Weight change, body weight and mortality: the impact of smoking and ill health

SG Wannamethee, AG Shaper and M Walker

Department of Primary Care and Population Sciences, Royal Free Hospital School of Medicine, Rowland Hill St, London NW3 2PF, UK. E-mail: goya{at}pcps.ucl.ac.uk

Abstract

Objectives This paper examines the influence of cigarette smoking and ill health on the relationship between weight change, body weight and subsequent mortality to determine whether weight loss and leanness in middle to older age is deleterious to health.

Methods Men aged 40–59 years at screening drawn from one general practice in each of 24 British towns, who completed a questionnaire 5 years after screening (Q5) and provided full information on changes in weight and smoking status (n = 7065) were then followed up for an average of 13.8 years.

Results In all men a shallow U-shaped relationship was seen between body mass index (BMI) at Q5 and all-cause mortality rates. Weight loss and substantial weight gain (>=10%) were associated with increased mortality rates compared to the stable weight group. The increased risk associated with weight loss was seen in long- term non-smokers (n = 4101) and recent ex-smokers (n = 722) but not in current smokers (n = 2242) after adjustment for a wide range of potential confounders. However, the increased risk was markedly attenuated after exclusion of those with ill health (relative risk [RR] = 1.16, 95% CI : 0.84–1.59 and RR = 0.79, 95% CI : 0.29–2.20 for long-term non-smokers and recent ex-smokers, respectively). Moderate weight gain (4–10%) was associated with lower risk of mortality than observed in those with stable weight but only in recent ex-smokers and in current smokers, not in long-term non-smokers. A positive association was seen between BMI at Q5 and all-cause mortality in non-smokers and this was strengthened by exclusion of men with weight loss.

Conclusion The increased risk of mortality associated with weight loss or low body weight in middle-aged and older men appears to be a direct consequence of ill health leading to weight loss and leanness. In healthy non-smoking men weight loss and leaness are not associated with increased mortality and moderate weight gain (4–10%) was neither deleterious nor beneficial.

Keywords Weight change, weight loss, body weight, smoking, mortality

Accepted 14 August 2000

The relationships between weight change, body weight and mortality have been of much concern in recent years. Weight loss and leaness have both been associated with increased mortality19 and there is controversy regarding the public health implications of these findings. It has been suggested that the increased mortality may reflect confounding by smoking and by pre-existing illness associated with weight loss. Most studies on weight change and mortality have attempted to address this by controlling for smoking in multivariate analyses and by excluding men with pre-existing disease (variously defined) or early death. Despite these adjustments most studies still support the basic finding that weight loss is associated with increased mortality.6 The limitations of these studies and the adequacy of these approaches have been questioned.9 Given the strong relationship between smoking and body weight10 and given that the relations between body mass index (BMI) and mortality in this and other cohorts differs in smokers and non-smokers,1113 adjustment for smoking status in multivariate analyses may not take into account adequately the effects of smoking experience. Only a few studies have reported on stratification by smoking status and their results have been inconsistent.1,4,8,12,14 In two recent studies that have stratified by smoking status and excluded subjects with pre-existing disease, no increased risk was observed with weight loss in healthy men12 and women14 who had never smoked, suggesting that the increased mortality associated with weight loss may be a result of confounding.

An earlier report from the British Regional Heart Study, a large prospective study of middle-aged men, examined weight change in relation to subsequent 4-year mortality.2 The present paper, using much longer follow-up (13.8 years) and many more deaths enables us to address several of the methodological issues concerning the confounding role of smoking and pre-existing disease on body weight, weight loss and mortality. The aim of this paper is to (i) examine the relationship between weight change and mortality stratified by smoking, taking into account detailed information on current smoking patterns and changes in smoking patterns and both pre-existing disease and early death, and (ii) to assess the relationship between body weight and mortality taking weight loss into account. Such information may provide a better understanding of the relationship between BMI and mortality in older age.

