Unraveling the link between cardiorespiratory fitness and cancer: a state-of-the-art review.

Cardiorespiratory fitness (CRF) not only reflects an individual's capacity to perform physical activities but also encapsulates broader effects on the basic biology of aging. This review aims to summarize the evidence on the influence of CRF on overall and site-specific cancer risks. It delves into the biological mechanisms through which CRF may exert its effects, explores the clinical implications of these findings, identifies gaps in the current evidence base, and suggests directions for future research. The synthesis of findings reveals that higher CRF levels (general threshold of > 7 METs) are consistently associated with a reduced risk of a range of cancers, including head and neck, lung, breast, gastrointestinal, particularly pancreatic and colorectal, bladder, overall cancer incidence and mortality, and potentially stomach and liver, bile duct, and gall bladder cancers. These inverse associations between CRF and cancer risk do not generally differ across age groups, sex, race, or adiposity, suggesting a universal protective effect of CRF. Nonetheless, evidence linking CRF with skin, mouth and pharynx, kidney, and endometrial cancers is limited and inconclusive. Conversely, higher CRF levels may be potentially linked to an increased risk of prostate cancer and hematological malignancies, such as leukemia and myeloma, although the evidence is still not conclusive. CRF appears to play a significant role in reducing the risk of several cancers through various biological mechanisms, including inflammation reduction, immune system enhancement, hormonal regulation, and metabolic improvements. Overall, enhancing CRF through regular physical activity offers a vital, accessible strategy for reducing cancer risk and extending the health span. Future research should aim to fill the existing evidence gaps regarding specific cancers and elucidate the detailed dose-response relationships between CRF levels and cancer risk. Studies are also needed to elucidate the causal relationships and mechanistic pathways linking CRF to cancer outcomes.

Chronic use of Antihypertensive Medications and Peak Exercise Blood Pressure in Adult Men and Women from the BALL ST Cohort.

PURPOSE: To determine if individuals chronically (>1 year) prescribed antihypertensive medications have a normal BP response to peak exercise compared to unmedicated individuals. METHODS: Participants included 2,555 adults from the Ball State Adult Fitness Longitudinal Lifestyle STudy cohort who performed a peak treadmill exercise test. Participants were divided into groups by sex and antihypertensive medication status. Individuals prescribed antihypertensive medications for >1 year were included. Exaggerated and blunted SBP within each group was categorized using the Fitness Registry and the Importance of Exercise: A National Database (FRIEND) and absolute criteria as noted by the Amercian Heart Association. RESULTS: The unmedicated group had a greater prevalence (p < 0.05) of blunted SBP responses, whereas the medicated group had a higher prevalence (p < 0.05) of exaggerated SBP responses using both the FRIEND and absolute criteria. Peak SBP was higher (p < 0.01) in medicated compared to unmedicated participants in the overall cohort when controlling for age and sex, but not after controlling for resting SBP (p = 0.613), risk factors (p = 0.104), or cardiorespiratory fitness (p = 0.191). When men and women were assessed independently, peak SBP remained higher in the medicated women after controlling for age and resting SBP (p = 0.039), but not for men (p = 0.311). Individuals on beta-blockers had a higher peak SBP even after controlling for age, sex, risk factors and cardiorespiratory fitness (p = 0.022). CONCLUSIONS: Individuals on antihypertensive medications have a higher peak SBP response to exercise. Given the prognostic value of exaggerated peak SBP, control of exercise BP should be considered in routine BP assessment and in the treatment of hypertension.

2023 update: The importance of cardiorespiratory fitness in the United States.

