Eur J Epidemiol (2013) 28:35–43 DOI 10.1007/s10654-012-9758-7
MORTALITY
Body mass index, smoking, and risk of death between 40 and 70 years of age in a Norwegian cohort of 32,727 women and 33,475 men Vidar Hjellvik • Randi Selmer • Ha˚kon Kristian Gjessing • Aage Tverdal Stein Emil Vollset
•
Received: 19 October 2012 / Accepted: 20 December 2012 / Published online: 22 January 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract Overweight-obesity and smoking are two main preventable causes of premature death. Because the relationship between smoking and body mass index (BMI) complicates the interpretation of associations between BMI and death risks, direct estimates of risks associated with joint exposures are helpful. We have studied the relationships of BMI and smoking to middle age (40–69 years) death risk—overall and by causes—in a Norwegian cohort of 32,727 women and 33,475 men who were 35–49 years old when baseline measurements and lifestyle information were collected in 1974–1988. Individuals with a history of cancer, cardiovascular disease or diabetes at baseline were excluded. Mortality follow-up was through 2009. The relationship between BMI and middle age death risk was U-shaped. Overall middle age death risks were 11 % in women and 21 % in men. The combination of obesity and heavy smoking resulted in fivefold increase in middle age death risks in both women and men: For women middle age death risk ranged from 6 % among never smokers in the 22.5–24.9 BMI group to 31 % (adjusted 28 %) in obese (BMI [ 30 kg/m2) heavy smokers (C20 cigarettes/day). The corresponding figures in men were 10 % and 53 % (adjusted 45 %). Obese never smokers and light (1–9 cigarettes/day) smokers in the 22.5–24.9 BMI groups both Electronic supplementary material The online version of this article (doi:10.1007/s10654-012-9758-7) contains supplementary material, which is available to authorized users. V. Hjellvik (&) R. Selmer H. K. Gjessing A. Tverdal S. E. Vollset Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, N-0403 Oslo, Norway e-mail:
[email protected] H. K. Gjessing S. E. Vollset University of Bergen, P.O. Box 7800, 5020 Bergen, Norway
experienced a twofold increase in middle age risks of death. For women, cancer (56 %) was the most common cause of death followed by cardiovascular disease (22 %). In men, cardiovascular disease was most common (41 %) followed by cancer (34 %). Cardiovascular disease deaths were more strongly related to BMI than were cancer deaths. Keywords Body mass index Smoking Middle age death risk Cause specific death risk Cohort study Norway
Introduction Smoking and overweight-obesity [body mass index (BMI) C25; weight in kilograms divided by the square of height in meters] are major preventable causes of death in men and women under 70 years of age in the United States in 2005 [1]. Whereas smoking prevalence has decreased in developed countries since 1975 [2], increasing numbers of men and women are overweight or obese [3]. In the United States 36 % of adult men and women are obese (BMI C 30) [4]. The epidemic of overweight and obesity has received wide attention, and a series of studies have reported on the relation between BMI and all-cause and cause-specific mortality [5–7]. In 2009 a large collaborative study of 900,000 adults—mainly in western Europe and North America—reported increased mortality associated with both under- and over-weight for a variety of causes of death [8]. Similar associations have been found in Japanese, Chinese, and Korean populations [9–12], but one study concluded that overweight and obesity was not associated with increased death rate in Indians and Bangladeshis [12]. Some studies have also investigated the combined effect of smoking and high BMI [13–17],
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concluding that obese smokers had notably higher mortality risk, in particular for CVD deaths. In the current study we assess associations between BMI and smoking and premature deaths between 40 and 70 years of age in men and women. Whereas most other studies have focused on relative risk estimates, we also present direct estimates of the middle age (40–69 years) absolute death risk, overall and by causes [18], which makes it easier to understand the impact of the risk factors on premature mortality. Many large studies on BMI and mortality have not accounted for the intricate relationships of BMI and smoking as risk factors. Therefore we focus on the combined effect of smoking and BMI on middle age death risk. Data are from the Norwegian Counties Studies. Linkage to the Cancer Registry of Norway allowed us to exclude individuals who were diagnosed with cancer before the baseline examination or during the first year of follow-up. We also excluded individuals with pre-existing cardiovascular disease and diabetes.
