The primary finding of this study is that maintaining or improving fitness was associated with a lower risk of both all-cause and CVD mortality compared with losing fitness in 14 345 adult men, during 11.4 years of follow-up. Every 1 maximal MET improvement was associated with 15% and 19% lower risk of all-cause and CVD mortality, respectively. Also, men who became fit or remained fit had a lower risk of all-cause and CVD mortality compared with men who remained unfit. These associations were observed after accounting for possible confounding effects of baseline risk factors, changes in lifestyle factors and medical conditions, and simultaneous change in BMI. Moreover, these findings were consistent regardless of their baseline fitness levels, and exclusion of early deaths did not alter the results. Only two previous cohort studies on fitness change and mortality reported similar results, indicating a reduced mortality risk with improvements in fitness. Our earlier ACLS report found that both healthy and unhealthy men who maintained or improved fitness were less likely to die over 5 years of follow-up.10
A Norwegian study found an inverse relation between fitness change and mortality in 1428 men aged 40–60 at baseline after excluding those with any recognized disease.11
Compared with these previous studies, our current study has much larger sample size over a wider age range (20 to 100 years at baseline) and a longer follow-up time. We also take changes in lifestyle factors, medical conditions, and BMI into account. A recent meta-analysis on the association between a single assessment of fitness and mortality reported that a 1-MET higher level of fitness at baseline was associated with 13% lower risk of all-cause mortality during follow-up.2
Our current results of 15% and 19% lower risk of all-cause and CVD mortality, respectively, with every 1-MET improvement after further adjusting for BMI change confirms the strong effects of not only baseline fitness but also fitness change on all-cause and CVD mortality, independently of simultaneous change in BMI.
The most important original finding from our combined analysis is that men who lost fitness had a higher mortality risk regardless of BMI change compared with the reference group, men who improved fitness and lost BMI. However, men who maintained or improved their fitness were more likely to attenuate the potentially negative effects of BMI increase on all-cause and CVD mortality. Because we could not find similar studies examining the combined associations of changes in fitness and BMI with mortality, we could not directly compare our results with others. However, in our earlier studies on the joint associations of fitness and BMI at a single baseline assessment with mortality, we found comparable results indicating the higher risk of all-cause and CVD mortality associated with being unfit regardless of BMI status in adult men,22
and men with diabetes21
Also, other studies reported a higher risk of all-cause and CVD mortality in unfit men regardless of their BMI status.24,25
In the relations between change in fitness and changes in lifestyle factors and medical conditions, men who became sedentary, started smoking, or developed disease such as hypertension or diabetes were more likely to decrease their fitness levels, after adjusting for BMI change (data not shown), as stated earlier.3,10,31,32
The strongest association was observed between changes in physical activity and fitness indicating that among men who became active, 80% of them maintained or improved their fitness, whereas among men who became sedentary, 47% of them lost their fitness levels (data not shown). Although fitness has some genetic components, it is suggested that physical activity is likely one of the important mechanisms explaining fitness change.
In this study, BMI change was not significantly associated with all-cause mortality, and the observed higher risk of CVD mortality associated with BMI gain was no longer significant once fitness change was taken into account, indicating modifiable effects by fitness change on the association between BMI change and CVD mortality. These findings were consistent after further consideration of subclinical conditions by excluding early deaths, and also irrespective of baseline BMI status. Although overweight and obesity defined at a single baseline assessment are well-established mortality predictors,7–9,33
prospective studies of long-term BMI change and mortality have remained controversial. Some studies showed similar results to ours, indicating no significant associations between BMI or weight change and all-cause or CVD mortality after taking preexisting diseases into account.34–36
Others reported that BMI or weight loss is associated with a higher mortality risk.37–40
However, it is suggested that the association between BMI or weight loss and a higher mortality risk may be due to failure to control medical conditions.34,36,41
In fact, many studies reporting a higher risk of mortality associated with BMI or weight loss appeared to have some limitations due to lack of adequate health and medical information or failure to control for preexisting diseases or subclinical conditions, leading to both weight loss and a high risk of mortality. We excluded men with CVD, cancer, underweight (BMI<18.5 kg/m2
), or men not reaching 85% of age-predicted maximal heart rate on the treadmill test not only at the baseline but also at the last examination prior to the subsequent mortality follow-up. We also excluded men reporting unexplained weight change at the last examination. Furthermore, changes in lifestyle factors and medical conditions were taken into account in the analysis. We believe these extensive exclusion criteria and comprehensive analysis can minimize the possible bias from preexisting or subclinical conditions on the associations of changes in fitness and BMI with mortality. Because none of the previous studies on weight change have considered fitness change in their analyses, it is hard to assess whether BMI or weight change is associated with mortality independent of fitness change in other studies.
There are several other important issues to consider regarding BMI or weight loss and mortality. First, some observational studies show that intentional weight loss may be beneficial to longevity,13,42,43
but recent reviews report conflicting findings in studies on intentional weight loss and mortality requiring well-designed further studies.13,15
Although overall weight loss may be deleterious, fat loss may possibly be associated with greater longevity, as suggested from the Tecumseh Community Health Study and the Framingham Heart Study.37
However, our data showed no significant trends in all-cause or CVD mortality across fifths of change in % body fat, similar to BMI change. There is evidence that weight variability or fluctuation is associated with higher mortality risk.34,35,44,45
An additional analysis in our sample with 8150 men, with at least three medical examinations, indicated that every 1 kg of weight variability (defined as intrapersonal standard deviation of weight change) was associated with higher mortality risk even after adjusting for BMI change (data not shown). Therefore, it is still possible that weight variability instead of weight loss or gain may be associated with a higher mortality risk. The Finnish Twin Cohort study observed no excess mortality risk following weight loss among those exercising, but found a higher mortality risk in those dieting to lose weight.46
It is therefore important to determine how different methods used for weight loss can affect mortality, and well-designed randomized clinical trials are needed.
This study expands our knowledge and understanding of the roles of fitness and obesity on mortality by exploring the independent and combined associations of changes in fitness and BMI with all-cause and CVD mortality. A relatively large sample size across a wide age-range, extensive mortality follow-up, objectively-measured fitness and BMI, and extensive control of potential biases caused by preexisting diseases or subclinical conditions strengthen our findings. A major limitation is that our sample consists of well-educated white men from middle-to-upper socioeconomic strata. However, physiologic characteristics of men in the ACLS are similar to representative population samples.27
Also, the socioeconomic homogeneity reduces the possible confounding effects of education, income, and ethnicity. The current results may not apply to severely obese or extremely unfit individuals because the population in this study was, on average, slightly overweight with 90% having a BMI of 30 kg/m2
or under, and relatively fit at baseline. It is possible that change in BMI may be more important on mortality in individuals who are morbidly obese. We could not take into account dietary factors due to lack of adequate dietary information. However, in a subgroup of 11 795 men who reported the number of meals per week, additional adjustment for dietary changes did not alter our findings.
In conclusion, maintaining or improving fitness is associated with a lower risk of premature deaths from all-causes and CVD in adult men. Preventing fitness loss with age, regardless of whether BMI changes, is important for mortality risk reduction. Also, maintaining or improving fitness may attenuate some potentially negative effects of weight gain on mortality. To date, extensive attention has been given to weight loss. However, the long-term effect of fitness change, primarily resulting from increasing physical activity, is likely to be at least as important as weight loss, if not more important, for reducing premature mortality. Increased attention needs to be placed on strategies to maintain or improve fitness.