TABLE 6.—Continued Reference Population Payanini-Hill etal. (1981) Cases: 91 postmenopausal women aged >80 with hip fractures Controls: 182 age, race-matched postmenopausal women Kreiger et al. Cases: 98 postmenopausal women aged (1982), Kreiger 45-74 yr hospitalized with hip fracture and Hilditch Trauma Controls: 83 postmenopausal (1986) women hospitalized for trauma Nontrauma Controls: 884 postmenopausal women hospitalized for medical iHness Williams et al. Cases: 344 (355) white women aged (1982); 50-74 with hip or forearm fracture Alderman et al. Controls: 567 (S62) white women from a (1986) household survey Hip and/or forearm fractures Comparison 1-10 cig/day vs. none 211 cig/day vs. none Ever vs. never smokers Trauma controls Nontrauma controls Among estrogen nonusers Hip fractures Average weight ever smoker vs. obese never smoker Thin ever smoker vs. obese hever smoker Forearm fracture Thin ever smoker vs. obese never smoker <1 ppd vs. never >! ppd vs. never Estimated relative risk 1.05 1.96 ty te ey 13.5° 5.4? 1.0 > Comments Adjusted for age, age at menopause, Quetelet’s Index, physical activity, alcohol consumption, and exogenous estrogen use Adjusted for age, Quetelet’s Index, months breast feeding, ovariectomy, and estrogen use Smokers and nonsmokers were not directly compared; the comparison group for all analyses was obese nonsmokers who had used estrogen for 21 yr; controlled for sex and race only cSP TABLE 6.—Continued Reference Cooper, Barker, Wickham (1988) Lau et al. (1988) Hip and/or forearm fractures Population Comparison Estimated relative risk Comments Cases: 300 men and women aged 250 Smokers vs. nonsmokers 1.7 Controlled for age and sex only hospitalized for hip fracture in England Controls: 600 community volunteers matched for age and sex Cases: 400 men and women hospitalized Smokers vs. nonsmokers 1.3 Controlled for age and sex only for hip fracture in Hong Kong Controls: 400 hospitalized and 400 community volunteers matched for age and sex NOTE: ppd=packs/day. “Calculated from data in paper cited. "p<0.08, large samples from the Framingham Heart Study, the Nurses Health Study, and the first National Health and Nutrition Examination Survey. In the largest study by Hemenway and colleagues (1988), 96,508 nurses reported 975 hip or forearm fractures during an average 4 years of observation. The relative risk of fracture was 1.0 in each smoking category (former smokers, smokers of 1-14 cigarettes/day, 15-25 cigarettes/day. and >25 cigarettes/day) compared with never smokers. Smoking Cessation and Osteoporosis and Fracture No studies have evaluated the effect of smoking cessation on osteoporosis and fracture, nor are there studies of the risk of osteoporosis or fracture in former smokers compared with continuing smokers. Summary There is insufficient evidence to conclude that smoking decreases bone mineral content and the risk of osteoporotic fractures. Some studies have found lower bone mineral content in smokers compared with nonsmokers, but others have not. Some, but not all, case—control studies have found a higher risk of osteoporotic fracture among smokers. Most negative studies were limited by small sample size, and most positive studies were not designed to control for potentially strong confounding variables. Analysis of data in five cohort studies has found no association of smoking with increased risk of fracture. Skin Wrinkling Introduction Although wrinkling of the facial skin is nearly universal among elderly persons, it is rarely mentioned in textbooks of dermatology or medicine, and little research has been published concerning its etiology or risk factors. Skin wrinkling is associated with sun exposure (Kligman 1969; Allen, Johnson, Diamond 1973; Daniell 1971; Knox. Cockerell, Freeman 1962; Rook, Wilkinson, Ebling 1979). Wrinkling occurs with increasing age (Daniell 1971; Knox, Cockerell, Freeman 1962: Rook, Wilkinson. Ebling 1979), but even among the elderly, wrinkling usually is confined to sun-exposed areas (Kligman 1969; Allen, Johnson, Diamond 1973; Knox, Cockerell, Freeman 1962). There is limited evidence that dramatic weight loss is associated with skin wrinkling (Daniell 1971). Pathophysiologic Framework Itis not clear how cigarette smoking may promote skin wrinkling. Some investigators have concluded that a localized finding such as wrinkling of the face and hands could not be caused by a systemic factor such as the absorbed components of cigarette smoke. 453 PSP TABLE 7.