Fitness and Mortality Among Persons 70 Years and Older Across the Spectrum of Cardiovascular Disease Risk Factor Burden: The FIT Project.

OBJECTIVE: To determine whether fitness could improve mortality risk stratification among older adults compared with cardiovascular disease (CVD) risk factors. METHODS: We examined 6509 patients 70 years of age and older without CVD from the Henry Ford ExercIse Testing Project (FIT Project) cohort. Patients performed a physician-referred treadmill stress test between 1991 and 2009. Traditional categorical CVD risk factors (hypertension, hyperlipidemia, diabetes, and smoking) were summed from 0 to 3 or more. Fitness was grouped as low, moderate, and high (<6, 6 to 9.9, and ≥10 metabolic equivalents of task). All-cause mortality was ascertained through US Social Security Death Master files. We calculated age-adjusted mortality rates, multivariable adjusted Cox proportional hazards, and Kaplan-Meier survival models. RESULTS: Patients had a mean age of 75±4 years, and 3385 (52%) were women; during a mean follow-up of 9.4 years, there were 2526 deaths. A higher fitness level (P<.001), not lower CVD risk factor burden (P=.31), was associated with longer survival. The age-adjusted mortality rate per 1000 person-years was 56.7 for patients with low fitness and 0 risk factors compared with 24.9 for high fitness and 3 or more risk factors. Among patients with 3 or more risk factors, the adjusted mortality hazard was 0.68 (95% CI, 0.61 to 0.76) for moderate and 0.51 (95% CI, 0.44 to 0.60) for high fitness compared with the least fit. CONCLUSION: Among persons aged 70 years and older, there was no significant difference in survival of patients with 0 vs 3 or more risk factors, but a higher fitness level identified older persons with good long-term survival regardless of CVD risk factor burden.

Association of BMI, Fitness, and Mortality in Patients With Diabetes: Evaluating the Obesity Paradox in the Henry Ford Exercise Testing Project (FIT Project) Cohort.

OBJECTIVE: To determine the effect of fitness on the association between BMI and mortality among patients with diabetes. RESEARCH DESIGN AND METHODS: We identified 8,528 patients with diabetes (self-report, medication use, or electronic medical record diagnosis) from the Henry Ford Exercise Testing Project (FIT Project). Patients with a BMI <18.5 kg/m2 or cancer were excluded. Fitness was measured as the METs achieved during a physician-referred treadmill stress test and categorized as low (<6), moderate (6-9.9), or high (≥10). Adjusted hazard ratios for mortality were calculated using standard BMI (kilograms per meter squared) cutoffs of normal (18.5-24.9), overweight (25-29.9), and obese (≥30). Adjusted splines centered at 22.5 kg/m2 were used to examine BMI as a continuous variable. RESULTS: Patients had a mean age of 58 ± 11 years (49% women) with 1,319 deaths over a mean follow-up of 10.0 ± 4.1 years. Overall, obese patients had a 30% lower mortality hazard (P < 0.001) compared with normal-weight patients. In adjusted spline modeling, higher BMI as a continuous variable was predominantly associated with a lower mortality risk in the lowest fitness group and among patients with moderate fitness and BMI ≥30 kg/m2. Compared with the lowest fitness group, patients with higher fitness had an ∼50% (6-9.9 METs) and 70% (≥10 METs) lower mortality hazard regardless of BMI (P < 0.001). CONCLUSIONS: Among patients with diabetes, the obesity paradox was less pronounced for patients with the highest fitness level, and these patients also had the lowest risk of mortality.

Exercise Capacity and the Obesity Paradox in Heart Failure: The FIT (Henry Ford Exercise Testing) Project.