The American Heart Association issued a Policy Statement in 2013 that characterized the importance of cardiorespiratory fitness (CRF) as an essential marker of health outcomes and specifically the need for increased assessment of CRF. This statement summarized the evidence demonstrating that CRF is "one of the most important correlates of overall health status and a potent predictor of an individual's future risk of cardiovascular disease." Subsequently, this Policy Statement led to the development of a National Registry for CRF (Fitness Registry and the Importance of Exercise: A National Data Base [FRIEND]) which established normative reference values for CRF for adults in the United States (US). This review provides an overview of the progress made in the past decade to further our understanding of the importance of CRF, specifically related to prevention and for clinical populations. Additionally, this review overviews the evolvement and additional uses of FRIEND and summarizes a hierarchy of assessment methods for CRF. In summary, continued efforts are needed to expand the representation of data from across the US, and to include data from pediatric populations, to further develop the CRF Reference Standards for the US as well as further develop Global CRF Reference Standards.

Update to the 2016 American Heart Association cardiorespiratory fitness statement.

In 2016 the American Heart Association published a scientific statement that summarized a large body of evidence concluding that cardiorespiratory fitness (CRF) was a powerful marker of cardiovascular disease (CVD) and CVD-mortality risk; its association with morbidity and mortality was independent of commonly obtained risk factors, and consequently, that it should be a routine measure in all health care settings. Since 2016 the interest in CRF as a prognostic for human health and performance has increased exponentially. This review will summarize a growing body of evidence that reinforces the notion that the assessment of CRF improves patient/client management. Feasible means of CRF assessment in health care settings is considered, and the expected response of CRF to exercise consistent with consensus recommendations is reviewed. The association between CRF and health care costs is also explored. The evidence reviewed will reinforce the conclusions drawn in 2016; that overwhelming evidence demands that CRF should be a routine assessment in all health care settings - a vital sign.

Improving Reporting of Exercise Capacity Across Age Ranges Using Novel Workload Reference Equations.

Exercise capacity (EC) is an important predictor of survival in the general population and in subjects with cardiopulmonary disease. Despite its relevance, considering the percent-predicted workload (%pWL) given by current equations may overestimate EC in older adults. Therefore, to improve the reporting of EC in clinical practice, our main objective was to develop workload reference equations (pWL) that better reflect the relation between workload and age. Using the Fitness Registry and the Importance of Exercise National Database (FRIEND), we analyzed a reference group of 6,966 apparently healthy participants and 1,060 participants with heart failure who underwent graded treadmill cardiopulmonary exercise testing. For the first group, the mean age was 44 years (18 to 79); 56.5% of participants were males and 15.4% had obesity. Peak oxygen consumption was 11.6 ± 3.0 METs in males and 8.5 ± 2.4 METs in females. After partition analysis, we first developed sex-specific pWL equations to allow comparisons to a healthy weight reference. For males, pWL (METs) = 14.1-0.9×10-3×age2 and 11.5-0.87×10-3×age2 for females. We used those equations as denominators of %pWL, and based on their distribution, we determined thresholds for EC classification, with average EC defined by the range corresponding to 85% to 115%pWL. Compared with %pWL using current equations, the new equations yielded better-calibrated %pWL across different age ranges. We also derived body mass index-adjusted pWL equations that better assessed EC in subjects with heart failure. In conclusion, the novel pWL equations have the potential to impact the report of EC in practice.

A Machine Learning Approach to Developing an Accurate Prediction of Maximal Heart Rate During Exercise Testing in Apparently Healthy Adults.

