eAppendix. Adjusted Odds Ratios (95% CIs) of Outcomes by Baseline Body Mass Index
Rillamas-Sun E, LaCroix AZ, Waring ME, Kroenke CH, LaMonte MJ, Vitolins MZ, Seguin R, Bell CL, Gass M, Manini TM, Masaki KH, Wallace RB. Obesity and Late-Age Survival Without Major Disease or Disability in Older Women. JAMA Intern Med. 2014;174(1):98-106. doi:10.1001/jamainternmed.2013.12051
Copyright 2014 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
The effect of obesity on late-age survival in women without disease or disability is unknown.
To investigate whether higher baseline body mass index and waist circumference affect women’s survival to 85 years of age without major chronic disease (coronary disease, stroke, cancer, diabetes mellitus, or hip fracture) and mobility disability.
Design, Setting, and Participants
Examination of 36 611 women from the Women’s Health Initiative observational study and clinical trial programs who could have reached 85 years or older if they survived to the last outcomes evaluation on September 17, 2012. Recruitment was from 40 US clinical centers from October 1993 through December 1998. Multinomial logistic regression models were used to estimate odds ratios and 95% CIs for the association of baseline body mass index and waist circumference with the outcomes, adjusting for demographic, behavioral, and health characteristics.
Main Outcomes and Measures
Mutually exclusive classifications: (1) survived without major chronic disease and without mobility disability (healthy); (2) survived with 1 or more major chronic disease at baseline but without new disease or disability (prevalent diseased); (3) survived and developed 1 or more major chronic disease but not disability during study follow-up (incident diseased); (4) survived and developed mobility disability with or without disease (disabled); and (5) did not survive (died).
Mean (SD) baseline age was 72.4 (3.0) years (range, 66-81 years). The distribution of women classified as healthy, prevalent diseased, incident diseased, disabled, and died was 19.0%, 14.7%, 23.2%, 18.3%, and 24.8%, respectively. Compared with healthy-weight women, underweight and obese women were more likely to die before 85 years of age. Overweight and obese women had higher risks of incident disease and mobility disability. Disability risks were striking. Relative to healthy-weight women, adjusted odds ratios (95% CIs) of mobility disability were 1.6 (1.5-1.8) for overweight women and 3.2 (2.9-3.6), 6.6 (5.4-8.1), and 6.7 (4.8-9.2) for class I, II, and III obesity, respectively. Waist circumference greater than 88 cm was also associated with higher risk of earlier death, incident disease, and mobility disability.
Conclusions and Relevance
Overall and abdominal obesity were important and potentially modifiable factors associated with dying or developing mobility disability and major chronic disease before 85 years of age in older women.
The number of women 85 years and older in the United States is increasing rapidly, with 11.6 million projected by 2050.1 Aging without affliction of a major chronic disease or disability is a desired goal for individuals and could ease disability-related health care costs, which was approximately 27% of US health care expenditures in 2006.2
Obesity prevalence in older US women is also increasing. In 2007-2010, 40% of women aged 65 to 74 years and 29% of women 75 years and older were obese—up by 4% and 5%, respectively, from 2003-2006.3 Obesity is a modifiable risk factor for physical disability4,5 and for many diseases that are highly prevalent in older women, including cardiovascular disease, diabetes mellitus, and some cancers.6- 8 Whether obesity affects women’s capacity to reach late adulthood without major disease or disability is unknown. Characteristics associated with healthy survival in older men have been explored in the Honolulu Heart Program/Honolulu Asia Aging Study (HHP/HAAS),9,10 which found greater likelihood of late-age survival without disease and disability among men who were leaner in midlife. However, studies in older women, who live longer and whose rates of obesity, disease, and disability differ from men, are lacking. Using an ethnically diverse population of Women’s Health Initiative (WHI) participants who could be followed up to 85 years of age or death, we investigated whether obesity in older women decreased survival to 85 years of age without major disease or disability and determined whether any risks conferred varied by race/ethnicity and baseline smoking behavior.
The study sample was from the WHI observational study (OS) and clinical trial (CT) programs, which have been previously described.11,12 Briefly, postmenopausal women 50 to 79 years of age were recruited from 40 US clinical centers from October 1993 through December 1998. Enrollees participated in 1 to 3 CTs or an OS. By March 2005, all surviving participants were invited to enroll in the WHI extension study for collection of health information beyond 2005. Written informed consent was obtained from all study participants. Procedures and protocols were approved by institutional review boards at all participating institutions.