Subjects and Methods

The British Regional Heart Study (BRHS) is a prospective study of cardiovascular disease involving 7735 men aged 40–59 years selected from the age-sex registers of one group general practice in each of 24 towns in England, Wales and Scotland and examined January 1978–July 1980. Men with pre-existing cardiovascular disease or on regular medical treatment were not excluded. The overall response rate was 78%. The criteria for selecting the town, the general practice and the subjects as well as the methods of data collection have been reported.15 Research nurses administered to each man a standard questionnaire (Q1) which included questions on smoking habits, alcohol intake and medical history. Physical measurements including height and weight were made, and blood samples (non-fasting) were taken for measurement of biochemical and haematological variables. Classification methods for smoking status, alcohol intake, social class and BMI have been reported.13

Five years after the initial examination (1983–1985), a postal questionnaire (Q5) similar to the one administered at screening, was sent to all surviving men and detailed information obtained on medical history, changes in smoking and drinking behaviour and in other risk factors including body weight. This report is initially concerned with the 7275 men, 98% of the available survivors, who completed the fifth-year questionnaire.

Body mass index
At initial examination weight and height were measured and BMI, calculated as weight/height2 (kg/m2), was used as an index of relative weight. Five years later (Q5) the men were asked to state their weight in pounds or kilograms and BMI was calculated for each man based on their reported weight and on measured height at initial screening. Obesity is defined as BMI >=28 kg/m2 which represents the top quintile of the BMI distribution in all men at baseline. Reported BMI at Q5 was used to examine the relationship between body weight and mortality on subsequent follow-up as this allowed us to take into account weight change occurring in the 5 years between screening and Q5. The men were grouped into six categories on the basis of their BMI levels <20, 20–21.9, 22.0–23.9, 24.0–25.9, 26.0–27.9 and >=28.0 kg/m2.

Measures of weight change
An index for weight change was determined for each man calculated as the percentage change in body weight between screening (Q1) and Q5.2 Those with weight loss were defined as men who had lost >=4% in body weight; weight gain was defined as those who had gained >=4% or more in body weight. Those who gained or lost less than 4% in body weight were classified as stable. The men were grouped into four weight change categories (i) weight loss (ii) stable (iii) gain of 4–10% and (iv) gain of >10% in body weight. Complete information on weight change was available in 7100 men.

Cigarette smoking status
At Q1 the men were classified as those who had never smoked, ex-cigarette smokers and current smokers. At Q5 the men were asked whether they were currently smoking or not and the number of cigarettes they smoked. Those who had only ever smoked pipe or cigars were classified as never-smoked. Ex-cigarette smokers who smoked pipe or cigars were regarded as ex-cigarette smokers. Complete information on smoking habits at Q1 and Q5 was not available for 35 men and they have been excluded from the analyses leaving 7065 men. From the combined information on cigarette smoking obtained at screening and 5 years later the men were classified into four groups: (i) Never-smoked (n = 1709); (ii) Long-term ex-cigarette smokers—ex-cigarette smokers at screening and who were not smoking 5 years later (n = 2392); (iii) Recent ex-cigarette smokers—men who gave up cigarette smoking between baseline and Q5, i.e. ex-cigarette smokers at Q5 (n = 722); (iv) Current cigarette smokers at Q5. This included 2099 smokers at baseline who remained current cigarette smokers at Q5 as well as 143 non-cigarette smokers at baseline (predominantly ex-smokers) who were smoking cigarettes at Q5 (n = 2242).

In the analyses stratified by smoking status (Tables 2 and 5GoGo), groups (i) and (ii) have been combined (long-term non-smokers). Measurements of serum cotinine for validation of baseline smoking status were not available but blood cadmium level measured at screening and considered to be a strong biological marker of smoking has been shown to be strongly associated with smoking status in this cohort.16


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Table 2 Weight change over 5 years and subsequent mortality over 13.8 years (mean) follow-up in 4101 men who were non-smoking at baseline and Q5a
 

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Table 5 Body mass index (BMI) (Q5) and adjusted relative risk of total mortality by smoking status in 7065 men. (A) Adjusted for age, social class, alcohol intake, physical activity, forced expiratory volume in one second (FEV1) and ex-smoking status/number of cigarettes smoked at baseline. (B) Adjusted for above and excluding 995 who had lost weight
 
Confounding variables
Adjustments for confounders were primarily based on risk factors assessed at initial screening (Q1) prior to the weight change.

