Abstract

Objective To examine and summarise evidence from meta-analyses of cohort studies that evaluated the predictive associations between baseline cardiorespiratory fitness (CRF) and health outcomes among adults.

Design Overview of systematic reviews.

Data source Five bibliographic databases were searched from January 2002 to March 2024.

Results From the 9062 papers identified, we included 26 systematic reviews. We found eight meta-analyses that described five unique mortality outcomes among general populations. CRF had the largest risk reduction for all-cause mortality when comparing high versus low CRF (HR=0.47; 95% CI 0.39 to 0.56). A dose–response relationship for every 1-metabolic equivalent of task (MET) higher level of CRF was associated with a 11%–17% reduction in all-cause mortality (HR=0.89; 95% CI 0.86 to 0.92, and HR=0.83; 95% CI 0.78 to 0.88). For incident outcomes, nine meta-analyses described 12 unique outcomes. CRF was associated with the largest risk reduction in incident heart failure when comparing high versus low CRF (HR=0.31; 95% CI 0.19 to 0.49). A dose–response relationship for every 1-MET higher level of CRF was associated with a 18% reduction in heart failure (HR=0.82; 95% CI 0.79 to 0.84). Among those living with chronic conditions, nine meta-analyses described four unique outcomes in nine patient groups. CRF was associated with the largest risk reduction for cardiovascular mortality among those living with cardiovascular disease when comparing high versus low CRF (HR=0.27; 95% CI 0.16 to 0.48). The certainty of the evidence across all studies ranged from very low-to-moderate according to Grading of Recommendations, Assessment, Development and Evaluations.

Conclusion We found consistent evidence that high CRF is strongly associated with lower risk for a variety of mortality and incident chronic conditions in general and clinical populations.

Data availability statement

Data are available on reasonable request.

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WHAT IS ALREADY KNOWN ON THIS TOPIC

• Many systematic reviews have examined the prospective link between baseline cardiorespiratory fitness and health outcomes, but no study has compiled all the evidence to help identify important gaps in the literature.

Introduction

Cardiorespiratory fitness (CRF) is a physical trait that reflects the integrated function of numerous bodily systems to deliver and use oxygen to support muscle activity during sustained, rhythmic, whole-body, large muscle physical activity.1 CRF can be objectively measured using direct (usually by maximal exercise testing with concomitant gas exchange analysis)2 or indirect (exercise predicted equations)3 4 methods with a variety of maximal or submaximal protocols using different modalities (eg, stationary cycling, treadmill running/walking, bench stepping, field-based running/walking). Non-exercise prediction equations with reasonable validity are also available when direct CRF measurement is not feasible.5 6 CRF is commonly expressed as the maximum or peak rate of oxygen consumption per kilogram of body mass (common units: mL/kg/min) or metabolic equivalents of task (METs). Nearly half of the variance in CRF is attributable to genetics, with the remainder modified primarily through habitual physical activity.7 For example, brisk walking for approximately 150 min per week can result in large relative improvements in CRF among sedentary and unfit individuals.8 9 Even those with severe chronic disease can improve CRF through well-planned aerobic physical activity programmes.10

Low CRF is considered a strong chronic disease risk factor that is not routinely assessed in clinical practice.11 Evidence suggests that the inclusion of CRF as a clinical vital sign would enhance patient management by improving the classification of those at high risk of adverse outcomes.11 The evidence supporting CRF as an important risk factor has accumulated since the 1980s through large cohort studies that investigated the prospective risk of all-cause mortality and cardiovascular events associated with CRF.12–14 Research has linked CRF to the incidence of some cancers (eg, colon/rectum, lung),15 type 2 diabetes,16 metabolic syndrome,17 stroke18 and depression.19 Higher CRF may even improve the prognosis in those with chronic conditions such as cancer,20 peripheral artery disease,21 heart failure22 and chronic kidney disease.23

Given the mounting evidence supporting CRF as an important risk factor, numerous systematic reviews with meta-analyses summarising results of primary studies for various health outcomes have been published. Kodama et al 24 published the first meta-analysis on the health-related predictive validity of CRF and found that a 1-MET (3.5 mL/kg/min) higher level of CRF was associated with a 13% and 15% reduction in the risk of all-cause mortality and cardiovascular disease (CVD) events, respectively. This study helped to establish the meaningful clinically important difference (MCID) of 1-MET for exercise trials. Since Kodama’s study, there have been several systematic reviews with meta-analyses, with several published in recent years (ie, 2020+). Most systematic reviews have focused on a single health outcome. To date, there has not been a systematic synthesis of the relationships between CRF and a broad range of health outcomes. To help summarise the breadth of evidence, an overview of reviews provides a systematic method to examine evidence across a range of outcomes for a specific exposure.25 Thus, the objective of this study was to conduct an overview of systematic reviews with meta-analyses from cohort studies that investigated relationships between CRF and prospective health-related outcomes among adults. We also aimed to assess the certainty of the evidence for each identified health outcome.

