0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Midlife Cardiorespiratory Fitness, Incident Cancer, and Survival After Cancer in Men The Cooper Center Longitudinal Study FREE

Susan G. Lakoski, MD, MS1; Benjamin L. Willis, MD2; Carolyn E. Barlow, MS2; David Leonard, PhD2; Ang Gao, MS3; Nina B. Radford, MD2; Stephen W. Farrell, PhD2; Pamela S. Douglas, MD4; Jarett D. Berry, MD3; Laura F. DeFina, MD2; Lee W. Jones, PhD5
[+] Author Affiliations
1Vermont Cancer Center, Division of Hematology/Oncology, University of Vermont, Burlington
2The Cooper Institute, Dallas, Texas
3Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
4Duke University Medical Center, Durham, North Carolina
5Memorial Sloan Kettering Cancer Center, New York, New York
JAMA Oncol. 2015;1(2):231-237. doi:10.1001/jamaoncol.2015.0226.
Text Size: A A A
Published online

Importance  Cardiorespiratory fitness (CRF) as assessed by formalized incremental exercise testing is an independent predictor of numerous chronic diseases, but its association with incident cancer or survival following a diagnosis of cancer has received little attention.

Objective  To assess the association between midlife CRF and incident cancer and survival following a cancer diagnosis.

Design, Setting, and Participants  This was a prospective, observational cohort study conducted at a preventive medicine clinic. The study included 13 949 community-dwelling men who had a baseline fitness examination. All men completed a comprehensive medical examination, a cardiovascular risk factor assessment, and incremental treadmill exercise test to evaluate CRF. We used age- and sex-specific distribution of treadmill duration from the overall Cooper Center Longitudinal Study population to define fitness groups as those with low (lowest 20%), moderate (middle 40%), and high (upper 40%) CRF groups. The adjusted multivariable model included age, examination year, body mass index, smoking, total cholesterol level, systolic blood pressure, diabetes mellitus, and fasting glucose level. Cardiorespiratory fitness levels were assessed between 1971 and 2009, and incident lung, prostate, and colorectal cancer using Medicare Parts A and B claims data from 1999 to 2009; the analysis was conducted in 2014.

Main Outcomes and Measures  The main outcomes were (1) incident prostate, lung, and colorectal cancer and (2) all-cause mortality and cause-specific mortality among men who developed cancer at Medicare age (≥65 years).

Results  Compared with men with low CRF, the adjusted hazard ratios (HRs) for incident lung, colorectal, and prostate cancers among men with high CRF were 0.45 (95% CI, 0.29-0.68), 0.56 (95% CI, 0.36-0.87), and 1.22 (95% CI, 1.02-1.46), respectively. Among those diagnosed as having cancer at Medicare age, high CRF in midlife was associated with an adjusted 32% (HR, 0.68; 95% CI, 0.47-0.98) risk reduction in all cancer-related deaths and a 68% reduction in cardiovascular disease mortality following a cancer diagnosis (HR, 0.32; 95% CI, 0.16-0.64) compared with men with low CRF in midlife.

Conclusions and Relevance  There is an inverse association between midlife CRF and incident lung and colorectal cancer but not prostate cancer. High midlife CRF is associated with lower risk of cause-specific mortality in those diagnosed as having cancer at Medicare age.

Figures in this Article

A well-established, graded, inverse association exists between cardiorespiratory fitness (CRF) and risk of cardiovascular disease (CVD) as well as all-cause mortality in numerous healthy and clinical adult populations.13 Compared with those classified in the lowest CRF category (<7.9 metabolic equivalents [METs]), individuals in the highest CRF category (≥10.9 METs) have a 1.6- to 1.7-fold lower risk of CVD and all-cause mortality, respectively.4 Accordingly, measurement of CRF via formalized exercise testing provides a wealth of diagnostic and decision-making information in cardiovascular medicine.5

In contrast, the value of CRF for prediction of primary cancer risk has received little attention.13,6,7 The reasons for the paucity of interest are not known; however, it is now clear that CVD and cancer account for most deaths in the United States,8 with these diseases sharing common risk factors (eg, tobacco use, poor diet, insufficient physical activity).9 The powerful value of CRF in the prediction of CVD indicates that such a measure may also be of importance for the prediction of the primary risk of cancer. Evaluation of this question is important for several reasons.

First, given that individual risk (of CVD and cancer) is determined by multiple factors, current guidelines advocate for global or multiple-risk factor assessment, using tools such as the Framingham Risk Score. Currently, CRF is not included as an aspect of general prevention screening guidelines for all average-risk adults. However, CRF improves the discrimination and reclassification of CVD mortality risk prediction,10 as well as refinement of Framingham Risk Score among adults, even among those at low risk of CVD.11

Second, cancer incidence is projected to increase by approximately 45% over the next 2 decades,12 largely as a result of the rapidly aging population combined with the fact that most cancer diagnoses occur in individuals older than 65 years.13 Thus, investigation of the predictive value of CRF on primary cancer incidence could have important public health implications because it will provide medical professionals with a quantitative as well as modifiable risk factor (as opposed to a subjective behavioral risk factor) that simultaneously predicts risk of the most common chronic diseases.14

Third, there is growing evidence that lifestyle behaviors performed years, even decades, prior to a cancer diagnosis may influence outcomes after diagnosis. Indeed, midlife body mass index (BMI) and physical activity are predictors of cancer-specific as well as all-cause mortality in multiple cancer diagnoses.1521 To our knowledge, no study to date has investigated whether objective measures of exercise exposures (ie, CRF) in apparently healthy persons at midlife is predictive of primary risk of cancer as well as cause-specific mortality in those who are subsequently diagnosed as having cancer. Prediction of cause-specific mortality after a cancer diagnosis is becoming increasingly important given that individuals diagnosed as having certain forms of cancer now have sufficient survival to be at risk for noncancer competing causes of mortality, primarily CVD, owing to the chronic and late effects of treatment.22

Herein, we report on a prospective investigation of 13 949 men from the Cooper Center Longitudinal Study (CCLS) to examine the association between CRF assessed before age 65 years and (1) incidence of lung, colorectal, or prostate cancer and (2) cause-specific mortality in men diagnosed as having cancer at age 65 years or older (Medicare age). We hypothesized that higher midlife CRF would be associated with reduced incidence of lung, colorectal, and prostate cancer and lower risk of cancer and CVD-related mortality in those subsequently diagnosed as having cancer.