Social class
The longest held occupation of each man was recorded at screening and the men were grouped into one of six social classes: I, II, III non-manual, and III manual, IV and V. Those whose longest occupation was in the Armed Forces formed a separate group.

Physical activity
A physical activity score was derived for each man based on frequency and type of activity in leisure time reported at initial screening and the men were grouped into six broad categories based on their total score: inactive, occasional, light, moderate, moderately-vigorous and vigorous.17

Alcohol intake
The men were classified into five groups based on estimated weekly intake at Q1: none, occasional, light, moderate and heavy drinkers.18 Regular drinkers at Q1 who became non-drinkers at Q5 (recent ex-drinkers) were separated, as giving up drinking is associated with ill health and increased risk of mortality.19 Heavy drinking is defined as drinking >6 units (1UK unit = 8–10 g alcohol) daily or on most days.

Lung function
Forced expiratory volume in one second (FEV1) was measured at baseline with a Vitalograph spirometer with the subject seated. The FEV1 measurements were height standardized to 1.73 m, the average height of the men in the present study.

Measures of ill health
Self-perception of health
At Q5 the men were asked to describe their present health status—excellent, good, fair or poor.

Doctor diagnoses
At both the initial screening (Q1) and 5 years later (Q5) men were asked whether a doctor had ever told them that they had angina or myocardial infarction (heart attack, coronary thrombosis), stroke, diabetes and a number of other disorders.

Illness and injury
At Q5 the men were asked if they had in the last 5 years had any illness or injury which has kept them off work for more than one month and if yes, how many times—once, twice or three or more times.

Follow-up
All men, whether or not they had evidence of cardiovascular disease at initial examination, have been followed up for all-cause mortality and for cardiovascular morbidity from the initial screening in 1978–1980.20 All deaths occurring in the period up to December 1997 have been recorded and follow-up has been achieved for 99% of the cohort. This report is concerned only with the 7065 men who had complete information on weight change and smoking status at Q5 and with mortality subsequent to Q5, a mean follow-up period of 13.8 years (range 12.5–15 years). Information on death was collected through the established ‘tagging’ procedures provided by the National Health Service registers in Southport (England and Wales) and Edinburgh (Scotland).

Statistical methods
The Cox proportional hazards model21 was used to assess the independent contributions of weight change and BMI to the risk of mortality. Because of (i) the non-linear relationship between weight change and mortality, (ii) the possible differing relationship between weight change by smoking status and (iii) because one would not necessarily expect a graded change in risk from the continuum of weight change from maximum weight loss to maximum weight gain we have grouped the men into weight change categories and presented grouped data. This makes no assumption of any linear relationship. Hazard ratios for mortality were obtained for specific levels of weight change using the stable group as the reference group. However, where appropriate we have tested for curvilinear trends (presence of a U-shaped curve) by fitting linear and quadratic terms using weight change as a continuous variable (negative values for weight loss and positive values for weight gain). In the adjustment, age and FEV1 were fitted as continuous variables. Physical activity (six levels), alcohol intake (six levels) and social class (seven groups) were fitted as categorical variables. Because of the non-linear relationship between BMI and mortality we have divided the men into groups on the basis of their BMI levels. However, tests for linear or quadratic trends for BMI were assessed fitting BMI in its original continuous form. Direct standardization was used to obtain age-adjusted rates per 1000 person-years using the study population as the standard.

Results

During the mean follow-up period of 13.8 years from Q5 in the 7065 men with complete data on weight change and smoking status there were 1457 deaths from all causes (722 cardiovascular, 735 non-cardiovascular causes), a crude rate of 16.6/1000 person- years. The average BMI at screening was 25.5 kg/m2 (SD 3.37) and this rose to 25.8 kg/m2 (SD 3.21) 5 years later. In all men (Figure 1Go) a U-shaped relationship was seen between BMI measured at Q5 and age-adjusted total mortality with the lowest risks seen in those with BMI levels 22–27.9 kg/m2 (test for quadratic trend P < 0.0001). Weight loss and substantial weight gain (>=10%) were both associated with significantly increased all-cause mortality (both P < 0.01) compared to those with stable weight (test for quadratic trend P < 0.0001).