Methods Study population Between 1974 and 1978, all 35–49 years old residents of the three rural Norwegian counties Oppland, Sogn og Fjordane, and Finnmark, were invited to a cardiovascular health screening examination, and 89 % chose to participate. Data on risk factors and other relevant information were obtained, partly by measurements (e.g. height and weight) and partly by use of questionnaires (e.g. smoking and physical activity). About 5 and 10 years after the first examination, the same individuals were invited to followup surveys where information on the same variables was obtained. In addition, some residents of the same three counties who reached 35 years between the first and the second/third survey were invited to these surveys. Only subjects who were between 35 and 49 years old the year a survey started in the county in which they resided, and who had at least one valid BMI measurement, were eligible for inclusion in our current study (37,149 men and 36,080 women). Of these, we excluded 7,027 participants for various reasons (see eMethods in Online Resource). Using data obtained by individual linkage to the Cancer Registry of Norway, 1,524 subjects who received a cancer diagnosis between 1953 and 1 year after the first examination with valid BMI measurement (start of follow-up) were excluded. We also excluded individuals who reported a history of cardiovascular disease or diabetes, and all individuals with missing values for diabetes/cardiovascular history or for one or more of the covariates entered in regression
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models (see below) were excluded. Thus, 66,202 persons (33,475 men and 32,727 women) remained for analysis. We also studied the effect of the health-related exclusions by comparing survival curves for the study populations with (n = 66,202) and without (n = 71,158) the health related exclusions applied. Mortality follow-up Mortality follow-up was through the year 2009. The health survey data for each individual were linked to the Cause of Death Registry kept by Statistics Norway that contains date and underlying cause of death. The deaths were classified in seven categories using the European short-list for causes of death (ESD) [19] and the International classification of diseases (ICD8-10): lung cancer (ESD 15), breast cancer (ESD 17), other cancer (ESD 7,except 15 and 17), cardiovascular disease (ESD 33), external causes (accidents and violence; ESD 58), diseases in the respiratory system including tuberculosis in the lungs (ESD 37 plus ICD8/9 010-012 and ICD10 A15-16) and other disease illness (the remaining ESD codes except 55: ‘‘symptoms, signs, abnormal findings, ill-defined causes’’). Deaths with ESD 55 were proportionally distributed on the seven categories when calculating cause-specific mortality (see eMethods in Online Resource for details). A total of 325 individuals emigrated in the follow-up period, and were censored on the date of emigration. Average follow-up time was 25 years. Study variables Height and weight were measured to the nearest cm and kg, respectively, using standardized methods, and the body mass index (BMI) was calculated as weight (kg) divided by height squared (m2), and categorized into 7 groups: \20, 20–22.4, 22.5–24.9, 25–27.4, 27.5–29.9, 30–32.4, and C32.5 kg/m2. For subjects having two or three valid BMI measurements, the first was used. Information on smoking was obtained by a self-administered questionnaire. Smoking habits were categorized into seven groups according to daily use of cigarettes: 0 (neversmokers), 1–9, 10–19, 20? for current smokers, and 1–9, 10–19, 20? for former smokers. Note that since ‘smoking’ is defined by ‘daily smoking’ in this study (the questionnaires only contained questions about daily smoking), the group of never-smokers includes occasional smokers. For subjects attending several surveys, we used the information from the same survey as the first valid height and weight (BMI) measurements. Information that was missing for a given subject in this particular survey, entered the analysis as ‘missing’ even if it was available from another survey. To contrast groups with extreme combinations of smoking habits and BMI we compared never-smokers with
Body mass index, smoking, and risk of death
37
BMI of 22.5–24.9 to obese (BMI C 30) current heavy smokers (C20 cigarettes/day) and underweight (BMI \ 20) current heavy smokers. In regression analyses we included year of birth, county of residence, educational level, and marital status in the models in addition to BMI and smoking. Education level was obtained by linkage to census information obtained by Statistics Norway in 1970, 1980 and 1990. We used the highest reported education from these three census years, and used 6 levels, ranging from elementary school (9 years) or less to higher university education (C17 years). See eMethods in Online Resource for details. Marital status was obtained from the Central Population Registry and dichotomized into married and unmarried (including divorced and widowed). Baseline levels of total cholesterol, triglycerides, and blood pressure were measured at each survey as described previously [20], and leisure time physical activity during the last year was reported on questionnaires on each survey as a four-level variable: (1) sedentary, (2) walking/biking etc. at least 4 h/week, (3) moderate exercising at least 4 h/ week, or (4) regular hard exercising/competition (see eMethods in Online Resource for details).