OBJECTIVES: To assess the influence of exercise capacity and body mass index (BMI) on 10-year mortality in patients with heart failure (HF) and to synthesize these results with those of previous studies. PATIENTS AND METHODS: This large biracial sample included 774 men and women (mean age, 60±13 years; 372 [48%] black) with a baseline diagnosis of HF from the Henry Ford Exercise Testing (FIT) Project. All patients completed a symptom-limited maximal treadmill stress test from January 1, 1991, through May 31, 2009. Patients were grouped by World Health Organization BMI categories for Kaplan-Meier survival analyses and stratified by exercise capacity (<4 and ≥4 metabolic equivalents [METs] of task). Associations of BMI and exercise capacity with all-cause mortality were assessed using multivariable-adjusted Cox proportional hazards models. RESULTS: During a mean follow-up of 10.1±4.6 years, 380 patients (49%) died. Kaplan-Meier survival plots revealed a significant positive association between BMI category and survival for exercise capacity less than 4 METs (log-rank, P=.05), but not greater than or equal to 4 METs (P=.76). In the multivariable-adjusted models, exercise capacity (per 1 MET) was inversely associated, but BMI was not associated, with all-cause mortality (hazard ratio, 0.89; 95% CI, 0.85-0.94; P<.001 and hazard ratio, 0.99; 95% CI, 0.97-1.01; P=.16, respectively). CONCLUSION: Maximal exercise capacity modified the relationship between BMI and long-term survival in patients with HF, upholding the presence of an exercise capacity-obesity paradox dichotomy as observed over the short-term in previous studies.

Fitness, Fatness, and Mortality: The FIT (Henry Ford Exercise Testing) Project.

BACKGROUND: The combined influence of fitness and fatness on mortality risk in diverse populations has not been adequately explored. Our aim was to assess the relative impact of exercise capacity and body mass index (BMI) on all-cause mortality. METHODS: We included 29,257 men and women (mean age 53 years; 27% African American) from The Henry Ford Exercise Testing (FIT) Project without cardiovascular disease and diabetes mellitus at baseline. All patients completed a symptom-limited maximal treadmill stress test between 1991 and 2009. Patients were grouped for analysis by exercise capacity (≥10 metabolic equivalents of task [METs] and <10 METs) and obesity status (≥30 kg/m(2) and <30 kg/m(2)), forming 4 subgroups. Independent and joint associations of BMI and exercise capacity with all-cause mortality were assessed using Cox proportional hazard models. RESULTS: During a mean follow-up of 10.8 years, 1898 patients (6.5%) died. We observed a strong inverse association between exercise capacity (per 1 MET unit) and all-cause mortality (hazard ratio [95% confidence interval], 0.86 [0.85-0.88]). Body mass index (per 1 BMI unit) was inversely related to mortality (hazard ratio [95% confidence interval], 0.98 [0.97-0.99]). In joint analysis, the highest mortality risk was in the <10 METs/<30 kg/m(2) subgroup. CONCLUSIONS: Reduced exercise capacity was a strong independent risk factor for all-cause mortality in this racially diverse population. Given the comparatively limited impact of BMI, more emphasis should be placed on measuring exercise capacity and developing strategies for its improvement in cardiovascular disease prevention programs.

Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status.

The evolution from hunting and gathering to agriculture, followed by industrialization, has had a profound effect on human physical activity (PA) patterns. Current PA patterns are undoubtedly the lowest they have been in human history, with particularly marked declines in recent generations, and future projections indicate further declines around the globe. Non-communicable health problems that afflict current societies are fundamentally attributable to the fact that PA patterns are markedly different than those for which humans were genetically adapted. The advent of modern statistics and epidemiological methods has made it possible to quantify the independent effects of cardiorespiratory fitness (CRF) and PA on health outcomes. Based on more than five decades of epidemiological studies, it is now widely accepted that higher PA patterns and levels of CRF are associated with better health outcomes. This review will discuss the evidence supporting the premise that PA and CRF are independent risk factors for cardiovascular disease (CVD) as well as the interplay between both PA and CRF and other CVD risk factors. A particular focus will be given to the interplay between CRF, metabolic risk and obesity.

