Clinical Perspectives on Incorporating Cardiorespiratory Fitness in Clinical Practice

Cardiorespiratory fitness (CRF) has been documented as a strong, independent predictor of non-communicable disease and mortality in both clinical and apparently healthy populations. This well-established relationship has impelled organizations, including the American Heart Association, to release scientific statements highlighting the importance of accurate quantification of CRF. Current knowledge of the relationship between CRF and mortality is predominantly based on estimated CRF obtained from varying indirect methods. Cardiopulmonary exercise testing (CPX), the gold standard method of CRF measurement, provides a more accurate and reliable quantification of CRF compared to estimated methods. This review provides support for the diagnostic and prognostic use of CRF based on the current literature and makes a case for the use of CPX when available, as well as the need for standardization of normative values defining CRF levels to increase the efficacy of the risk assessment. Further, clinical applications of CPX-derived CRF are discussed, providing clinicians with recommendations on how to use and interpret this measure in practice to guide clinical decisions and improve patient outcomes

A systematic review of economic evaluations of therapy in asthma

Katayoun Bahadori1, Bradley S Quon2, Mary M Doyle-Waters1, Carlo Marra3, J Mark FitzGerald21Centre for Clinical Epidemiology and Evaluation (C2E2), 2Department of Medicine, Respiratory Division, 3Faculty of Pharmaceutical Sciences, UBC, Vancouver, BC, CanadaBackground: Asthma’s cost-effectiveness is a major consideration in the evaluation of its treatment options. Our objective was to perform a systematic review of the cost-effectiveness of asthma medications.Methods: We performed a systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, OHE-HEED, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Health Technology Assessments Database, NHS Economic Evaluation Database, and Web of Science and reviewed references from key articles between 1990 and Jan 2008.Results: A total of 49 RCTs met the inclusion criteria. Maintenance therapy with inhaled corticosteroids was found to be very cost-effective and in uncontrolled asthmatics patients currently being treated with ICS, the combination of an ICS/LABA represents a safe, cost-effective treatment. The simplified strategy using budesonide and formoterol for maintenance and reliever therapy was also found to be as cost-effective as salmeterol/fluticasone plus salbutamol. Omalizumab was found to be cost-effective. An important caveat with regard to the published literature is the relatively high proportion of economic evaluations which are funded by the manufacturers of specific drug treatments.Conclusion: Future studies should be completed independent of industry support and ensure that the comparator arms within studies should include dosages of drugs that are equivalent.Keywords: asthma, medication, cost-effectiveness, cost of illness, economic cost

The effects of chronic AMPK activation on hepatic triglyceride accumulation and glycerol 3-phosphate acyltransferase activity with high fat feeding

BACKGROUND: High fat feeding increases hepatic fat accumulation and is associated with hepatic insulin resistance. AMP Activated Protein Kinase (AMPK) is thought to inhibit lipid synthesis by the acute inhibition of glycerol-3-phosphate acyltransferase (GPAT) activity and transcriptional regulation via sterol regulatory element binding protein-1c (SREBP-1c). METHODS: The purpose of this study was to determine if chronic activation of AMPK prevented an increase in GPAT1 activity in rats fed a high fat diet. Rats were fed a control (C), or a high fat (HF) diet (60% fat) for 6 weeks and injected with saline or a daily aminoimidazole carboxamide ribnucleotide (AICAR) dose of 0.5 mg/g body weight. RESULTS: Chronic AMPK activation by AICAR injections resulted in a significant reduction in hepatic triglyceride accumulation in both the C and HF fed animals (C, 5.5±0.7; C+AICAR, 2.7 ±0.3; HF, 21.8±3.3; and HF+AICAR, 8.0±1.8 mg/g liver). HF feeding caused an increase in total GPAT and GPAT1 activity, which was not affected by chronic AMPK activation (GPAT1 activity vs. C, C+AICAR, 92±19%; HF, 186±43%; HF+AICAR, 234±62%). Markers of oxidative capacity, including citrate synthase activity and cytochrome c abundance, were not affected by chronic AICAR treatment. Interestingly, HF feeding caused a significant increase in long chain acyl-CoA dehydrogenase or LCAD (up 66% from C), a marker of fatty acid oxidation capacity. CONCLUSIONS: These results suggest that chronic AMPK activation limits hepatic triglyceride accumulation independent of a reduction in total GPAT1 activity

The Influence of Change in Cardiorespiratory Fitness With Short-Term Exercise Training on Mortality Risk From The Ball State Adult Fitness Longitudinal Lifestyle Study