model with the 22.5–24.9 BMI group as reference. Adjustments were made for year of birth (5-year grouping), smoking, education, marital status (all categorized as described in the covariate section), and county of residence.
Statistical analysis
Middle age death risk
Survival
A total of 3,232 women and 6,224 men died during followup through 2009. The middle age (40–69 years) death risk was 11 % in women and 21 % in men (Table 2). The relationship between BMI and middle age death risk was U-shaped (Fig. 1—left panels). Across BMI categories, the lowest middle age death risks for both women (10 %) and men (19 %) were observed in the 22.5–24.9 BMI-group (Table 2). Middle age death risk was 16 and 33 % in women and men with BMI under 20, and 18 % (women) and 36 % (men) among individuals with BMI of 32.5 or above. Adjustments lowered these risk estimates only moderately (Table 2). Our data also allowed us to compare the strength of associations of smoking and BMI to middle age death risk. For example, compared to never smokers in the 22.5–24.9 BMI group, both light smokers (1–9 cigs/d) in the 22.5–24.9 BMI group and obese never smokers experienced similar increases in middle age death risks (1.7–1.9 fold for women and 2.1 fold for men; Fig. 2; Table 3).
Kaplan–Meier survival curves from 40 to 70 years were estimated separately for men and women and for each BMIcategory with age as the time scale. The curves started at 100 % at age 40 since the subjects that emigrated or died before reaching 40 were excluded. The survfit function of R, version 2.11.0, was used for the computations. We calculated adjusted survival by first predicting survival probabilities for each individual from the Cox model with covariates (year of birth, education, marital status, and smoking) and second averaging predicted individual survival for all observed covariate combinations [21, 22]. Cause-specific mortality Cause-specific probabilities of death between 40 and 70 years of age were calculated separately for men and women for each BMI group in a competing risk framework [23]. Confidence intervals were calculated using the bootstrap. See eMethods in Online Resource for details. Middle age death risk ratios Middle age death risk (hazard) ratios for the different BMI groups were estimated using the Cox proportional hazards
Results Baseline characteristics We studied 32,727 women and 33,475 men who were 35–49 years old when they attended cardiovascular health screening examinations between 1974 and 1988. Table 1 and eFig. 1 in Online Resource show baseline characteristics of the participants and associations of body mass index to these characteristics and risk factors for adult disease. There was a strong gradient in prevalence of smoking by BMI category. In particular, people with BMI below 20 or in the lower range of the 20–25 BMI group smoked more than those in the upper BMI groups. For men in particular, there was a strong relation between previous smoking and overweight-obesity (Table 1).
Risks of middle age death associated with combined levels of BMI and smoking The combination of obesity and heavy smoking (C20 cigs/ day) gave fivefold increases in middle age death risk. In women middle age death risk ranged from 6 % in never smokers in the 22.5–24.9 BMI group to 31 % (adjusted
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Table 1 Baseline characteristics of the 66,202 participants aged 35–49 years by body mass index Characteristics
Body mass index (kg/m2) \20.0
20.0–22.4
All 22.5–24.9
25.0–27.4
27.5–29.9
30.0–32.4
C 32.5
Women Participants (No.)