At enrollment, participants completed standardized questionnaires on demographic characteristics, health behaviors, and medical histories. Race/ethnicity was self-selected as American Indian/Alaskan Native, Asian/Pacific Islander, black/African American, Hispanic/Latina, white, or other. Hormone therapy use was self-reported (OS) or based on randomized assignment (CT). Smoking behavior was categorized into never, past, or current use. Alcohol consumption was classified into never, past, light, or moderate to heavy drinkers. Physical activity was summarized in metabolic equivalents per week, computed from self-reported duration and frequency of recreational walking or exercise.13 Depressive symptoms were assessed using the Burnham adaptation of the Center for Epidemiologic Studies Depression Scale short form.14
Trained staff measured participants’ height and weight at baseline. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Using standard World Health Organization (WHO) cut points,6 BMI was categorized as follows: underweight (<18.5), healthy weight (18.5 to <25), overweight (25 to <30), obese I (30 to <35), obese II (35 to <40), and obese III (≥40). Asian/Pacific Islander women were evaluated using WHO cut points for Asian populations15: underweight (<18.5), healthy weight (18.5 to <23), overweight (23 to <27.5), and obese (≥27.5). Waist circumference (WC) was measured during expiration at the narrowest section of the torso and dichotomized at a cut point of 88 cm.6
Major chronic diseases included coronary and cerebrovascular disease, cancer (excluding nonmelanoma skin cancer), diabetes, and hip fracture. These conditions were selected because they greatly increase a woman’s risk of death and disability and collectively account for a large proportion of later-life morbidity. Disabling diseases, such as arthritis, were captured through identification of impaired mobility. Baseline disease status was self-reported. Incident disease surveillance occurred throughout study follow-up via periodic clinic visits and mailed questionnaires, which occurred biannually for CT participants and annually for OS and extension study participants. Except for diabetes, incident disease was confirmed by physician-adjudicated medical record review. Diabetes was defined by self-reported physician diagnosis of diabetes that included oral medication or insulin treatment.16
Women who needed crutches, a walker, or a wheelchair to walk on a level surface or who self-reported on the RAND 36-Item Health Survey17 that their health greatly limited their ability to walk one block or up one flight of stairs were characterized as mobility disabled. For CT participants, assessment of mobility impairment was collected at baseline, in year 1 of follow-up, and at study closeout. A subsample of CT participants completed the assessment every 3 years from baseline to study closeout. Participants in the OS were evaluated 3 years after baseline, and extension study participants completed assessments annually.
Participant deaths were confirmed by physician adjudication of hospital records, autopsy reports, or death certificates. Periodic checks of the National Death Index for all participants, including those lost to follow-up, were performed.
We identified 43 590 WHI participants who could live to 85 years of age by surviving until September 17, 2012, the date when outcomes were last evaluated. Women were classified into mutually exclusive outcomes, modeled after the HHP/HAAS cohort of older men10: (1) survived with no major chronic disease or mobility disability (healthy); (2) survived with 1 or more major chronic disease at baseline but did not develop new disease or mobility disability during study follow-up (prevalent diseased); (3) survived and developed 1 or more major chronic disease but not mobility disability during study follow-up (incident diseased); (4) survived and developed mobility disability with or without disease (disabled); and (5) died before 85 years of age (died). Incident chronic disease and mobility disability were identified before the 85th birth year.
The potential to live to 85 years of age was the study’s only eligibility criterion. However, women who did not provide health information within 18 months of their 85th birth year (n = 5629) and women with baseline mobility disability (n = 1350) were excluded. Therefore, 36 611 women whose mean (SD) baseline age was 72.4 (3.0) years and who had up to 19 years of follow-up data were analyzed.
Baseline body measures and demographic, behavioral, and health characteristics were compared across the outcomes. Because 5 nominal outcomes were possible, multinomial logistic regression models were used to examine the association of baseline BMI or WC with the outcomes. Using maximum likelihood, we simultaneously fit models to estimate the odds ratios (ORs) and 95% CIs of classification as prevalent or incident diseased, disabled, or died relative to classification as healthy (the referent).18 All models included baseline age. Fully adjusted models also included study membership (CT vs OS), race/ethnicity, educational level, marital status, baseline hormone therapy use, smoking status, alcohol use, physical activity, and depression. The correlation between BMI and WC was evaluated. Regression models that examined baseline BMI were fit with and without adjustment for WC. The WC models were adjusted for BMI to determine any additional risk conferred by central adiposity. Analyses were repeated after excluding deaths that occurred in the first 2 years of study follow-up to address potential confounding from underlying illness. Because obesity prevalence varies by race/ethnicity and smoking behavior, stratified analyses were conducted to evaluate the consistency of associations. All analyses were completed using SAS statistical software, version 9.2 (SAS Institute Inc).
