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During 12.5 years' follow-up, on average, 12,017 deaths occurred: 6,635 in men and 5,382 in women. Subjects tended to be lean at age 18 years (Table 1) but to gain considerable weight over the 18–35 and 35–50 age intervals (Table 2). Weight gain was highest in the youngest age interval and lowest in the oldest age interval. Relatively large proportions of subjects lost weight during the 50–69 age interval, particularly those reporting poor or fair health (16.9%). Subjects with a less optimal health status appeared more likely to lose weight and less likely to maintain stable weight or avoid weight gain than those in better health. Nearly half of the subjects (48.6%) reported regularly engaging in leisure-time physical activity (activity that lasted at least 20 minutes and caused either sweating or increases in breathing or heart rate) 3 or more times per week, whereas only 15.8% reported rarely or never doing so.
BMI at age 18 years was strongly positively related to total mortality in men and women (Table 3). Total mortality risk was elevated in all categories above the lean referent group (BMI 18.5–22.4), including the upper-normal weight category (BMI 22.5–24.9), and further increased in the heavier BMI categories. Similarly, mortality risk was greater in the 2 upper CDC-defined BMI percentile-for-age categories. Weighted average BMI was strongly associated with mortality in both men and women. Comparing hazard ratios for a given BMI category at ages 18, 35, and 50 years, associations were strongest for BMI at age 18 years and then declined somewhat with increasing age, although there was often considerable overlap in confidence intervals. For example, hazard ratios for a BMI of 25.0–27.4 at ages 18, 35, and 50 years were 1.40, 1.14, and 1.11, respectively, in men and 1.52, 1.45, and 1.24, respectively, in women. Age-adjusted mortality rates for a BMI in the 18.5–22.4 referent group were stable across the 3 age periods. Age-adjusted total mortality rates increased with BMI category within each age period and gender. Because the overall relationships appeared similar in men and women, the genders were combined in subsequent analyses. BMI at ages 18, 35, and 50 years was associated with mortality for each of the 4 cause-of-death groupings (see Web Table 1, available at http://aje.oxfordjournals.org/). The strongest associations were observed for CVD-related deaths. The hazard ratio for a mildly overweight BMI (25.0–27.4) at age 18 years was 1.65, and the risk increased to 2.42 for a BMI of 27.5 or more.
We evaluated the relationships between weight change and total mortality over 3 successive age intervals, combining men and women (Table 4). Weight gain was strongly associated with mortality in the 18–35 and 35–50 age intervals, with risk increasing at each increment of weight gain. In contrast, in the 50–69 age interval, mild weight gain of >0.2–0.6 kg/year was associated with slightly lower risk (hazard ratio (HR) = 0.91) and higher weight gain of >1 kg/year was associated with only modestly increased risk (HR = 1.17). Observed associations between weight change in the 50–69 age interval and mortality appeared to differ according to health status at entry. For subjects reporting very good to excellent health, a weight gain greater than 0.6 kg/year was associated with modestly increased mortality risk. In contrast, among subjects who reported good or poor-to-fair health, no linear trend was observed between weight gain and total mortality, and intermediate categories of weight gain were associated with statistically significant or borderline-significant lower risk. Age-adjusted mortality rates in the stable-weight reference categories in the 50–69 age interval were comparable to those in the 18–35 and 35–50 age groups. However, age-adjusted mortality rates in the 50–69 age interval for stable-weight (referent group) subjects in poor to fair health were sharply higher than corresponding rates for those in very good to excellent health. Weight loss in the 50–69 age interval was associated with greater risk regardless of health status.
Similar patterns were observed in cause-specific analyses, although the magnitudes of association differed by underlying cause of death (Web Table 2). Weight gain was most strongly associated with CVD mortality. In the 18–35 and 35–50 age intervals, weight gain greater than 1 kg/year was associated with a doubling of CVD mortality (HR = 2.10 and HR = 2.08, respectively). However, in the 50–69 age interval, weight gain greater than 1 kg/year was associated with only a 20% increase in CVD mortality (HR = 1.21). Weight gain in the 18–35 and 35–50 age intervals was associated with cancer mortality, but weight gain in the 50–69 age interval was not.
We then examined the combined influence of BMI and weight change on total mortality risk for each of the 3 age intervals (Table 5). The referent group for these analyses was BMI less than 25.0 at the beginning of the interval (e.g., 18 years) with stable weight over the subsequent interval. In the 18–35 and 35–50 age intervals, mortality risk generally increased progressively with both higher initial body mass (i.e., body mass at ages 18 and 35 years) and subsequent weight gain. In the 18–35 age interval, for example, mortality risk was greatest among subjects who had an initial BMI of 25.0 or more (at age 18 years) and also gained more than 1 kg/year by age 35 (HR = 2.69). Mortality risk was intermediate in subjects who either had an initially normal BMI but gained weight over the interval (HR = 1.63 for weight gain of more than 1 kg/year) or who had an initially high BMI (≥25.0) but did not gain weight (HR = 1.44). In the 50–69 age interval, positive associations of combined initial BMI and weight change with mortality were observed, but the associations were weaker than in younger age intervals, at least among subjects with an initially normal BMI. In this group, weight gain of 1 kg/year or less was not associated with increased mortality risk. Among subjects reporting very good or excellent health, both initial BMI and weight gain in the 50–69 age interval were positively associated with mortality. However, these associations appeared to be attenuated in subjects with less optimal health. Among subjects in poor to fair health and normal BMI at age 50 years, mortality risk was lower in those who gained weight (P-trend = 0.008) than in subjects with a stable weight.
CVD mortality risk increased sharply with both initial BMI and weight gain in the 18–35 and 35–50 age intervals (Web Table 3). In the 50–69 age interval, we did not observe statistically significant associations between weight gain and CVD mortality risk in subjects who were initially normal-weight or who had elevated initial BMI but gained 1 kg or less in body weight per year.
Finally, we considered the age at which excess weight (BMI ≥25.0) was first attained, based on the 4 age periods for which data were available (Table 6). The referent group in these analyses (in contrast with Table 3) consisted of subjects who maintained a BMI less than 25.0 over all 4 age periods (BMI at entry was included in this analysis). Entering adulthood with a BMI of 25.0 or higher at age 18 years was strongly associated with mortality (HR = 1.68 in men, HR = 2.04 in women) as compared with maintaining normal weight throughout adulthood. The hazard ratio for first attaining a BMI greater than or equal to 25.0 at age 50 years appeared weaker (HR = 1.12 in men, HR = 1.26 in women) but retained statistical significance. All analyses were repeated using the subjects with no missing height and weight data (i.e., BMI available at all 3 time points); results were essentially unchanged.
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