and those who were currently receiving treatment for hypertension, diabetes mellitus, and dyslipidemia (n= 2038) were excluded. Finally, 4656 men were included in the analysis. Smoking status was determined by the response to the following question: “Do you smoke cigarettes now?” The response choices were “Never have smoked,” “Used to smoke,” and “Yes,” and the subjects were divided accordingly into 3 groups. All subjects provided a written informed consent, and the protocol was approved by the review board of the Seoul National University Hospital. Subject characteristics For each subject, the following data were obtained from a self-administered questionnaire during the health examination: age, weekly alcohol intake, regular exercise, education level, and current medication of diabetes mellitus, hypertension, and dyslipidemia. The weekly alcohol consumption was calculated using data on the type and volume of alcohol consumed and the frequency of drinking, after factoring in the ethanol content. According to the National Institute of Alcohol Abuse and Alcoholism (NIAAA) guidelines, we defined atrisk drinking as >14 drinks or >168 g of alcohol per week (NIAAA, 2005). For education status, subjects were asked to choose their attained level from 5 categories: b 9 years, 9–11 years, 12–15 years, 16–17 years, or ≥18 years. For exercise, subjects had to report whether they exercised regularly. For smoking history, current and former smokers reported the duration and the average number of cigarettes. We defined pack-years (PY) as the average number of cigarettes smoked per day during the time the subjects smoked divided by 20 and multiplied by the number of smoking years. Waist circumference was measured at the midpoint between the lower part of the last rib and the top of the hip.
Descriptive statistics were used to show the basic clinical and socio-economic characteristics of the subjects according to their smoking status. An analysis of variance F test and the Pearson chi-square test were used to assess the statistical significance of the difference across the 3 groups—never smokers, former smokers, and current smokers. The multiple comparisons between the smokers and never smokers were performed using Bonferroni's method. The adjusted least square VAT and SAT means were compared according to the smoking status by using analysis of covariance (ANCOVA) adjusted for age, regular exercise (yes or no), weekly alcohol intake (g), and education (b16 years/≥ 16 years). Current smokers were further divided into 3 groups according to the number of cigarettes per day (CPD) that they smoked: 1–10, 11–20, and > 20. Former smokers were subdivided into 3 groups or tertiles according to the duration of smoking (years), CPD, pack-years (PY), and duration of abstinence. We then adjusted the multiple comparisons by Bonferroni's method by using never smokers as a reference. After subdividing the subjects into 7 groups (current smokers, never smokers, and former smokers with b 2, 2–4, 5–9, 10–19, and ≥ 20 years of smoking abstinence), the adjusted means of both VAT and SAT of the subjects according to the duration of smoking abstinence were further evaluated. We also tested the difference between never smokers and the other groups by using a paired t-test. We conducted all analyses by using the STATA software (version 11.0) and defined P b 0.05 as statistically significant.
Results Characteristics of participants Table 1 shows the subjects' general characteristics by the smoking status. The mean age of the participants (n=4656) was 49.3 years (range, 19–79; SD, 9.5), and the mean BMI (SD) was 24.5 (2.7) kg/m2. Current smokers tended to exercise less regularly, have a lower educational attainment, and have a higher rate of metabolic syndrome as compared to never smokers. Current smokers consumed significantly more alcohol than never smokers did. Current smokers had significantly higher mean BMI, WC, VAT, and TAT than never smokers did (Pb 0.01 for each).
Measurement of abdominal adipose tissue mass
Abdominal adipose tissue according to smoking status The abdominal adipose tissue mass was estimated using cross-sectional images obtained by a standardized and validated CT technique (Borkan et al., 1982; Goodpaster, 2002; Kvist et al., 1988) described in detail in a previous study (Chung et al., 2008). Briefly, each subject was examined in the supine position with a 16-detector row CT scanner (Somatom Sensation 16; Siemens Medical Solutions, Forchheim, Germany). We obtained a single 5-mm slice image, at the level of the umbilicus, at 120 kVp and 260 mA with a scan time of 0.5 s. We calculated the total abdominal adipose tissue area (TAT: subcutaneous adipose tissue (SAT) area plus VAT) by using specialized software (Rapidia 2.8; Infinitt, Seoul, Korea) with the attenuation values for the region of interest within a range of −250 to −50 Hounsfield Units. We used VAT≥100 cm2 as the criterion for visceral obesity (Han et al., 2008).
Current smokers who consumed 11 or more CPD, as well as former smokers had significantly higher adjusted mean VAT than never smokers (P b 0.05 for each) but did not differ in SAT (Table 2). When current smokers were classified into three categories (1–10, 11–20, >20 CPD) and the adjusted mean VAT was compared between them and never smokers, an increase in CPD was significantly associated with higher mean VAT (P b 0.01). The mean VAT of current smokers who consumed more than 20 CPD was 12.2% higher (15.1 cm 2 of difference) than that of never smokers. There was no significant association between CPD and SAT.