Obesity and prognosis in chronic diseases--impact of cardiorespiratory fitness in the obesity paradox.

The effects of overweight and obesity on chronic diseases, particularly on cardiovascular disease (CVD), and its impact on increasing CVD risk factors and total CVD are reviewed. However despite the adverse effects of obesity on CVD risk factors and CVD, obesity has a surprising association with prognosis in patients with established diseases, often showing an "obesity paradox," [corrected] where overweight (body mass index (BMI), 25 to 29.9 kg·m(-2)) and obese patients (BMI, ≥30 kg·m(-2)) with established CVD frequently have a better prognosis than that of their leaner counterparts (BMI, <25 kg·m(-2)) with the same diseases. Fitness-versus-fatness debate is summarized also, including the critical role that fitness plays to alter the relationship between adiposity and subsequent prognosis.

Cardiorespiratory fitness and the paradoxical BMI-mortality risk association in male veterans.

OBJECTIVE: To assess the effect of fitness status on the paradoxical body mass index (BMI)-mortality risk association. PATIENTS AND METHODS: From February 1, 1986, through December 30, 2011, we assessed fitness and BMI in 18,033 male veterans (mean age, 58.4 ± 11.4 years) in 2 Veterans Affairs Medical centers. We established 3 fitness categories on the basis of peak metabolic equivalents achieved during an exercise test as well as 5 BMI categories. The primary outcome was all-cause mortality. RESULTS: During the follow-up period (median, 10.8 years, comprising a total of 207,168 person-years), 5070 participants (28%) died. After adjusting for age, risk factors, muscle-wasting diseases, medications, and year of entry, mortality risk was higher for individuals with a BMI of 20.1 to 23.9 kg/m(2) (hazard ratio [HR], 1.21; 95% CI, 1.12-1.30) and 18.5 to 20.0 kg/m(2) (HR, 1.56; 95% CI, 1.37-1.77) than for those with a BMI of 24.0 to 27.9 kg/m(2); mortality risk was not increased for those with a BMI of 28.0 kg/m(2) or greater. When stratified by fitness, the trend was similar for low-fit and moderate-fit individuals. However, mortality risk was not increased for high-fit individuals across BMI categories. When fitness status was considered within each BMI category, mortality risk increased progressively with decreased fitness and was more pronounced for moderate-fit (HR, 2.52; 95% CI, 2.06-3.08) and low-fit (HR, 2.48; 95% CI, 2.0-3.06) individuals with a BMI of 18.5-20.0 kg/m(2). Mortality risk was not significantly increased for high-fit individuals (HR, 1.17; 95% CI, 0.78-1.78; P=.45). CONCLUSION: A high mortality risk associated with low BMI levels was observed only in moderate-fit and low-fit individuals, and not in high-fit individuals. Thus, fitness greatly affects the paradoxical BMI-mortality risk association. Furthermore, our findings indicate that lower BMI levels do not increase the risk for premature death as long as they are associated with high fitness. Thus, the paradoxically higher mortality risk observed with lower body weight as represented by lower BMI is likely the result of unhealthy reduction in body weight and, perhaps most importantly, considerable loss of lean body mass.

Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox.

Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrated an association of mild obesity and, particularly, overweight on improved survival. We review in detail the obesity paradox in CV diseases where overweight and at least mildly obese patients with most CV diseases seem to have a better prognosis than do their leaner counterparts. The implications of cardiorespiratory fitness with prognosis are discussed, along with the joint impact of fitness and adiposity on the obesity paradox. Finally, in light of the obesity paradox, the potential value of purposeful weight loss and increased physical activity to affect levels of fitness is reviewed.

Contribution of cardiorespiratory fitness to the obesity paradox.

