PURPOSE:To determine if individuals chronically (>1 yr) prescribed antihypertensive medications have a normal BP response to peak exercise compared with unmedicated individuals. METHODS:Participants included 2555 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 yr 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 American 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 with 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.

Widening of pulse pressure with age is associated with arterial stiffening and increased risk of cardiovascular disease. High cardiorespiratory fitness (CRF) is associated with lower age-related arterial stiffening but the relationship between CRF and change in pulse pressure over time has not been examined in cohorts that include both men and women. PURPOSE: Examine the relationship between directly measured CRF and change in pulse pressure over time in apparently healthy men and women. METHODS: The sample included 749 normotensive (resting blood pressure < 140/90 mmHg and unmedicated for blood pressure) individuals (476 males, 273 females) with mean age 42 ± 11 yr from the Ball State Adult Fitness Longitudinal Lifestyle Study (BALL ST) who completed a maximal cardiopulmonary exercise test for the assessment of CRF (i.e., VO2max) and cardiometabolic risk factor assessment. Linear regression analysis was performed to assess the relationship between baseline CRF and the change in pulse pressure over time. Models were performed using CRF as VO2max (ml/kg/min) and as percentile based on age and sex-adjusted normative values from the Fitness Registry of the Importance of Exercise National Database (FRIEND). RESULTS: The change in pulse pressure was calculated over a follow-up period of 10.0 ± 9.3 yr. CRF expressed as VO2max was related to the change in pulse pressure in the univariate model (r = -0.123, P < 0.05) and after adjusting for age, sex, follow-up years, and test year (r = -0.117, P < 0.05) but not after further controlling for traditional risk factors (obesity, dyslipidemia, diabetes, physical activity, and smoking) (r = -0.147, P > 0.05). CRF expressed as FRIEND percentile was associated with the change in pulse pressure (r = -0.066, P < 0.05), even after adjusting for age, sex, follow-up years, test years, and traditional risk factors. CONCLUSION: These data suggest the cardioprotective effects of CRF are mediated, at least partially, through reducing arterial stiffening and widening of pulse pressure with aging.

An excessive rise in systolic blood pressure (SBP) during exercise is linked to increased risk of cardiovascular disease (CVD). Hypertensive individuals are more likely to have an exaggerated SBP response to exercise. However, research is limited on the impact of antihypertensive medication use on the exercise blood pressure response. PURPOSE: To determine if individuals on antihypertensive medications (excluding beta-blockers) have a normal blood pressure response to maximal exercise compared to unmedicated individuals. METHODS: Participants included 2,555 apparently healthy adults from the Ball State Adult Fitness Longitudinal Lifestyle STudy (BALL ST) cohort. Participants were divided into groups by sex and antihypertensive medications status (Male medicated, Male unmedicated, Female medicated, Female unmedicated). A 2-way analysis of covariance (Sex x Medication Status) was used to assess peak SBP between groups. A chi-squared test was used to determine the prevalence of exaggerated and blunted responses within each group using the Fitness Registry and the Importance of Exercise: A National Database (FRIEND) and absolute criteria (FRIEND Exaggerated ≥90th percentile, Blunted ≤10th percentile; Absolute exaggerated >210 mmHg for men and > 190 mmHg for women, Blunted <140 mmHg). RESULTS: Peak SBP was higher in medicated compared to unmedicated subjects (p < 0.01) in the overall cohort when controlling for age and resting SBP. When men and women were assessed independently, peak SBP remained higher in the medicated women compared to unmedicated women (p < 0.05), however the difference in peak SBP between medicated and unmedicated men was not significant after controlling for age and resting SBP (p = 0.31). Further, the unmedicated group had a greater prevalence of blunted SBP responses, whereas the medicated group had a higher prevalence of exaggerated SBP responses using both the FRIEND and absolute criteria. CONCLUSION: Individuals on antihypertensive medications had a higher prevalence of an exaggerated peak SBP response than unmedicated. Given the prognostic value of exaggerated peak SBP, individuals on antihypertensive medications should be monitored closely during peak exercise to lower risk of an adverse cardiovascular event.