PURPOSE: Maximal heart rate (HR max ) continues to be an important measure of adequate effort during an exercise test. The aim of this study was to improve the accuracy of HR max prediction using a machine learning (ML) approach. METHODS: We used a sample from the Fitness Registry of the Importance of Exercise National Database, which included 17 325 apparently healthy individuals (81% males) who performed a maximal cardiopulmonary exercise test. Two standard formulas for HR max prediction were tested: Formula1 = 220 - age (yr), root-mean-squared error (RMSE) 21.9, relative root-mean-squared error (RRMSE) 1.1; and Formula2 = 209.3 - 0.72 × age (yr), RMSE 22.7 and RRMSE 1.1. For ML model prediction, we used age, weight, height, resting HR, and systolic and diastolic blood pressure. The following ML algorithms to predict HR max were applied: lasso regression (LR), neural networks (NN), support vector machine (SVM) and random forests (RF). An evaluation was performed using cross-validation and by computing the RMSE and RRMSE, Pearson correlation, and Bland-Altman plots. The best predictive model was explained with Shapley Additive Explanations (SHAP). RESULTS: The HR max for the cohort was 162 ± 20 bpm. All ML models improved HR max prediction and reduced RMSE and RRMSE compared with Formula1 (LR: 20.2%, NN: 20.4%, SVM: 22.2%, and RF: 24.7%). The predictions of all algorithms significantly correlated with HR max ( r = 0.49, 0.51, 0.54, 0.57, respectively; P < .001). Bland-Altman analysis demonstrated lower bias and 95% CI for all ML models in comparison with standard equations. The SHAP explanation showed a high impact of all selected variables. CONCLUSIONS: Machine learning, particularly the RF model, improved prediction of HR max using readily available measures. This approach should be considered for clinical application to refine HR max prediction.

Cardiorespiratory fitness as a vital sign of CVD risk in the COVID-19 era.

The severe health consequences of the corona virus disease 2019 (COVID-19) pandemic have been exacerbated by the prevalence of cardiovascular disease (CVD) risk factors, such as physical inactivity, obesity, hypertension, and diabetes. Further, policy decisions during the pandemic augmented unhealthy lifestyle behaviors and health inequalities, likely increasing the global disease burden. Cardiorespiratory fitness (CRF) is a well-established biomarker associated with CVD risk. Emerging data demonstrate that high CRF offers some protection against severe outcomes from COVID-19 infection, highlighting the importance of CRF for population health and the potential for limiting the severity of future pandemics. CRF is best assessed by cardiopulmonary exercise testing (CPET), which will be an important tool for understanding the prolonged pathophysiology of COVID-19, the emergence of long-COVID, and the lasting effects of COVID-19 on CVD risk. Utilization of CRF and CPET within clinical settings should become commonplace because of lessons learned from the COVID-19 pandemic.

Oxygen Uptake Efficiency Slope as a Predictor of Mortality Risk: THE BALL STATE ADULT FITNESS LONGITUDINAL LIFESTYLE STUDY (BALL ST).

PURPOSE: Oxygen uptake efficiency slope (OUES), defined as the slope of the linear relationship between oxygen uptake and the semilog transformed ventilation rate measured during an incremental exercise test, may have prognostic utility. The objective of this investigation was to examine the relationship between assessments of OUES and all-cause mortality in a cohort of apparently healthy adults. METHODS: The sample included 2220 apparently healthy adults (48% females) with a mean age of 44.7 ± 12.9 yr who performed cardiopulmonary exercise testing. The OUES was calculated from the entire test, using data from the initial 50% (OUES 50 ) and 75% (OUES 75 ) of test time, and normalized to body surface area. Cox proportional hazard models assessed the relationship between measures of OUES and mortality. Prognostic peak oxygen uptake (V˙ o2peak ) and OUES models were compared using the concordance index. RESULTS: There were 310 deaths (29% females) over a follow-up period of 19.8 ± 11.1 yr. For males, OUES, OUES 75 , and normalized OUES had an inverse association with mortality, even after adjusting for traditional risk factors ( P < .05). For females, only the unadjusted OUES, OUES 75 , and normalized OUES models were associated with mortality ( P < .05). The concordance index values indicated that unadjusted OUES 50 and OUES 75 models had lower discrimination than the unadjusted OUES and V˙ o2peak models ( P < .05). Furthermore, OUES did not complement the fully adjusted V˙ o2peak model ( P ≥ .32). CONCLUSIONS: Assessments of OUES are related to all-cause mortality in males but not in females. These findings suggest that OUES can have prognostic utility in apparently healthy males. Moreover, submaximal determinations of OUES could have value when measuring V˙ o2peak is not feasible.

