We addressed the single and joint associations among CRF, BMI, and the risk of mortality among women with IFG
and undiagnosed DM. Low CRF was associated with a significantly higher risk of all-cause mortality, and this inverse association remained significant after the analyses were adjusted for age, year of examination, smoking status, alcohol intake, prevalence of hypertension, hypercholesterolemia, family history of DM, and BMI at baseline. No association was observed between being overweight or obese and overall deaths. The protective effect of CRF held true for overweight or obese women, whereas the death rate among unfit women with higher BMI (≥25 kg/m2) was more than twice that among fit women with higher BMI.
We have found no previous reports of an association between CRF and risk of all-cause mortality among women with IFG or undiagnosed DM. Most of the few published studies focused on patients with abnormal glucose metabolism or on men only or a combination of women and men. Wei et al8
examined this association among 1263 middle-aged men and found that the adjusted risk of all-cause mortality among men in the low CRF group was 2.1-fold higher (95% CI, 1.5- to 2.9-fold) than that of physically active men and that the adjusted risk of all-cause mortality among men classifying themselves as physically inactive was 1.7-fold higher (95% CI, 1.2-fold to 2.3-fold) than that among men who were physically active. They also found that both low CRF and physical inactivity were independent predictors of all-cause mortality among men with DM. A study by Church et al9
involving 2196 middle-aged men with DM found that the mortality risk was 4.5 (95% CI, 2.6-7.6), 2.8 (95% CI, 1.6-4.7), and 1.6 (95% CI, 0.93-2.76) across the first 3 fitness quartiles; the fourth quartile served as the reference group (P
for trend <.0001). This steep inverse association between CRF and all-cause mortality was found to be independent of BMI.9
Kavanagh et al28,29
also found an inverse association between CRF and risk of all-cause mortality among men who either had undergone a heart transplant or were candidates for cardiovascular rehabilitation. Most studies focusing on the association between CRF and mortality have focused on sedentary but apparently healthy persons.12
Our results provide evidence that supports the formal assessment of CRF among women with IFG and the use of this
information in physical activity counseling aimed at reducing the risk of premature death.
Although it is well recognized that IFG is a risk factor for the development of DM, Barr et al1
demonstrated that IFG is an independent risk factor for increased mortality, not simply an antecedent of DM. These findings suggest that strategies aimed at preventing premature mortality should focus on persons at earlier stages of metabolic dysfunction, such as IFG, and not only on those with frank DM. Thompson et al30
found that young, urban Native American women with lower CRF levels were at a higher risk of IFG, but not of metabolic syndrome, when the statistical analyses were adjusted for BMI. This finding further supports the suggestion by Barr et al1
that IFG is an important risk factor for premature mortality. The findings of these 2 studies also further support our recommendation that the CRF of women with IFG be assessed by formal treadmill testing for a determination of which groups are at higher risk of mortality. These women should be counseled to intensify their physical activity as a part of primary prevention efforts.
Obesity is an independent risk factor for mortality among women,13-17
but little is known about the mortality risk of women with IFG and DM. The current study found
no association between obesity and mortality, a finding that agrees with the observations of Johnson et al.31
Some studies have also found an inverse association between BMI and mortality, a finding termed the obesity paradox
The mechanism responsible for this paradox is currently unclear, but the finding is more common among patients with CVD.32,33
This paradox may be explained by nonpurposeful weight loss before study participation or by dyspnea due to deconditioning (caused by factors other than CVD) among obese patients.33
Another explanation for the paradox may be the limitations associated with using BMI to define at-risk obesity. However, Lavie et al found that a higher percentage of body fat predicts a better prognosis for patients with heart failure33
and coronary heart disease.34
Further research is warranted in this area, but these findings are in direct contrast to those of most other studies, which have found either a J-shaped or a U-shaped association between BMI and mortality risk.13-17
In the current study, low fitness was associated with a higher risk of mortality in 51% of obese patients, 20% of overweight patients, and 10% of patients of normal weight; these rates were higher than those of women with all other combinations of CRF and BMI (). This association between low fitness and higher risk of mortality was also found when the overweight and obese groups were combined. Higher fitness was associated with a lower risk of overall mortality for overweight or obese women but not for normal-weight women, although there was a nonsignificant trend in this direction.
Although CRF has a genetic component (25%-40% of cases),12,35,36
the primary determinant of fitness is the physical activity routine. Recently, Church et al37
reported that women with activity levels as low as 4 kcal/kg/wk (approximately 72 min/wk of moderate-intensity walking) experienced significant improvements in CRF when they were compared with women in a control group who did not exercise. Engaging in activities such as brisk walking, bicycling, or jogging for 30 minutes or more on most days of the week30
would move most of these women out of the low fitness category.
This study has several strengths, including the extensive baseline examination aimed at detecting subclinical disease, the use of measured risk factors, the relatively long follow-up period (average, 15 years), and the broad age range of the study population (20-79 years).
One limitation of this study is homogeneity of the patient population: patients were predominantly white, well-educated, middle- to upper-class, and female. This homogeneity limits our ability to generalize our findings to a broader population but should not affect the internal validity of the study. There is no strong reason to assume that CRF assessment would have fewer benefits for men or other ethnic groups. Our previous studies, in which the number of deaths that occurred was sufficient to allow parallel analyses of women and men, showed that the inverse gradient of mortality across CRF groups is similar for men and women.9,38-40
In terms of exposure assessment, we classified women according to CRF at the time of study enrollment, but in the current analysis we were unable to evaluate the effect on outcome of changes in fitness or BMI over time. During the follow-up interval, many women in the low fitness category may have increased their fitness levels, and many obese women may have decreased their BMI. Therefore, we cannot determine whether changes in fitness, obesity status, or both occurred during follow-up or if there were any other exposures. However, such misclassification of exposure would probably lead to an underestimation of the magnitude of the associations observed in the current study.