Study Overview
Objective. To determine whether having a body mass index (BMI) in the obese range (30 kg/m 2) as an older adult woman is associated with changes in late-age survival and morbidity.
Design. Observational cohort study.
Setting and participants. This study relied upon data collected as part of the Women’s Health Initiative (WHI), an observational study and clinical trial focusing on the health of postmenopausal women aged 50–79 years at enrollment. For the purposes of the WHI, women were recruited from centers across the United States between 1993 and 1998 and could participate in several intervention studies (hormone replacement therapy, low-fat diet, calcium/vitamin D supplementation) or an observational study [1].
For this paper, the authors utilized data from those WHI participants who, based on their age at enrollment, could have reached age 85 years by September of 2012. The authors excluded women who did not provide follow-up health information within 18 months of their 85th birthdays or who reported mobility disabilities at their baseline data collection. This resulted in a total of 36,611 women for analysis.
There were a number of baseline measures collected on the study participants. Via written survey, participants self-reported their race and ethnicity, hormone use status, smoking status, alcohol consumption, physical activity level, depressive symptoms, and a number of demographic characteristics. Study personnel objectively measured height and weight to calculate baseline BMI and also measured waist circumference (WC, in cm).
The primary exposure measure for this study was BMI category at trial entry categorized as follows: underweight (< 18.5 kg/m 2), healthy weight (18.5–24.9 kg/m 2), overweight (25.0–29.9 kg/m 2) or obese class I (30–34.9 kg/m 2), II (35–39.9 kg/m 2) or III (≥ 40 kg/m 2), using standard accepted cut-points except for Asian/Pacific Islander participants, where alternative World Health Organization (WHO) cut-points were used. The WHO cut-points are slightly lower to account for usual body habitus and disease risk in that population. BMI changes over study follow-up were not included in the exposure measure for this study. WC (dichotomized around 88 cm) was also used as an exposure measure.
Main outcome measures. Disease-free survival status during the follow-up period. In the year at which participants were supposed to reach their 85th birthdays, they were categorized as to whether they had survived or not. Survival status was ascertained by hospital record review, autopsy reports, death certificates and review of the National Death Index. Those who survived were sub-grouped according to type of survival into 1 of the following categories: (1) no incident disease and no mobility disability (healthy), (2) baseline disease present but no incident disease or mobility disability during follow-up (prevalent disease), (3) incident disease but no mobility disability during follow-up (incident disease), and (4) incident mobility disability with or without incident disease (disabled).
Diseases of interest (prevalent and incident) included coronary and cerebrovascular disease, cancer, diabetes and hip fracture—the conditions the investigators felt most increased risk of death or morbidity and mobility disability in this population of aging women. Baseline disease status was defined using self-report, but incident disease in follow-up was more rigorously defined using self-report plus medical record review, except for incident diabetes, which required only self-report of diagnosis plus report of new oral hypoglycemic or insulin use.
Because the outcome of interest (survival status) had 5 possible categories, multinomial logistic regression was used as the analytic technique, with baseline BMI category and WC categories as predictors. The authors adjusted for baseline characteristics including age, race/ethnicity, study arm (intervention or observational for WHI), educational level, marital status, smoking status, ethanol use, self-reported physical activity and depression symptoms. Because of the possibly interrelated predictors (BMI and WC), the authors built BMI models with and without WC, and when WC was the primary predictor they adjusted for a participant’s BMI in order to try to isolate the impact of central adiposity. Additionally, they performed the analyses stratified by race and ethnicity as well as by smoking status.
Results. The mean (SD) baseline age of participants was 72.4 (3) years, and the vast majority (88.5%) self-identified as non-Hispanic white. At the end of the follow-up period, of the initial 36,611 participants, 9079 (24.8%) had died, 6702 (18.3%) had become disabled, 8512 (23.2%) had developed incident disease without disability, 5366 (14.6%) had prevalent but no incident disease, and 6952 (18.9%) were categorized as healthy. There were a number of potentially confounding baseline characteristics that differed between the survival categories. Importantly, race was associated with survival status—non-Hispanic white women were more likely to be in the “healthy” category at follow-up than their counterparts from other races/ethnicities. Baseline smokers were more likely not to live to 85 years, and those with less than a high school education were also more likely not to live to 85 years.