Objective To assess the influence of changes in cardiorespiratory fitness (CRF) after exercise training on mortality risk in a cohort of self-referred, apparently healthy adults. Patients and Methods A total of 683 participants (404 men, 279 women; mean age: 42.7±11.0 y) underwent two maximal cardiopulmonary exercise tests (CPX) between March 20, 1970, and December 11, 2012, to assess CRF at baseline (CPX1) and post-exercise training (CPX2). Participants were followed for an average of 29.8±10.7 years after their CPX2. Cox proportional hazards models were performed to determine the relationship of CRF change with mortality, with change in CRF as a continuous variable, as well as a categorical variable. A Wald chi-square test was used to compare the coefficients estimating the relationship of peak oxygen consumption (VO2peak) at CPX1 with VO2peak measured at CPX2 with time until death for all-cause mortality. Results During the follow-up period there were 180 deaths. When assessed independently, there were 20% (95% CI, 10–49%) and 38% (95% CI, 7–66%) lower mortality risks per 1 metabolic equivalent improvement in CRF (P\u3c.01) in men and women, respectively, after multivariable adjustment. Those that remained unfit had ∼2-fold higher risk for all-cause mortality compared with those that remained fit and CRF at CPX2 was a stronger predictor of all-cause mortality than at CPX1 (P=.02). Conclusion Improving CRF through exercise training lowers mortality risk. Clinicians should encourage individuals to participate in exercise training to improve CRF to lower risk of mortality

Normalizing Cardiorespiratory Fitness To Fat-free Mass Improves Mortality Risk Prediction In Overweight Adults From The Ball St Cohort: 2361 Board #280 May 28 3:00 PM - 4:30 PM

Cardiorespiratory fitness(CRF) is a significant predictor of mortality outcomes in various populations, including overweight and obese adults. However, CRF is commonly expressed normalized to total body weight (VO2peakTBW) which may weaken the relationship in obese adults as fat-free mass (FFM) is directly related to CRF, and increased body fat is associated with lower CRF in adults. Therefore, this study aimed to assess the relationship between CRF normalized for FFM(VO2peakFFM) and all-cause mortality, as well as compare the predictive ability of VO2peakFFM and VO2peakTBW in a cohort of self-referred overweight and obese adults

The Association between the Change in Directly Measured Cardiorespiratory Fitness across Time and Mortality Risk

Background The relationship between cardiorespiratory fitness (CRF) and mortality risk has typically been assessed using a single measurement, though some evidence suggests the change in CRF over time influences risk. This evidence is predominantly based on studies using estimated CRF (CRFe). The strength of this relationship using change in directly measured CRF over time in apparently healthy men and women is not well understood. Purpose To examine the association of change in CRF over time, measured using cardiopulmonary exercise testing (CPX), with all-cause and disease-specific mortality and to compare baseline and subsequent CRF measurements as predictors of all-cause mortality. Methods Participants included 833 apparently healthy men and women (42.9 ± 10.8 years) who underwent two maximal CPXs, the second CPX being ≥1 year following the baseline assessment (mean 8.6 years, range 1.0 to 40.3 years). Participants were followed for up to 17.7 (SD 11.8) years for all-cause-, cardiovascular disease- (CVD), and cancer mortality. Cox-proportional hazard models were performed to determine the association between the change in CRF, computed as visit 1 (CPX1) peak oxygen consumption (VO2peak [mL·kg−1·min−1]) – visit 2 (CPX2) VO2peak, and mortality outcomes. A Wald-Chi square test of equality was used to compare the strength of CPX1 to CPX2 VO2peak in predicting mortality. Results During follow-up, 172 participants died. Overall, the change in CPX-CRF was inversely related to all-cause, CVD, and cancer mortality (p < 0.05). Each 1 mL·kg−1·min−1 increase was associated with a ~11, 15, and 16% (all p < 0.001) reduction in all-cause, CVD, and cancer mortality, respectively. The inverse relationship between CRF and all-cause mortality was significant (p < 0.05) when men and women were examined independently, after adjusting for years since first CPX, baseline VO2peak, and age. Further, the Wald Chi-square test of equality found CPX2 VO2peak to be a significantly stronger predictor of all-cause mortality than CPX1 VO2peak (p < 0.05). Conclusion The change in CRF over time was inversely related to mortality outcomes, and mortality was better predicted by CRF measured at subsequent test than CPX1 CRF. These findings emphasize the importance of adopting lifestyle behaviors that promote CRF, as well as support the need for routine assessment of CRF in clinical practice to better assess risk