Box Section Ref ID

At a Glance
  • Does cardiorespiratory fitness (CRF) prevent or improve outcomes in cancer?

  • High CRF was associated with reduced incident lung (HR, 0.45 [95% CI, 0.29-0.68]) and colorectal cancer (HR, 0.56 [95% CI, 0.36-0.87]) in white men.

  • High CRF is associated with a one-third risk reduction in all cancer-related deaths among men who developed lung, colorectal, or prostate cancer at age 65 years or older compared with low CRF.

  • High CRF is associated with a two-thirds reduction in cardiovascular death compared with low CRF among men who developed cancer at age 65 years or older.

Participants and Procedures

The CCLS is a prospective observational cohort study of participants undergoing a preventive health examination at the Cooper Clinic in Dallas, Texas. Patients enrolled in the CCLS signed an informed consent, and the Cooper Institute’s institutional review board approved this study. Patients were not compensated for their participation. A detailed overview of the methods and procedures of the CCLS has been described previously.3,23,24 The sampling frame for the present study included 25 575 individuals in the CCLS completing an incremental treadmill exercise test between 1971 and 2009 and enrolled in Medicare between 1999 and 2009 (the available years of claims data at the time of this study). The following participants were excluded: (1) women (n = 5871), (2) those lacking traditional fee-for-service Medicare for whom individual claims data were not available (n = 998), (3) individuals without a complete set of baseline variables (n = 2096), (4) participants with myocardial infarction or stroke at their midlife examination visit (n = 413), (5) individuals with a cancer diagnosis or death prior to Medicare age (n = 1640), and (6) participants with a first CCLS visit at age 65 years or older (n = 552) or a chronic illness requiring Medicare coverage prior to age 67 years (n = 56). The final cohort included 13 949 men. Medicare surveillance continued until 2009. The analysis was conducted in 2014.

Midlife Exposures

The preventive health examination consisted of an extensive medical history, laboratory analysis, blood pressure ascertainment, and an incremental exercise treadmill test. Age, sex, and personal medical history were obtained by self-administered questionnaires; all data were physician verified. Blood pressure was measured with standard auscultatory methods, and BMI was calculated as weight in kilograms divided by height in meters squared. Diabetes mellitus was defined by self-report or blood glucose level of 126 mg/dL or higher. Smoking history was categorized as current, former, or never. A 12-hour fasting antecubital venous blood sample was obtained, and plasma concentrations of glucose and lipids were determined with automated bioassays in the CCLS laboratory. (To convert glucose to millimoles per liter, multiply by 0.0555.)

Cardiorespiratory fitness was assessed by an incremental treadmill test using a modified-Balke protocol as described previously.23 In brief, treadmill speed was set at 3.3 mph (88 m/min) at a grade of 0% in the first minute, followed by 2% in the second minute with an increase of 1% every minute thereafter. After 25 minutes, the grade was unchanged while the speed was increased by 0.3 mph (5.4 m/min) every additional minute until volitional exhaustion. Using well-characterized regression equations, treadmill time using the Balke protocol permits estimation of peak METs.25 Time to volitional exhaustion is correlated with direct measurement of maximal oxygen uptake (r = 0.92).26 We defined CRF as both a continuous and categorical variable. We used our previously published age- and sex-specific distribution of treadmill duration from the overall CCLS population27 to define CRF categories as follows: low (lowest 20%; mean [SD], 8.4 [1.2] METs), moderate (middle 40%; 10.4 [1.2] METs), and high (upper 40%; 13.0 [1.8] METs). All CRF assessments were performed prior to 2009.

Outcomes

Medicare inpatient claims data were obtained from Centers for Medicare and Medicaid Services (CMS) for participants aged 65 years or older. The CMS data contain 100% of claims paid by Medicare for covered inpatient and outpatient health care services. The earliest date of a cancer diagnosis in a patient of Medicare age was determined through the Chronic Condition Warehouse (CCW) included in the Beneficiary Annual Summary File. Chronic conditions are defined within the CCW from well-established algorithms.2831Three cancer diagnoses (ie, lung, colorectal, and prostate) were evaluated in the present report for men in this sample of the CCLS. The National Death Index was the primary data source for CVD and all-site cancer mortality outcomes. Thus, the outcomes available for analysis were incident lung, colorectal, and prostate cancer, as well as death from CVD and all-site cancer. Table 1 shows the transitions evaluated in this study and includes (1) healthy men in midlife who had an interim lung, prostate, or colorectal cancer event at Medicare age and died of cancer (n = 219) or CVD (n = 64); (2) healthy men in midlife who subsequently died of cancer but were not diagnosed as having prostate, lung, or colorectal cancer at Medicare age (n = 281) (eg, a man with a history of prostate cancer without a Medicare claim between 2001 and 2009 or a man with cancer other than prostate, lung, or colorectal cancer); and (3) healthy men in midlife without prostate, lung, or colorectal cancer at Medicare age who died of CVD (n = 495).

Table Graphic Jump LocationTable 1.  Association Between Midlife Cardiorespiratory Fitness (CRF) and Later-Life Incident Cancer and Cause-Specific Mortality in the CCLSa
Statistical Analysis

Differences in means and proportions of baseline characteristics across increasing categories of CRF were tested using the Jonckheere-Terpstra nonparametric method. Proportional hazards regression models were used to estimate hazard ratios (HRs) for site-specific cancer incidence and cause-specific mortality (incident lung, colorectal, and prostate cancer HRs by CRF category, adjusting for age at CCLS examination, BMI, cholesterol level, smoking, systolic blood pressure, blood glucose, diabetes mellitus, and examination year). Differences were considered statistically significant for P < .05. Attained age was used as the time scale in the proportional hazards models, which ensures that survival comparisons are among individuals of the same age. Left and right censoring for entry to and exit from Medicare surveillance was implemented using the counting process form of the proportional hazards model, and we assessed the proportional hazards assumption by testing for linear trends in covariate effects across the surveillance period. The analysis of multivariate failures, including incident cancer and CVD or cancer mortality (in those either diagnosed as having cancer or not), was constructed from similarly structured marginal proportional hazards models,32 using the robust variance estimate33 to account for the simultaneous presence of the same individual among risk sets of multiple outcomes.

