Background The effect of age on optimal body weight is controversial,and few studies have had adequate numbers of subjects to analyzemortality as a function of body-mass index across age groups.
Methods We studied mortality over 12 years among white men andwomen who participated in the American Cancer Society's CancerPrevention Study I (from 1960 through 1972). The 62,116 menand 262,019 women included in this analysis had never smokedcigarettes, had no history of heart disease, stroke, or cancer(other than skin cancer) at base line in 1959–1960, andhad no history of recent unintentional weight loss. The dateand cause of death for subjects who died were determined fromdeath certificates. The associations between body-mass index(defined as the weight in kilograms divided by the square ofthe height in meters) and mortality were examined for six agegroups in analyses in which we adjusted for age, educationallevel, physical activity, and alcohol consumption.
Results Greater body-mass index was associated with higher mortalityfrom all causes and from cardiovascular disease in men and womenup to 75 years of age. However, the relative risk associatedwith greater body-mass index declined with age. For example,for mortality from cardiovascular disease, the relative riskassociated with an increment of 1 in the body-mass index was1.10 (95 percent confidence interval, 1.04 to 1.16) for 30-to-44-year-oldmen and 1.03 (95 percent confidence interval, 1.02 to 1.05)for 65-to-74-year-old men. For women, the corresponding relativerisk estimates were 1.08 (95 percent confidence interval, 1.05to 1.11) and 1.02 (95 percent confidence interval, 1.02 to 1.03).
Conclusions Excess body weight increases the risk of death fromany cause and from cardiovascular disease in adults between30 and 74 years of age. The relative risk associated with greaterbody weight is higher among younger subjects.
Whether recommended body weight should remain constant throughoutadulthood or should be higher for older adults is controversial.The Department of Agriculture's 1990 Dietary Guidelines forAmericans1 recommended age-specific ranges of weight for height,with heavier weights indicated for people 35 years of age orolder, but age-specific weight recommendations were omittedfrom the 1995 Dietary Guidelines for Americans,2 presumablybecause the information to support the need for different recommendedweights was inadequate.
The debate sparked by the dietary guidelines made it evidentthat more studies were needed to clarify whether age modifiesthe relation between body weight and mortality. Studies thatcompare the relations between the body-mass index (the weightin kilograms divided by the square of the height in meters)and mortality among age groups in a single cohort provide evidenceto confirm or refute the usefulness of age-specific guidelines,but studies of sufficient size to generate meaningful age-specificestimates are rare. Previous analyses from the American CancerSociety's Cancer Prevention Study I,3,4 a study of personalhealth habits and mortality, did examine the relation of bodyweight and mortality in a very large cohort; however, comparisonswere made with use of the mean weight within each age group,a measure that varied by as much as 14 lb (6.4 kg) among agegroups. Therefore, direct comparisons among age groups couldnot be made. Using data on the subjects in the Cancer PreventionStudy I, we analyzed the associations between body-mass indexand mortality from all causes and from cardiovascular diseasein six age groups of healthy white men and women.
Methods
Subjects
Over 1 million men and women 30 years of age or older in 26states were recruited by 68,000 American Cancer Society volunteersbetween October 1959 and March 1960 to participate in the firstCancer Prevention Study.3 The participants were enrolled infamily groups with at least one member over 45 years of age,and all members of a household over 30 years of age were askedto answer the questionnaire. The cohort was formed as a conveniencesample (not a random sample). These subjects had higher levelsof educational attainment than the general population in thesame decade, and subjects who smoked or had a family historyof cancer were oversampled.5
In order to avoid confounding by smoking status, we restrictedthe present analysis to subjects who had never smoked. The subjectswere classified as never having smoked if they reported thatthey did not currently smoke cigarettes and had never smokedcigarettes regularly. Race or ethnic group was obtained fromsubjects' choices among categories on a checklist. We had previouslyfound that the relation between body-mass index and mortalitywas less strong among the black women in this cohort than amongthe white women.6 Since the numbers of blacks and members ofother minorities were relatively small (<2 percent of thecohort), they were excluded from this analysis.