In models adjusting for baseline covariates, with BMI category as the primary predictor, women with an obese baseline BMI had significantly increased odds of not living to 85 years of age, relative to women in a healthy baseline BMI category, with increasing odds of death among those with higher baseline BMI levels (class I obesity odds ratio [OR] 1.72 [95% CI 1.55–1.92], class II obesity OR 3.28 [95% CI 2.69–4.01], class III obesity OR 3.48 [95% CI 2.52–4.80]). Amongst survivors, baseline obesity was also associated with greater odds of developing incident disease, relative to healthy weight women (class I obesity OR 1.65 [95% CI 1.48–1.84], class II obesity OR 2.44 (95% CI 2.02–2.96), class III obesity OR 1.73 [95% CI 1.21–2.46]). There was a striking relationship between baseline obesity and the odds of incident disability during follow-up (class I obesity OR 3.22 [95% CI 2.87–3.61], class II obesity OR 6.62 [95% CI 5.41–8.09], class III obesity OR 6.65 [95% CI 4.80–9.21]).
Women who were overweight at baseline also displayed statistically significant but more modestly increased odds of incident disease, mobility disability, and death relative to their normal-weight counterparts. Importantly, even in multivariable models, being underweight at baseline was also associated with significantly increased odds of death before age 85 relative to healthy weight individuals (OR 2.09 [95% CI 1.54–2.85]) but not with increased odds of incident disease or disability.
When WC status was adjusted for in the “BMI-outcome” models, the odds of death, disability, and incident disease were attenuated for obese women but remained elevated, particularly for women with class II or III obesity. When WC was examined as a primary predictor in multivariable models (adjusted for BMI category), those women with baseline WC ≥ 88 cm experienced increased odds of incident disease (OR 1.47 [95% CI 1.33–1.62]), mobility disability (OR 1.64 [95% CI 1.49–1.84]) and death (OR 1.83 [95% CI 1.66–2.03]) compared to women with smaller baseline WC.
When participants were stratified by race/ethnicity, the relationships for increasing odds of incident disease/disability with baseline obesity persisted for non-Hispanic white and black/African-American participants. Hispanic/Latina participants who were obese at baseline, however, did not have significantly increased odds of death before 85 years relative to healthy weight counterparts, although there were far fewer of these women represented in the cohort (n = 600). Asian/Pacific Islander (API) participants (n = 781), the majority of whom were in the healthy weight range at baseline (57%), showed a somewhat different pattern. Odds ratios for incident disease and death among obese API women were not significantly elevated relative to healthy weight women (although the “n ”s for these groups was relatively small), however the odds of incident disability was significantly elevated amongst API women who were obese at baseline (OR 4.95 [95% CI 1.51–16.23]).
Conclusion. Compared to older women with a healthy BMI, obese women and those with increased abdominal circumference had a lower chance of surviving to age 85 years. Those who did survive were more likely to develop incident disease and/or disability than their healthy weight counterparts.
Commentary
The prevalence of obesity has risen substantially over the past several decades, and few demographic groups have found themselves spared from the epidemic [2]. Although much focus is placed on obesity incidence and prevalence among children and young adults, adults over age 60, a growing segment of the US population, are heavily impacted by the rising rates of obesity as well, with 42% of women and 37% of men in this group characterized as obese in 2010 [2]. This trend has potentially major implications for policy makers who are tasked with cutting the cost of programs such as Medicare.