Participant Characteristics

Participant characteristics are presented in Table 2. The mean (SD) age and CRF levels were 49 (9) years and 11.0 (2.3) METs, respectively. For the overall sample, BMI, total cholesterol level, smoking, glucose levels, and blood pressure decreased across increasing CRF category (P < .001 for all comparisons).

Table Graphic Jump LocationTable 2.  Baseline Characteristics of Cooper Center Longitudinal Study
Primary Cancer Incidence

Medicare surveillance included a total of 91 366 person-years of follow-up for incident lung, colorectal, and prostate cancer in 13 949 men, for an average 6.5 years of surveillance. During this time, 1310 were diagnosed as having prostate cancer (14.3 per 1000 person-years), 200 men were diagnosed as having lung cancer (incidence 2.2 per 1000 person-years), and 181 were diagnosed as having colorectal cancer (2.0 per 1000 person-years).

There was a significant inverse and graded association across low, moderate, and high CRF and incidence of lung (P < .001) and colorectal cancer (P < .001) (Figure). Compared with men in the low CRF category, the adjusted HRs for lung cancer incidence were 0.57 (95% CI, 0.41-0.81) for moderate CRF and 0.45 (95% CI, 0.29-0.68) for high CRF. The corresponding HRs for colorectal cancer were 0.67 (95% CI, 0.46-0.98) for moderate CRF and 0.56 (95% CI, 0.36-0.87) for high CRF relative to the lowest CRF category, respectively (Table 3). A 1-MET increase in CRF was associated with a 17% (95% CI, 0.77-0.90) and 9% (95% CI, 0.84-0.99) relative risk reduction in the risk of lung and colorectal cancer, respectively. There was a significant positive and graded association across low, moderate, and high CRF and incident prostate cancer (P = .004). Compared with men in the low CRF category, the adjusted HR for prostate cancer incidence was 1.04 (95% CI, 0.88-1.23) for moderate CRF and 1.22 (95% CI, 1.02-1.46) for high CRF. It is important to note that, considering the mixed association of CRF with incident site-specific lung and colorectal vs prostate cancer, the model demonstrated no association between midlife CRF and incident combined lung, colorectal, and prostate cancer (HR, 0.91 [95% CI, 0.80-1.05]; P = .19, moderate vs low CRF; HR, 0.99 [95% CI, 0.86-1.15]; P = .93, high vs low CRF) (Table 1).

Place holder to copy figure label and caption
Figure.
Cardiorespiratory Fitness (CRF) and Risk of Incident Lung, Colorectal, and Prostate Cancer

The low CRF group is the referent group relative to moderate and high fitness. The error bars for moderate and high fitness represent the 95% confidence limits. Adjusted for age, examination year, body mass index, smoking, total cholesterol level, systolic blood pressure, diabetes mellitus, and fasting glucose level.

Graphic Jump Location
Table Graphic Jump LocationTable 3.  Association Between Midlife Cardiorespiratory Fitness (CRF) and Later-Life Incident Cancer in the Cooper Center Longitudinal Study
Cause-Specific Mortality in Men Diagnosed as Having Lung, Colorectal, or Prostate Cancer

We analyzed the prognostic importance of CRF using a model that allowed for differences in the patterns of mortality following a diagnosis of cancer (Table 1). High midlife CRF was associated with a lower risk of cancer mortality (high vs low CRF HR, 0.68 [95% CI, 0.47-0.98]) and CVD mortality (high vs low CRF HR, 0.32 [95% CI, 0.16-0.64]) following a diagnosis of cancer. It is important to note that midlife CRF remained prognostic of cancer mortality among men diagnosed as having cancer who were not identified during the Medicare surveillance period or among those who died of cancers other than prostate, lung, or colorectal cancer (high vs low CRF HR, 0.66 [95% CI, 0.48-0.91]). Finally, as expected, there was an inverse association between midlife fitness and CVD mortality (high vs low CRF HR, 0.38 [95% CI, 0.29-0.48]) among men without a diagnosis of cancer at Medicare age.

Sensitivity Analysis Among Nonsmokers

We performed a sensitivity analysis to determine associations between CRF and both colorectal and lung cancer as well as survival after a cancer diagnosis among nonsmokers. Compared with men in the low CRF category, the adjusted HR for lung cancer incidence was 0.74 (95% CI, 0.44-1.24) for moderate CRF and 0.55 (95% CI, 0.31-0.68) for high CRF among nonsmokers. The corresponding HRs for colorectal cancer were 0.63 (95% CI, 0.40-0.99) for moderate CRF and 0.42 (95% CI, 0.25-0.70) for high CRF relative to the lowest CRF category. A similar trend of lower mortality was observed among those in the high CRF group in midlife who developed cancer and were nonsmokers (high vs low CRF HR, 0.77 [95% CI, 0.49-1.21]). Finally, high midlife CRF was associated with a lower risk of CVD mortality (high vs low CRF HR, 0.34 [95% CI, 0.15-0.77]) following a diagnosis of cancer among nonsmoking men.

Using a large, prospective cohort study, we found a graded, inverse association between midlife CRF and incident lung and colorectal cancers. This association was not demonstrated for midlife CRF and prostate cancer. Notably, midlife CRF was associated with a lower risk of both cancer and CVD mortality following a diagnosis of lung, colorectal, or prostate cancer in men. Our data suggest that higher levels of midlife CRF provide a mortality benefit into older age even in the setting of a cancer diagnosis.

In the current study, high CRF conferred a 55% and 44% reduction in the risk of lung and colorectal cancer, respectively, compared with low CRF. Every 1-MET increase in CRF was associated with 17% and 9% relative risk reductions in lung and colorectal cancer risk, respectively. These results are similar to those of the Kuopio Ischemic Heart Disease Risk Factor Study,34 which found that a 1-MET increase in CRF was associated with a 20% and 12% reduction in the relative risk of lung and colorectal cancer, respectively, in 2268 asymptomatic Finnish men. Interestingly, in contrast to lung and colorectal cancer, high CRF was a risk factor for prostate cancer even after adjusting for potential confounding variables. The current results are similar to those of 2 other studies in the literature on CRF and prostate cancer. Laukkanen et al34 found that a 1-MET increase in CRF was associated with a nonsignificant increase in prostate cancer risk (HR, 1.03; 95% CI, 0.94-1.12), Byun et al,6 using data from the Aerobics Center Longitudinal Study, found that compared with men in the lowest CRF category, those with moderate or high CRF had adjusted HRs of 1.68 (95% CI, 1.13-2.48) and 1.74 (95% CI, 1.15-2.62) for incident prostate cancer, respectively.

