Quantifying assumptions underlying peak oxygen consumption equations across the body mass spectrum.

The goal of this study is to quantify the assumptions associated with the Wasserman-Hansen (WH) and Fitness Registry and the Importance of Exercise: A National Database (FRIEND) predictive peak oxygen consumption (pVO2) equations across body mass index (BMI). Assumptions in pVO2 for both equations were first determined using a simulation and then evaluated using exercise data from the Stanford Exercise Testing registry. We calculated percent-predicted VO2 (ppVO2) values for both equations and compared them using the Bland-Altman method. Assumptions associated with pVO2 across BMI categories were quantified by comparing the slopes of age-adjusted VO2 ratios (pVO2/pre-exercise VO2) and ppVO2 values for different BMI categories. The simulation revealed lower predicted fitness among adults with obesity using the FRIEND equation compared to the WH equations. In the clinical cohort, we evaluated 2471 patients (56.9% male, 22% with BMI >30 kg/m2, pVO2 26.8 mlO2/kg/min). The Bland-Altman plot revealed an average relative difference of -1.7% (95% CI: -2.1 to -1.2%) between WH and FRIEND ppVO2 values with greater differences among those with obesity. Analysis of the VO2 ratio to ppVO2 slopes across the BMI spectrum confirmed the assumption of lower fitness in those with obesity, and this trend was more pronounced using the FRIEND equation. Peak VO2 estimations between the WH and FRIEND equations differed significantly among individuals with obesity. The FRIEND equation resulted in a greater attributable reduction in pVO2 associated with obesity relative to the WH equations. The outlined relationships between BMI and predicted VO2 may better inform the clinical interpretation of ppVO2 values during cardiopulmonary exercise test evaluations.

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.

Challenging obesity and sex based differences in resting energy expenditure using allometric modeling, a sub-study of the DIETFITS clinical trial.

BACKGROUND & AIMS: Resting energy expenditure (REE) is a major component of energy balance. While REE is usually indexed to total body weight (BW), this may introduce biases when assessing REE in obesity or during weight loss intervention. The main objective of the study was to quantify the bias introduced by ratiometric scaling of REE using BW both at baseline and following weight loss intervention. DESIGN: Participants in the DIETFITS Study (Diet Intervention Examining The Factors Interacting with Treatment Success) who completed indirect calorimetry and dual-energy X-ray absorptiometry (DXA) were included in the study. Data were available in 438 participants at baseline, 340 at 6 months and 323 at 12 months. We used multiplicative allometric modeling based on lean body mass (LBM) and fat mass (FM) to derive body size independent scaling of REE. Longitudinal changes in indexed REE were then assessed following weight loss intervention. RESULTS: A multiplicative model including LBM, FM, age, Black race and the double product (DP) of systolic blood pressure and heart rate explained 79% of variance in REE. REE indexed to [LBM0.66 × FM0.066] was body size and sex independent (p = 0.91 and p = 0.73, respectively) in contrast to BW based indexing which showed a significant inverse relationship to BW (r = -0.47 for female and r = -0.44 for male, both p < 0.001). When indexed to BW, significant baseline differences in REE were observed between male and female (p < 0.001) and between individuals who are overweight and obese (p < 0.001) while no significant differences were observed when indexed to REE/[LBM0.66 × FM0.066], p > 0.05). Percentage predicted REE adjusted for LBM, FM and DP remained stable following weight loss intervention (p = 0.614). CONCLUSION: Allometric scaling of REE based on LBM and FM removes body composition-associated biases and should be considered in obesity and weight-based intervention studies.

SWAP-MEAT Athlete (study with appetizing plant-food, meat eating alternatives trial) - investigating the impact of three different diets on recreational athletic performance: a randomized crossover trial.