Table 1 Basic characteristics of subjects (N = 4656), Korea, Republic of (2008–2010). Characteristic
Never smokers (n = 1064)
Former smokers (n = 1857)
Current smokers (n = 1735)
Pa
Mean (SD) age, year Mean (SD) body mass index, kg/m2 Mean (SD) waist circumference, cm Mean (SD) smoking, pack-years Mean (SD) alcohol consumption, g/week Regular exercise, % Education b 16 years, % Mean (SD) visceral adipose tissue area, cm2 Mean (SD) subcutaneous adipose tissue area, cm2 Mean (SD) total abdominal adipose tissue area, cm2
49.6 (10.1) 24.3 (2.7) 86.7 (7.3) – 103.8 (255.1) 68.8 15.5 124.3 (51.8) 136.9 (56.1) 261.2 (94.9)
51.6⁎⁎ (8.6) 24.5 (2.4) 87.6⁎⁎ (6.7) 18.3 (15.2) 163.4⁎⁎ (240.0) 77.4 17.0 136.7⁎⁎ (51.5) 133.6 (48.6) 270.3⁎ (87.7)
47.1⁎⁎ (8.5) 24.7⁎⁎ (2.8) 87.9⁎⁎ (7.5) 25.2 (16.2) 212.2⁎⁎ (370.2) 56.9 19.6 135.2⁎⁎ (51.9) 139.5 (56.0) 274.7⁎⁎ (96.2)
b0.001 0.001 b0.001 – b0.001 b0.001 0.016 b0.001 0.004 0.001
a
P-values for Pearson chi-square test for categorical variables, P-values for analysis of variance F test for continuous variables. P b 0.05, compared to never smokers. ⁎⁎ P b 0.01, compared to never smokers. ⁎
K. Lee et al. / Preventive Medicine 55 (2012) 183–187 Table 2 Adjusted means (SE)a of VAT and SAT according to smoking status, Korea, Republic of (2008–2010). VAT (cm2) Never Former Current cigarettes/day
1–10 11–20 >20
124.0 136.0 132.9 131.9 139.1
(1.7) (1.3) (2.8) (1.9) (3.2)
P
SAT (cm2)
P
b0.001 0.06 0.017 b0.001
135.9 136.2 136.4 132.1 136.6
>0.99 >0.99 >0.99 >0.99
(1.7) (1.3) (2.8) (1.9) (3.3)
VAT, visceral adipose tissue area; SAT, subcutaneous adipose tissue area. a Analysis of covariance with never smokers as reference group, adjusted for age, weekly alcohol drink, regular exercise (yes/no), and education level (≤15 years/≥16 years).
Table 3 Adjusted means (SE) of VAT and SAT according to past smoking history (tertiles), Korea, Republic of (2008–2010). VAT (cm2) Never smoker Former, duration of smoking, years Former, cigarettes/day
Former, pack-years
Former, years since quitting
≤ 15 16–22 ≥ 23 ≤ 10 11–20 ≥ 21 ≤ 10 10.1–20 > 20 ≥ 15 6–14 ≥5
123.8 133.1⁎⁎ 135.7⁎⁎ 139.1⁎⁎ 132.0⁎ 135.5⁎ 145.7⁎⁎ 128.5 138.6⁎ 140.8⁎⁎ 129.9 136.6⁎ 140.2⁎⁎
(1.7) (2.1) (2.5) (2.3) (2.3) (1.8) (3.5) (2.2) (2.3) (2.4) (2.4) (2.2) (2.3)
P for trend b 0.001
b 0.001
b 0.001
b 0.001
SAT (cm2) 134.1 133.9 132.4 135.1 132.9 134.1 136.4 130.7 135.3 135.4 132.0 133.4 136.8
(1.7) (2.1) (2.4) (2.2) (2.2) (1.8) (3.5) (2.2) (2.3) (2.3) (2.3) (2.1) (2.2)
P for trend 0.909
0.696
0.531
0.621
VAT, visceral adipose tissue area; SAT, subcutaneous adipose tissue area. Adjusted for age, weekly alcohol intake (g), regular exercise (yes/no), and education level (≤15 years/≥ 16 years). ⁎ P b 0.05, compared to never smokers. ⁎⁎ P b 0.01, compared to never smokers.