Until recently, cardiorespiratory fitness (CRF) has been overlooked as a potential modifier of the inverse association between obesity and mortality (the so-called obesity paradox), observed in patients with known or suspected cardiovascular (CV) disease. Evidence from five observational cohort studies of 30,104 patients (87% male) with CV disease indicates that CRF significantly alters the obesity paradox. There is general agreement across studies that the obesity paradox persists among patients with low CRF, regardless of whether adiposity is assessed by body mass index, waist circumference, or percentage body fat. However, among patients with high CRF, risk of all-cause mortality is lowest for the overweight category in some, but not all, studies, suggesting that higher levels of fitness may modify the relationship between body fatness and survival in patients manifesting an obesity paradox. Further study is needed to better characterize the joint contribution of CRF and obesity on mortality in diverse populations.

Physical activity, measures of obesity, and cardiometabolic risk: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: The influence of higher physical activity on the relationship between adiposity and cardiometabolic risk is not completely understood. METHODS: Between 2000-2002, data were collected on 6795 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Self-reported intentional physical activity in the lowest quartile (0-105 MET-minutes/week) was categorized as inactive and the upper three quartiles (123-37,260 MET-minutes/week) as active. Associations of body mass index (BMI) and waist circumference categories, stratified by physical activity status (inactive or active) with cardiometabolic risk factors (dyslipidemia, hypertension, upper quartile of homeostasis model assessment of insulin resistance [HOMA-IR] for population, and impaired fasting glucose or diabetes) were assessed using logistic regression analysis adjusting for age, gender, race/ethnicity, and current smoking. RESULTS: Among obese participants, those who were physically active had reduced odds of insulin resistance (47% lower; P < .001) and impaired fasting glucose/diabetes (23% lower; P = .04). These associations were weaker for central obesity. However, among participants with a normal waist circumference, those who were inactive were 63% more likely to have insulin resistance (OR [95% CI] 1.63 [1.24-2.15]) compared with the active reference group. CONCLUSIONS: Physical activity was inversely related to the cardiometabolic risk associated with obesity and central obesity.

Fitness, fatness, and survival in adults with prediabetes.

OBJECTIVE: The purpose of this study was to examine independent and joint associations of cardiorespiratory fitness (CRF) and different adiposity measures with mortality risk in individuals with prediabetes (or impaired fasting glucose). RESEARCH DESIGN AND METHODS: We examined associations of CRF and fatness with cardiovascular disease (CVD) and all-cause mortality in a cohort of 17,044 participants (89% men) with prediabetes (defined as 100 mg/dL ≤ fasting plasma glucose < 126 mg/dL), who did not have a history of diabetes, CVD, or cancer. RESULTS: We identified 832 deaths (246 from CVD) during 13.9 ± 7.0 years (mean ± SD) follow-up. Normal-weight individuals who were unfit (lowest one-third) had a higher risk of all-cause (hazard ratio 1.70 [95% CI 1.32-2.18]) and CVD (1.88 [1.13-3.10]) mortality compared with the normal-weight and fit (upper two-thirds) reference group in a model adjusted for age, sex, examination year, and multiple risk factors. The mortality risk for fit individuals who were overweight or obese did not differ significantly from the reference group. Similar patterns were observed for sex-specific thirds of waist circumference and % body fat. CONCLUSIONS: CRF markedly modifies the relationship between adiposity and mortality in persons with prediabetes. Unfit individuals have a higher and fit individuals have a lower mortality risk irrespective of adiposity level in this high-risk group.

The obesity paradox and cardiorespiratory fitness.