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Figure 1 Age-adjusted relative risk for total mortality over 13.8 years (mean) follow-up according to body mass index (BMI) (Q5a) and weight change (Q1b to Q5) in 7065 men

a Questionnaire 5 years after baseline.

b Questionnaire at baseline.

 
This pattern of weight change-mortality relationship remained the same when examined by initial BMI (<25, 25–27.9, >28 kg/m2).

Table 1Go shows the mean BMI at baseline and 5 years later and the percentage with stable weight, weight loss and weight gain by four cigarette smoking categories. Long-term ex-smokers and never smokers showed similar BMI levels and patterns of weight change. Giving up smoking after baseline (recent ex-smokers) was strongly associated with weight gain and these men were the heaviest group at Q5. Current smokers were the lightest group at Q1 and Q5.


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Table 1 Cigarette smoking status, mean body mass index (BMI) at baseline questionnaire (Q1) and after 5 years (Q5) and percentage distribution of weight change Q1 to Q5 in 7065 men
 
Because of the strong association between smoking, body weight and weight change the relationship between weight change and mortality and between BMI and mortality was examined separately by three groups of smoking categories in Tables 2–5GoGoGoGo: (i) long-term non-smokers (‘non-smokers’) at both Q1 and Q5 including those who were never smokers and ex-smokers at baseline (n = 4101), (ii) current smokers at Q5 (n = 2242) and (iii) smokers at baseline who had given up by Q5 (‘recent ex-smokers’) (n = 722). Never smokers and ex-smokers at baseline were combined because they showed relatively similar BMI levels and weight change patterns. Presumably, the majority of ex-smokers at screening would have experienced their weight gain before screening. In addition, our recent report using BMI measured at baseline showed similar patterns of relationship between BMI and mortality in men who were never smokers or ex-smokers at baseline.11


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Table 3 Weight change over 5 years and subsequent mortality over 13.8 years (mean) follow-up in 2242 men who were current smokers at Q5a
 

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Table 4 Weight change over 5 years and subsequent mortality over 13.8 years (mean) follow up in 722 men who had given up smoking in the 5 years since screening
 
Weight change and mortality by smoking status
Non-smokers
The relationships between weight change and mortality for all causes, cardiovascular and non-cardiovascular causes are shown in Table 2Go. Men with stable weight and those who experienced moderate weight gain showed similar age-adjusted mortality rates. Weight loss was associated with a significant increase in all-cause mortality compared to the stable group and this was seen for both cardiovascular and non-cardiovascular causes. Men who experienced substantial weight gain showed a significant increase in cardiovascular mortality but not for non-cardiovascular mortality. After adjustment for age, social class, ex-smoking status, physical activity, alcohol intake, lung function and initial BMI, the increased risk of all-cause mortality in the weight loss group remained significant although it was slightly attenuated. Tests for a U-shaped curve for total mortality and cardiovascular mortality were highly significant (quadratic trend P = 0.0008 and P = 0.001, respectively). In order to take into account pre-existing disease which may have been associated with weight loss, we excluded men with recall of a doctor diagnosis of coronary heart disease, stroke, diabetes, self-reported ‘poor health’ or who had been off sick for at least one month more than three times in the last 5 years as well as men who died within 4 years of follow-up (total exclusion 643 men, 285 deaths). The increased risk in the weight loss group was markedly reduced after these exclusions and this was seen for both cardiovascular and non-cardiovascular causes. The tests for a U-shaped curve for total mortality and cardiovascular mortality were no longer significant.