The adjusted means of VAT and SAT according to past smoking history (duration of smoking, CPD, PY, and years since quitting) are presented in Table 3. Former smokers were divided by tertiles for each category. Former smokers who had a longer duration of smoking, higher
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consumption of cigarettes, higher PY, and a shorter period since quitting were more likely to have a higher VAT (all P for trendb 0.01). SAT was not associated with smoking history. Ex-smokers who consumed more than 20 CPD had about 17.7% higher VAT than never smokers. The means of VAT and SAT according to smoking status are shown in Fig. 1. We subdivided former smokers into five groups: b2, 2–4, 5–9, 10–19, and ≥20 years of abstinence from smoking. Never smokers had the lowest VAT (123.8 cm2), whereas the mean VAT was highest in former smokers within 2 years of quitting (143.5 cm2) and was about 16% higher than that of never smokers (P b 0.01). There was a decrease in the mean VAT after 2 years of quitting among former smokers. No significant difference in the mean VAT between never smokers and ex-smokers who stopped smoking ≥ 20 years ago was observed. Current smokers had a significantly higher VAT (134.6 cm2) than never smokers (P b 0.01). The mean SAT did not show any correlation with the smoking status. Discussion In this large cross-sectional study in Korean men, we demonstrated that both current and former smokers had more VAT mass than the never smokers, and after adjusting for various confounders, the effect was proportional to the degree of exposure to cigarette smoking, in both current and former smokers. We also found that a longer smoking duration, higher cigarette consumption per day before quitting, and shorter abstinence duration showed a trend of increasing VAT in former smokers. Our findings reinforced the association between cigarette smoking and higher VAT by demonstrating a detailed dose–response relationship. In a Japanese study of 450 men, there was a positive but insignificant relation to VAT was observed (Komiya et al., 2006). In a Turkish study of 157 adults (79 men), after adjustment for age and physical activity, a significant inverse association was observed only in women (Onat et al., 2009). In a cross-sectional study comprising 1505 male participants, both current and former smokers had higher levels of VAT (Molenaar et al., 2009). In another Japanese study of 5697 men (the Hitachi Health Study) VAT was not significantly different between never smokers and current smokers, whereas former smokers with less than 15 years of abstinence had significantly higher VAT than current smokers
Fig. 1. Adjusted mean (± 1 SE) values of VAT, SAT, and WC according to period of quitting, Korea, Republic of (2008–2010). Percentage means the difference of VAT, compared to never smokers. VAT, visceral adipose tissue area; SAT, subcutaneous adipose tissue area; WC, waist circumference. Adjusted for age, weekly alcohol intake (g), education level, and regular exercise (yes/no) by ANCOVA, Korea, Republic of (2008–2010). ⁎: P b 0.05; ⁎⁎: P b 0.01 — multiple comparison by Bonferroni method compared to never smokers.
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(Matsushita et al., 2011). While partially compatible with these previous investigations with conflicting data, in the present study, we demonstrated that both the intensity and the duration of exposure to active smoking tended to be associated with increased VAT in both former and current smokers as compared to never smokers. Two large studies, published after 2009, reported similar results that smoking exposure can be a risk factor for increased visceral adipose tissue, which was inconsistent with two small studies published before 2009. Our study also supports these recent findings, and furthermore we found a dose–response relationship between exposure to cigarette smoking and increased visceral adipose tissue, both in current and former smokers, and to our knowledge, our study is the first to report this finding. Our findings strengthen the hypothesis suggested by several studies that chronic exposure to cigarette smoking affects the accumulation of visceral fat (Audrain-McGovern and Benowitz, 2011; Benowitz, 2003; Chiolero et al., 2008; Valassi et al., 2008). A recent prospective study has reported that former smokers had an increased risk for incident diabetes that peaked within 3 years of quitting but declined gradually, which is compatible with our finding that the mean VAT in former smokers was highest within 2 years of abstinence (Yeh et al., 2010). Several previous studies have attempted to explain the biologic mechanisms of the effect of smoking on abdominal obesity and VAT. The waist-to-hip ratio, one of the indicator of the amount of abdominal obesity, is higher in smokers than in never smokers (Canoy et al., 2005; Jee et al., 2002), and varies directly with the number of cigarettes smoked (Canoy et al., 2005; Shimokata et al., 1989). Nicotine affects various hormone systems such as leptin, neuropeptide Y, and orexins (Li et al., 2000; Valassi et al., 2008). Smoking stimulates sympathetic nervous system activity and causes the release of catecholamines (Benowitz, 2003; Staley et al., 2001). Higher plasma cortisol concentrations and decreased serum testosterone levels might be associated with increased VAT mass in smokers as compared to never smokers (Meikle et al., 1988; Travison et al., 2007; Vermeulen