—Summary of cohort studies of smoking and fractures Reference Jensen (1986) Hemenway etal. (1988) Felson et al. (1988) Holbrook, Barrett-Connor, Wingard (1988) Farmer et al. (1989) Population/outcome Population-based study of 70-year-old women in Copenhagen, Denmark: 77 smoked daily for 220 yr, 103 never smoked. Outcome: all fractures 96.508 nurses aged 35-59 at baseline (1980) followed for 4 yr. Outcome: self-report of 975 fractures of hip or forearm 5.209 men and women in the Framingham Heart Study followed retrospectively for about 30 yr. Outcome: 217 documented hip fractures 975 men and women aged 50-79 at baseline followed for 14 yr. Outcome: 33 documented hip fractures 3,595 white women in NHANES-I aged 40-77 at baseline (1971-75) followed for an average of 10 yr. Outcome: 84 documented hip fractures Comparison % smokers with fracture vs. % nonsmokers with fracture: All postmenopausal fractures Osteoporotic fractures? Age-adjusted fracture rate compared to: never smokers Ex-smokers Smokers 1-14 cig/day 15-24 cig/day 225 cip/day Based on cig/day Smokers vs. nonsmokers Based on number of yr smoked at baseline exam Relative risk 0.9" 0.7" 1.0 L.0 1.0 1.0 No increase No increase Comments All subjects were 70-yr-old women: no control for other confounders A very large cohort study producing narrow Cls (upper limit 1.25), but most women were middle-aged or younger; controlled for age only No data given, but reported no association in any analysis Cox regression model, adjusted for age, sex, body mass index, dietary calcium, and alcohol consumption No data given, but reported no significant association; analysis adjusted for age, body mass index, menopausal status, calcium consumption, and activity NOTE: Cl=confidence interval, NHANES-I=National Health and Nutrition Examination Survey I. * Calculated from data in reference. Femoral neck, proximal humerus, lower forearm, vertebral crush. However, facial skin, and to a lesser extent, the skin of the hands contain an intradermal elastic tissue mesh that is denser and more complex than in other areas (Shelley and Wood 1974). Thus. the toxic effect of both sunlight and smoking may be most damaging in these more susceptible areas. Alternatively, damage from sunlight and smoking may simply be additive, and the threshold for clinically apparent changes from smoking may not be reached in sun-protected areas of the skin. Histopathologic examination of sun-exposed skin commonly shows abnormalities of collagen in the dermis that decrease the elastic properties of the skin. a condition known as elastosis (Marks 1976; Shelley and Wood 1974). However. the mechanism by which sunlight might cause these changes is uncertain, and there is no evidence that smoking is associated with elastosis. Cigarette smoking has been shown to decrease capillary and arteriolar blood flow in the skin acutely (Klemp. Staberg. Thomsen 1982: Reus et al. 1984; Richardson 1987), and hence. may cause tissue hypoxia. However, there is no evidence that this causes changes in skin transparency and turgor or produces wrinkles. Smoking and Skin Wrinkling Several studies have reported that smoking is associated with prominent skin wrin- kling, particularly in the periorbital or “crow’s foot” area of the face. Ippen and Ippen (1965) defined “cigarette skin” as appearing pale, grayish, and wrinkled, especially on the cheeks, with thick skin between the wrinkles. In an examination of women aged 35 to 84, 66 of the 84 smokers had cigarette skin compared with 27 of the 140 nonsmokers (relative risk=4.1, p<0.01). This study did not adjust for differences in age or sun exposure between the smokers and nonsmokers (Ippen and Ippen 1965). Daniell (1971) examined facial wrinkles and smoking status among 1,104 subjects. most of whom were patients or visitors to his medical practice in Redding, CA. Skin wrinkling was assessed in the crow’s foot area and the adjacent areas of the forehead and cheeks and graded as one of six categories of severity. Potential confounders such as age, race (98 percent of the subjects were white), sex, sun exposure, and body weight were also measured. Smokers were more often prominently wrinkled (wrinkle score 4-6) than nonsmokers. Prominent skin wrinkling was also more common in relation to increasing age and sun exposure. The association between smoking and prominent wrinkling was found in each age, sex, and sun exposure subgroup and was statistically significant in most of the subgroups. The most heavily wrinkled class in each age—sex group was composed entirely of smokers. Wrinkling increased with duration of smoking and number of cigarettes smoked daily. Prominent skin wrinkling was more common among smokers aged 40 to 49 than among nonsmokers aged 60 to 69 years. This study provided strong evidence that smoking is associated with skin wrinkling (Daniell 1971). However, the measurements of wrinkling are not very precise, and although an attempt was