2,305
8,697
9,940
5,833
3,011
1,533
1,408
32,727
Never smokers, %
36.0
44.1
47.6
51.7
54.7
56.2
55.5
48.0
Former smokers, %
9.8
13.3
15.6
14.9
14.4
13.1
14.3
14.2
Current smokers, %
54.3
42.6
36.9
33.3
30.8
30.7
30.3
37.9
Physical activity, sedentary, %
22.0
19.0
19.2
20.8
25.0
26.4
31.1
21.0
Not married, % Low education level, %
16.6 39.3
12.0 38.4
10.9 42.2
11.4 47.1
11.7 52.3
12.6 55.4
14.6 59.4
12.0 44.2
Total cholesterol (mmol/L)a,b
5.8
5.9
6.1
6.2
6.4
6.4
6.5
6.1
HDL cholesterol (mmol/L)a,b,c
1.6
1.6
1.5
1.5
1.4
1.4
1.3
1.5
Triglycerides (mmol/L)a,d
1.1
1.2
1.3
1.4
1.6
1.8
1.9
1.3
Systolic blood pr. (mmHg)a,e
123.9
125.5
127.7
131.0
134.4
138.5
142.1
129.2
Men Participants (No.)
737
5,051
11,330
9,626
4,637
1,510
584
33,475
Never smokers, %
17.2
23.0
26.7
26.5
24.9
25.0
23.6
25.5
Former smokers, %
10.4
15.8
23.0
27.9
30.1
29.8
31.2
24.5
Current smokers, %
72.3
61.3
50.3
45.6
45.0
45.2
45.2
50.1
Physical activity, sedentary, %
23.2
16.8
16.0
17.7
21.4
25.8
31.7
18.2
Not married, %
25.0
19.0
15.9
16.6
18.5
23.6
30.1
17.7
Low education level, %
46.3
40.3
38.9
41.8
46.3
48.9
50.0
41.8
Total cholesterol (mmol/L)a,b
6.0
6.0
6.2
6.4
6.6
6.7
6.8
6.3
HDL cholesterol (mmol/L)a,b,c Triglycerides (mmol/L)a,d
1.4 1.5
1.3 1.6
1.3 1.8
1.2 2.1
1.1 2.5
1.1 2.9
1.0 3.3
1.2 2.0
Systolic blood pr. (mmHg)a,e
130.0
131.6
133.6
135.9
138.4
141.7
146.8
135.2
Norwegian three counties studies 1974–1988 Cigs cigarettes, HDL high-density lipoprotein a
Mean values
b
To convert cholesterol from mmol/L to mg/dl, multiply by 39
c
HDL-cholesterol is missing for 72 % of the study population
d
To convert triglycerides from mmol/L to mg/dl, multiply by 89
e
To convert blood pressure from mmHg to kPa, multiply by 0.133
28 %) in obese heavy smokers. The corresponding figures in men were 10 and 53 % (adjusted 45 %) (Table 3). Particularly in men the combination of low BMI (under 20) and heavy smoking was associated with high middle age death risk (50 %; adjusted 45 %). Middle age death risks by causes of death For women, cancer (56 %) was the most common cause of death in middle age followed by cardiovascular disease (22 %). In men, cardiovascular disease deaths accounted for 41 % of the middle age mortality and cancer deaths for 34 % (eTable 1 in Online Resource). The middle age cardiovascular disease death risk increased with increasing BMI from the reference group of
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22.5–24.9. In women the increase was from 2 % (22.5–24.9 BMI group) to 5 % points (BMI of 32.5 or higher). The corresponding figures in men were 7 and 17 % points (Fig. 1 and eTable 1 in Online Resource). There was also an increase in middle age death risks for respiratory diseases, but not lung cancer, in individuals with BMI of 32.5 and above compared to the 22.5–24.9 BMI group. The relative risks were 2.4 for women and 2.6 for men (adjusted estimates) (eTable 2 in Online Resource). This risk increase was not present in overweight or moderately obese (BMI 30–32.4) individuals. Furthermore there were significant risk elevations by BMI increases in cancers other than lung- and breast cancer among women, and in noncancer-non-cardiovascular diseases other than respiratory diseases in men (eTable 2 in Online Resource).