A total of 27 532 women lived to 85 years of age, of whom 6952 (25.3%) were classified as healthy, 5366 (19.5%) had prevalent disease, 8512 (30.9%) developed incident disease, and 6702 (24.3%) were classified as mobility disabled. These distributions differed by race/ethnicity and baseline smoking status (Table 1). Most women (88.5%) were white, and 19.6% of white women were classified as healthy. In contrast, the proportion classified as healthy was 12.6% and 13.3% for both black/African American and Hispanic/Latina women, respectively. Among current smokers at baseline, 48.6% died before 85 years of age compared with 20.9% and 27.1% who were never and past smokers, respectively, at baseline.
Obese women at baseline had a higher proportion of mobility disability by 85 years of age (Table 1). Although 12.0% of healthy-weight women were classified as disabled by 85 years of age, for women in the obese I, II, and III groups at baseline, the proportions were 25.5%, 33.3%, and 34.1%, respectively. Similarly, 24.8% of women with a baseline WC greater than 88 cm were categorized as disabled compared with 14.2% of women with a baseline WC of 88 cm or less.
Being underweight at baseline was not associated with having prevalent disease or with developing incident disease or a mobility disability by 85 years of age (Table 2). However, the adjusted OR (95% CI) of dying before 85 years of age was 2.1 (1.5-2.9) for underweight women compared with healthy-weight women. Similarly, the risk of earlier death was higher among obese women relative to healthy-weight women (Table 2). With an adjusted OR (95% CI) of 1.1 (1.0-1.2) compared with healthy-weight women, overweight women also had a higher, albeit moderate, risk of death before 85 years of age. However, women overweight or obese at baseline had higher risks of developing an incident disease or a mobility disability by 85 years of age relative to healthy-weight women at baseline. For women in the overweight and obese I, II, and III groups at baseline, the adjusted ORs (95% CIs) of mobility disability were 1.6 (1.5-1.8), 3.2 (2.9-3.6), 6.6 (5.4-8.1), and 6.7 (4.8-9.2), respectively, relative to healthy-weight women at baseline. Women in the obese I group at baseline had slightly higher odds of having prevalent disease compared with healthy-weight women at baseline; otherwise, no other differences in the odds of having prevalent disease were observed.
The correlation coefficient between WC and BMI was 0.8. The ORs for baseline BMI and the outcomes were attenuated but remained elevated when WC was included in the adjustments (see the eAppendix in the Supplement). Similarly, the adjusted ORs (95% CIs) of developing an incident disease or a mobility disability among women with a baseline WC greater than 88 cm, which included adjustment for baseline BMI, were 1.5 (1.3-1.6) and 1.7 (1.5-1.8), respectively, compared with women with a baseline WC of 88 cm or less. The risk of death before 85 years of age was also higher among women with a WC greater than 88 cm at baseline relative to women with a WC of 88 cm or less at baseline (Table 2). Excluding deaths from the first 2 years of study follow-up (n = 532) did not change these findings.
The association between baseline BMI and WC and the outcomes did not vary by baseline smoking status (data not shown). By race/ethnicity, 24.5%, 43.8%, 31.5%, and 6.9% of white, black/African American, Hispanic/Latina, and Asian/Pacific Islander women, respectively, were obese (Table 3). Using the WHO cut points for Asian populations, 17.2% of Asian/Pacific Islander women were obese. Black/African American women who were overweight or who had a WC greater than 88 cm at baseline and Hispanic/Latina women who were obese at baseline had higher risks of incident disease relative to their white counterparts (Table 3). Likewise, when using the WHO cut points for Asian populations, the adjusted OR (95% CI) of incident disease before 85 years of age was 2.1 (1.3-3.5) for overweight Asian/Pacific Islander women compared with overweight white women (P = .02) (data not shown).
This study of older women with a baseline age range of 66 to 81 years and nearly 19 years of follow-up found that obesity and higher WC were associated with a higher risk of death, major chronic disease, and mobility disability before reaching 85 years of age. These associations persisted after adjustment for behavioral and socioeconomic risk factors, including physical activity, smoking status, and educational level.
Women in our study demonstrated prolonged longevity, with 75.2% surviving to 85 years of age and nearly one-fifth doing so without mobility disability or a major age-related morbidity defined as a diagnosis of coronary disease, stroke, cancer, diabetes, or hip fracture. In the Cardiovascular Health Study All Stars study,19 63% of 1677 men and women 77 to 102 years of age had no physical impairment. The Framingham Heart Study20 of 2531 older adults who could survive to 85 years of age reported 36% overall survival and 22% survival without major morbidities, including cardiovascular disease, stroke, cancer, and dementia. In the HHP/HAAS,10 42% of 5820 Japanese American men survived to 85 years of age, 11% without disease and disability.