made to blind the wrinkle assessment. the subjects were patients and friends of the investigator. who may have known their smoking status. Allen, Johnson, and Diamond (1973), reported on a study that they claimed refuted the above findings, but the data presented actually supported an association between smoking and skin wrinkling in whites (Boston 1973: Daniell 1973: Weiss 1973). Using Daniell’s 6 categories of wrinkling severity, Allen, Johnson, and Diamond (1973) examined 650 persons and obtained information on age, race, sex. smoking status, and sun exposure. Biopsies of the crow’s foot area also were performed on some subjects. As evidence that there is no association between smoking and skin wrinkling, the researchers reported that among 137 black subjects, only 2 had prominent wrinkling, regardless of sun exposure or smoking status. Although only fragmentary data are presented, wrinkle scores among white smokers who were exposed to the sun less than 2 hours daily were significantly higher than wrinkle scores for white nonsmokers with limited sun exposure, In a survey of 122 new patients attending a general medical practice in England, all but 1 of whom was white, wrinkling and other skin changes were found to be much more common among smokers than nonsmokers (Model 1985). “Smoker’s face” was defined as exhibiting one or more of the following: lines or wrinkles on the face. typically radiating from the corners of the lips or eyes; gaunt facial features; grayish skin; and a plethoric complexion. Smoker's face was found among 46 percent of smokers, and none of the nonsmokers were classified as having smoker's face. The association of smoking and smoker's face was statistically significant (p<0.001) and remained so after controlling for age. social class, sun exposure, and recent weight change. Although this study shows a striking difference between smokers and non- smokers, it is not clear that prominent skin wrinkling is the major or most common criterion for the diagnosis of smoker’s face. Thus, the association reported may not be specific for wrinkling. Smoking Cessation and Skin Wrinkling No studies have assessed the effect of smoking cessation on skin wrinkling. Daniell (1971) noted that prominent wrinkling was common in former smokers, but supporting data were not presented. Model (1985) reported that 8 percent of former smokers had smoker's face compared with 46 percent of smokers. Summary There is limited but consistent evidence that smoking is associated with prominent facial skin wrinkling among whites (Allen, Johnson, Diamond 1973: Daniell 1971: Ippen and Ippen 1965; Model 1985) but not among blacks (Allen, Johnson, Diamond 1973). Itis not clear whether former smokers are less wrinkled than smokers (Daniell 1971; Model 1985). CONCLUSIONS 1. Smokers have an increased risk of development of both duodenal and gastric ulcer, and this increased risk is reduced by smoking cessation. tN Ulcer disease is more severe among smokers than among nonsmokers. Smokers are less likely to experience healing of duodenal ulcers and are more likely to have 456 recurrences of both duodenal and gastric ulcers within specified timeframes. Most ulcer medications fail to alter these tendencies. 3. Smokers with gastric or duodenal ulcers who stop smoking improve their clinical course relative to smokers who continue to smoke. 4. 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January 1982. 468 CHAPTER 10 SMOKING CESSATION AND BODY WEIGHT CHANGE 469 CONTENTS Introduction 2.2... cece tet e enter eens 473 Amount of Weight Gain After Smoking Cessation and Likelihood of Gaining Weight 2.0... ec teen tenet n ene eens 473 Causes of Postcessation Weight Gain ..... 0.0... ee eee 483 Food Intake 2.0... centre eens 484 Physical Activity 00... 0.2 eee eee 486 Energy Expenditure 2... 0.22. eect tenet eee tenes 487 Relationship Between Overweight and Adverse Medical and Psychosocial QULCOMES 26 en eee e etna 490 Change in Weight-Related Health Risks After Smoking Cessation ............ 497 Strategies to Control Postcessation Weight Gain 2.200... ee eee eee ee eee 500 Behavioral Methods for Reducing Postcessation Weight Gain ............. 500 Pharmacologic Methods for Reducing Postcessation Weight Gain .......... 502 Conclusions 6.2.2... cece eevee ete e eet ett ett teen tet eee ress, 505 References 6.2.22... 