Current smokers (Table 3Go)
In the 2242 men who were current smokers at Q5, weight loss was associated with only a small and non-significant increase in total mortality compared to those with stable weight after adjustment for confounders. Substantial weight gain in current smokers was associated with a significant increase in mortality due almost entirely to the increase in cardiovascular mortality. Those with modest weight gain showed the lowest mortality risk. A test for a curvilinear trend for total mortality was significant (P = 0.0001). Exclusion of men with ill health (477 men) reduced the risk of total mortality in the weight loss group further but the lowest risk was still seen in the moderate weight gain group. A test for a curvilinear trend for total mortality remained significant (P = 0.03). For cardiovascular disease mortality, the significant increase in risk associated with weight gain was attenuated after exclusion of men with ill-health, possibly due to the presence of heart failure and fluid retention in many in this group.

Recent ex-smokers (Table 4Go)
In the 722 men who had given up smoking at some time during the 5 years since baseline there were relatively few men who had weight loss but these men showed by far the highest total mortality rates. All men who gained weight showed lower total mortality rates than those who were stable and this was significant in those with moderate weight gain. A test for curvilinear trend for total mortality was significant (P = 0.03). Exclusion of 205 men with ill health (B) markedly reduced the increased risk of total mortality in the weight loss group but weight gain was still associated with the lowest mortality risk although the test for curvilinear trend in total mortality was no longer significant.

Body mass index at Q5 and mortality by smoking status
Figure 2Go shows the relationship between reported BMI at Q5 and age-adjusted total mortality rates according to smoking status. Because of the small number of men with BMI <20 kg/m2, these men have been combined with the 20–21.9 group and five groups are used. In the non-smokers a significant positive association was seen between BMI and total mortality (test for trend P = 0.005) although the lowest rates were in those with BMI 22–23.9 kg/m2. Adjustment for confounders and ex-smoking status (Table 5Go) made minor differences to the relationship and although the lowest risk was now seen in the <22 kg/m2 group a significant trend was still seen (P = 0.04). No significant association was seen with total mortality among current smokers although the highest mortality was in the lean men (<22.0 kg/m2). In recent ex-smokers the number of lean men was very small but they showed by far the highest mortality rates and there was a tendency for risk to decrease (non-significantly) with increasing BMI up to a level of 27.9 kg/m2 beyond which risk increased. After adjustment (Table 5Go,A) lean men still showed the highest risk but there was little difference between the other groups (Table 5Go).



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Figure 2 Age-adjusted total mortality rates per 1000 person-years over 13.8 years (mean) follow-up for body mass index (BMI) groups at Q5 by smoking status—dotted line indicates exclusion of men who have lost weight in non-smokers

 
The influence of weight loss on the BMI-mortality relationship
Figure 2Go also shows the effects of excluding 995 men who experienced weight loss (>=4%) on the BMI-total mortality relationship in non-smoking men and Table 5Go shows the adjusted relative risk for total mortality by the five BMI groups after such exclusion (B). In non-smokers exclusion of men who lost weight reduced the risk in the leanest men and a more significant positive relationship was seen between BMI and all-cause mortality with the lowest risk in the BMI <22 kg/m2 group (P = 0.02). In current smokers and recent ex-smokers, exclusion made minor difference to the pattern of relationship seen.

Discussion

In the majority of prospective studies weight loss has been associated with increased risk of mortality even after attempts have been made to control for the confounding effects of smoking and ill health.19 This has led to the belief that weight loss per se may be harmful. The approaches and limitations in these studies have been extensively reviewed and it was concluded that the evidence is still far from conclusive.9 Despite the importance of the confounding role of smoking, most studies to date have used multivariate analyses in controlling for smoking and few prospective studies have examined the relationship stratified by smoking status. Furthermore, attempts to take pre-existing disease into account have usually been confined to exclusion of early deaths. This method has been criticised as being inadequate to take pre-existing disease into account.22 In the present study, the increased mortality associated with weight loss was largely due to pre-existing disease. Exclusion of early deaths and of men with various indicators of pre-existing disease markedly attenuated the increased risk for total mortality in all non-smokers, recent ex-smokers and current smokers and the residual differences were not significant.