Methods

This overview followed the methods outlined in the Cochrane handbook,25 and additional methods that were published elsewhere.26 We adhered to both the Preferred Reporting Items for Overviews of Reviews statement27 and the Meta-analyses of Observational Studies in Epidemiology reporting standards.28 The overview was prospectively registered with the PROSPERO international prospective register of systematic reviews (#CRD42022370149). Here, we present a condensed methods section with the full methods available in online supplemental methods.

Results

We identified 9062 records after removing duplicates, assessed 199 full-text papers, and excluded 165 papers during full-text screening, and 8 papers because of high or very high overlap based on the CCA calculation (see figure 1 and online supplemental appendix 2 for full texts with reasons for exclusion). The proportion of agreement between reviewers for title and abstract screening ranged from 95% to 100% while the agreement for full-text screening ranged from 75% to 100%. We included 26 systematic reviews with meta-analyses representing over 20.9 million observations from 199 unique cohort studies, including 21 mortality or incident chronic disease outcomes. We identified CCA values in the high or very high range for sudden cardiac mortality (CCA=33%; n=2), incident heart failure (33%; n=2), incident depression (50%; n=2), incident type 2 diabetes (25%; n=4) and all-cause mortality among those living with heart failure (14%; n=3; see online supplemental appendix 2 for more details). We included multiple systematic reviews for all-cause mortality because the CCA was moderate (10%; n=3).

Tables 1–3 describe the study characteristics. We identified 8 systematic reviews that investigated mortality outcomes, with pooled data from 95 unique primary cohort studies. Nine systematic reviews investigated incident outcomes, pooling data from 63 unique primary cohort studies. The remaining 9 systematic reviews investigated health-related outcomes among populations living with chronic conditions, which represented data from 51 unique primary cohort studies. 11 reviews were of critically low quality, 4 were low, 8 were moderate and 3 were of high quality as assessed using the AMSTAR2 (see online supplemental table 2). See online supplemental table 3 for a detailed summary of findings with the certainty of the evidence for each outcome.

Figure 2 illustrates results for CRF as a predictor of mortality outcomes, which included all-cause, CVD, sudden cardiac, all cancer and lung cancer mortality. When comparing high versus low CRF across all outcomes, there was a 41% (HR for all-cause mortality24=0.59; 95% CI 0.52 to 0.66) to 53% (HR for all-cause mortality35=0.47; 95% CI 0.39 to 0.56) reduction in the risk of premature mortality. The certainty of the evidence was assessed as very low-to-moderate, mainly due to serious indirectness (ie, most studies only included male participants). In assessing the dose–response relationship, a 1-MET higher level of CRF was associated with a 7% (HR for all cancer mortality35=0.93; 95% CI 0.91 to 0.96) to 51% (HR for sudden cardiac mortality36=0.49; 95% CI 0.33 to 0.73) reduction in the risk of premature mortality. The certainty of the evidence ranged from very low-to-moderate, largely due to serious indirectness from a large proportion of male-only studies. Sex differences were similar between outcomes with larger CIs for females because of smaller samples (see online supplemental figure 1). For example, there were 1 858 274 male participants compared with 180 202 female participants for all-cause mortality.

Figure 3 describes results for CRF as a predictor of newly diagnosed chronic conditions, including: hypertension, heart failure, stroke, atrial fibrillation, dementia, chronic kidney disease, depression and type 2 diabetes. Online supplemental figure 2 describes results for all cancer (male only), lung cancer (male only), colon/rectum cancer (male only) and prostate cancer. When comparing high versus low CRF, there was a 37% (HR for incident hypertension37=0.63; 95% CI 0.56 to 0.70) to 69% (HR for incident heart failure38=0.31; 95% CI 0.19 to 0.49) reduction in the risk of incident conditions. The certainty of this evidence was rated as very low-to-low largely due to inconsistency and indirectness (ie, high heterogeneity that could not be described by subgroup analysis and largely male populations). The dose–response relationship per 1-MET higher level of CRF was associated with a 3% (HR for incident stroke39=0.97; 95% CI 0.96 to 0.98) to 18% (HR for incident heart failure38=0.82; 95% CI 0.79 to 0.84) reduction in the risk of incident conditions. The certainty of the evidence ranged from very low-to-low due to inconsistency and indirectness. Only two studies reported results for females separately. High versus low CRF was more protective for incident stroke and type 2 diabetes among females compared with males (online supplemental figure 2). Among men, there was a null association between high versus low CRF for prostate cancer (HR=1.15; 95% CI 1.00 to 1.30).40