Body mass index, smoking, and risk of death
39
Table 2 Risk of middle age death (between 40 and 70 years) by body mass index Body mass index (kg/m2)
All
\20.0
20.0–22.4
22.5–24.9
25.0–27.4
27.5–29.9
30.0–32.4
C 32.5
315
821
847
539
308
185
217
3232 11.2 (10.9–11.6)
Women Deaths (No.)
Risk (%) of middle age death (95 % CI) Unadjusted
15.8 (14.2–17.4)
10.8 (10.1–11.5)
9.7 (9.1–10.4)
10.4 (9.6–11.3)
11.4 (10.1–12.6)
13.5 (11.6–15.3)
17.6 (15.4–19.8)
Adjusteda
13.8
10.5
9.7
10.6
11.8
13.6
17.4
Hazard ratio (95 % CI) Unadjusted
1.7 (1.5–1.9)
1.1 (1.0–1.2)
REF
1.1 (1.0–1.2)
1.2 (1.1–1.4)
1.4 (1.2–1.7)
1.9 (1.6–2.2)
Adjustedb
1.5 (1.3–1.7)
1.1 (1.0–1.2)
REF
1.1 (1.0–1.2)
1.2 (1.1–1.4)
1.4 (1.2–1.7)
1.9 (1.6–2.2)
210
959
1851
1686
949
393
176
6224 21.3 (20.8–21.7)
Men Deaths (No.)
Risk (%) of middle age death (95 % CI) Unadjusted
33.0 (29.1–36.6)
21.5 (20.2–22.7)
18.6 (17.8–19.3)
20.0 (19.1–20.9)
23.8 (22.5–25.2)
30.3 (27.7–32.8)
35.9 (31.4–40.2)
Adjusteda
26.5
19.7
18.5
20.2
23.3
28.3
32.2
Hazard ratio (95 % CI) Unadjusted 1.9 (1.6–2.2) Adjustedb
1.5 (1.3–1.8)
1.2 (1.1–1.3)
REF
1.1 (1.0–1.2)
1.3 (1.2–1.4)
1.7 (1.6–1.9)
2.1 (1.8–2.4)
1.1 (1.0–1.2)
REF
1.1 (1.0–1.2)
1.3 (1.2–1.4)
1.6 (1.5–1.8)
1.9 (1.7–2.3)
Follow-up of Norwegian three counties studies 1974–2009 CI confidence interval a
Adjusted for county, year of birth (5-year groups), education, marital status, and smoking by averaging predicted individual survival for all observed covariate combinations
b
Adjusted for county, year of birth (continuous), education, marital status, and smoking
The upturn in middle age death risk in the low BMI (\20) group was strongest for respiratory disease and external causes. It was only moderate for lung cancer (Fig. 1, and eTable 2 in Online Resource). For the group with BMI\20 the relative death risks were typically reduced substantially after adjusting for smoking habits, education, marital status, county, and birth year, whereas for the 32.5 and above BMI group, adjustment had less impact on relative death risks (eTable 2 in Online Resource). Exclusion of individuals with pre-existing disease To assess the impact of exclusion of individuals with a history of cancer (including cancer diagnosed in the first year of follow-up), cardiovascular disease and diabetes, we estimated survival curves for the cohorts with and without exclusions applied. As can be seen from eFigure 2 in Online Resource these exclusions had only minor impact on overall death risks observed by smoking and BMI categories.