0.0000 eeee eects eee eee Lette ete e tees eee e ees. 507 471 INTRODUCTION Cigarette smoking is associated with decreased body weight. and many smokers report that a major reason they smoke is to reduce body weight (Grunberg 1986: Klesges et al. 1989; US DHHS 1988a). However. as documented in this Chapter. the weight gain associated with smoking cessation is generally small and poses a minimal health risk. This Chapter is organized into six sections. Drawing from prospective investigations meeting specific criteria, the first section of this Chapter determines average weight gain following smoking cessation compared with continued smoking. assesses the percentage of continuing smokers and quitters gaining weight. and calculates the risk of gaining weight after smoking cessation versus continued smoking. The next section of this Chapter discusses the mechanisms responsible for weight gain after smoking cessation. The available literature is reviewed on dietary. activity. and metabolic changes after smoking cessation . The third section reviews the relationship between body weight and adverse medical and psychosocial outcomes. The fourth section examines whether weight-related health effects accompany weight gain in ex-smokers. The fifth section presents potential treatments for reducing postcessation weight gain. including pharmacologic (e.g., nicotine polacrilex gum. phenylpropanolamine, and d-fenfluramine) and nonpharmacologic approaches. The sixth section presents con- clusions regarding smoking cessation and body weight change. AMOUNT OF WEIGHT GAIN AFTER SMOKING CESSATION AND LIKELIHOOD OF GAINING WEIGHT To evaluate postcessation weight gain and to determine the likelihood or relative risk of gaining weight after smoking cessation, longitudinal investigations after 1970 of postcessation weight gain were examined. Only studies that included a control group of continuing smokers were evaluated. Requirements for studies in this review included a minimum followup period of 1 month and at least 10 smokers who quit. Studies were excluded if a weight loss component or severe caloric restriction was part of the intervention or if an agent known to affect body weight (e.g., nicotine polacrilex gum) was used; however, placebo conditions within drug trials were considered. A few Studies were excluded for methodologic or interpretive reasons, such as relapsed subjects included in data analysis along with quit subjects or whenever a weight change could not be calculated. Table | summarizes the 15 studies that fulfilled these inclusionary and exclusionary criteria. The following information is included for each study listed in Table 1: the study reference, the followup or period of abstinence, the mean weight gain among in- dividuals who quit smoking, the mean weight gain of subjects who did not quit smoking. the percentage of subjects quitting smoking who gained weight from baseline to the followup period, the percentage of nonabstinent subjects who gained weight during the same period, and the relative risk of gaining any weight after smoking cessation versus continued smoking. Adjusted averages of weight gain are provided to summarize across all studies, These adjusted averages control for differing sample sizes and assign 373 tlt TABLE 1.—Summary of prospective studies on smoking and body weight Mean weight % quitters % continuing Relative risk Sample Number of Quit gain (1b) who gain smokers who of gaining Reference size quitters period Quitters Continuing smokers weight gain weight weight Bossé. Garvey, Costa 705 237 S ye 6.35 2.01 —_ ad (1980) Cambien et al, 475 41 2yr 75 a _— —_ (1981) Coates and Li 335 13 lyr 5.15 0.04 76.9 46.3 1.66 (1983) Comstock and Stone 290 46 Syr 11.2 2.4 87.0 60.7 1.43 (1972) Friedman and Siegelaub 9539 2.738 1% mo 3.18 0.9 — — — (1980) (median) Grity, Carr, Marcus 554 ol lyr 6.1 0.3 —_ — — (L988) Hickey and Mulcahy RY 60 2 yr 1.6 0.9 — — - (1973) Kramer 134 SY lyr _ 78.0 56.0 1.39 (1982) Lund-Larsen and Treth OS80 1.047 3yr 6.94 0.44 —_— _ —_ (1982) Noppa and Bengtsson 526 72 6 yr 77 2.4 80.6 61.7 1.31 (1980) sdt TABLE 1.—Continued Mean weight gain (tb) % quitters “ continuing Relative risk Sample Number of Quit who gain smokers who of gaining Reference size quitters period Quitters Continuing smokers weight gain weight weight Puddey et al. 28 [4 1.5 mo 3.97 0.44 — — — (1985) Rabkin 107 35 3 mo 4.4 0.7 _— — —_— (1984b) Rodin 42 24 1.5 mo 3.18 0.30 58.3 33.3 1.75 (1987) Seltzer 318 104 S yr 79 3.5 _ - (1974) Tuomilehto et al. 496 155 S yr 6.02 1.57 _ — — (1986) Total sample size=20,217 Median followup Average Average Average Average Average Average sample size=1,348 period=2 yr weight gain weight gain G of quitters % of continuing relative risk Number of studies reported=15 among among who gain smokers who of gaining quitters=4.6; continuing weight=79% ¢ gain weizht=56%> weight=1.45: N=4.647 smokers=0.8: Number of Number of Number of N=15.046 studies reporting=5; studies studies “N=214 reporting=5; reporting=5; N=1113 N=1 327 NOTE: Averages are weighted for differing sample sizes.