et al., 1999; Yoshida et al., 1999). In addition, lower plasma adiponectin, which is associated with insulin resistance (Ravussin, 2002), was observed in smokers as compared to never smokers (Miyazaki et al., 2003). Insulin resistance, which is associated with increased VAT, is related to cigarette smoking in a dose dependent manner (Eliasson et al., 1994). Study strengths and limitations Our study has several strengths, including a large sample size and precise quantification of VAT and SAT by CT. Second, a more detailed smoking data were included in the analysis as compared to previous studies (Komiya et al., 2006; Matsushita et al., 2011; Molenaar et al., 2009; Onat et al., 2009), in addition to adjusting for various confounders such as age, alcohol intake, exercise, and education. The abovementioned studies did not provide the dose–response relationship between cigarette smoking and VAT in smokers. Only the Hitachi Health Study examined the abstinence duration in former smokers. Third, we excluded the subjects currently receiving treatment for hypertension, diabetes, and dyslipidemia from our analysis because of the possibilities of inverse causality, since smokers who developed chronic disease may tend to quit their smoking. There are also some limitations to our study. First, the crosssectional design did not allow us to infer causality. In addition, our results were subject to survival bias, for we excluded subjects with chronic disease because of the possibilities of inverse causality. However, the Hitachi Health Study that also analyzed data excluding subjects with chronic disease confirmed the same results (Matsushita et al., 2011). It was, therefore, unlikely that our analysis to avoid the inverse causality strongly biased the relationship between exposure to smoking and visceral obesity. Second, since our subjects were Korean men, our results might not be generalizable to other populations. Third, since the smoking data were self-reported, they might not have been
completely accurate. However, a previous study that compared selfreported smoking status with biochemical evidence showed that it was usually correct, especially for observational studies (Patrick et al., 1994). Fourth, we did not examine the diet or the caloric intake, which could have been a confounding factor. Finally, we did not classify SAT as superficial or deep—the 2 functionally distinct compartments of adipose tissue in relation to insulin resistance (Kelley et al., 2000). Conclusion In conclusion, a higher VAT mass was observed in both current and former smokers as compared to never smokers. The intensity and duration of chronic exposure to active smoking in former smokers showed a trend towards increasing VAT mass. After smoking cessation, increased abdominal fat mass was due to accumulation of VAT, not SAT. To smokers, especially those with fear of obesity, our findings provide new insights that smoking more cigarettes could be rather related to being viscerally obese, and long-term smoking cessation might help reduce the visceral obesity in former smokers. Further prospective studies are warranted to elucidate the effects of smoking and smoking cessation on visceral obesity. Source of funding This work was supported by grant 04-2010-073 from the Seoul National University Hospital Research Fund. Conflict of interest statement The authors declare that there are no conflicts of interest.
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Preventive Medicine journal homepage: www.elsevier.com/locate/ypmed
Associations of smoking and smoking cessation with CT-measured visceral obesity in 4656 Korean men Kiheon Lee a, Cheol Min Lee b,⁎, Hyuk Tae Kwon b, Seung-Won Oh b, Hochun Choi c, Jin Ho Park c, BeLong Cho c a b c
Department of Family Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, South Korea Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
a r t i c l e
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Available online 20 June 2012 Keywords: Smoking Smoking cessation Visceral obesity Visceral adipose tissue Subcutaneous adipose tissue Abdominal obesity
a b s t r a c t Objectives. Although obesity is shown to be less common among current smokers than never smokers, the association between visceral obesity and smoking remains uncertain. Methods. For this cross-sectional analysis, we recruited 4656 Korean men of 19 to 79 years who received a regular checkup at a health examination center between 2008 and 2010. Computed tomography was performed to measure the area of visceral and subcutaneous adipose tissue (VAT and SAT). We compared the mean VAT by multiple regression analysis across smoking status after adjusting for confounders. Results. Both current and former smokers had more mean VAT than never smokers. Current smokers who consumed more than 20 cigarettes per day had 11% higher mean VAT than never smokers (Pb 0.01). Longer smoking duration, higher daily cigarette consumption before quitting, and shorter abstinence duration among ex-smokers were associated with increasing mean VAT (all P for trendb 0.01). The mean VAT in former smokers was highest within 2 years of abstinence. There was no significant difference of mean VAT between ex-smokers with >20 years of abstinence duration and never smokers. Conclusion. Both current and former smoking is associated with increased VAT. The risk of visceral obesity is proportional to the degree of exposure to cigarette smoking. © 2012 Elsevier Inc. All rights reserved.