In our study, women with a BMI of 35 or higher had a more than 6-fold higher risk of mobility disability by 85 years of age compared with women with a BMI ranging from 18.5 to 24.9. Remaining mobile substantially affects quality of life, functional independence, long-term care, and risk of institutionalization.21- 23 Persons with disability use more health care services and incur an economic burden to society.24,25 In 2006, nearly 27% of total US health care costs were spent on disability-related health care expenditures.2 The population of older women is expected to increase, and the prevalence of obesity in this age group continues to rise. Thus, preventing or reducing obesity in older postmenopausal women has important individual, public health, and economic implications on later-life morbidity. There is evidence of successful interventions for weight loss in older obese women, which also demonstrated improvements in cardiometabolic risk factors.26 The risks and benefits of weight reduction strategies should continue to be researched.
Our finding of an association of BMI-defined obesity and increased risk of disability was stronger than in previous studies of older populations.5,27- 30 The differences might have occurred because our sample was older and comprised only postmenopausal women and our disability measure primarily focused on impaired mobility. Reuser et al29 reported a hazard ratio (95% CI) for disability of 2.8 (2.2-3.6) for women with a BMI of 35 or higher relative to women with a BMI of 18.5 to 24.9. Most published literature, including the study by Reuser et al, characterized disability using measures that reflect severe self-care limitations rather than measures predominantly related to impaired mobility. Obesity negatively affects the musculoskeletal system and is an important risk factor for conditions that affect mobility, such as arthritis.31 Indeed, a study32 of 282 older adults found a 7-fold higher risk of poor overall lower-extremity performance, which included walking and balancing, among persons with a BMI of 35 or higher relative to those with a BMI less than 24.9. Our definition of disability as a measure of mobility impairment may better reflect obesity-related associations.
We also reported a higher risk of mobility disability among overweight women and those with a higher WC. The association between overweight and later-life disability in the literature is mixed. Some reported an increased risk,5,29,30 whereas others found no association.4,27 Diehr et al28 reported that overweight persons spent more years without an activity-of-daily-living difficulty than healthy-weight persons, although findings were less stable in older women than men. Studies33,34 consistently reported that higher WC was a strong predictor of future mobility disability in older women.
Obese and overweight women and those with a higher WC also had increased risk of developing coronary disease, stroke, cancer, diabetes, and/or hip fracture before 85 years of age. Overall and abdominal obesity are well-established risk factors for many of these age-related chronic diseases.7,8 However, studies in exclusively older populations suggest that the magnitude of the risk might not be as strong as in younger populations. The Cardiovascular Health Study35 described no differences in the risk of myocardial infarction, stroke, and cancer among 2752 overweight, obese, and healthy-weight women 65 years or older. In another study of 70-year-old women, obesity was not associated with incident coronary disease36 or stroke.37 Folsom et al38 identified a weak increased risk of incident cancer in obese women only but a protective dose-response relationship for BMI and WC with hip fracture incidence. In contrast, studies35,38- 40 consistently reported a strong association between higher BMI and WC and increased diabetes risk. To complicate matters, many older people have multimorbidities.41 Our results suggested overweight and obesity were associated with an increased risk of developing chronic disease in late life. However, we found a weak association between BMI and survival to 85 years of age among women with major chronic disease at baseline who did not develop any new morbidity during follow-up. These women were demographically similar to the healthy survival group. This finding could be explained by self-selection. Women who entered the study with prevalent disease may be less affected by their disease history than women with these diseases who elected not to join the study. In this study, we did not delineate type, duration, severity, or number of diseases, and we did not examine characteristics associated with disease management, which are important considerations but not within the scope of this study. Of note, women characterized as “healthy” in our study were not necessarily disease free and might have had health conditions that did not cause mobility disability but were not considered, such as eye diseases.
Our results revealed a J-shaped association between BMI and mortality. This observation is consistent with the published literature27,42- 45 and suggests further consideration of healthy-weight ranges and appropriate weight reduction goals for overweight older people.35,46 Debate persists about the appropriate definition of obesity for older adults.46- 49 Waist circumferences may better represent excess abdominal fat in older people.49,50 Yet, literature on WC and mortality in older populations is mixed. In a study of women 55 years and older, only those in the highest quintile of WC (>96 cm) had an increased all-cause mortality risk, although their estimations did not adjust for BMI.38 However, women 50 years and older with a WC greater than 75 cm were found to have a higher BMI-adjusted risk of all-cause mortality, with risks increasing further as WC increased.51 We observed an increased risk of death before 85 years of age in women with a WC greater than 88 cm that was independent of BMI, suggesting that both BMI and WC may be important determinants of mortality in older women.