Conflicting data exist in the literature regarding the impact of CRF on prostate cancer risk.35 The exact reasons for the observed positive association between CRF and incident prostate cancer risk are not known, but differences in related health behaviors, such as screening, may be an important contributing factor. Specifically, men with higher CRF may also be more likely to undergo more frequent preventive health care screening and/or detection visits and, thus, had greater opportunity to be diagnosed as having localized prostate cancer relative to men with lower CRF, possibly with less frequent preventive health care visits. Notably, these findings are also consistent with those of several studies on physical activity and prostate cancer risk, an important predictor of attained CRF.36 Understanding how screening may affect the association between CRF and prostate cancer, as well as studying the association between CRF and incident advanced-stage prostate cancer, are important areas of future research.

A key, novel finding in the current study was that CRF was an independent predictor of the transition from cancer and ultimately death from either cancer or CVD. High CRF was associated with a 32% risk reduction in cancer death among men who developed lung, colorectal, or prostate cancer at Medicare age compared with those with low CRF. Moreover, CRF was a powerful predictor of CVD death among men. Specifically, high CRF was associated with a 68% reduction in CVD death compared with low CRF among men who developed cancer. It is important to note that the number of individuals living with cancer in the United State is projected to increase from 13.7 million in 2012 to 18 million over the next decade.37 Simultaneously, owing to important improvements in screening and adjuvant therapy, the 5-year relative survival rate for all cancers has increased from 49% in 1975 to 67% in 2007.38 Consequently, patients with early-stage cancer now have sufficient survival to be at risk for noncancer competing causes of mortality, particularly CVD. This point is of particular importance given that 70% of cancer-related mortality will occur in individuals 65 years or older.13 As such, the current findings are of timely importance and shed new light on remaining fit throughout the lifespan in an effort to decrease the morbidity and mortality related to cancer.

Notably, we chose to focus on CRF as the exposure of interest rather than physical activity for several reasons. It is well established that level of physical activity significantly influences level of CRF,24 and structured exercise training is associated with 10% to 25% improvements in measures of CRF.39 Moreover, regular physical activity is associated with significant reductions in the risk of certain forms of cancer, with the evidence classified as convincing for breast and colon cancer.40,41 Several epidemiological studies42,43 suggest that, in general, self-reported regular exercise (eg, brisk walking for 30 minutes, 5 days a week) is associated with substantial reductions in the risk of cancer-specific death following a diagnosis of cancer. Notably, physical activity and CRF are correlated but provide distinct information.44 Cardiorespiratory fitness is also highly reproducible and objectively assessed via incremental exercise tolerance testing compared with physical activity, which is largely determined by self-report questionnaires. A prior study45 demonstrated that CRF is be a more potent marker of mortality than physical activity. As such, given the current study findings and prior evidence, we contend that measurement of CRF should be used more frequently in the cancer prevention setting.

Our findings do not address whether improvements in CRF via exercise training interventions are an effective strategy to lower cancer incidence or reduce the risk of death following a cancer diagnosis in men. However, there is considerable evidence that aerobic training interventions following standard exercise prescription guidelines are associated with a 15% to 30% CRF improvement in men with chronic conditions but without cancer,46,47 as well as in those with cancer.48 In addition, exercise training also has been shown to modulate circulating host pathways postulated to mediate the association of CRF with cancer incidence and/or prognosis.42 Nevertheless, the predictive value of CRF on cancer incidence and mortality does not necessarily indicate that CRF augmentation will lower cancer and /or CVD events.49 Adequately powered randomized clinical trials are required to definitively address these questions.

Important limitations need to be considered when interpreting the present findings. First, we were unable to determine the length and intensity of smoking in the CCLS. To overcome this limitation, we performed a sensitivity analysis among nonsmokers, finding similar associations between fitness and both cancer risk and survival after cancer. Second, we were not able to identify outcomes that occurred between study entry and the onset of Medicare eligibility, as the cancer outcome was derived from administrative data from the CMS. However, Medicare data have been shown to be a reliable source of information across multiple clinical cancer outcomes.50,51 Furthermore, Medicare data represent a cost-effective resource, providing the ability to assess associations between CRF and both cancer incidence and long-term mortality outcomes that would be prohibitively expensive to replicate in a prospective cohort study of comparable size and duration. Third, CRF was assessed years prior to a diagnosis of lung, colorectal, or prostate cancer or death in men diagnosed as having cancer. Thus, it is not known how changes in CRF and related behaviors, such as physical activity from the initial preventive health care to cancer diagnosis as well as changes in CRF and physical activity after diagnosis, may have had an impact on these current findings. Fourth, it is not known how CRF may differentially have an impact on cancer prognosis among those who are diagnosed at different stages of cancer, because cancer stage was not captured in the current study. Finally, the specific nature of cancer treatments provided to each patient on an individual level was not characterized, and so the impact of chemotherapy, radiation, and or surgical interventions in the sample could not be quantified.

To our knowledge, this is the first study to demonstrate that CRF is predictive of site-specific cancer incidence, as well as risk of death from cancer or CVD following a cancer diagnosis. These findings provide further support for the effectiveness of CRF assessment in preventive health care settings. Future studies are required to determine the absolute level of CRF necessary to prevent site-specific cancer as well as evaluating the long-term effect of cancer diagnosis and mortality in women.

Corresponding Author: Susan G. Lakoski, MD, MS, Vermont Cancer Center, Department of Internal Medicine, University of Vermont, 208 S Park Dr, Colchester, VT 05446 (susan.lakoski@uvm.edu).

Accepted for Publication: February 10, 2015.

Published Online: March 26, 2015. doi:10.1001/jamaoncol.2015.0226.

Author Contributions: Dr Lakoski had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Lakoski, Barlow, Berry, Jones.

Acquisition, analysis, or interpretation of data: Lakoski, Willis, Leonard, Gao, Radford, Farrell, Douglas, DeFina, Jones.

Drafting of the manuscript: Lakoski, DeFina, Jones.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Willis, Barlow, Leonard, Gao, Jones.