Cardiorespiratory fitness as an explanation for the obesity paradox warrants further examination. We evaluated independent and joint associations of cardiorespiratory fitness and adiposity with all-cause mortality in 811 middle-aged (age, 53.3 ± 7.2 years) male never smokers without documented cardiopulmonary disease or diabetes from the Veterans Exercise Testing Study (VETS). Cardiorespiratory fitness was quantified in metabolic equivalents (METs) using final treadmill speed and grade achieved on a maximal exercise test. Subjects were grouped for analysis by METs: unfit (lowest third) and fit (upper two-thirds); and by body mass index (kg/m(2)): nonobese (18.5-29.9) and obese (≥30.0). Associations of baseline fitness and adiposity measures with all-cause mortality were determined by Cox proportional hazards analysis adjusted for age, ethnicity, hypertension, hypercholesterolemia, family history of coronary artery disease, and cardiovascular medication use. In multivariate analysis, mortality risk for obese/fit men did not differ significantly from the nonobese/fit reference group. However, compared to the reference group, nonobese and obese unfit men were 2.2 (P = 0.01) and 1.9 (P = 0.03) times more likely to die, respectively. Cardiorespiratory fitness altered the obesity paradox such that mortality risk was lower for both obese and nonobese men who were fit.

The obesity paradox, cardiorespiratory fitness, and coronary heart disease.

OBJECTIVE: To investigate associations of cardiorespiratory fitness (CRF) and different measures of adiposity with cardiovascular disease (CVD) and all-cause mortality in men with known or suspected coronary heart disease (CHD). PATIENTS AND METHODS: We analyzed data from 9563 men (mean age, 47.4 years) with documented or suspected CHD in the Aerobics Center Longitudinal Study (August 13, 1977, to December 30, 2002) using baseline body mass index (BMI) and CRF (quantified as the duration of a symptom-limited maximal treadmill exercise test). Waist circumference (WC) and percent body fat (BF) were measured using standard procedures. RESULTS: There were 733 deaths (348 of CVD) during a mean follow-up of 13.4 years. After adjustment for age, examination year, and multiple baseline risk factors, men with low fitness had a higher risk of all-cause mortality in the BMI categories of normal weight (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.24-2.05), obese class I (HR, 1.38; 95% CI, 1.04-1.82), and obese class II/III (HR, 2.43; 95% CI, 1.55-3.80) but not overweight (HR, 1.09; 95% CI, 0.88-1.36) compared with the normal-weight and high-fitness reference group. We observed a similar pattern for WC and percent BF tertiles and for CVD mortality. Among men with high fitness, there were no significant differences in CVD and all-cause mortality risk across BMI, WC, and percent BF categories. CONCLUSION: In men with documented or suspected CHD, CRF greatly modifies the relation of adiposity to mortality. Using adiposity to assess mortality risk in patients with CHD may be misleading unless fitness is considered.

Long-term effects of changes in cardiorespiratory fitness and body mass index on all-cause and cardiovascular disease mortality in men: the Aerobics Center Longitudinal Study.

BACKGROUND: The combined associations of changes in cardiorespiratory fitness and body mass index (BMI) with mortality remain controversial and uncertain. METHODS AND RESULTS: We examined the independent and combined associations of changes in fitness and BMI with all-cause and cardiovascular disease (CVD) mortality in 14 345 men (mean age 44 years) with at least 2 medical examinations. Fitness, in metabolic equivalents (METs), was estimated from a maximal treadmill test. BMI was calculated using measured weight and height. Changes in fitness and BMI between the baseline and last examinations over 6.3 years were classified into loss, stable, or gain groups. During 11.4 years of follow-up after the last examination, 914 all-cause and 300 CVD deaths occurred. The hazard ratios (95% confidence intervals) of all-cause and CVD mortality were 0.70 (0.59-0.83) and 0.73 (0.54-0.98) for stable fitness, and 0.61 (0.51-0.73) and 0.58 (0.42-0.80) for fitness gain, respectively, compared with fitness loss in multivariable analyses including BMI change. Every 1-MET improvement was associated with 15% and 19% lower risk of all-cause and CVD mortality, respectively. BMI change was not associated with all-cause or CVD mortality after adjusting for possible confounders and fitness change. In the combined analyses, men who lost fitness had higher all-cause and CVD mortality risks regardless of BMI change. CONCLUSIONS: Maintaining or improving fitness is associated with a lower risk of all-cause and CVD mortality in men. Preventing age-associated fitness loss is important for longevity regardless of BMI change.