Cardiorespiratory fitness (CRF) has been associated with future risk of hypertension (HTN); however, this relationship has not been examined in apparently healthy cohorts that include both men and women. PURPOSE: Examine the relationship between directly measured CRF and incident HTN in apparently healthy men and women. METHODS: The sample included 749 individuals (476 males, 273 females) with mean age 42 +/- 11 yr from the Ball State Adult Fitness Longitudinal Lifestyle Study (BALL ST) who completed a maximal cardiopulmonary exercise test for the assessment of CRF (i.e., VO2max) and cardiometabolic risk factor assessment. Cox proportional hazard models were performed to assess the relationship between CRF and incident HTN. Models were performed using CRF as a continuous variable and as a categorical variable based on age and sex-adjusted percentiles from the Fitness Registry and the Importance of Exercise National Database (low CRF: <34th %tile; average CRF: 34th-66th %tile; high CRF: >66th %tile). RESULTS: A total of 212 participants (28% of sample) developed HTN during a follow-up period of 10.0 +/- 9.3 yr. CRF was associated (P < 0.05) with incident HTN (hazard ratio [HR], 95% confidence interval [CI]: 0.977, 0.954-0.982) even after controlling for age, sex, and test year but not after further controlling for traditional risk factors (obesity, dyslipidemia, diabetes, physical activity, and smoking) (HR, 95% CI, 0.983, 0.961-1.006). Further, individuals with average CRF (HR, 95% CI, 0.594, 0.408-0.865, P < 0.05) and high CRF (HR, 95% CI, 0.566, 0.392-0.819, P < 0.05) were less likely to develop HTN compared to those with low CRF. CONCLUSION: These data support the important role of CRF in preventing the development of HTN. Additional large cohort studies are needed to comprehensively assess potential sex differences in these relationships.

BACKGROUND: Reference standards for ventilatory threshold (VT) have recently been established by the Fitness Registry Importance of Exercise National Database (FRIEND) registry based on age and sex. Based on these values, on average VT occurs at 51-74% of VO2max. The reason for variability in these values is unknown and may be influenced by fitness level. PURPOSE: To examine the impact of fitness level on VT expressed as a percentage of VO2max in apparently healthy men and women of varying fitness levels. METHODS: Participants included 1,784 self-referred male and female participants from the Ball State Adult Fitness Longitudinal Lifestyle STudy (BALL ST) cohort that performed resting health measurements and a maximal cardiopulmonary exercise test (CPET) between 1992 and 2020. Percentage of VT to VO2max was determined by dividing the confirmed VT by the confirmed VO2max derived from the CPET. Fitness level was determined by using the FRIEND registry percentiles with low fit being 33rd percentile, moderate fit 33rd-66th percentile, and high fit >66th percentile. An ANCOVA was performed to determine the differences between fitness levels controlling for age and sex. RESULTS: The mean percentage for VT to VO2max was higher in low fit (65.2 ± 10.4%) than the moderate (61.3 ± 10.9%) and high fit populations (60.8 ± 10.9%) (p < 0.05). CONCLUSION: Low fit individuals have a higher VT when expressed as a percentage of VO2max, and thus likely have a higher range for moderate intensity exercise compared to higher fitness level populations relative to their own exercise capacity. Exercise physiologists should take this information into consideration when prescribing exercise to this population.

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.

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.

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.

Cardiorespiratory fitness (CRF) is not only an objective measure of physical activity, but also a useful diagnostic and prognostic health indicator for patients in clinical settings. There is a well-established inverse relationship between cardiorespiratory fitness (CRF) and mortality. However, the effect of CRF on mortality status might be different on subgroups of individuals and could be higher or lower than the estimated average effect of CRF. Thus, the objective of the study is to identify subgroups with higher or lower impact of CRF on mortality status. In addition, we evaluate and compare both tree-based and non-tree-based algorithms for identifying predictive features and subgroups. A penalized logistic regression with least absolute shrinkage and selection operator (LASSO) penalty is performed to identify the features that may be associated with low CRF and all-cause mortality. The algorithms considered are: virtual twins classification (VT(C)), generalized unbiased interaction detection and estimation (GUIDE) classification (Gc), GUIDE sum (Gs), GUIDE interaction (Gi) to find subgroups of participants where CRF exerts positive or negative association with all-cause mortality from the Ball State Adult Fitness Longitudinal Lifestyle Study (BALL ST) data. The overall result suggests that tree-based (VT and GUIDE) methods naturally define subgroups with fewer predictors and the non-tree-based method (logistic-LASSO) fails to find subgroups, only identify predictors that have impact on mortality status. In terms of predictive variable selection and subgroup identification, Gi is the best method compared to other tree-based and non-tree-based algorithms. Our study identifies subgroups that may be benefited from higher CRF.

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 (Vo(2peak)) 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 Vo(2peak), 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 Vo(2peak) models (P < .05) and Vo(2peak) 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.