Obtained funding: Berry.

Administrative, technical, or material support: Willis, Radford, Douglas.

Study supervision: Lakoski, Douglas, DeFina.

Conflict of Interest Disclosures: Dr Jones is a cofounder of a commercial company, Exercise by Science Inc.

Funding/Support: Dr Lakoski is supported in part by the National Institute of General Medical Sciences/ National Institutes of Health (NIGMS/NIH) (P20GM103644-01A1). Dr Jones is supported in part by research grants from the National Cancer Institute (NCI).

Role of the Funder/Sponsor: The NIGMS/NIH and NCI had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Blair  SN, Wei  M, Lee  CD.  Cardiorespiratory fitness determined by exercise heart rate as a predictor of mortality in the Aerobics Center Longitudinal Study. J Sports Sci. 1998;16(suppl):S47-S55.
PubMed   |  Link to Article
Lee  CD, Blair  SN, Jackson  AS.  Cardiorespiratory fitness, body composition, and all-cause and cardiovascular disease mortality in men. Am J Clin Nutr. 1999;69(3):373-380.
PubMed
Blair  SN, Kohl  HW  III, Paffenbarger  RS  Jr, Clark  DG, Cooper  KH, Gibbons  LW.  Physical fitness and all-cause mortality: a prospective study of healthy men and women. JAMA. 1989;262(17):2395-2401.
PubMed   |  Link to Article
Kodama  S, Saito  K, Tanaka  S,  et al.  Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA. 2009;301(19):2024-2035.
PubMed   |  Link to Article
Kaminsky  LA, Arena  R, Beckie  TM,  et al; American Heart Association Advocacy Coordinating Committee, Council on Clinical Cardiology, and Council on Nutrition, Physical Activity and Metabolism.  The importance of cardiorespiratory fitness in the United States: the need for a national registry: a policy statement from the American Heart Association. Circulation. 2013;127(5):652-662.
PubMed   |  Link to Article
Byun  W, Sui  X, Hébert  JR,  et al.  Cardiorespiratory fitness and risk of prostate cancer: findings from the Aerobics Center Longitudinal Study. Cancer Epidemiol. 2011;35(1):59-65.
PubMed   |  Link to Article
Blair  SN, Kampert  JB, Kohl  HW  III,  et al.  Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA. 1996;276(3):205-210.
PubMed   |  Link to Article
Murphy  SI, Xu  JQ, Kochanek  KD. Death: Final Data for 2010. Hyattsville, MD: National Center for Health Statistics; 2013. National Vital Statistics Reports. Vol 61, No. 4.
Eyre  H, Kahn  R, Robertson  RM,  et al; American Cancer Society; American Diabetes Association; American Heart Association.  Preventing cancer, cardiovascular disease, and diabetes. Circulation. 2004;109(25):3244-3255.
PubMed   |  Link to Article
Gupta  S, Rohatgi  A, Ayers  CR,  et al.  Cardiorespiratory fitness and classification of risk of cardiovascular disease mortality. Circulation. 2011;123(13):1377-1383.
PubMed   |  Link to Article
Barlow  CE, DeFina  LF, Radford  NB,  et al.  Cardiorespiratory fitness and long-term survival in “low-risk” adults. J Am Heart Assoc. 2012;1(4):e001354.
PubMed   |  Link to Article
Smith  BD, Smith  GL, Hurria  A, Hortobagyi  GN, Buchholz  TA.  Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27(17):2758-2765.
PubMed   |  Link to Article
Pal  SK, Katheria  V, Hurria  A.  Evaluating the older patient with cancer. CA Cancer J Clin. 2010;60(2):120-132.
PubMed   |  Link to Article
Archer  E, Blair  SN.  Physical activity and the prevention of cardiovascular disease: from evolution to epidemiology. Prog Cardiovasc Dis. 2011;53:387-396.
Link to Article
Zhou  Y, Chlebowski  R, LaMonte  MJ,  et al.  Body mass index, physical activity, and mortality in women diagnosed with ovarian cancer: results from the Women’s Health Initiative. Gynecol Oncol. 2014;133(1):4-10.
PubMed   |  Link to Article
Keegan  TH, Milne  RL, Andrulis  IL,  et al.  Past recreational physical activity, body size, and all-cause mortality following breast cancer diagnosis. Breast Cancer Res Treat. 2010;123(2):531-542.
PubMed   |  Link to Article
Pettersson  A, Lis  RT, Meisner  A,  et al.  Modification of the association between obesity and lethal prostate cancer by TMPRSS2:ERG. J Natl Cancer Inst. 2013;105(24):1881-1890.
PubMed   |  Link to Article
Murphy  TK, Calle  EE, Rodriguez  C, Kahn  HS, Thun  MJ.  Body mass index and colon cancer mortality in a large prospective study. Am J Epidemiol. 2000;152(9):847-854.
PubMed   |  Link to Article
Rodriguez  C, Patel  AV, Calle  EE, Jacobs  EJ, Chao  A, Thun  MJ.  Body mass index, height, and prostate cancer mortality in two large cohorts of adult men in the United States. Cancer Epidemiol Biomarkers Prev. 2001;10(4):345-353.
PubMed
Kampert  JB, Blair  SN, Barlow  CE, Kohl  HW  III.  Physical activity, physical fitness, and all-cause and cancer mortality: a prospective study of men and women. Ann Epidemiol. 1996;6(5):452-457.
PubMed   |  Link to Article
Hu  G, Tuomilehto  J, Silventoinen  K, Barengo  NC, Peltonen  M, Jousilahti  P.  The effects of physical activity and body mass index on cardiovascular, cancer and all-cause mortality among 47 212 middle-aged Finnish men and women. Int J Obes (Lond). 2005;29(8):894-902.
PubMed   |  Link to Article
Jones  LW, Haykowsky  MJ, Swartz  JJ, Douglas  PS, Mackey  JR.  Early breast cancer therapy and cardiovascular injury. J Am Coll Cardiol. 2007;50(15):1435-1441.
PubMed   |  Link to Article
Blair  SN, Kohl  HW  III, Barlow  CE, Paffenbarger  RS  Jr, Gibbons  LW, Macera  CA.  Changes in physical fitness and all-cause mortality. JAMA. 1995;273(14):1093-1098.