A Nonexercise Prediction of Peak Oxygen Uptake for Patients With Cardiovascular Disease: DATA FROM THE FITNESS REGISTRY AND THE IMPORTANCE OF EXERCISE INTERNATIONAL DATABASE (FRIEND).

PURPOSE: Nonexercise predictions of peak oxygen uptake (V˙ o2peak ) are used clinically, yet current equations were developed from cohorts of apparently healthy individuals and may not be applicable to individuals with cardiovascular disease (CVD). Our purpose was to develop a CVD-specific nonexercise prediction equation for V˙ o2peak . METHODS: Participants were from the Fitness Registry and Importance of Exercise International Database (FRIEND) with a diagnosis of coronary artery bypass surgery (CABG), myocardial infarction (MI), percutaneous coronary intervention (PCI), or heart failure (HF) who met maximal effort criteria during a cardiopulmonary exercise test (n = 15 997; 83% male; age 63.1 ± 10.4 yr). The cohort was split into development (n = 12 798) and validation groups (n = 3199). The prediction equation was developed using regression analysis and compared with a previous equation developed on a healthy cohort. RESULTS: Age, sex, height, weight, exercise mode, and CVD diagnosis were all significant predictors of V˙ o2peak . The regression equation was:V˙ o2peak (mL · kg -1 · min -1 ) = 16.18 - (0.22 × age [yr]) + (3.63 × sex [male = 1; female = 0]) + (0.14 × height [cm]) - (0.12 × weight [kg]) + (3.62 × mode [treadmill = 1; cycle = 0]) - (2.70 × CABG [yes = 1, no = 0]) - (0.31 × MI [yes = 1, no = 0]) + (0.37 × PCI [yes = 1, no = 0]) - (4.47 × HF [yes = 1, no = 0]). Adjusted R 2 = 0.43; SEE = 4.75 mL · kg -1 · min -1 .Compared with measured V˙ o2peak in the validation group, percent predicted V˙ o2peak was 141% for the healthy cohort equation and 100% for the CVD-specific equation. CONCLUSIONS: The new equation for individuals with CVD had lower error between measured and predicted V˙ o2peak than the healthy cohort equation, suggesting population-specific equations are needed for predicting V˙ o2peak ; however, errors associated with nonexercise prediction equations suggest V˙ o2peak should be directly measured whenever feasible.

Reference Standards for Peak Rating of Perceived Exertion during Cardiopulmonary Exercise Testing: Data from FRIEND.

INTRODUCTION: Peak rating of perceived exertion (RPE) is measured during clinical cardiopulmonary exercise testing (CPX) and is commonly used as a subjective indicator of maximal effort. However, no study to date has reported reference standards or the distribution of peak RPE across a large cohort of apparently healthy individuals. PURPOSE: This study aimed to determine reference standards for peak RPE when using the 6-20 Borg scale for both treadmill and cycle tests. METHODS: The analysis included 9551 tests (8821 treadmill, 730 cycle ergometer) from 13 laboratories within the Fitness Registry and Importance of Exercise National Database (FRIEND). Using data from tests conducted January 1, 1980, to January 1, 2021, percentiles of peak RPE for men and women were determined for each decade from 20 to 89 yr of age for treadmill and cycle exercise modes. Two-way ANOVA was used to compare differences in peak RPE values between sexes and across age groups. RESULTS: There were statistically significant differences in RPE between age groups whether the test was performed on a treadmill or cycle ergometer ( P < 0.05). However, the mean and median RPE for each sex, age group, and test mode were between 18 and 19. In addition, 83% of participants met the traditional RPE criteria of ≥18 for indicating sufficient maximal effort. CONCLUSIONS: This report provides the first normative reference standards for peak RPE in both male and female individuals performing CPX on a treadmill or cycle ergometer. Furthermore, these reference standards highlight the general consistency of peak RPE responses during CPX.

Cardiorespiratory fitness estimations and their ability to predict all-cause mortality in patients with cardiovascular disease.