Discussion In this prospective cohort study of Norwegian men and women followed for 24 years, both overweight-obesity and
smoking had substantial impact on middle age death risk. The combination of heavy smoking and obesity was associated with particularly high middle age death risks in both men and women. There was a U-shaped association between BMI and mortality with lowest middle age death risks in the 22.5–24.9 BMI group. The main strengths of the study were the high participation and complete mortality follow-up for an average of 24 years. With individual linkage to the Cancer Registry of Norway, we were able to exclude all participants who had had a cancer diagnosis between 1953 and 1 year after start of follow-up. Individuals with cardiovascular disease and diabetes were excluded based on self-report at baseline examination. The impact of these exclusions on the death risks were, however, minor, and similar in the various BMI and smoking groups. To check whether the mortality upturn at low BMI could be due to reverse causation, i.e. weight loss due to pre-existing disease, we excluded 514 deaths during the first 5 years of follow-up, resulting in almost identical BMI-death relationships as in the main analysis (data not shown). This support the view of Flegal et al. [24] that reverse causation is not an important cause of mortality upturn at low BMI. A limitation of the study is that changes in BMI and smoking habits during follow-up (24 years on average) were not taken into account. Thus, there is probably an
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30.0-32.4
>32.5
27.5-29.9
25.0-27.4
22.5-24.9
>32.5
0 30.0-32.4
0
External causes Other diseases Respiratory CVD Other cancer Breast cancer Lung cancer
<20
0
>32.5
10
30.0-32.4
10
27.5-29.9
10
25.0-27.4
20
22.5-24.9
20
<20
20
20.0-22.4
30
>32.5
30
30.0-32.4
30
27.5-29.9
40
25.0-27.4
40
22.5-24.9
40
<20
Male never-smokers
50
27.5-29.9
Male current smokers
50
All males
25.0-27.4
0
22.5-24.9
0
<20
0
20.0-22.4
5
>32.5
5
30.0-32.4
5
27.5-29.9
10
25.0-27.4
10
22.5-24.9
10
<20
15
20.0-22.4
15
>32.5
15
30.0-32.4
20
27.5-29.9
20
25.0-27.4
20
22.5-24.9
25
<20
25
20.0-22.4
25
50
Female never-smokers
30
20.0-22.4
Female current smokers
30
All females
20.0-22.4
Probability of dying between 40 and 70
30
2
BMI (kg m ) Fig. 1 Middle age (40–69 years) death risk (%) by BMI group, smoking, and cause of death with 95 % confidence intervals (based on 200 bootstrap replicates) for total mortality. The numbers behind the figure are given in eTable 1 in Online Resource. 399 deaths with ESD 55 were proportionally redistributed
underestimation of the effect of smoking on middle age death risk that is due to smoking cessation among study participants during the two last decades of follow-up. The smoking prevalence in Norway in the age group 16–74 years fell from 50 % in men and 30 % in women in 1973 to 20 % in both men and women in 2009 (Statistics Norway). We had, however, data from up to three surveys of the same individuals. Analyses of changes from first to third survey showed that the BMI categories were very stable. For individuals who took part in the first and third survey (n = 29,174) there was on average an increase of 1 BMI unit over the 10 year period in all categories except in the highest BMI group where a lesser increase was observed.
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The smoking habits were less stable. Some participants had stopped smoking and some had increased the number of cigarettes smoked daily from first to third screening. We calculated middle age death risks with updated smoking habits when available (using cigarettes per day as a time dependent covariate), but observed only non-important changes in the results. Our findings of a U-shaped association between body mass index and middle age death risk are in accordance with previous study findings [25–27]. The results for cause specific middle age death risks accord with the recent Prospective studies collaboration 2009 [8]. A strikingly high death risk in obese smokers has also been reported in other studies [13, 14, 28]. What the present study adds, is a
Body mass index, smoking, and risk of death
41
Fig. 2 Kaplan-Meier survival curves showing the percentage of women and men who were alive in the age range of 40–69 years for selected combinations of BMI and smoking
direct estimate of middle age death risk according to combinations of BMI and smoking habits. One previous study with follow-up from 1948 to 1990 of the Framingham study participants used the same metric (40–69 years death risk) in categories of smoking and BMI [15]. Absolute risks of middle age death by obesity and smoking were remarkably similar despite the different setting and calendar periods of follow-up. However, our estimates were based on much larger number of events, and we additionally partitioned the absolute middle age death risks into main cause-of-death groups. As expected from other studies [7, 8, 29–31] there was a positive association between high BMI levels and middle age deaths from cardiovascular diseases. In women we observed increased middle age death risk from cancer other than lung- and breast cancer. This is in accordance with a recent review [32]. It is established that women with high BMI have increased risk of several cancers including breast
cancer and colorectal cancer [32], but in our study the death risk from breast cancer did not increase with BMI. In men we observed an increase in death risk from non-cancer-non-cardiovascular diseases other than respiratory diseases. This is in accord with other studies [33, 34]. Many studies have reported an upturn in mortality at low levels of BMI, most pronounced in smokers [7, 8, 29, 30]. Possible explanations are residual confounding by smoking [7] and reverse causation by preexisting disease. We confirmed the former explanation as confounding adjustment decreased the excess risks at low BMI notably more than at high BMI levels. Our exclusion of previous cancer and preexisting disease coupled with long (upto 30 years) follow-up strongly counters the reverse causation hypothesis. The upturn at low BMI was mainly associated with deaths from respiratory diseases, non-cancer-non-cardiovascular other diseases, and external causes. These inverse associations are not fully explained, but one may speculate
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Table 3 Risk of middle age death (between 40 and 70 years) by selected combinations of body mass index and smoking Body mass index (kg/m2) and smoking status Smoking: BMI:
Never 22.5–24.9
Never C 30
1–9 cigs/day 22.5–24.9
C 20 cigs/day \20
C 20 cigs/day 22.5–24.9
C 20 cigs/day C 30
263
174
161
23
68
27
Women Deaths (No.)