PubMed   |  Link to Article
Lakoski  SG, Barlow  CE, Farrell  SW, Berry  JD, Morrow  JR  Jr, Haskell  WL.  Impact of body mass index, physical activity, and other clinical factors on cardiorespiratory fitness (from the Cooper Center longitudinal study). Am J Cardiol. 2011;108(1):34-39.
PubMed   |  Link to Article
Pollock  ML, Bohannon  RL, Cooper  KH,  et al.  A comparative analysis of four protocols for maximal treadmill stress testing. Am Heart J. 1976;92(1):39-46.
PubMed   |  Link to Article
Pollock  ML, Foster  C, Schmidt  D, Hellman  C, Linnerud  AC, Ward  A.  Comparative analysis of physiologic responses to three different maximal graded exercise test protocols in healthy women. Am Heart J. 1982;103(3):363-373.
PubMed   |  Link to Article
Willis  BL, Morrow  JR  Jr, Jackson  AW, DeFina  LF, Cooper  KH.  Secular change in cardiorespiratory fitness of men: Cooper Center Longitudinal Study. Med Sci Sports Exerc. 2011;43(11):2134-2139.
PubMed   |  Link to Article
Daviglus  ML, Liu  K, Pirzada  A,  et al.  Cardiovascular risk profile earlier in life and Medicare costs in the last year of life. Arch Intern Med. 2005;165(9):1028-1034.
PubMed   |  Link to Article
Virnig  BA, McBean  M.  Administrative data for public health surveillance and planning. Annu Rev Public Health. 2001;22:213-230.
PubMed   |  Link to Article
Gorina  Y, Kramarow  EA.  Identifying chronic conditions in Medicare claims data: evaluating the Chronic Condition Data Warehouse algorithm. Health Serv Res. 2011;46(5):1610-1627.
PubMed   |  Link to Article
Wolff  JL, Starfield  B, Anderson  G.  Prevalence, expenditures, and complications of multiple chronic conditions in the elderly. Arch Intern Med. 2002;162(20):2269-2276.
PubMed   |  Link to Article
Wei  L, Lin  DY, Weissfield  L.  Regression analysis of multivariate incomplete failure time data by modeling marginal distributions. J Am Stat Assoc. 1989;84(408):1065-1073.
Link to Article
Lin  DW.  The robust inference for the Cox proportional hazards model. J Am Stat Assoc. 1989;84:1074-1078.
Link to Article
Laukkanen  JA, Pukkala  E, Rauramaa  R, Mäkikallio  TH, Toriola  AT, Kurl  S.  Cardiorespiratory fitness, lifestyle factors and cancer risk and mortality in Finnish men. Eur J Cancer. 2010;46(2):355-363.
PubMed   |  Link to Article
Oliveria  SA, Kohl  HW  III, Trichopoulos  D, Blair  SN.  The association between cardiorespiratory fitness and prostate cancer. Med Sci Sports Exerc. 1996;28(1):97-104.
PubMed   |  Link to Article
Kohl  HW, Blair  SN, Paffenbarger  RS  Jr, Macera  CA, Kronenfeld  JJ.  A mail survey of physical activity habits as related to measured physical fitness. Am J Epidemiol. 1988;127(6):1228-1239.
PubMed
Siegel  R, DeSantis  C, Virgo  K,  et al.  Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220-241.
PubMed   |  Link to Article
Siegel  R, Naishadham  D, Jemal  A.  Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10-29.
PubMed   |  Link to Article
Warburton  DE, Nicol  CW, Bredin  SS.  Prescribing exercise as preventive therapy. CMAJ. 2006;174(7):961-974.
PubMed   |  Link to Article
Friedenreich  CM.  Physical activity and breast cancer: review of the epidemiologic evidence and biologic mechanisms. Recent Results Cancer Res. 2011;188:125-139.
PubMed
Friedenreich  CM, Orenstein  MR.  Physical activity and cancer prevention. J Nutr. 2002;132(11)(suppl):3456S-3464S.
PubMed
Betof  AS, Dewhirst  MW, Jones  LW.  Effects and potential mechanisms of exercise training on cancer progression: a translational perspective. Brain Behav Immun. 2013;30(suppl):S75-S87.
PubMed   |  Link to Article
Ballard-Barbash  R, Friedenreich  CM, Courneya  KS, Siddiqi  SM, McTiernan  A, Alfano  CM.  Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104(11):815-840.
PubMed   |  Link to Article
Archer  E, Blair  SN.  Physical activity and the prevention of cardiovascular disease. Prog Cardiovasc Dis. 2011;53(6):387-396.
PubMed   |  Link to Article
Lee  DC, Sui  X, Ortega  FB,  et al.  Comparisons of leisure-time physical activity and cardiorespiratory fitness as predictors of all-cause mortality in men and women. Br J Sports Med. 2011;45(6):504-510.
PubMed   |  Link to Article
Sandercock  G, Hurtado  V, Cardoso  F.  Changes in cardiorespiratory fitness in cardiac rehabilitation patients: a meta-analysis. Int J Cardiol. 2013;167(3):894-902.
PubMed   |  Link to Article
Boulé  NG, Kenny  GP, Haddad  E, Wells  GA, Sigal  RJ.  Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia. 2003;46(8):1071-1081.
PubMed   |  Link to Article
Speck  RM, Courneya  KS, Mâsse  LC, Duval  S, Schmitz  KH.  An update of controlled physical activity trials in cancer survivors. J Cancer Surviv. 2010;4(2):87-100.
PubMed   |  Link to Article
Lauer  MS.  How will exercise capacity gain enough respect? Circulation. 2011;123(13):1364-1366.
PubMed   |  Link to Article
Welch  HG, Sharp  SM, Gottlieb  DJ, Skinner  JS, Wennberg  JE.  Geographic variation in diagnosis frequency and risk of death among Medicare beneficiaries. JAMA. 2011;305(11):1113-1118.
PubMed   |  Link to Article
Willis  BL, Gao  A, Leonard  D, Defina  LF, Berry  JD.  Midlife fitness and the development of chronic conditions in later life. Arch Intern Med. 2012;172(17):1333-1340.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure.
Cardiorespiratory Fitness (CRF) and Risk of Incident Lung, Colorectal, and Prostate Cancer