Other studies
In the few prospective studies that have examined weight change by smoking status, the results have been inconsistent.1,4,8,12,14 In the MRFIT Study8 weight loss over 6–7 years was associated with increased risk even in men who had never smoked. However, this study was based on only 3.8 years follow-up and only men with diagnosed cancer and clinical evidence of coronary heart disease were excluded. The increased risk which remained may still have been due to subclinical disease or to other diseases associated with weight loss resulting in early death. In the Framingham Study weight loss from age 55 years to age 65 years was associated with increased risk in never-smokers but pre-existing disease was not taken into account.1 In the Harvard Alumni Study weight loss over 11–15 years was increased in non-smoking men which included ex-smokers.4 However, in this latter study only men with diagnosed cardiovascular disease and cancer were excluded. If we had limited exclusions in our study to men with diagnosed cancer and cardiovascular disease, weight loss would have remained associated with a significant increase in risk in long-term non-smokers. However, in our study further exclusion of men with self-reported ‘poor health’, those who had been off sick for long periods and diabetes and early deaths diminished the risk. Thus the increased risk still seen in the Harvard Alumni Study may be due to failure to eliminate all subjects with pre-existing illness likely to experience weight loss and increased mortality. By contrast, in two recent studies that have stratified by smoking status and excluded subjects with various indicators of pre-existing disease, no increased risk was observed with weight loss over 6 years in healthy men (Honolulu Heart Study)12 and weight loss in women from age 18 (Nurses Health Study)14 who had never smoked, suggesting that the increased mortality associated with weight loss is due to confounding. A further study in Swedish men showed that those who had lost weight from age 20 years to middle-age (45–75 years) had an increased risk of coronary heart disease mortality on 20 years follow-up, but only in men who were smokers.23 The present study provides further evidence that weight loss in healthy individuals is not associated with increased risk and supports previous suggestions that the increased risk associated with weight loss is an artifact of ill health.

Weight gain and mortality
Whilst substantial weight gain is associated with increased mortality compared to those with stable weight in the majority of studies, moderate weight gain has often been associated with the lowest mortality rates and it has been suggested that weight gain with increasing age may be desirable.6 In the present study when men with pre-existing disease were not excluded, moderate weight gain was associated with lower risk than stable weight only in recent ex-smokers and in current smokers but not in the long-term non-smokers. Smoking is strongly associated with body weight and in particular giving up smoking is associated with weight gain.10,24,25 However, the benefit of giving up smoking outweighs the adverse effect of weight gain, as all heavier ex-smokers showed lower mortality rates than all current smokers. The recent ex-smokers who gained weight, particularly those with substantial weight gain tended to report better health overall despite being more likely to have been heavier smokers. They were lighter in weight at screening than those whose weight remained stable and this is consistent with other studies showing that heavier smokers gain more weight than lighter smokers after quitting.25 Exclusion of men with ill health increased the risk of total mortality seen in those with moderate weight gain but moderate weight gain was still associated with lower risk, although the difference was not statistically significant. Moderate but not substantial weight gain in current smokers was also associated with lower risk compared to those with stable weight and this was significant even after exclusion of men with ill health. Those who gained weight were more likely to be heavier smokers and lighter in weight at screening but were more likely to have made a reduction in the number of cigarettes smoked. However, adjustment for the amount of cigarettes smoked made little difference to the risk. Smokers tend to have lighter body weight, possibly a consequence of the metabolic effects of nicotine,26 and moderate weight gain in smokers may reflect metabolic changes influencing weight and a better prognosis.

By contrast, in long-term non-smokers (never smokers and long-term ex-smokers) whose weight gain is unlikely to have been influenced by the metabolic effects of smoking or smoking cessation, moderate weight gain is not associated with benefit and substantial weight gain is associated with increased risk. Even when long-term ex-smokers were separated from never smokers (data not shown), moderate weight gain in long-term ex-smokers was not associated with significantly lower risk as seen in the recent ex-smokers.