We also excluded several groups of subjects in order to improvethe quality and completeness of the data and to eliminate subjectswho may have had weight loss due to illness at the time of thebase-line measurements (Table 1). The final sample included62,116 men and 262,019 women. The men and women whom we excludedwere older than those included (mean age, 59 vs. 54 years formen [P<0.001] and 59 vs. 53 years for women [P<0.001])and had a higher age-adjusted death rate (3191 vs. 1811 per100,000 person-years for men [P<0.001] and 2147 vs. 1159per 100,000 person-years for women [P<0.001]). The mean age-adjustedbody-mass index was the same for the excluded and the includedmen (25.5) and only slightly higher among the excluded womenthan among the included women (24.8 vs. 24.7, P<0.001).
Table 1. Subjects Excluded from or Included in the Study Cohort.
End Points
The vital status of 98 percent of the total cohort was tracedthrough September 1971, and that of 93 percent through September1972. Vital status was determined annually in October from 1960through 1965 and again in 1971 and 1972. Personal inquiriesby American Cancer Society volunteers generated reports of thedates and places of all deaths, which were sent to the AmericanCancer Society central office. Death certificates were thenobtained from state health departments and coded by a nosologist.The cause of death was coded according to the codes of the InternationalClassification of Diseases, 7th Revision (ICD-7).7 Deaths dueto cardiovascular disease were identified by ICD-7 codes 330through 334, 400 through 434, and 450 through 468. Only 0.4percent of deaths were not coded with an underlying cause.
Risk Factors
The study subjects completed a four-page questionnaire on personalhealth practices and medical history. Weight in pounds and heightin feet and inches were written on blank lines after the words"present weight (indoor clothing)" and "height (without shoes)."Body-mass index was calculated from the reported values. Inour categorical analyses, the body-mass-index categories wereas follows: <19.0, 19.0 to 21.9, 22.0 to 24.9, 25.0 to 26.9,27.0 to 28.9, 29.0 to 31.9, and >32.0. These categories correspondto approximately <90 percent, 90 to 99 percent, 100 to 114percent, 115 to 119 percent, 120 to 129 percent, 130 to 139percent, and >140 percent of desirable weight according tothe 1983 Metropolitan Life Insurance tables.8,9
Educational attainment was assessed in five categories: grammarschool, some high school, high-school graduation, some college,and college graduation. Physical activity was assessed by asking,"How much exercise do you get (work or play): none, slight,moderate, or heavy?" Alcohol intake was assessed by asking,"How many cups, glasses, or `drinks' do you usually consumeper day (beer, wine, whiskey, gin, etc.)?" We categorized alcoholconsumption as none, occasional light, occasional heavy, onedrink per day, two to four drinks per day, and five or moredrinks per day.
Statistical Analysis
We used proportional-hazards analysis (PROC PHREG, SAS Institute,Cary, N.C.) to assess associations between body-mass index andmortality from all causes and from cardiovascular disease. Body-massindex was examined as both a continuous and a categorical variable.Likelihood-ratio tests were used to test for interactions inthe proportional-hazards models.10 The linear trends for therelative risks associated with an increase of 1 in the body-massindex across age groups were tested by weighted linear regressionanalysis.11 The inverse of the variance of the risk estimateswas used for the weight.
Results
During the 12 years of follow-up, the crude incidence of deathranged from 2 to 3 percent among 30-to-44-year-old women andmen to 89 to 91 percent among subjects who were 85 years ofage or older at base line (Table 2). The percentage of deathsthat were due to cardiovascular disease also increased withage. Among the men, the mean body-mass index was relativelyconstant (approximately 25.7) from 30 to 74 years of age, butit was lower in the older groups. Among women, the mean body-massindex increased from 23.8 among the 30-to-44-year-olds to 25.2among those 55 to 64 years old, then declined in the older agecategories.
Table 2. Outcomes and Body-Mass Indexes at Base Line in the Study Cohort of Healthy White Men and Women Who Had Never Smoked.