The low CRF group is the referent group relative to moderate and high fitness. The error bars for moderate and high fitness represent the 95% confidence limits. Adjusted for age, examination year, body mass index, smoking, total cholesterol level, systolic blood pressure, diabetes mellitus, and fasting glucose level.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1.  Association Between Midlife Cardiorespiratory Fitness (CRF) and Later-Life Incident Cancer and Cause-Specific Mortality in the CCLSa
Table Graphic Jump LocationTable 2.  Baseline Characteristics of Cooper Center Longitudinal Study
Table Graphic Jump LocationTable 3.  Association Between Midlife Cardiorespiratory Fitness (CRF) and Later-Life Incident Cancer in the Cooper Center Longitudinal Study

References

Blair  SN, Wei  M, Lee  CD.  Cardiorespiratory fitness determined by exercise heart rate as a predictor of mortality in the Aerobics Center Longitudinal Study. J Sports Sci. 1998;16(suppl):S47-S55.
PubMed   |  Link to Article
Lee  CD, Blair  SN, Jackson  AS.  Cardiorespiratory fitness, body composition, and all-cause and cardiovascular disease mortality in men. Am J Clin Nutr. 1999;69(3):373-380.
PubMed
Blair  SN, Kohl  HW  III, Paffenbarger  RS  Jr, Clark  DG, Cooper  KH, Gibbons  LW.  Physical fitness and all-cause mortality: a prospective study of healthy men and women. JAMA. 1989;262(17):2395-2401.
PubMed   |  Link to Article
Kodama  S, Saito  K, Tanaka  S,  et al.  Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA. 2009;301(19):2024-2035.
PubMed   |  Link to Article
Kaminsky  LA, Arena  R, Beckie  TM,  et al; American Heart Association Advocacy Coordinating Committee, Council on Clinical Cardiology, and Council on Nutrition, Physical Activity and Metabolism.  The importance of cardiorespiratory fitness in the United States: the need for a national registry: a policy statement from the American Heart Association. Circulation. 2013;127(5):652-662.
PubMed   |  Link to Article
Byun  W, Sui  X, Hébert  JR,  et al.  Cardiorespiratory fitness and risk of prostate cancer: findings from the Aerobics Center Longitudinal Study. Cancer Epidemiol. 2011;35(1):59-65.
PubMed   |  Link to Article
Blair  SN, Kampert  JB, Kohl  HW  III,  et al.  Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA. 1996;276(3):205-210.
PubMed   |  Link to Article
Murphy  SI, Xu  JQ, Kochanek  KD. Death: Final Data for 2010. Hyattsville, MD: National Center for Health Statistics; 2013. National Vital Statistics Reports. Vol 61, No. 4.
Eyre  H, Kahn  R, Robertson  RM,  et al; American Cancer Society; American Diabetes Association; American Heart Association.  Preventing cancer, cardiovascular disease, and diabetes. Circulation. 2004;109(25):3244-3255.
PubMed   |  Link to Article
Gupta  S, Rohatgi  A, Ayers  CR,  et al.  Cardiorespiratory fitness and classification of risk of cardiovascular disease mortality. Circulation. 2011;123(13):1377-1383.
PubMed   |  Link to Article
Barlow  CE, DeFina  LF, Radford  NB,  et al.  Cardiorespiratory fitness and long-term survival in “low-risk” adults. J Am Heart Assoc. 2012;1(4):e001354.
PubMed   |  Link to Article
Smith  BD, Smith  GL, Hurria  A, Hortobagyi  GN, Buchholz  TA.  Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27(17):2758-2765.
PubMed   |  Link to Article
Pal  SK, Katheria  V, Hurria  A.  Evaluating the older patient with cancer. CA Cancer J Clin. 2010;60(2):120-132.
PubMed   |  Link to Article
Archer  E, Blair  SN.  Physical activity and the prevention of cardiovascular disease: from evolution to epidemiology. Prog Cardiovasc Dis. 2011;53:387-396.
Link to Article
Zhou  Y, Chlebowski  R, LaMonte  MJ,  et al.  Body mass index, physical activity, and mortality in women diagnosed with ovarian cancer: results from the Women’s Health Initiative. Gynecol Oncol. 2014;133(1):4-10.
PubMed   |  Link to Article
Keegan  TH, Milne  RL, Andrulis  IL,  et al.  Past recreational physical activity, body size, and all-cause mortality following breast cancer diagnosis. Breast Cancer Res Treat. 2010;123(2):531-542.
PubMed   |  Link to Article
Pettersson  A, Lis  RT, Meisner  A,  et al.  Modification of the association between obesity and lethal prostate cancer by TMPRSS2:ERG. J Natl Cancer Inst. 2013;105(24):1881-1890.
PubMed   |  Link to Article
Murphy  TK, Calle  EE, Rodriguez  C, Kahn  HS, Thun  MJ.  Body mass index and colon cancer mortality in a large prospective study. Am J Epidemiol. 2000;152(9):847-854.
PubMed   |  Link to Article
Rodriguez  C, Patel  AV, Calle  EE, Jacobs  EJ, Chao  A, Thun  MJ.  Body mass index, height, and prostate cancer mortality in two large cohorts of adult men in the United States. Cancer Epidemiol Biomarkers Prev. 2001;10(4):345-353.
PubMed
Kampert  JB, Blair  SN, Barlow  CE, Kohl  HW  III.  Physical activity, physical fitness, and all-cause and cancer mortality: a prospective study of men and women. Ann Epidemiol. 1996;6(5):452-457.
PubMed   |  Link to Article
Hu  G, Tuomilehto  J, Silventoinen  K, Barengo  NC, Peltonen  M, Jousilahti  P.  The effects of physical activity and body mass index on cardiovascular, cancer and all-cause mortality among 47 212 middle-aged Finnish men and women. Int J Obes (Lond). 2005;29(8):894-902.
PubMed   |  Link to Article
Jones  LW, Haykowsky  MJ, Swartz  JJ, Douglas  PS, Mackey  JR.  Early breast cancer therapy and cardiovascular injury. J Am Coll Cardiol. 2007;50(15):1435-1441.
PubMed   |  Link to Article
Blair  SN, Kohl  HW  III, Barlow  CE, Paffenbarger  RS  Jr, Gibbons  LW, Macera  CA.  Changes in physical fitness and all-cause mortality. JAMA. 1995;273(14):1093-1098.