Background: In cardiac rehabilitation programs, cardiorespiratory fitness is commonly estimated (eCRF) from the maximum workload achieved on a graded exercise test. This study compared four well-established eCRF equations in their ability to predict mortality in patients with cardiovascular disease (CVD). Methods: A total of 7269 individuals with CVD were studied (81% male; age 59.4 ± 10.3yr). eCRF was calculated using equations from the American College of Sports Medicine, Bruce et al., the Fitness Registry and the Importance of Exercise International Database, and McConnell and Clark. The eCRF from each equation was compared with a RMANOVA. Cox proportional hazard models assessed the relationship between the eCRF equations and mortality risk. The predictive ability of the models was compared using the concordance index. Results: There were 284 deaths (85% male) over a follow-up period of 5.8 ± 2.8yr. Although differences in eCRF were observed between each equation (P < 0.05), the eCRF from each of the four equations was predictive of mortality (P < 0.05). The concordance index values for each of the models were the same (0.77) indicating similar predictive performance. Conclusions: The four well-established eCRF equations did not differ in their ability to predict mortality in patients with CVD, indicating any could be used for this purpose. However, the differences in eCRF from each of the equations suggest potential differences in their ability to guide clinical care and should be the focus of future research.

A consensus method for estimating physical activity levels in adults using accelerometry.

Identifying the best analytical approach for capturing moderate-to-vigorous physical activity (MVPA) using accelerometry is complex but inconsistent approaches employed in research and surveillance limits comparability. We illustrate the use of a consensus method that pools estimates from multiple approaches for characterising MVPA using accelerometry. Participants (n = 30) wore an accelerometer on their right hip during two laboratory visits. Ten individual classification methods estimated minutes of MVPA, including cut-point, two-regression, and machine learning approaches, using open-source count and raw inputs and several epoch lengths. Results were averaged to derive the consensus estimate. Mean MVPA ranged from 33.9-50.4 min across individual methods, but only one (38.9 min) was statistically equivalent to the criterion of direct observation (38.2 min). The consensus estimate (39.2 min) was equivalent to the criterion (even after removal of the one individual method that was equivalent to the criterion), had a smaller mean absolute error (4.2 min) compared to individual methods (4.9-12.3 min), and enabled the estimation of participant-level variance (mean standard deviation: 7.7 min). The consensus method allows for addition/removal of methods depending on data availability or field progression and may improve accuracy and comparability of device-based MVPA estimates while limiting variability due to convergence between estimates.

Peak Circulatory Power during Maximal Cardiopulmonary Exercise Testing: Reference Standards from the FRIEND Registry.

PURPOSE: Normative standards for key cardiopulmonary exercise (CPX) test variables, including peak circulatory power (CircP), are needed to guide the interpretation of clinical exercise responses in individuals with and without disease. OBJECTIVE: This study aimed to establish age- and sex-specific reference standards for peak CircP derived from a healthy cohort from the Fitness Registry and the Importance of Exercise: A National Database (FRIEND). METHODS: CPX test data from apparently healthy males and females from eight FRIEND United States exercise laboratories were considered. Inclusion criteria included ages 20-79 yr and a maximal, symptom-limited exercise test performed on a treadmill or cycle ergometer. CircP was calculated as the product of peak oxygen consumption and peak systolic blood pressure. Reference values were determined on both treadmill and cycle ergometer for males and females per age decade. A stepwise linear regression to predict CircP was derived from two-thirds of the sample while the remaining one-third was used as a validation cohort. RESULTS: A total of 6736 CPX tests (47% treadmill, 53% female) were included in the analysis. Overall, CircP was higher in males, higher on tests conducted on a treadmill, and decreased with age. Sex, exercise mode, age, and body mass index were the most significant contributors to CircP (multiple R = 0.75, R2 = 0.57, root-mean-square error = 1200 mm Hg·mL O 2 ·kg -1 ·min -1 , P < 0.001). Using the generated prediction equation, the average percent-predicted CircP for the validation cohort was 101.3% ± 28.1%. CONCLUSIONS: These results establish reference standards for CircP, a potentially important prognostic indicator of cardiovascular health. Future research exploring the role of percentiles and percent-predicted values for CircP is necessary as they may provide additional prognostic insight.