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% (OUES50) and 75% (OUES75) 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˙o 2peak) 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, OUES75, and normalized OUES had an inverse association with mortality, even after adjusting for traditional risk factors (P < .05). For females, only the unadjusted OUES, OUES75, and normalized OUES models were associated with mortality (P < .05). The concordance index values indicated that unadjusted OUES50 and OUES75 models had lower discrimination than the unadjusted OUES and V˙o 2peak models (P < .05). Furthermore, OUES did not complement the fully adjusted V˙o 2peak 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˙o 2peak is not feasible.

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˙o 2peak) 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˙o 2peak, 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˙o 2peak models (P < .05) and V˙o 2peak 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.

Several variables derived from maximal cardiopulmonary exercise testing (CPET) have prognostic utility for predicting mortality risk in clinical populations. However, the relationship between oxygen uptake efficiency slope (OUES), a marker of cardiorespiratory functional reserve, and mortality is not well understood. PURPOSE: To determine the relationship between OUES and mortality in apparently healthy adults from the Ball State Adult Fitness Longitudinal Lifestyle Study (BALL ST) cohort. METHODS: Participants included 2392 apparently healthy adults (1123 women, 1269 men, age 44.6 ± 12.5 yr) who underwent CPET to determine OUES. Participants were followed up for 19.9 ± 10.8 yr for all-cause and cardiovascular disease (CVD) mortality. Cox-proportional hazard models were performed to determine the relationship of OUES and OUES normalized for body surface area (OUESnorm) with mortality outcomes. RESULTS: There were 329 events during follow-up. OUES was inversely related to CVD (hazard ratio [HR]: 0.736; 95% confidence interval [CI]: 0.569 to 0.952) but not all-cause mortality (HR: 0.884; 95% CI: 0.772 to 1.014) after adjustment for age, sex, test year, obesity, hypertension, dyslipidemia, diabetes, physical activity, and smoking. OUESnorm was inversely related to CVD (HR: 0.545; 95% CI: 0.315 to 0.941) and all-cause mortality (HR: 0.709; 95% CI:0.528 to 0.951) after multivariable adjustment. However, this relationship was no longer significant after further adjusting for VO2max. CONCLUSION: OUES is related to all-cause and CVD mortality in apparently healthy adults. The assessment of OUES does not require maximal exertion, thus OUES may have unique clinical utility when the assessment of VO2max is not feasible or if only submaximal exercise testing is performed.

Cardiorespiratory fitness (CRF), measured as maximal oxygen uptake (VO2max), is inversely associated with mortality. However, the relationship between peak exercise ventilation (VEpeak) and mortality is largely unknown PURPOSE: To assess the relationship between VEpeak and all-cause, cardiovascular disease (CVD), and cancer mortality in apparently healthy men and women from the Ball State Adult Fitness Longitudinal Lifestyle Study (BALL ST) cohort. METHODS: Participants included 2,358 apparently healthy adults (1,245 men, 1,113 women; age: 44.7 ± 12.7 yrs, BMI: 27.7 ± 5.8 kg/m2) who underwent cardiopulmonary exercise testing with determination of CRF and VEpeak (L/min). Participants were followed for 19.2 ± 10.4 yrs (8.8 to 29.6 yrs) and Cox-proportional hazard models were used to determine the relationship between VEpeak and mortality. RESULTS: During follow up, 288 participants died from all-causes which included 84 from CVD, and 90 from cancer. VEpeak was inversely associated with all-cause (hazard ratio [HR]: 0.992; 95% confidence interval [CI]: 0.986 to 0.997), CVD (HR: 0.988; 95% CI: 0.978 to 0.999), and cancer (HR: 0.987; 95% CI: 0.977 to 0.996) mortality. Further, these relationships remained significant after adjusting for the following factors: test year, age, sex, obesity, hypertension, dyslipidemia, diabetes, physical inactivity, and smoking (p < 0.05, all) but not VO2max (p > 0.05). CONCLUSION: VEpeak has significant prognostic value for all-cause and disease-specific mortality outcomes. These data suggest VEpeak should be considered in guiding clinicians to assess relative risk of mortality.