Introduction Both cigarette smoking and abdominal obesity are strong independent risk factors for cardiovascular disease (CVD). In particular, the combination of smoking and obesity or abdominal obesity is related to a much higher mortality (Chouraki et al., 2008; Despres et al., 2008; Hansson et al., 1999; Koster et al., 2008; Lakka et al., 2002; Manson et al., 1990). The majority of smokers who quit smoking gain weight and harmful changes in cardiovascular risk factors associated with smoking cessation may be mainly secondary to weight gain (Yoon et al., 2010). Smoking cessation also results in substantial increase in central fat, which might attenuate some of the beneficial effects of smoking cessation (Pisinger and Jorgensen, 2007). The association between smoking and abdominal obesity is not fully understood. There is increasing evidence that smoking is conducive to greater accumulation of visceral fat (Chiolero et al., 2008) and one
⁎ Corresponding author at: Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Gangnam Finance Center, 152 Teheran-ro, Gangnam-gu, Seoul 135-984, South Korea. Fax: + 82 2 2112 5636. E-mail address: [email protected] (C.M. Lee). 0091-7435/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.ypmed.2012.06.009
might speculate that the weight gain after smoking cessation mostly occurs in the subcutaneous region of the body (Filozof et al., 2004). The majority of these previous studies chose waist circumference as an alternative for abdominal obesity, which does not allow for the differentiation between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Visceral obesity, which provides a more precise assessment of CVD risk, is evaluated by computed tomography (CT) and VAT may be a pathogenic fat compartment (Pascot et al., 1999). To our knowledge, only four cross-sectional studies have explored the association between smoking status and visceral obesity by CT method, but considerable disagreement remains regarding the change of VAT and SAT according to smoking status (Komiya et al., 2006; Matsushita et al., 2011; Molenaar et al., 2009; Onat et al., 2009). Data from the Framingham heart study reported that both current and former smoking was associated with higher VAT than never smokers (Molenaar et al., 2009), but current smokers had the lowest VAT than former smokers in one Japanese study that comprised 5697 subjects (Matsushita et al., 2011). The change of SAT was also inconsistent in a few studies. Furthermore, they did not include the detailed smoking data of current and former smokers in their analyses. Here, we aimed to investigate the association between smoking habits in Korean men, obtained from the detailed smoking data, and visceral obesity determined by evaluating the VAT area with CT.
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Statistics
Methods Study population We used data from 7141 men aged over 18 years who voluntarily received a routine comprehensive health checkup including CT scan analyses of abdominal adipose tissue, between March 2008 and February 2010 at the Healthcare System Gangnam Center of Seoul National University Hospital in Korea. Subjects lacking a smoking history (n= 99), those who underwent repeated abdominal CT scans (n = 348) to avoid the inverse causality of the relationship between smoking cessation and obesity, and those who were currently receiving treatment for hypertension, diabetes mellitus, and dyslipidemia (n= 2038) were excluded. Finally, 4656 men were included in the analysis. Smoking status was determined by the response to the following question: “Do you smoke cigarettes now?” The response choices were “Never have smoked,” “Used to smoke,” and “Yes,” and the subjects were divided accordingly into 3 groups. All subjects provided a written informed consent, and the protocol was approved by the review board of the Seoul National University Hospital. Subject characteristics For each subject, the following data were obtained from a self-administered questionnaire during the health examination: age, weekly alcohol intake, regular exercise, education level, and current medication of diabetes mellitus, hypertension, and dyslipidemia. The weekly alcohol consumption was calculated using data on the type and volume of alcohol consumed and the frequency of drinking, after factoring in the ethanol content. According to the National Institute of Alcohol Abuse and Alcoholism (NIAAA) guidelines, we defined atrisk drinking as >14 drinks or >168 g of alcohol per week (NIAAA, 2005). For education status, subjects were asked to choose their attained level from 5 categories: b 9 years, 9–11 years, 12–15 years, 16–17 years, or ≥18 years. For exercise, subjects had to report whether they exercised regularly. For smoking history, current and former smokers reported the duration and the average number of cigarettes. We defined pack-years (PY) as the average number of cigarettes smoked per day during the time the subjects smoked divided by 20 and multiplied by the number of smoking years. Waist circumference was measured at the midpoint between the lower part of the last rib and the top of the hip.
Descriptive statistics were used to show the basic clinical and socio-economic characteristics of the subjects according to their smoking status. An analysis of variance F test and the Pearson chi-square test were used to assess the statistical significance of the difference across the 3 groups—never smokers, former smokers, and current smokers. The multiple comparisons between the smokers and never smokers were performed using Bonferroni's method. The adjusted least square VAT and SAT means were compared according to the smoking status by using analysis of covariance (ANCOVA) adjusted for age, regular exercise (yes or no), weekly alcohol intake (g), and education (b16 years/≥ 16 years). Current smokers were further divided into 3 groups according to the number of cigarettes per day (CPD) that they smoked: 1–10, 11–20, and > 20. Former smokers were subdivided into 3 groups or tertiles according to the duration of smoking (years), CPD, pack-years (PY), and duration of abstinence. We then adjusted the multiple comparisons by Bonferroni's method by using never smokers as a reference. After subdividing the subjects into 7 groups (current smokers, never smokers, and former smokers with b 2, 2–4, 5–9, 10–19, and ≥ 20 years of smoking abstinence), the adjusted means of both VAT and SAT of the subjects according to the duration of smoking abstinence were further evaluated. We also tested the difference between never smokers and the other groups by using a paired t-test. We conducted all analyses by using the STATA software (version 11.0) and defined P b 0.05 as statistically significant.