The crude death rates varied among both body-mass-index andage categories. For example, for 30-to-44-year-old women, therewere 22 deaths from cardiovascular disease per 100,000 person-yearsamong those with body-mass indexes of 19.0 to 21.9, as comparedwith 51 per 100,000 person-years among those with indexes of29.0 to 31.9. For 65-to-74-year-old women, there were 1494 deathsdue to cardiovascular disease per 100,000 person-years amongthose with body-mass indexes of 19.0 to 21.9, as compared with1854 per 100,000 person-years among those whose body-mass indexeswere 29.0 to 31.9. For men and women over 75 years of age, thecrude death rate did not increase with body-mass index. Forexample, among 75-to-84-year-old women, there were 5259 deathsdue to cardiovascular disease per 100,000 person-years in thegroup with body-mass indexes of 19.0 to 21.9, as compared with5227 per 100,000 person-years in the group with indexes of 29.0to 31.9.
The distributions of several characteristics associated withlongevity and body-mass index varied with age. Younger subjectswere more highly educated, more likely to report a high levelof physical activity, and more likely to drink alcoholic beveragesthan were older subjects (data not shown).
The relative risks of death from all causes (Figure 1) and deathfrom cardiovascular disease (Figure 2) according to body-mass-indexcategory were estimated in models that included age, education,physical activity, and alcohol consumption as covariates. Separateanalyses were conducted for the six age groups, with the body-mass-indexcategory 19.0 to 21.9 used as the reference category. Relative-riskestimates are not reported for groups defined by age and body-massindex that had five or fewer deaths. For both death from allcauses and death from cardiovascular disease, the increase inrisk associated with a higher body-mass index tended to be greateramong younger subjects.
Figure 1. Relative Risk of Death from Any Cause According to Age Group and Body-Mass-Index Category among Healthy White Men and Women Who Had Never Smoked.
All relative risks were adjusted for age, education, physical activity, and alcohol consumption. The reference category was made up of subjects with body-mass indexes of 19.0 to 21.9. The bars represent 95 percent confidence limits. Relative-risk estimates are not shown for age–body-mass-index groups with five or fewer deaths.
Figure 2. Relative Risk of Death from Cardiovascular Disease According to Age Group and Body-Mass-Index Category among Healthy White Men and Women Who Had Never Smoked.
All relative risks were adjusted for age, education, physical activity, and alcohol consumption. The reference category was made up of subjects with body-mass indexes of 19.0 to 21.9. The bars represent 95 percent confidence limits. Relative-risk estimates are shown for age–body-mass-index groups with five or fewer deaths.
Using the same covariates, we tested models in the six age groups,with body-mass index examined as a continuous linear term andas a quadratic term (the square of the body-mass index). Formen, the linear term for body-mass index was appropriate, whereasfor women body-mass index squared was significant in 6 of the12 tests (P<0.05). Because the main focus of this analysiswas to compare the effect of excess adiposity among age groups,it was desirable to fit the same model in each age category.Comparisons of the magnitude of the effects indicated that theresults of the two models were very similar for women, althoughsome differences in risk ratios were greater than 10 percent.Therefore, we have presented two sets of analyses for the women.
In the first, the quadratic model was fitted in all the agegroups, and the body-mass index at the nadir of the relativerisk was calculated. In groups of subjects less than 75 yearsold, the body-mass index at the nadir was below 20.0 for bothmortality from all causes and mortality from cardiovasculardisease in all but one test. In that instance the quadraticterm was negative (and not statistically significant), and thenadir was not calculated since it had little meaning. In thetwo oldest age groups, the nadirs for risk were at much higherbody-mass indexes (27.4 and 28.5).
In the second series of analyses, models were fitted with onlythe linear term for body-mass-index. Figure 3 shows the relative-riskestimates from the models examining body-mass index as a linearterm among women and among men. The relative risk associatedwith increasing body-mass index tended to be slightly lowerfor women than for men. Among women, body-mass index was positivelyassociated with mortality from all causes and from cardiovasculardisease in the four younger age groups. Among men, body-massindex was significantly associated with mortality from all causesand from cardiovascular disease in all but the oldest age group.
