Previous Analysis of Weight Loss and Death

In a recently published study [16], we examined the relation between weight loss and subsequent death among 2140 men and 2550 women between 45 to 74 years old who participated in the first National Health and Nutrition Examination Survey (NHANES I, 1971 to 1975). Weight loss was assessed as the difference between self-reported maximum lifetime weight and weight measured at baseline. Vital status was determined through 1987. Risk for death associated with relative weight loss (< 5%, 5% to 14%, 15% or more) was estimated for three strata of maximum body mass index (BMI; weight[kg]/height[m]²)—less than 26, between 26 and 29, and 29 or more. We used Cox proportional-hazards models to adjust for age, race, parity (for women), cigarette smoking (never, former, or current), and maximum BMI as well as preexisting illnesses associated with weight loss (cancer, chronic bronchitis, or emphysema), preexisting illnesses associated with excess weight (heart attack, heart failure, stroke, hypertension, and diabetes), and diagnosis of both types of conditions. In addition, the analysis excluded persons who died in the first 5 years after the baseline examination.

We found that, at maximum BMIs of 29 or more, weight losses of 5% to 14% appeared to be protective for men but not for women. Among men and women whose maximum BMI was less than 29, the risk for death increased with increasing weight loss; among participants who had been moderately overweight (maximum BMIs between 26 and 29), those who lost 15% or more had more than twice the mortality risk of those losing less than 5%.

Additional Analyses

This report used several more rigorous exclusionary criteria to test the consistency of these findings. We first examined the effect of excluding "early" death by estimating relative risks associated with weight loss for the full cohort (2453 men and 2739 women), and for persons surviving for 5 and 8 years after the baseline examination, respectively. Within each stratum of maximum BMI, adjusted risk estimates for death from all causes, cardiovascular disease (ICD 9 codes 401 to 459 and 798), and noncardiovascular disease (all other ICD 9 codes except those for external injury) [17] were calculated relative to persons who had lost less than 5% of their maximum weight. We compared these results with those obtained by limiting the analysis to persons with no preexisting medical conditions except for hypertension or diabetes.

Because weight loss may have implications for the elderly that are different than those for younger persons [9, 10], we also estimated adjusted mortality risks for persons who were 45 to 64 years old at baseline. The variables for smoking status included in the model may not have allowed adequate adjustment for confounding. We repeated the analysis of all-cause mortality risk for persons who, at baseline, reported that they had never smoked.

Results

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The mortality risks associated with weight loss in men are shown in Table 1. If loss from maximum weight were a marker for occult illness, we would expect the relative risk estimates associated with weight loss to be reduced after excluding persons who died within the first 5 years after baseline and perhaps to be reduced even further after excluding deaths occurring in the first 8 years. Among men in this study, however, extension of the exclusionary period did not produce this type of consistent effect on the relative risk estimates.

After excluding deaths occurring in the first 8 years after baseline, the risk for death from noncardiovascular disease increased with the amount of weight lost among men with maximum BMIs of less than 26. Among men whose maximum BMI was between 26 and 29, weight losses of 5% to 14% were associated with an increased risk for death from cardiovascular disease, and weight loss of 15% or more was associated with a more than twofold mortality risk for both cardiovascular and noncardiovascular diseases. For men whose maximum BMI was 29 or more, however, weight losses of 5% to 14% appeared to reduce the risk for death from cardiovascular disease by approximately 30%. The risk for death from cardiovascular disease was not reduced among men who lost 15% or more, and the risk for death from noncardiovascular disease appeared to be moderately increased; however, this result was not statistically significant.

The results for women are shown in Table 2. The exclusion of early death had little effect on the risk for death from cardiovascular disease. After limiting the analysis to women who survived at least 8 years after baseline, we continued to find a strong, direct association between weight loss and risk for death from cardiovascular disease among women whose maximum BMI was less than 29. We found a moderate, but not statistically significant, association for those with a maximum BMI of 29 or more. Extension of the exclusionary period, however, reduced the association between weight loss and death from noncardiovascular disease for women in the lowest and highest strata of maximum BMI.

We repeated the analysis after excluding all persons with previously diagnosed medical conditions except for hypertension and diabetes and after excluding deaths that occurred within the first 5 years after baseline. For both sexes, the relative risk estimates were similar to those obtained by excluding persons who died within the first 8 years (data not shown). The estimated relative risks for persons 45 to 64 years old at baseline were either the same as or higher than those estimated for the entire group (data not shown).