Results Characteristics of participants Table 1 shows the subjects' general characteristics by the smoking status. The mean age of the participants (n=4656) was 49.3 years (range, 19–79; SD, 9.5), and the mean BMI (SD) was 24.5 (2.7) kg/m2. Current smokers tended to exercise less regularly, have a lower educational attainment, and have a higher rate of metabolic syndrome as compared to never smokers. Current smokers consumed significantly more alcohol than never smokers did. Current smokers had significantly higher mean BMI, WC, VAT, and TAT than never smokers did (Pb 0.01 for each).
Measurement of abdominal adipose tissue mass
Abdominal adipose tissue according to smoking status The abdominal adipose tissue mass was estimated using cross-sectional images obtained by a standardized and validated CT technique (Borkan et al., 1982; Goodpaster, 2002; Kvist et al., 1988) described in detail in a previous study (Chung et al., 2008). Briefly, each subject was examined in the supine position with a 16-detector row CT scanner (Somatom Sensation 16; Siemens Medical Solutions, Forchheim, Germany). We obtained a single 5-mm slice image, at the level of the umbilicus, at 120 kVp and 260 mA with a scan time of 0.5 s. We calculated the total abdominal adipose tissue area (TAT: subcutaneous adipose tissue (SAT) area plus VAT) by using specialized software (Rapidia 2.8; Infinitt, Seoul, Korea) with the attenuation values for the region of interest within a range of −250 to −50 Hounsfield Units. We used VAT≥100 cm2 as the criterion for visceral obesity (Han et al., 2008).
Current smokers who consumed 11 or more CPD, as well as former smokers had significantly higher adjusted mean VAT than never smokers (P b 0.05 for each) but did not differ in SAT (Table 2). When current smokers were classified into three categories (1–10, 11–20, >20 CPD) and the adjusted mean VAT was compared between them and never smokers, an increase in CPD was significantly associated with higher mean VAT (P b 0.01). The mean VAT of current smokers who consumed more than 20 CPD was 12.2% higher (15.1 cm 2 of difference) than that of never smokers. There was no significant association between CPD and SAT.
Table 1 Basic characteristics of subjects (N = 4656), Korea, Republic of (2008–2010). Characteristic
Never smokers (n = 1064)
Former smokers (n = 1857)
Current smokers (n = 1735)
Pa
Mean (SD) age, year Mean (SD) body mass index, kg/m2 Mean (SD) waist circumference, cm Mean (SD) smoking, pack-years Mean (SD) alcohol consumption, g/week Regular exercise, % Education b 16 years, % Mean (SD) visceral adipose tissue area, cm2 Mean (SD) subcutaneous adipose tissue area, cm2 Mean (SD) total abdominal adipose tissue area, cm2
49.6 (10.1) 24.3 (2.7) 86.7 (7.3) – 103.8 (255.1) 68.8 15.5 124.3 (51.8) 136.9 (56.1) 261.2 (94.9)
51.6⁎⁎ (8.6) 24.5 (2.4) 87.6⁎⁎ (6.7) 18.3 (15.2) 163.4⁎⁎ (240.0) 77.4 17.0 136.7⁎⁎ (51.5) 133.6 (48.6) 270.3⁎ (87.7)
47.1⁎⁎ (8.5) 24.7⁎⁎ (2.8) 87.9⁎⁎ (7.5) 25.2 (16.2) 212.2⁎⁎ (370.2) 56.9 19.6 135.2⁎⁎ (51.9) 139.5 (56.0) 274.7⁎⁎ (96.2)
b0.001 0.001 b0.001 – b0.001 b0.001 0.016 b0.001 0.004 0.001
a
P-values for Pearson chi-square test for categorical variables, P-values for analysis of variance F test for continuous variables. P b 0.05, compared to never smokers. ⁎⁎ P b 0.01, compared to never smokers. ⁎
K. Lee et al. / Preventive Medicine 55 (2012) 183–187 Table 2 Adjusted means (SE)a of VAT and SAT according to smoking status, Korea, Republic of (2008–2010). VAT (cm2) Never Former Current cigarettes/day
1–10 11–20 >20
124.0 136.0 132.9 131.9 139.1
(1.7) (1.3) (2.8) (1.9) (3.2)
P
SAT (cm2)
P
b0.001 0.06 0.017 b0.001
135.9 136.2 136.4 132.1 136.6
>0.99 >0.99 >0.99 >0.99
(1.7) (1.3) (2.8) (1.9) (3.3)
VAT, visceral adipose tissue area; SAT, subcutaneous adipose tissue area. a Analysis of covariance with never smokers as reference group, adjusted for age, weekly alcohol drink, regular exercise (yes/no), and education level (≤15 years/≥16 years).