Obesity has only recently been recognized as a disease by the American Medical Association, and yet it has long been associated with costly and debilitating chronic conditions such as type 2 diabetes, hypertension, sleep apnea, and degenerative joint disease [3]. Despite this fact, several epidemiologic studies have suggested an “obesity paradox”—older adults who are mildly obese have mortality rates similar to normal weight adults, and those who are overweight appear to have lower mortality [4]. These papers have generated controversy among obesity researchers and epidemiologists who have grappled with the following question: How is it possible that overweight and obesity, while clearly linked to so many chronic conditions that increase mortality and morbidity, might be a good thing? Is there such a thing as a “healthy level of obesity,” or, can you be “fit and fat?” In the midst of these discussions and the media storm that inevitably surrounds them, patients are confronted with confusing mixed messages, possibly making them less likely to attempt to maintain a healthy body weight. Unfortunately, as many prior authors have asserted, most of the epidemiologic studies that assert this protective effect of overweight and obesity have not accounted for potentially important confounders of the “weight category–mortality” relationship, such as smoking status [5]. Among older adults, a substantial fraction of those in the normal weight category are at a so-called healthy BMI for very unhealthy reasons, such as cigarette smoking, cancer, or other chronic conditions (ie, they were heavier but lost weight due to underlying illness). Including these sick (but so-called “healthy weight”) people alongside those who are truly healthy and in a healthy BMI range muddies the picture and does not effectively isolate the impact of weight status on morbidity and mortality.
This cohort study by Rillamas-Sun et al makes an important contribution to the discussion by relying on a very large and comprehensive dataset, with an impressive follow-up period of nearly 2 decades, to more fully isolate the relationship between BMI category and survival for postmenopausal women. By adjusting for important potential confounders such as baseline smoking status, alcohol use, chronic disease status and a number of sociodemographic factors, and by separating out the chronically ill patients from the beginning, the investigators reached conclusions that seem to align better with all that we know about the increased health risks conferred by obesity. They found that postmenopausal women who were obese but without prevalent disease at baseline had increased odds of death before age 85, as well as increased odds of incident chronic disease (such as cardiovascular disease or diabetes) and increased odds of incident disability relative to postmenopausal women starting out in a healthy BMI range. Degree of obesity seemed to matter as well; those with class II and III obesity had significantly increased odds of developing mobility impairment, in particular, relative to normal weight women. This is particularly important when viewed through the lens of caring for an aging population—those who have significant mobility impairment will have a much harder time caring for themselves as they age. Furthermore, they found that overweight women also faced slightly increased odds of these outcomes relative to normal weight women. Abdominal adiposity, in particular, appeared to confer risk of death and disease, as elevated odds of mortality and incident disease or disability persisted in women with waist circumference ≥ 88 cm even after adjusting for BMI. As has been suggested by prior research on this topic, this study also supported the finding that being underweight increases ones odds of death, however, there was no increased incidence of disease or mobility disability for underweight women (relative to healthy starting weight).
The authors of the study made a wise decision in separating women with baseline chronic illness from those who had not yet been diagnosed with diabetes, cardiovascular disease or other chronic condition at baseline. As is pointed out in an editorial accompanying this study [6], this creates a scenario where the exposure (obesity) clearly predates the outcome (chronic illness), helping to avoid contamination of risk estimates by reverse causation (ie, is chronic illness leading to increased obesity, with the downstream increase in mortality actually due to the chronic illness?).
Despite the clear strengths of the study, there are several important limitations that must be acknowledged in interpreting the results. The most obvious is that BMI status was only measured at baseline. There is no way of knowing either what a participant’s weight trajectory had been in their younger years, or what happened to the BMI during the study follow-up period, both of which could certainly impact a participant’s risk of morbidity or mortality. Given a follow-up period of nearly 20 years, it is possible that there was crossover between BMI (exposure) categories after baseline assignment. Furthermore, the study does not address the very important question of how an intervention to promote weight loss in older women might impact morbidity and mortality—it is possible that encouraging weight loss in this population may in fact worsen health outcomes for some patients [6].
The generalizability of the study may be somewhat limited. The study population itself represented a group of women who were likely relatively healthy and motivated, having self-selected to participate in the WHI, thus they could have been healthier than groups studied in previous population-based samples. Furthermore, the study results may not generalize to men, however other similar cohort studies with male participants have reached similar conclusions [7].
Applications for Clinical Practice
To promote longevity and maintenance of independence in our growing population of postmenopausal women, it is important that physicians continue to educate and assist their patients in maintaining a healthy weight as they age. Although the impact of intentional weight loss in obese older women is not addressed by this paper, it does support the idea that obese postmenopausal women are at higher risk of death before age 85 years and disability. Therefore, for these patients, physicians should take particular care to reinforce healthy lifestyle choices such as good nutrition and regular physical activity.
—Kristina Lewis, MD, MPH