Underweight women in our study were at increased risk of death before 85 years of age but only represented 1.2% of our population. Hypotheses regarding the increased mortality risk in underweight women include malnutrition, frailty, and underlying disease or disability.43 Studies27,43,44,49 often exclude data from the first few follow-up visits to account for this possible confounding, but sensitivity analyses that excluded earlier deaths did not change our results.
Compared with healthy-weight women of the same race/ethnicity, black/African American women who were overweight and Hispanic/Latina women who were obese at baseline had higher risks of developing a major chronic disease by 85 years of age than white women. In addition, black/African American women with a higher WC relative to those with a lower WC had a higher risk of incident disease before 85 years of age than white women. Research that examines differences by race/ethnicity in the association of BMI to risk of late-life disease in older women is limited. However, studies consistently report that these minority groups have disproportionately higher rates of overweight and obesity3,52,53 and higher rates of major chronic diseases, including diabetes,54,55 cardiovascular disease,56- 58 and cancer.59- 61 Debate continues about whether the standard WHO definitions for overweight and obesity are appropriate for Asian populations.15,62 Reanalysis using WHO cut points for Asian populations15 suggested that overweight Asian/Pacific Islander women also had a higher risk of incident disease by late age compared with overweight white women. Confirmation in larger samples is needed, but standard WHO cut points may underestimate disease risk for Asian/Pacific Islander women.
This study has limitations. The WHI participants may have been healthier at baseline than their age counterparts in the general population. However, strong associations of body size with the outcomes were still observed. We did not include all forms of disability, such as sensory or cognitive impairment. Yet, our focus on mobility disability acknowledged the importance of maintaining the ability to walk in healthy aging, and a strong link to obesity was described. Finally, we did not consider body size changes over time, which increases during the midlife but is variable in older ages.63,64 These anthropometric changes are likely to affect health and survival in later ages, but the temporality of these changes is complex and beyond the scope of this study.
The large, diverse sample of older women, high retention and outcome ascertainment rates, and the availability of adjudicated outcomes for major diseases were study strengths. Body size measurements were clinically measured and included WC. Our analyses included nearly 19 years of follow-up data from a prospective cohort study that included women who died before 85 years of age, which cannot be captured in de novo studies of long-lived persons.
Having a healthy BMI or WC was associated with a higher likelihood of surviving to older ages without a major disease or mobility disability. In contrast, higher BMI and WC was associated with an increased risk of death before reaching 85 years of age and with late-age survival with incident disease and mobility disability. Obese women, in particular, had an increased risk of developing a mobility disability by 85 years of age. Successful strategies aimed at maintaining healthy body weight, minimizing abdominal fat accretion, and guiding safe, intentional weight loss for those who are already obese should be further investigated and disseminated.
Accepted for Publication: September 13, 2013.
Corresponding Author: Eileen Rillamas-Sun, PhD, MPH, Fred Hutchinson Cancer Research Center, Public Health Sciences, 1100 Fairview Ave N/M3-410, PO Box 19024, Seattle, WA 98019 (email@example.com).
Published Online: November 11, 2013. doi:10.1001/jamainternmed.2013.12051.
Author Contributions: Drs Rillamas-Sun and LaCroix had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Rillamas-Sun, LaCroix.
Acquisition of data: LaCroix, Vitolins, Gass, Masaki.
Analysis and interpretation of data: Rillamas-Sun, LaCroix, Waring, Kroenke, LaMonte, Vitolins, Seguin, Bell, Manini, Wallace.
Drafting of the manuscript: Rillamas-Sun, LaCroix, LaMonte, Vitolins.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Rillamas-Sun, LaCroix, Kroenke.
Obtained funding: LaCroix, Wallace.
Administrative, technical, and material support: Seguin, Bell, Masaki.
Study supervision: LaCroix, Wallace.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by grants U01HL105268 and UL1RR031982 (Dr Waring) and K01HL108807-01 (Dr Seguin) from the National Institute of Health; the WHI program is funded by contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C from the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services.
Role of the Sponsor: The National Heart, Lung, and Blood Institute has representation on the WHI Steering Committee, which governed the design and conduct of the study, the interpretation of the data, and preparation and approval of manuscripts.
Additional Contributions: Chris Tachibana, PhD, of the Group Health Research Institute, reviewed the manuscript and provided editorial guidance. Dr Tachibana did not receive compensation for her contribution to the manuscript.