Table 3 Adjusted means (SE) of VAT and SAT according to past smoking history (tertiles), Korea, Republic of (2008–2010). VAT (cm2) Never smoker Former, duration of smoking, years Former, cigarettes/day
Former, pack-years
Former, years since quitting
≤ 15 16–22 ≥ 23 ≤ 10 11–20 ≥ 21 ≤ 10 10.1–20 > 20 ≥ 15 6–14 ≥5
123.8 133.1⁎⁎ 135.7⁎⁎ 139.1⁎⁎ 132.0⁎ 135.5⁎ 145.7⁎⁎ 128.5 138.6⁎ 140.8⁎⁎ 129.9 136.6⁎ 140.2⁎⁎
(1.7) (2.1) (2.5) (2.3) (2.3) (1.8) (3.5) (2.2) (2.3) (2.4) (2.4) (2.2) (2.3)
P for trend b 0.001
b 0.001
b 0.001
b 0.001
SAT (cm2) 134.1 133.9 132.4 135.1 132.9 134.1 136.4 130.7 135.3 135.4 132.0 133.4 136.8
(1.7) (2.1) (2.4) (2.2) (2.2) (1.8) (3.5) (2.2) (2.3) (2.3) (2.3) (2.1) (2.2)
P for trend 0.909
0.696
0.531
0.621
VAT, visceral adipose tissue area; SAT, subcutaneous adipose tissue area. Adjusted for age, weekly alcohol intake (g), regular exercise (yes/no), and education level (≤15 years/≥ 16 years). ⁎ P b 0.05, compared to never smokers. ⁎⁎ P b 0.01, compared to never smokers.
The adjusted means of VAT and SAT according to past smoking history (duration of smoking, CPD, PY, and years since quitting) are presented in Table 3. Former smokers were divided by tertiles for each category. Former smokers who had a longer duration of smoking, higher
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consumption of cigarettes, higher PY, and a shorter period since quitting were more likely to have a higher VAT (all P for trendb 0.01). SAT was not associated with smoking history. Ex-smokers who consumed more than 20 CPD had about 17.7% higher VAT than never smokers. The means of VAT and SAT according to smoking status are shown in Fig. 1. We subdivided former smokers into five groups: b2, 2–4, 5–9, 10–19, and ≥20 years of abstinence from smoking. Never smokers had the lowest VAT (123.8 cm2), whereas the mean VAT was highest in former smokers within 2 years of quitting (143.5 cm2) and was about 16% higher than that of never smokers (P b 0.01). There was a decrease in the mean VAT after 2 years of quitting among former smokers. No significant difference in the mean VAT between never smokers and ex-smokers who stopped smoking ≥ 20 years ago was observed. Current smokers had a significantly higher VAT (134.6 cm2) than never smokers (P b 0.01). The mean SAT did not show any correlation with the smoking status. Discussion In this large cross-sectional study in Korean men, we demonstrated that both current and former smokers had more VAT mass than the never smokers, and after adjusting for various confounders, the effect was proportional to the degree of exposure to cigarette smoking, in both current and former smokers. We also found that a longer smoking duration, higher cigarette consumption per day before quitting, and shorter abstinence duration showed a trend of increasing VAT in former smokers. Our findings reinforced the association between cigarette smoking and higher VAT by demonstrating a detailed dose–response relationship. In a Japanese study of 450 men, there was a positive but insignificant relation to VAT was observed (Komiya et al., 2006). In a Turkish study of 157 adults (79 men), after adjustment for age and physical activity, a significant inverse association was observed only in women (Onat et al., 2009). In a cross-sectional study comprising 1505 male participants, both current and former smokers had higher levels of VAT (Molenaar et al., 2009). In another Japanese study of 5697 men (the Hitachi Health Study) VAT was not significantly different between never smokers and current smokers, whereas former smokers with less than 15 years of abstinence had significantly higher VAT than current smokers
Fig. 1. Adjusted mean (± 1 SE) values of VAT, SAT, and WC according to period of quitting, Korea, Republic of (2008–2010). Percentage means the difference of VAT, compared to never smokers. VAT, visceral adipose tissue area; SAT, subcutaneous adipose tissue area; WC, waist circumference. Adjusted for age, weekly alcohol intake (g), education level, and regular exercise (yes/no) by ANCOVA, Korea, Republic of (2008–2010). ⁎: P b 0.05; ⁎⁎: P b 0.01 — multiple comparison by Bonferroni method compared to never smokers.