Liver attenuation, pericardial adipose tissue, obesity, and insulin resistance: the Multi-Ethnic Study of Atherosclerosis (MESA).

Insulin resistance is linked to general and abdominal obesity, but its relation to hepatic lipid content and pericardial adipose tissue is less clear. The purpose of this study was to examine cross-sectional associations of liver attenuation, pericardial adipose tissue, BMI, and waist circumference with insulin resistance. We measured liver attenuation and pericardial adipose tissue using the existing cardiac computed tomography scans in 5,291 individuals free of clinical cardiovascular disease and diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA) during the study's baseline visit (2000-2002). Low liver attenuation was defined as the lowest quartile and high pericardial adipose tissue as the upper quartile of volume (cm(3)). We used standard clinical definitions for obesity and abdominal obesity. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA(IR)) index. In multivariate linear regression with all adiposity measures in the model simultaneously, all adiposity measures were significantly (P < 0.0001) associated with insulin resistance: regression coefficients (±s.e.) were 0.31 (±0.02) for low liver attenuation, 0.27 (±0.02) for high pericardial adipose tissue, 0.27 (±0.02) for obesity, and 0.32 (±0.02) for abdominal obesity. We found significant differences (P = 0.003) between standardized liver attenuation and insulin resistance by ethnicity: regression coefficients per 1 s.d. increment were 0.10 ± 0.01 for whites, 0.11 ± 0.02 for Chinese, 0.08 ± 0.2 for blacks, and 0.14 ± 0.01 for Hispanics. Liver attenuation and pericardial adipose tissue were associated with insulin resistance, independent of BMI and waist circumference.

The obesity paradox and weight loss.

BACKGROUND: An "obesity paradox," in which overweight and obese individuals with established cardiovascular disease have a better prognosis than normal weight subjects, has been reported in a number of clinical cohorts, but little is known about the effects of weight loss on the obesity paradox and its association with health outcomes. METHODS: Weight was determined in 3834 men at the time of a clinically referred exercise test and again during a clinical evaluation a mean of 7 years later. The associations among weight changes, baseline fitness, and other risk markers with cardiovascular and all-cause mortality were determined by Cox proportional hazards analysis. RESULTS: During the follow-up period, 314 subjects died (72 of cardiovascular causes). In a multivariate analysis (including baseline weight, weight change, exercise capacity, and cardiovascular disease), weight gain was associated with lower mortality and weight loss was associated with higher mortality (4% higher per pound lost per year, P<.001) compared with stable weight. For all-cause mortality, the relative risks for the no change, weight gain, and weight loss groups were 1.0 (referent), 0.64 (95% confidence interval, 0.50-0.83), and 1.49 (95% confidence interval, 1.17-1.89), respectively (P<.001). Those who died and exhibited weight loss had a significantly higher prevalence of deaths due to cancer and cardiovascular causes. CONCLUSION: Weight loss was related to higher mortality and weight gain was related to lower mortality when compared with stable weight. The obesity paradox in our sample is explained in part by a combination of non-volitional weight loss related to occult disease and a protective effect of weight gain.

Obesity paradoxes.

In this review, we examine the original obesity paradox phenomenon (i.e. in cardiovascular disease populations, obese patients survive better), as well as three other related paradoxes (pre-obesity, "fat but fit" theory, and "healthy" obesity). An obesity paradox has been reported in a range of cardiovascular and non-cardiovascular conditions. Pre-obesity (defined as a body mass index of 25.0-29.9 kg · m⁻²) presents another paradox. Whereas "overweight" implies increased risk, it is in fact associated with decreased mortality risk compared with normal weight. Another paradox concerns the observation than when fitness is taken into account, the mortality risk associated with obesity is offset. The final paradox under consideration is the presence of a sizeable subset of obese individuals who are otherwise healthy. Consequently, a large segment of the overweight and obese population is not at increased risk for premature death. It appears therefore that low cardiorespiratory fitness and inactivity are a greater health threat than obesity, suggesting that more emphasis should be placed on increasing leisure time physical activity and cardiorespiratory fitness as the main strategy for reducing mortality risk in the broad population of overweight and obese adults.