Figure 3. Relative Risk of Death from Any Cause and from Cardiovascular Disease Associated with an Increment of 1.0 in Body-Mass Index among White Men and Women Who Had Never Smoked, According to Age Group.
Relative risks are from separate models tested within the age groups, with body-mass index entered as a continuous variable. All relative risks were adjusted for age, education, physical activity, and alcohol consumption. The bars represent 95 percent confidence limits. Among men, the test for trend was significant for mortality from all causes (P<0.01) and for mortality from cardiovascular disease (P<0.001). In women, the test for trend was significant for mortality from all causes (P<0.05) and for mortality from cardiovascular disease (P<0.01).
The relative risk associated with an increase in the body-massindex declined with age for both mortality from all causes andmortality from cardiovascular disease among men (P for trend,<0.01 and <0.001, respectively). The relative risk tendedto increase between the youngest two age groups among women,but overall the relative risk associated with higher levelsof body-mass index also declined with age for both mortalityfrom all causes and mortality from cardiovascular disease (Pfor trend, <0.05 and <0.01, respectively). The interactionbetween body-mass index and age was statistically significant(P<0.001) for both mortality from all causes and mortalityfrom cardiovascular disease among both men and women.
To illustrate the magnitude of the age-associated decline inthe relative risk associated with an elevated body-mass index,we calculated the body-mass index and weight associated witha 20 percent and a 50 percent increase in the risk of deathfrom all causes and from cardiovascular disease, using a body-massindex of 21.0 as the reference value (Table 3). The choice ofthis reference value was arbitrary, since the model assumesa constant increase in the log of the relative risk across theentire range of body-mass indexes. Nevertheless, the categoricalanalyses shown in Figure 1 and Figure 2 give some indicationthat the category 19.0 to 21.9 included the body-mass indexassociated with minimal risk in the majority of the age categoriesexamined. For both men and women, the increment in body-massindex or weight that was associated with a given increase inrisk rose slightly among the three younger age groups but rosemore sharply at 65 to 74 years of age.
Table 3. Body-Mass Index (BMI) and Body Weight Associated with 20 Percent and 50 Percent Increases in Mortality from All Causes and Mortality from Cardiovascular Disease (CVD).
Discussion
These results suggest that among men and women 30 through 74years of age, greater body weight increased the risk of deathfrom any cause and death from cardiovascular disease over a12-year period; however, the relative risk associated with excessweight was higher among younger subjects. Although the variousmodels used to examine relative risk resulted in consistentconclusions, different measures of risk could produce differentconclusions because of the large differences in the age-specificmortality rates. For example, whereas the relative risk associatedwith excess weight was higher among the 30-to-44-year-olds thanamong the 65-to-74-year-olds, the difference in the crude mortalityrates between overweight and lean subjects was larger amongthe older subjects. Among 30-to-44-year-old women, the differencein the crude rates of death from cardiovascular disease betweenwomen with body-mass indexes of 19.0 to 21.9 and those withvalues of 29.0 to 31.9 was 29 per 100,000 person-years, whereasthe difference was 455 per 100,000 person years among 65-to-74-year-oldwomen. We have emphasized the relative-risk estimate in thepresentation of results here because it is the most commonlyused measure of effect for the evaluation of the potency ofrisk factors.12
Approximately 400 events in each age group are required to detecta ratio of relative risks of 1.5, with body-mass index analyzedas a dichotomous variable divided at the median (with an alphalevel of 0.05 and 80 percent power).13 For example, if the relativerisk of death above the median body-mass-index value as comparedwith that below the median was 1.33 in one age group and 2.0in another, approximately 400 deaths would be required in eachage group for the study to detect this difference. In many ofthe studies that have provided age-specific risk estimates ofthe relation between body-mass index and mortality, there havebeen too few deaths for the study to make this statisticallypowerful a comparison.