Cardiorespiratory Optimal Point Is a Submaximal Exercise Test Variable and a Predictor of Mortality Risk: THE BALL STATE ADULT FITNESS LONGITUDINAL LIFESTYLE STUDY (BALL ST).

PURPOSE: The cardiorespiratory optimal point (COP) is the minimum ventilatory equivalent for oxygen. The COP can be determined during a submaximal incremental exercise test. Reflecting the optimal interaction between the respiratory and cardiovascular systems, COP may have prognostic utility. The aim of this investigation was to determine the relationship between COP and all-cause mortality in a cohort of apparently healthy adults. METHODS: The sample included 3160 apparently healthy adults (46% females) with a mean age of 44.0 ± 12.5 yr who performed a cardiopulmonary exercise test. Cox proportional hazards models were performed to assess the relationship between COP and mortality risk. Prognostic peak oxygen uptake (V˙ o2peak ) and COP models were compared using the concordance index. RESULTS: There were 558 deaths (31% females) over a follow-up period of 23.0 ± 11.9 yr. For males, all Cox proportional hazards models, including the model adjusted for traditional risk factors and V˙ o2peak , had a positive association with risk for mortality ( P < .05). For females, only the unadjusted COP model was associated with risk for mortality ( P < .05). The concordance index values indicated that unadjusted COP models had lower discrimination compared with unadjusted V˙ o2peak models ( P < .05) and V˙ o2peak did not complement COP models ( P ≥ .13). CONCLUSIONS: Cardiorespiratory optimal point is related to all-cause mortality in males but not females. These findings suggest that a determination of COP can have prognostic utility in apparently healthy males aged 18-85 yr, which may be relevant when a maximal exercise test is not feasible or desirable.

Exercise oscillatory breathing in heart failure with reduced ejection fraction: clinical implication.

AIM: The aim of the study is (i) to evaluate the impact of exercise oscillatory ventilation (EOV) in patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) during cardiopulmonary exercise testing (CPET) compared with no EOV (N-EOV); (ii) to identify the influence of EOV persistence (P-EOV) and EOV disappearance (D-EOV) during CPET on the outcomes of mortality and hospitalization in HFrEF patients; and (iii) to identify further predictors of mortality and hospitalization in patients with P-EOV. METHODS AND RESULTS: Three hundred and fifteen stable HFrEF patients underwent CPET and were followed for 35 months. We identified 202 patients N-EOV and 113 patients with EOV. Patients with EOV presented more symptoms [New York Heart Association (NYHA) III: 35% vs. N-EOV 20%, P < 0.05], worse cardiac function (LVEF: 28 ± 6 vs. N-EOV 39 ± 1, P < 0.05), higher minute ventilation/carbon dioxide production (V̇E/V̇CO2 slope: 41 ± 11 vs. N-EOV 37 ± 8, P < 0.05) and a higher rate of deaths (26% vs. N-EOV 6%, P < 0.05) and hospitalization (29% vs. N-EOV 9%, P < 0.05). Patients with P-EOV had more severe HFrEF (NYHA IV: 23% vs. D-EOV: 9%, P < 0.05), had worse cardiac function (LVEF: 24 ± 5 vs. D-EOV: 34 ± 3, P < 0.05) and had lower peak oxygen consumption (V̇O2) (12.0 ± 3.0 vs. D-EOV: 13.3 ± 3.0 mLO2 kg-1.min-1, P < 0.05). Among P-EOV, other independent predictors of mortality were V̇E/V̇CO2 slope ≥36 and V̇O2 peak ≤12 mLO2 kg-1 min-1; a V̇E/V̇CO2 slope≥34 was a significant predictor of hospitalization. Kaplan-Meier survival analysis showed that HFrEF patients with P-EOV had a higher risk of mortality and higher risk of hospitalization (P < 0.05) than patients with D-EOV and N-EOV. CONCLUSION: In HFrEF patients, EOV persistence during exercise had a strong prognostic role. In P-EOV patients, V̇E/V̇CO2 ≥36 and V̇O2 peak ≤12 mLO2 kg-1 min-1 had a further additive negative prognostic role.