Weight gain, mortality and smoking status
Very few studies have examined the relationship between moderate weight gain and mortality by smoking status. The MRFIT Study did not separate moderate weight gain from substantial weight gain and found weight gain overall to be associated with increased risk in never and continuous smokers but not in intermittent smokers.8 Our findings are very similar to those reported in the Harvard Alumni Study.4 This study found that moderate weight gain was associated with lower risk (non-significance) than those with stable weight in current smokers but not in non-smokers. Whilst there appears to be no harm in moderate weight gain with increasing age, there appears to be little evidence that moderate weight gain is protective or desirable in older age in non-smoking men.

Body mass index and mortality
Few studies have examined the relationship between BMI and mortality stratified by smoking but most of these find a positive association between BMI and all-cause mortality in never smokers or non-smokers1113,27 and no association in current smokers.1113 In our recent report using measured BMI, at screening a linear and positive association was seen between BMI and mortality in both never and ex-smokers at baseline from levels of 20 kg/m2 and above. In current smokers mortality was increased only at levels of 30 kg/m2 and beyond.11 In the present study using reported BMI 5 years after baseline and subsequent mortality, similar patterns of relationship were seen. A weaker but significant positive association was seen in long-term non-smokers (never and long-term ex-smokers combined) and no association was seen in current smokers.

The influence of weight loss on the BMI-mortality relationship
There has been much debate as to whether recommended body weight should be higher for older subjects as the optimal BMI associated with lowest mortality tends to increase with increasing age.2730 In most studies the relationship between BMI and mortality is based on one assessment in time and it is commonly observed that leaness is associated with increased risk. Body weight, like other behavioural patterns changes with time. In particular weight loss in older people is more likely to be unintentional, is often associated with ill health31 and may be an indication of serious or advanced ill health likely to lead to increased mortality. Leaner subjects are comprised of both those who choose to remain lean and those who have lost weight and become lean due to ill health. One study in men provides strong indication that illness-related weight loss from middle-age to older age may explain the excess risk in leaner subjects commonly observed in older men.32 In that study exclusion of men with weight loss and adjustment for health status eliminated the increased risk associated with leaness seen in subjects aged 70 and over. A study in women suggested that the impact of BMI on mortality is more significant if weight change is taken into account.14

In non-smoking men, after exclusion of men who had lost weight, lean men (<22 kg/m2) had the lowest mortality rate and the progressive effect of obesity on mortality became more evident. Our study clearly illustrates the influence that weight loss has on the BMI-mortality relationship in non-smoking men aged 45–65 and confirms previous reports in women14 showing that if weight loss is taken into account a more positive relationship is seen with total mortality.

Possible bias
It is unlikely that our findings would have been biased by non-responders and the exclusion of men who did not provide data on weight change as the number of non-responders were relatively low (1.9%) and only 2.3% of the survivors responded to the questionnaire but did not provide information on weight change. We can only speculate as to why these men did not answer the questions. If we had assumed that they did not experience any change in weight and included them in the reference group the results would have remained unchanged.

Conclusion

The increased risk of mortality associated with weight loss and with low body weight in middle-aged and older men appears to be a direct consequence of ill health leading to weight loss and increased mortality. In healthy non-smoking men, weight loss and low body weight are not significantly associated with increased mortality and in these men there is no evidence that moderate weight gain is desirable with increasing age. The benefits of being lean and maintaining a stable weight and the adverse effects of higher body weight are seen more clearly when analyses are stratified by smoking status and the effects of weight loss are taken into account. This study emphasizes the importance of taking smoking status and pre-existing disease into account in assessing the relationship between weight change, body weight and mortality especially in older age when ill health is more prevalent.


KEY MESSAGES

  • The relationship between weight change, body weight and mortality was examined among 7065 men aged 40–59 at screening who were followed up for an average of 13.8 years in the British Regional Heart Study.
  • In healthy non-smoking men low body weight and weight loss were not significantly associated with increased mortality and there was no evidence that moderate weight gain is desirable with increasing age.
  • The increased risk of mortality associated with low body weight or weight loss thus appears to be a direct consequence of ill health.
  • This study demonstrates the importance of taking smoking status and pre-existing disease into account when assessing the relationship between weight change, body weight and mortality.

 

Acknowledgments

The British Regional Heart Study is a British Heart Foundation Research Group and receives support from the Department of Health.

References

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