Cardiorespiratory fitness, different measures of adiposity, and total cancer mortality in women.

The objective was to examine associations among cardiorespiratory fitness (CRF), adiposity, and cancer mortality in women. Healthy women (N = 14,256) without cancer history completed a baseline health examination 1970-2005. Measures included BMI, percent body fat (%Fat), and CRF quantified as duration of a maximal treadmill test. CRF was classified as low (quintile 1), moderate (Q2-3), and high fit (Q4-5) by age. Standard BMI cutpoints were used, while participants were classified by %Fat quintiles. Cancer mortality rates were calculated following age, exam year, and smoking adjustment. During a mean follow-up period of 15.2 ± 9.4 years, 250 cancer deaths occurred. Adjusted mortality rates across BMI groups were 4.6, 5.7, and 8.8 (P trend 0.08); %Fat 3.0, 4.9, 2.9, 3.8, and 6.9 (P trend 0.17); and CRF 7.9, 5.5, and 2.9 (P trend 0.003). When grouped into categories of fit and unfit (upper 80% and lower 20% of CRF distribution), and using BMI as the adiposity exposure, cancer mortality rates of unfit-obese women were significantly higher than fit-normal weight women (9.8 vs. 4.1 deaths/10,000 woman-years; P = 0.02), while fit-overweight and fit-obese women had no greater risk of mortality than fit-normal weight women. Using %Fat as the adiposity exposure, unfit-obese women tended to have higher cancer mortality than fit-normal weight women (7.0 vs. 3.3 deaths/10,000 woman-years, P = 0.10). Higher levels of CRF are associated with lower cancer mortality risk in women and attenuate the risk of cancer mortality in overweight women. Using adiposity measures to estimate cancer mortality risk in women can be potentially misleading unless CRF is considered.

Cardiorespiratory fitness, adiposity, and all-cause mortality in women.

PURPOSE: To determine the prospective associations among cardiorespiratory fitness (CRF), different measures of adiposity, and all-cause mortality in women. METHODS: A total of 11,335 women completed a comprehensive baseline examination between 1970 and 2005. Clinical measures included body mass index (BMI), waist circumference (WC), waist-to-height ratio (W/HT), waist-to-hip ratio (W/Hip), percent body fat (%BF), and CRF quantified as duration of a maximal exercise test. Participants were classified by CRF as low (lowest 20%), moderate (middle 40%), and high (highest 40%) as well as by standard clinical cut points for adiposity measures. Hazard ratios (HR) were computed using Cox regression analysis. RESULTS: During a mean follow-up of 12.3 ± 8.2 yr, 292 deaths occurred. HR for all-cause mortality were 1.0, 0.60, and 0.54 for low, moderate, and high fit groups, respectively (P for trend G0.01). Adjusted death rates of overweight/obese women within each adiposity exposure were somewhat higher compared with normal-weight women and approached statistical significance for BMI, %BF, and W/HT (P = 0.08, P = 0.08, and P = 0.07, respectively). When grouped for joint analyses into categories of fit and unfit (upper 80% and lower 20% of CRF distribution, respectively), HR were significantly higher in unfit women within each stratum of BMI compared with fit­normal BMI women. Fit women with high %BF (HR = 1.0), high WC (HR = 0.9), and high W/HT (HR = 1.2) had no greater risk of death compared with fit­normal-weight women (referent). CONCLUSIONS: Low CRF in women was a significant independent predictor of all-cause mortality. Higher CRF was associated with lower mortality within each category of each adiposity exposure. Using adiposity measures as predictors of all-cause mortality in women may be misleading unless CRF is also considered.