Cardiorespiratory fitness (CRF) has a well-established relationship to all-cause mortality. More recently, ventilatory threshold (VO2@VT) has been shown to be related to cardiovascular events in middle-age men. However, this relationship has not been examined in women. PURPOSE: To examine the relationship between ventilatory threshold and all-cause mortality in apparently healthy men and women. METHODS: Participants (n = 1571, 820 men, 751 women) from the Ball State Adult Fitness Longitudinal Lifestyle Study (BALL ST) cohort with a mean age of 45.9 ± 15.2 yr performed maximal cardiopulmonary exercise testing to assess CRF and oxygen uptake at the ventilatory threshold (VO2@VT) between January 1992 and December 2016. Participants were followed for an average of 15.7 ± 8.3 yr for all-cause mortality. Cox proportional hazard models were completed to determine the relationship between VO2@VT and mortality, with VO2@VT as a continuous variable. RESULTS: During the follow-up period there were 119 deaths. The VO2@VT was inversely related to mortality (Hazard Ratio: 0.911, 0.867-0.957 95% CI, p < 0.001) after adjustment for age, sex, test year, obesity, hypertension, dyslipidemia, diabetes, physical inactivity, and smoking status. However, this relationship was no longer significant after further adjustment for CRF (Hazard Ratio: 0.948, 0.886-1.015 95% CI, p = 0.122). CONCLUSION: These results extend previous research to demonstrate that the VO2@VT is related to all-cause mortality in apparently healthy women and men. Since the assessment of VO2@VT does not require maximal exertion, VO2@VT may have clinical utility when the assessment of CRF (i.e., VO2max) is not feasible or if only submaximal exercise testing is preferred.

The goal of this study is twofold: i) identification of features associated with three cardiovascular disease (CVD) risk factors, and (ii) identification of subgroups with differential treatment effects. Multivariate analysis is performed to identify the features associated with the CVD risk factors: hypertension, diabetes, and dyslipidemia. For subgroup identification, we applied model-based recursive partitioning approach. This method fits a local model in each subgroup of the population rather than fitting one global model for the whole population. The method starts with a model for the overall effect of treatment and checks whether this effect is equally applicable for all individuals under the study based on parameter instability of M fluctuation test over a set of partitioning variables. The procedure produces a segmented model with a differential effect of cardio-respiratory fitness (CRF) corresponding to each subgroup. The subgroups are linked to predictive factors learned by the recursive partitioning approach. This approach is applied to the data from the Ball State Adult Fitness Program Longitudinal Lifestyle Study (BALL ST), where we considered the level of CRF as a treatment variable. The overall results indicate that CRF is inversely associated with hypertension, diabetes and dyslipidemia. The partitioning factors that are selected are related to these risk factors. The subgroup-specific results indicate that for each subgroup, the chance of hypertension, diabetes and dyslipidemia increases with low CRF.

Background The importance of cardiorespiratory fitness for stratifying risk and guiding clinical decisions in patients with cardiovascular disease is well‐established. To optimize the clinical value of cardiorespiratory fitness, normative reference standards are essential. The purpose of this report is to extend previous cardiorespiratory fitness normative standards by providing updated cardiorespiratory fitness reference standards according to cardiovascular disease category and testing modality. Methods and Results The analysis included 15 045 tests (8079 treadmill, 6966 cycle) from FRIEND (Fitness Registry and the Importance of Exercise National Database). Using data from tests conducted January 1, 1974, through March 1, 2021, percentiles of directly measured peak oxygen consumption (VO2peak) were determined for each decade from 30 through 89 years of age for men and women with a diagnosis of coronary artery bypass surgery, myocardial infarction, percutaneous coronary intervention, or heart failure. There were significant differences between sex and age groups for VO2peak (P<0.001). The mean VO2peak was 23% higher for men compared with women and VO2peak decreased by a mean of 7% per decade for both sexes. Among each decade, the mean VO2peak from treadmill tests was 21% higher than the VO2peak from cycle tests. Differences in VO2peak were observed among the age groups in both sexes according to cardiovascular disease category. Conclusions This report provides normative reference standards by cardiovascular disease category for both men and women performing cardiopulmonary exercise testing on a treadmill or cycle ergometer. These updated and enhanced reference standards can assist with patient risk stratification and guide clinical care.