The Build Study14 and Waaler's Norwegian study15 had adequatestatistical power but did not control for smoking. In the formerstudy, the relation between the body-mass index and mortalitywas U-shaped, and the body-mass index associated with minimalmortality increased with age. In the Norwegian study, plotsof the log of the mortality rate against body-mass-index categorieswere also U-shaped, but there was no evidence that the body-massindex associated with minimal mortality increased with age.
More recent studies of the effect of age on the relation betweenbody-mass index and mortality have controlled for smoking. Ina Finnish cohort of 17,159 women16 and 22,995 men17 who werefollowed for a median of 12 years, there was a U-shaped relationbetween body-mass index and mortality from all causes amongnonsmoking women 25 to 64 years of age. Among women 65 yearsof age or older, mortality varied little according to body-massindex; directly comparable analyses were not presented for themen. The 26-year risk of death among 12,576 Seventh-Day Adventistwomen, a subgroup of the women we studied, was recently reported.18Among the white women who never smoked and were relatively healthyat base line, the relative risk of death associated with elevatedbody-mass index was lower for women 55 to 74 years old thanfor those 30 to 54 years old. The lowest risk of death fromany cause among the younger women was found in those who hadbody-mass indexes from 21.3 to 22.9, but among the older womenthe lowest risk was in the group with body-mass indexes from23.0 to 24.8.
Taken together, these studies support the hypothesis that therelative risk of death associated with excess adiposity is lowerfor older than for younger adults. Variation in specific findingsmay be attributable to differences in exclusion criteria, incutoff points for categories of body-mass index, or in the variablescontrolled for in the analysis, or to unmeasured characteristicsof the study subjects.
Although the importance of smoking and preexisting illness asconfounders of the relation between body-mass index and mortalityhas been challenged,19,20 we thought it prudent to avoid potentialconfounding by these factors.21 Nevertheless, more older subjectsthan younger ones may have had reduced weight at base line becauseof preexisting illness. However, the fact that risk did notincrease at low body-mass indexes among the older men or allbut the oldest women (Figure 1 and Figure 2) argues againstthis possibility.
In the Cancer Prevention Study I, all data except those on mortalitywere obtained by questionnaire from the subjects themselves.In general, self-reported height and weight are highly correlatedwith measured height and weight (correlation coefficients, >0.9),but heavier persons tend to underreport their weight more thanleaner persons; underreporting of body weight may also increasewith age.22,23
In this study, body-mass index was estimated only once, at oneage, for each subject. Thus, no conclusions can be drawn aboutthe effect of changes in weight over time.24 The design of thisstudy also did not allow the effects of age to be distinguishedfrom temporal or birth-cohort effects. In addition, the factthat these data were collected between 1959 and 1972 may limitthe generalizability of our results. Another limitation is thenumber of years of follow-up. Twelve-year mortality in a cohortof 30-year-old subjects is very different from that among 85-year-oldsubjects. In the younger group, all deaths are premature, whereasnone could be termed premature in the older group.
Despite these limitations, the very large number of subjectsin a wide range of age groups, the 12 years of follow-up information,and the availability of information on both intended and unintendedweight loss made the Cancer Prevention Study I data set a richresource for these analyses. The numerous exclusions limit thegeneralizability of the results of our analyses, but they increasethe internal validity of those results. In healthy white adultsbelow the age of 75 who have never smoked cigarettes, our resultsare consistent with the healthy weight ranges proposed in the1995 Dietary Guidelines for Americans.
Supported by a grant (RO1 DK50776) from the National Instituteof Diabetes and Digestive and Kidney Diseases and by the Instituteof Nutrition.
Source Information
From the Departments of Nutrition (J.S.), Biostatistics (J.C.), and Epidemiology (J.S., J.L.W.), School of Public Health, University of North Carolina, Chapel Hill; the National Center for Health Statistics, Hyattsville, Md. (E.R.P.); the National Center for Chronic Disease Prevention and Health Promotion, Atlanta (D.F.W.); and the American Cancer Society, Atlanta (M.J.T.).
Address reprint requests to Dr. Stevens at the Departments of Nutrition and Epidemiology, CB 7400, University of North Carolina, Chapel Hill, NC 27599-7400.
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