PubMed   |  Link to Article
Lakoski  SG, Barlow  CE, Farrell  SW, Berry  JD, Morrow  JR  Jr, Haskell  WL.  Impact of body mass index, physical activity, and other clinical factors on cardiorespiratory fitness (from the Cooper Center longitudinal study). Am J Cardiol. 2011;108(1):34-39.
PubMed   |  Link to Article
Pollock  ML, Bohannon  RL, Cooper  KH,  et al.  A comparative analysis of four protocols for maximal treadmill stress testing. Am Heart J. 1976;92(1):39-46.
PubMed   |  Link to Article
Pollock  ML, Foster  C, Schmidt  D, Hellman  C, Linnerud  AC, Ward  A.  Comparative analysis of physiologic responses to three different maximal graded exercise test protocols in healthy women. Am Heart J. 1982;103(3):363-373.
PubMed   |  Link to Article
Willis  BL, Morrow  JR  Jr, Jackson  AW, DeFina  LF, Cooper  KH.  Secular change in cardiorespiratory fitness of men: Cooper Center Longitudinal Study. Med Sci Sports Exerc. 2011;43(11):2134-2139.
PubMed   |  Link to Article
Daviglus  ML, Liu  K, Pirzada  A,  et al.  Cardiovascular risk profile earlier in life and Medicare costs in the last year of life. Arch Intern Med. 2005;165(9):1028-1034.
PubMed   |  Link to Article
Virnig  BA, McBean  M.  Administrative data for public health surveillance and planning. Annu Rev Public Health. 2001;22:213-230.
PubMed   |  Link to Article
Gorina  Y, Kramarow  EA.  Identifying chronic conditions in Medicare claims data: evaluating the Chronic Condition Data Warehouse algorithm. Health Serv Res. 2011;46(5):1610-1627.
PubMed   |  Link to Article
Wolff  JL, Starfield  B, Anderson  G.  Prevalence, expenditures, and complications of multiple chronic conditions in the elderly. Arch Intern Med. 2002;162(20):2269-2276.
PubMed   |  Link to Article
Wei  L, Lin  DY, Weissfield  L.  Regression analysis of multivariate incomplete failure time data by modeling marginal distributions. J Am Stat Assoc. 1989;84(408):1065-1073.
Link to Article
Lin  DW.  The robust inference for the Cox proportional hazards model. J Am Stat Assoc. 1989;84:1074-1078.
Link to Article
Laukkanen  JA, Pukkala  E, Rauramaa  R, Mäkikallio  TH, Toriola  AT, Kurl  S.  Cardiorespiratory fitness, lifestyle factors and cancer risk and mortality in Finnish men. Eur J Cancer. 2010;46(2):355-363.
PubMed   |  Link to Article
Oliveria  SA, Kohl  HW  III, Trichopoulos  D, Blair  SN.  The association between cardiorespiratory fitness and prostate cancer. Med Sci Sports Exerc. 1996;28(1):97-104.
PubMed   |  Link to Article
Kohl  HW, Blair  SN, Paffenbarger  RS  Jr, Macera  CA, Kronenfeld  JJ.  A mail survey of physical activity habits as related to measured physical fitness. Am J Epidemiol. 1988;127(6):1228-1239.
PubMed
Siegel  R, DeSantis  C, Virgo  K,  et al.  Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220-241.
PubMed   |  Link to Article
Siegel  R, Naishadham  D, Jemal  A.  Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10-29.
PubMed   |  Link to Article
Warburton  DE, Nicol  CW, Bredin  SS.  Prescribing exercise as preventive therapy. CMAJ. 2006;174(7):961-974.
PubMed   |  Link to Article
Friedenreich  CM.  Physical activity and breast cancer: review of the epidemiologic evidence and biologic mechanisms. Recent Results Cancer Res. 2011;188:125-139.
PubMed
Friedenreich  CM, Orenstein  MR.  Physical activity and cancer prevention. J Nutr. 2002;132(11)(suppl):3456S-3464S.
PubMed
Betof  AS, Dewhirst  MW, Jones  LW.  Effects and potential mechanisms of exercise training on cancer progression: a translational perspective. Brain Behav Immun. 2013;30(suppl):S75-S87.
PubMed   |  Link to Article
Ballard-Barbash  R, Friedenreich  CM, Courneya  KS, Siddiqi  SM, McTiernan  A, Alfano  CM.  Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104(11):815-840.
PubMed   |  Link to Article
Archer  E, Blair  SN.  Physical activity and the prevention of cardiovascular disease. Prog Cardiovasc Dis. 2011;53(6):387-396.
PubMed   |  Link to Article
Lee  DC, Sui  X, Ortega  FB,  et al.  Comparisons of leisure-time physical activity and cardiorespiratory fitness as predictors of all-cause mortality in men and women. Br J Sports Med. 2011;45(6):504-510.
PubMed   |  Link to Article
Sandercock  G, Hurtado  V, Cardoso  F.  Changes in cardiorespiratory fitness in cardiac rehabilitation patients: a meta-analysis. Int J Cardiol. 2013;167(3):894-902.
PubMed   |  Link to Article
Boulé  NG, Kenny  GP, Haddad  E, Wells  GA, Sigal  RJ.  Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia. 2003;46(8):1071-1081.
PubMed   |  Link to Article
Speck  RM, Courneya  KS, Mâsse  LC, Duval  S, Schmitz  KH.  An update of controlled physical activity trials in cancer survivors. J Cancer Surviv. 2010;4(2):87-100.
PubMed   |  Link to Article
Lauer  MS.  How will exercise capacity gain enough respect? Circulation. 2011;123(13):1364-1366.
PubMed   |  Link to Article
Welch  HG, Sharp  SM, Gottlieb  DJ, Skinner  JS, Wennberg  JE.  Geographic variation in diagnosis frequency and risk of death among Medicare beneficiaries. JAMA. 2011;305(11):1113-1118.
PubMed   |  Link to Article
Willis  BL, Gao  A, Leonard  D, Defina  LF, Berry  JD.  Midlife fitness and the development of chronic conditions in later life. Arch Intern Med. 2012;172(17):1333-1340.
PubMed   |  Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

19,295 Views
0 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
Jobs
JAMAevidence.com

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed
From Evidence to Recommendations

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed
Overall Confidence in Effect Estimates