Change in Metabolic Syndrome and Cardiorespiratory Fitness Following Exercise Training - The Ball State Adult Fitness Longitudinal Lifestyle Study (BALL ST).

Purpose: To evaluate how the changes in directly measured cardiorespiratory fitness (CRF) relate to the changes in metabolic syndrome (MetS) status following 4-6 months of exercise training. Methods: Maximal cardiopulmonary exercise (CPX) tests and MetS risk factors were analyzed prospectively from 336 adults (46% women) aged 45.8 ± 10.9 years. MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III criteria, as updated by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI). Pearson correlations, chi-squares, and dependent 2-tail t-tests were used to assess the relationship between the change in CRF and the change in MetS risk factors, overall number of MetS risk factors, and a MetS severity score following 4-6 months of participation in a self-referred, community-based exercise program. Results: Overall prevalence of MetS decreased from 23% to 14% following the exercise program (P < 0.05), while CRF improved 15% (4.7 ± 8.4 mL/kg/min, P < 0.05). Following exercise training, the number of positive risk factors declined from 1.4 ± 1.3 to 1.2 ± 1.2 in the overall cohort (P < 0.05). The change in CRF was inversely related to the change in the overall number of MetS risk factors (r = -0.22; P < 0.05) and the MetS severity score (r = -0.28; p < 0.05). Conclusion: This observational cohort study indicates an inverse relationship between the change in CRF and the change in MetS severity following exercise training. These results suggest that participation in a community-based exercise program yields significant improvements in CRF, MetS risk factors, the prevalence of the binary MetS, and the MetS severity score. Improvement in CRF through exercise training should be a primary prevention strategy for MetS.

Cardiopulmonary Exercise Responses in Individuals with Metabolic Syndrome: The Ball State Adult Fitness Longitudinal Lifestyle Study.

Background: The association between cardiorespiratory fitness (CRF) and metabolic syndrome (MetSyn) is well established. Additional variables derived from cardiopulmonary exercise testing (CPET) have shown prognostic value in some chronic diseases, however, there is limited information on how cardiopulmonary responses to exercise may be altered in individuals with MetSyn. Thus, the purpose of this study was to examine the association between cardiopulmonary variables derived from CPET and MetSyn. Methods: A cohort of 3181 participants (1714 men, 1467 women), aged 20-79 years, completed CPET and metabolic risk factor assessment between January 1, 1971, and November 1, 2020. Cardiopulmonary variables assessed included CRF defined as the maximum volume of oxygen uptake (VO2max), ventilatory threshold (VO2@VT), oxygen uptake efficiency slope (OUES), the ratio of ventilation to VO2 at peak exercise (peak VE/VO2) and the VE/VCO2slope. MetSyn was defined using the National Cholesterol Education Program/Adult Treatment Panel. Results: VO2max, VO2@VT, and OUES were lower (P < 0.001) and VE/VCO2slope was higher (P < 0.001) in individuals with MetSyn (n = 774), whereas no difference between groups existed for peak VE/VO2. Logistic regression analysis revealed that VO2max [0.91, 0.89-0.93; odds ratio (OR), 95% confidence interval (CI)], VO2@VT (0.91, 0.87-0.95; OR, 95% CI), OUES (0.32, 0.20-0.52; OR, 95% CI), and VE/VCO2slope (1.03, 1.01-1.05 OR, 95% CI) were all associated with the presence of MetSyn (P ≤ 0.001). Conclusion: These results indicate that MetSyn is associated with altered cardiopulomary function that may provide insight into the underlying pathophysiology of MetSyn.