BACKGROUND: Plant-based diets are known to be beneficial for cardiovascular health and promote environmental sustainability. However, many athletes avoid plant-based diets due to concerns of protein inadequacy. OBJECTIVES: To investigate the impact of two predominately plant-based diets-whole food plant-based (WFPB) and plant-based meat alternatives (PBMA)-vs. an omnivorous diet, favoring red meat and poultry (Animal), on endurance and muscular strength. METHODS: 12 recreational runners and 12 resistance trainers were assigned to three diets-WFPB, PBMA, and Animal-for 4 weeks each, in random order. Primary outcomes for runners (12-minute timed run) and resistance trainers (composite machine strength) were collected at baseline and after diets, along with secondary performance outcomes and dietary data. RESULTS: 22 recreational athletes completed the study (age: 26.2 ± 4.4 years; sex: 10 female, 12 male; BMI: 23.1 ± 2.4 kg/m2). Mean differences in 12-minute timed run - WFPB vs. Animal (- 23.4 m; 95% CI: - 107 to 60.0 m) and PBMA vs. Animal (- 2.9 m; 95% CI: - 119 to 113 m) - were not significant. Mean percent differences in composite machine strength - WFPB vs. Animal (- 2.7%; 95% CI: - 5.8 to 0.4% and PBMA vs. Animal (- 0.7%; 95% CI: - 3.5 to 2.2%) - were not significant. Average protein intake for all diets met International Society for Sports Nutrition recommendations. CONCLUSIONS: Our findings suggest recreational athletes can maintain athletic performance on both an omnivorous diet and two diets that are predominately plant-based. TRIAL REGISTRATION: NCT05472701. Retrospectively registered.

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.

Comparison of the FRIEND and Wasserman-Hansen Equations in Predicting Outcomes in Heart Failure.

Background Percentage of age-predicted peak oxygen uptake (VO2) achieved (ppVO2) has been widely used to stratify risk in patients with heart failure. However, there are limitations to traditional normal standards. We compared the recently derived FRIEND (Fitness Registry and the Importance of Exercise: A National Data Base) equation to the widely used Wasserman-Hansen (WH) ppVO2 equation to predict outcomes in patients with heart failure. Methods and Results A subgroup of 4055 heart failure patients from the FRIEND registry (mean age 53±15 years) was followed for a mean of 28±16 months. The FRIEND and WH equations along with measured peak VO2 expressed in mL/kg-1 per min-1 were compared for mortality and composite cardiovascular events. ppVO2 was higher for the FRIEND versus the WH equation (66±30% versus 58±25%; P<0.001). The areas under the receiver operating characteristic curves were slightly but significantly higher for the FRIEND equation for mortality (0.74 versus 0.72; P=0.03) and cardiac events (0.70 versus 0.68; P=0.008). Area under the receiver operating characteristic curve for measured peak VO2 was 0.70 (P<0.001) for mortality and 0.73 (P<0.001) for cardiovascular events. For each 1-SD higher ppVO2 for the FRIEND equation, mortality was reduced by 18% (hazard ratio, 0.82; 95% CI, 0.69-0.97; P<0.02); for each 1-SD higher ppVO2 for the WH equation, the mortality was reduced by 17% (hazard ratio, 0.83; 95% CI, 0.71-0.97; P=0.02). The corresponding reductions in risk per 1 SD for cardiovascular events for the FRIEND and WH equations were 23 and 21%, respectively (both P<0.001). Conclusions Peak VO2 expressed as percentage of an age-predicted standard strongly predicts mortality and major cardiovascular events in patients with heart failure. The FRIEND registry equation exhibited test characteristics slightly superior to the commonly used WH equation.

Genomic variations in EBNA3C of EBV associate with posttransplant lymphoproliferative disorder.

Epstein-Barr Virus (EBV) is a ubiquitous virus linked to a variety of lymphoid and epithelial malignancies. In solid organ and hematopoietic stem cell transplant recipients, EBV is causally associated with posttransplant lymphoproliferative disorder (PTLD), a group of heterogeneous lymphoid diseases. EBV+ B cell lymphomas that develop in the context of PTLD are generally attributed to the immunosuppression required to promote graft survival, but little is known regarding the role of EBV genome diversity in the development of malignancy. We deep-sequenced the EBV genome from the peripheral blood of 18 solid organ transplant recipients, including 6 PTLD patients. Sequences from 6 EBV+ spontaneous lymphoblastoid B cell lines (SLCL) were similarly analyzed. The EBV genome from PTLD patients had a significantly greater number of variations than EBV from transplant recipients without PTLD. Importantly, there were 15 nonsynonymous variations, including 8 in the latent cycle gene EBNA3C that were associated with the development of PTLD. One of the nonsynonymous variations in EBNA3C is located within a previously defined T cell epitope. These findings suggest that variations in the EBV genome can contribute to the pathogenesis of PTLD.