Figures 1 and 2 show the relative risks for death due to all causes for participants who had never smoked at baseline. Because fewer than one third of the men in the study cohort had never smoked, we preserved sample size by excluding only men who died in the first 5 years after baseline. The results are consistent with those in Table 1, although the relative risk is not significantly elevated for men with maximum BMIs between 26 and 29 who lost 5% to 14% of their maximum weight (see Figure 1). Relative risk estimates for women who never smoked excluded deaths that occurred within the first 8 years after baseline. Compared with the results in Table 2, the relative risk for death associated with weight loss was only slightly lower for women who never smoked and only if their maximum BMI was less than 29.

View larger version (15K): [in this window] [in a new window]   Figure 1. Relative risk for death among men who never smoked, by maximum body mass index and percentage of maximum weight lost. Deaths in the first 5 years after baseline were excluded. (—-) 95% CI.

View larger version (15K): [in this window] [in a new window]   Figure 2. Relative risk for death among women who never smoked, by maximum body mass index and percentage of maximum weight lost. Deaths in the first 8 years after baseline were excluded. (—-) 95% CI.

Discussion

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The exclusion of participants with known medical conditions may not fully control for the effect of illness-associated weight loss on the risk for death because some illnesses may not have been diagnosed. The procedure usually used to remove the effect of subclinical illness involves the exclusion of death occurring within 2 to 5 years after baseline [15]. We showed that, among women, extension of the exclusionary period consistently attenuated the adverse association between weight loss and risk for death from noncardiovascular disease. This effect was strongest for women in the lowest and highest strata of maximum BMI.

For both sexes, the relative risk estimates for persons who survived for at least 8 years after baseline were similar to those estimated after exclusion of persons with diagnosed illnesses other than hypertension and diabetes in addition to exclusion of those who died in the first 5 years after baseline. It therefore seems plausible that this attenuation resulted from removal of the influence of illness-associated weight loss. We should also consider, however, that weight change after baseline may have influenced this result. For example, women who were originally classified as having lost less than 5% of their maximum weight may have lost more weight by 8 years after baseline.

This analysis shows the need for studies that clearly differentiate voluntary from involuntary weight loss. The only study that assessed volition of weight loss—the 1959 to 1965 Cancer Prevention Study—found that, for persons who reported a weight loss of 20 pounds or more in the previous 5 years, death from coronary heart disease and stroke was generally higher than for persons in the same initial weight category with no weight loss. According to the study's authors, results were similar for persons who tried to lose weight and those whose weight loss was involuntary [4]. The benefit of voluntary weight loss may have been obscured, however, by not separately examining its effect among persons with weight-associated illnesses. To assess adequately the relation between voluntary weight loss and longevity, studies should be large enough to allow effects to be estimated within relevant subgroups and for various causes of death.

In particular, this study shows the need to assess the effect of weight loss by level of initial BMI or relative weight. Our examination of the NHANES I cohort found that moderate weight loss (5% to 14% of maximum weight) among very overweight men (maximum BMI 29) was significantly associated with a reduced risk for death due to cardiovascular disease. This association translated into a modest, although not statistically significant, reduction in overall risk for death similar to that reported in the 1959 Build and Blood Pressure Study [1].

For persons with maximum BMIs between 26 and 29, we consistently found a direct association between weight loss and risk for death that was similar in magnitude to that found for persons with maximum BMIs less than 26, even though weight loss is generally considered healthy for persons with BMIs between 26 and 29 [18]. For persons of both sexes at this level of maximum BMI and for women with maximum BMI less than 26, we found a direct association between weight loss and increased risk for death due to cardiovascular disease that was not altered by excluding "early" death or persons with preexisting illness. In fact, for persons who had been moderately overweight (maximum BMIs between 26 and 29), all excess mortality risk associated with weight losses of 5% to 14% was due to increased risk for death from cardiovascular disease.

In a recently published analysis of 11- or 15-year weight change in Harvard Alumni, Lee and Paffenbarger [14] reported that, among men free of physician-diagnosed cardiovascular disease and cancer, risk for death due to coronary heart disease increased with increasing weight loss. They found no association between weight loss and risk for death due to cancer. The association between weight loss and death was approximately the same for men whose initial BMI was 25 or more as for those with a BMI of less than 25.

Our findings and those of Lee and Paffenbarger [14] are difficult to reconcile with the evidence that weight loss improves physiologic precursors of cardiovascular disease such as hypertension, hypercholesteremia, and insulin resistance [19–22]. They do, however, merit further investigation given that results from a recent survey suggest that, in the United States, nearly one third of men and more than one half of women with BMIs between 26 and 29 were actively trying to lose weight [23].