Risk (%) of middle age death (95 % CI) Unadjusted 6.2 (5.4–6.9) 11.7 (10.0–13.4) Adjusteda
6.5
10.9
12.6 (10.7–14.4)
24.2 (14.5–32.8)
24.9 (19.2–30.2)
31.0 (19.7–40.7)
11.7
22.5
22.5
27.5
Hazard ratio (95 % CI) Unadjusted
REF
1.9 (1.6–2.3)
2.0 (1.7–2.5)
3.9 (2.6–6.0)
4.1 (3.1–5.3)
5.4 (3.7–8.1)
Adjustedb
REF
1.7 (1.4–2.1)
1.9 (1.5–2.3)
3.8 (2.5–5.9)
3.8 (2.9–5.0)
4.8 (3.2–7.2)
255
96
230
60
386
144
Men Deaths (No.)
Risk (%) of middle age death (95 % CI) Unadjusted
9.7 (8.5–10.8)
21.9 (17.8–25.7)
22.1 (19.5–24.6)
50.5 (40.3–58.9)
30.4 (27.8–33.0)
52.7 (46.0–58.5)
Adjusteda
10.2
20.4
20.7
45.1
29.3
44.8
Hazard ratio (95 % CI) Unadjusted
REF
2.4 (1.9–3.0)
2.4 (2.0–2.9)
6.5 (4.9–8.6)
3.6 (3.1–4.2)
6.8 (5.5–8.3)
Adjustedb
REF
2.1 (1.7–2.7)
2.1 (1.8–2.6)
5.6 (4.2–7.5)
3.3 (2.8–3.8)
5.6 (4.5–6.9)
Follow-up of Norwegian three counties studies 1974–2009 BMI body mass index, Cigs cigarettes CI confidence interval a
Adjusted for county, year of birth (5-year groups), education, and marital status by averaging predicted individual survival for all observed covariate combinations
b
Adjusted for county, year of birth (continuous), education, and marital status
that underweight smokers could be more susceptible to infections and other diseases of the airways. The study cohort was established in 1974–1988. Only 4 % of the women and 2 % of the men were in the highest BMI category of 32.5 or above. The prevalence of obesity was also moderate, 9 % among women and 6 % among men. The BMI levels have since increased in most countries including Norway [3, 35, 36]. Thus our severe obesity group will have lower mean BMI compared to corresponding groups today, in particular in the US. Accordingly, our estimates of the effect of BMI greater than 32.5 are likely to be too low. Still the combination of heavy smoking and obesity in our study was associated with dramatically increased middle age death risk (fivefold). However, advances in medical treatment, in particular of cardiovascular disease in the decades since this study was initiated, would tend to lower the cardiovascular middle age death risk of a 40 year old obese person today [37]. Our mortality follow-up data of 66,000 middle aged women and men over a 35-year period from 1974 to 2009 showed that the combination of obesity and smoking dramatically increased middle age (40–69 years) death risks in both men and women. Knowledge of the deadly danger of combined obesity and smoking may motivate individuals
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