Figure 4 highlights results comparing high versus low CRF among individuals living with chronic conditions. There was a 19% (HR for adverse events among those living with pulmonary hypertension41=0.81; 95% CI 0.78 to 0.85) to 73% (HR for cardiovascular mortality among those living with CVD42=0.27; 95% CI 0.16 to 0.48) reduction in the risk of all-cause and type-specific mortality. Comparing delayed versus not delayed heart rate recovery was associated with an 83% reduced risk of adverse events among those living with coronary artery disease. The certainty of the evidence for mortality in those living with a chronic condition was rated as very low-to-low largely due to risk of bias, indirectness and imprecision (ie, low-quality studies, mainly male participants and small sample sizes). No evidence examining sex differences were available. See online supplemental table 3 for a detailed summary of findings.

Discussion

This overview of systematic reviews demonstrated that CRF is a strong and consistent predictor of risk across many mortality outcomes in the adult general population. Among populations living with chronic conditions such as cancer, heart failure and CVD, this study showed better prognosis for those with higher CRF. We also demonstrated that low CRF is an important risk factor for developing future chronic conditions such as hypertension, heart failure, stoke, atrial fibrillation, dementia and depression. Given that we summarised evidence from cohort studies, and randomised controlled trials cannot be used in our investigation, the results of this study may signal a causal relationship between CRF and future health outcomes. We also found a significant dose–response effect showing protection for every 1-MET higher level of CRF. This evidence further supports 1-MET as an MCID for CRF and could be considered as a target for interventions. The strength and consistency of the evidence across a wide range of outcomes supports the importance of CRF for clinical assessment and public health surveillance.

Several studies have identified the need for the routine measurement of CRF in clinical and public health practice.11 43 For instance, a scientific statement from the American Heart Association concluded that healthcare providers should assess CRF during annual routine clinical visits using submaximal tests (eg, treadmill, cycling or bench stepping tests) or self-report estimates and that patients living with chronic conditions should have CRF measured regularly using a symptom-limited direct measure.11 There are several benefits to regular measurement of CRF in clinical practice. First, CRF is an important risk factor that provides additional information beyond traditional risk factors such as blood pressure, total cholesterol and smoking status.44 Second, given the strong link with habitual physical activity, CRF could be a valuable tool to help guide exercise prescription. In those with low CRF (defined based on age, sex and health status), large relative improvements can be attained through additional moderate physical activity (ie, brisk walking at a heart rate of 50% of peakO₂).45 The largest health benefits have been observed when individuals move from being unfit to fit.46 Lastly, CRF measured using field-based tests are easy to implement with a variety of tests that could be adapted to suit space and time limitations.

Conclusion

Our findings showed that high CRF is strongly associated with lower risk of premature mortality, incident chronic conditions (ie, hypertension, heart failure, stroke, atrial fibrillation, dementia and depression), and poor prognosis in those with existing chronic conditions. The consistency of the evidence across a variety of health outcomes demonstrates the importance of CRF and the need to incorporate this measure in routine clinical and public health practice. Future studies should focus on outcomes with limited evidence and where the certainty of the evidence was rated as very low by improving study quality.

Data availability statement

Data are available on reasonable request.

Ethics statements

Acknowledgments

We would like to acknowledge the support of Valentine Ly, MLIS, Research Librarian at the University of Ottawa for her help with translating and conducting the search strategy in CINAHL and SPORTDiscus. We would also like to acknowledge the Health Library at Health Canada and the Public Health Agency of Canada for their support in constructing and carrying out the search strategy for MEDLINE, Embase and Scopus. The PRESS peer-review of the search strategy was carried out by Shannon Hayes, MLIS, research librarian, from the Health Library at Health Canada and the Public Health Agency of Canada. We would also like to thank Joses Robinson and Iryna Demchenko for their help with the paper.

• Supplementary Data

  This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

  • Data supplement 1