Background: Healthy vascular aging (HVA) and cardiorespiratory fitness (CRF) are each independently associated with lower cardiovascular disease-related mortality. It is unknown, however, whether the CRF-related reductions in cardiovascular disease risk are related to HVA. We hypothesized that HVA would be associated with higher CRF in men and women from the Ball State Adult Fitness Longitudinal Lifestyle STudy (BALL ST). Methods: Apparently healthy men and women ≥50 yr of age from the BALL ST cohort (n = 101) who underwent a maximal cardiopulmonary exercise test to assess CRF (V˙O 2peak) were included in the study. Participants were divided into either HVA, defined as brachial systolic blood pressure <140/90 mm Hg without taking medications and carotid-femoral pulse wave velocity <7.6 m/sec, or no HVA for subjects with SBP >140/90 mm Hg and/or PWV >7.6 m/sec. Results: Participants with HVA had a higher age- and sex-adjusted CRF percentile (62 ± 5 vs 47 ± 3, P < .05), with women having a greater prevalence of HVA than men (36% vs 15%, P < .05). Both carotid-femoral pulse wave velocity (r =−0.27, P < .05) and brachial systolic blood pressure (r =−0.23, P < .05) were independently and inversely associated with CRF for the entire cohort. Men and women with HVA were younger having a lower body fat percentage and higher low-density lipoprotein cholesterol (P < .05, all). Conclusions: These data demonstrate that HVA is associated with higher CRF, which may partially explain the preventative cardioprotective effects of CRF.

Pulse pressure (PP), a surrogate measure of arterial stiffness, is an independent predictor of cardiovascular disease (CVD) related events and mortality. Higher cardiorespiratory fitness (CRF) has also been shown to independently predict CVD mortality. It is currently unknown if CRF influences the relation between PP and all-cause mortality. PURPOSE: To determine if resting PP, independent of CRF, predicts all-cause mortality in apparently healthy adults. We hypothesized the ability of PP to predict all-cause mortality would be dependent on CRF. METHODS: Participants included 4,044 apparently healthy adults (2257 males and 1787 females from the Ball State Adult Fitness Longitudinal Lifestyle Study (BALL ST) cohort; Age: 42.7 ± 12.2 yrs) who underwent a maximal cardiorespiratory exercise test (CPET) between 1968 and 2016 to determine CRF. Resting PP was calculated by subtracting the resting diastolic from the resting systolic blood pressure. Measurements of body mass index, waist circumference, fasting glucose and cholesterol were also obtained. Participants were followed for 24.3 ± 11.9 yrs after CPET for all-cause mortality. Multiple Cox proportional hazard models were fit to the following data: 1) PP unadjusted; 2) PP adjusted for testing year, age, sex and risk factors (obesity, dyslipidemia, diabetes, physical inactivity and smoking status); and 3) PP further adjusted for CRF. RESULTS: Seven hundred and sixty-one participants died during the follow-up period. In the univariate model PP was positively related to all-cause mortality (HR: 1.03, 95% CI: 1.03-1.04; p < 0.001). The relation between PP and all-cause mortality remained in the multivariate model that included age, sex, test year and risk factors (HR: 1.01, 95% CI: 1.00-1.02; p < 0.05), but did not remain when CRF was added to the multivariate model (HR: 1.01, 95% CI: 0.99-1.01; p = 0.09). CONCLUSIONS: The current findings demonstrate PP predicts all-cause mortality independent of traditional risk factors, yet was not significant after including CRF.

Equations are often used to predict cardiorespiratory fitness (CRF) from submaximal or maximal exercise tests. However, no study has comprehensively compared these exercise-based equations with directly measured CRF using data from a single, large cohort. PURPOSE:This study aimed to compare the accuracy of exercise-based prediction equations with directly measured CRF and evaluate their ability to classify an individual's CRF. METHODS:The sample included 4871 tests from apparently healthy adults (38% female, age 44.4 ± 12.3 yr (mean ± SD)). Estimated CRF (eCRF) was determined from 2 nonexercise equations, 3 submaximal exercise equations, and 10 maximal exercise equations; all eCRF calculations were then compared with directly measured CRF, determined from a cardiopulmonary exercise test. Analysis included Pearson product-moment correlations, standard error of estimate values, intraclass correlation coefficients, Cohen κ coefficients, and the Benjamini-Hochberg procedure to compare eCRF with directly measured CRF. RESULTS:All eCRF values from the prediction equations were associated with directly measured CRF (P < 0.01), with intraclass correlation coefficient estimates ranging from 0.07 to 0.89. Although significant agreement was found when using eCRF to categorize participants into fitness tertiles, submaximal exercise equations correctly classified an average of only 51% (range, 37%-58%) and maximal exercise equations correctly classified an average of only 59% (range, 43%-76%). CONCLUSIONS:Despite significant associations between exercise-based prediction equations and directly measured CRF, the equations had a low degree of accuracy in categorizing participants into fitness tertiles, a key requirement when stratifying risk within a clinical setting. The present analysis highlights the limited accuracy of exercise-based determinations of eCRF and suggests the need to include cardiopulmonary measures with maximal exercise to accurately assess CRF within a clinical setting.