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(Matsushita et al., 2011). While partially compatible with these previous investigations with conflicting data, in the present study, we demonstrated that both the intensity and the duration of exposure to active smoking tended to be associated with increased VAT in both former and current smokers as compared to never smokers. Two large studies, published after 2009, reported similar results that smoking exposure can be a risk factor for increased visceral adipose tissue, which was inconsistent with two small studies published before 2009. Our study also supports these recent findings, and furthermore we found a dose–response relationship between exposure to cigarette smoking and increased visceral adipose tissue, both in current and former smokers, and to our knowledge, our study is the first to report this finding. Our findings strengthen the hypothesis suggested by several studies that chronic exposure to cigarette smoking affects the accumulation of visceral fat (Audrain-McGovern and Benowitz, 2011; Benowitz, 2003; Chiolero et al., 2008; Valassi et al., 2008). A recent prospective study has reported that former smokers had an increased risk for incident diabetes that peaked within 3 years of quitting but declined gradually, which is compatible with our finding that the mean VAT in former smokers was highest within 2 years of abstinence (Yeh et al., 2010). Several previous studies have attempted to explain the biologic mechanisms of the effect of smoking on abdominal obesity and VAT. The waist-to-hip ratio, one of the indicator of the amount of abdominal obesity, is higher in smokers than in never smokers (Canoy et al., 2005; Jee et al., 2002), and varies directly with the number of cigarettes smoked (Canoy et al., 2005; Shimokata et al., 1989). Nicotine affects various hormone systems such as leptin, neuropeptide Y, and orexins (Li et al., 2000; Valassi et al., 2008). Smoking stimulates sympathetic nervous system activity and causes the release of catecholamines (Benowitz, 2003; Staley et al., 2001). Higher plasma cortisol concentrations and decreased serum testosterone levels might be associated with increased VAT mass in smokers as compared to never smokers (Meikle et al., 1988; Travison et al., 2007; Vermeulen et al., 1999; Yoshida et al., 1999). In addition, lower plasma adiponectin, which is associated with insulin resistance (Ravussin, 2002), was observed in smokers as compared to never smokers (Miyazaki et al., 2003). Insulin resistance, which is associated with increased VAT, is related to cigarette smoking in a dose dependent manner (Eliasson et al., 1994). Study strengths and limitations Our study has several strengths, including a large sample size and precise quantification of VAT and SAT by CT. Second, a more detailed smoking data were included in the analysis as compared to previous studies (Komiya et al., 2006; Matsushita et al., 2011; Molenaar et al., 2009; Onat et al., 2009), in addition to adjusting for various confounders such as age, alcohol intake, exercise, and education. The abovementioned studies did not provide the dose–response relationship between cigarette smoking and VAT in smokers. Only the Hitachi Health Study examined the abstinence duration in former smokers. Third, we excluded the subjects currently receiving treatment for hypertension, diabetes, and dyslipidemia from our analysis because of the possibilities of inverse causality, since smokers who developed chronic disease may tend to quit their smoking. There are also some limitations to our study. First, the crosssectional design did not allow us to infer causality. In addition, our results were subject to survival bias, for we excluded subjects with chronic disease because of the possibilities of inverse causality. However, the Hitachi Health Study that also analyzed data excluding subjects with chronic disease confirmed the same results (Matsushita et al., 2011). It was, therefore, unlikely that our analysis to avoid the inverse causality strongly biased the relationship between exposure to smoking and visceral obesity. Second, since our subjects were Korean men, our results might not be generalizable to other populations. Third, since the smoking data were self-reported, they might not have been
completely accurate. However, a previous study that compared selfreported smoking status with biochemical evidence showed that it was usually correct, especially for observational studies (Patrick et al., 1994). Fourth, we did not examine the diet or the caloric intake, which could have been a confounding factor. Finally, we did not classify SAT as superficial or deep—the 2 functionally distinct compartments of adipose tissue in relation to insulin resistance (Kelley et al., 2000). Conclusion In conclusion, a higher VAT mass was observed in both current and former smokers as compared to never smokers. The intensity and duration of chronic exposure to active smoking in former smokers showed a trend towards increasing VAT mass. After smoking cessation, increased abdominal fat mass was due to accumulation of VAT, not SAT. To smokers, especially those with fear of obesity, our findings provide new insights that smoking more cigarettes could be rather related to being viscerally obese, and long-term smoking cessation might help reduce the visceral obesity in former smokers. Further prospective studies are warranted to elucidate the effects of smoking and smoking cessation on visceral obesity. Source of funding This work was supported by grant 04-2010-073 from the Seoul National University Hospital Research Fund. Conflict of interest statement The authors declare that there are no conflicts of interest.
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