Cardiorespiratory Fitness Normalized to Fat-Free Mass and Mortality Risk

Cardiorespiratory Fitness Normalized to Fat-Free Mass and Mortality Risk. Med. Sci. Sports Exerc., Vol. 52, No. 7, pp. 1532–1537, 2020. Purpose: Cardiorespiratory fitness (CRF) is known to be directly related to fat-free mass (FFM), therefore, it has been suggested that normalizing CRF to FFM (V˙O2peakFFM) may be the most accurate expression of CRF as related to exercise performance and cardiorespiratory function. However, the influence of ˙O2peakFFM (mL·kg FFM−1·min−1) on predicting mortality has been largely unexplored. This study aimeVd to primarily assess the relationship between V˙O2peakFFM and all-cause and disease-specific mortality risk in apparently healthy adults. Further, this study sought to compare the predictive ability of V˙O2peakFFM to V˙O2peak normalized to total body weight (V˙ O2peakTBW) for mortality out-comes. Methods: Participants included 2905 adults (1555 men, 1350 women) who completed a cardiopulmonary exercise test between 1970 and 2016 to determine CRF. Body composition was assessed using the skinfold method to estimate FFM. Cardiorespiratory fitness was expressed as V˙ O2peakTBW and V˙O2peakFFM. Participants were followed for 19.0 ± 11.7 yr after their cardiopulmonary exercise test for mortality outcomes. Cox-proportional hazard models were performed to determine the relationship of V˙O2peakFFM with mortality outcomes. Parameter estimates were assessed to compare the predictive ability of CRF expressed as V˙O2peakTBW and V˙O2peakFFM. Results: Overall, VO2peakFFM was inversely related to all-cause, cardiovascular disease, and cancer mortality, with a 16.2%, 8.4%, and 8.0% lower risk per 1 mL·kg FFM−1·min−1 improvement, respectively (P \u3c 0.01). Further, assessment of the parameter estimates showed V˙O2peakFFM to be a significantly stronger predictor of all-cause mortality than V˙ O2peakTBW (parameter estimates, −0.49 vs −0.16). Conclusions: Body composition is an important factor when considering the relationship between CRF and mortality risk. Clinicians should consider normalizing CRF to FFM when feasible, because it will strengthen the predictive power of the measure

Comparison of Non-Exercise Cardiorespiratory Fitness Prediction Equations in Apparently Healthy Adults

Aims: A recent scientific statement suggests clinicians should routinely assess cardiorespiratory fitness using at least non-exercise prediction equations. However, no study has comprehensively compared the many non-exercise cardiorespiratory fitness prediction equations to directly-measured cardiorespiratory fitness using data from a single cohort. Our purpose was to compare the accuracy of non-exercise prediction equations to directly-measured cardiorespiratory fitness and evaluate their ability to classify an individual\u27s cardiorespiratory fitness. Methods: The sample included 2529 tests from apparently healthy adults (42% female, aged 45.4 ± 13.1 years (mean±standard deviation). Estimated cardiorespiratory fitness from 28 distinct non-exercise prediction equations was compared with directly-measured cardiorespiratory fitness, determined from a cardiopulmonary exercise test. Analysis included the Benjamini-Hochberg procedure to compare estimated cardiorespiratory fitness with directly-measured cardiorespiratory fitness, Pearson product moment correlations, standard error of estimate values, and the percentage of participants correctly placed into three fitness categories. Results: All of the estimated cardiorespiratory fitness values from the equations were correlated to directly measured cardiorespiratory fitness (p \u3c 0.001) although the R2 values ranged from 0.25-0.70 and the estimated cardiorespiratory fitness values from 27 out of 28 equations were statistically different compared with directly-measured cardiorespiratory fitness. The range of standard error of estimate values was 4.1-6.2 ml·kg-1·min-1. On average, only 52% of participants were correctly classified into the three fitness categories when using estimated cardiorespiratory fitness. Conclusion: Differences exist between non-exercise prediction equations, which influences the accuracy of estimated cardiorespiratory fitness. The present analysis can assist researchers and clinicians with choosing a non-exercise prediction equation appropriate for epidemiological or population research. However, the error and misclassification associated with estimated cardiorespiratory fitness suggests future research is needed on the clinical utility of estimated cardiorespiratory fitness. Keywords: Prognosis; cardiopulmonary exercise test; exercise test; fitness algorithm; maximum oxygen consumption

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

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

Accuracy of Nonexercise Prediction Equations for Assessing Longitudinal Changes to Cardiorespiratory Fitness in Apparently Healthy Adults: BALL ST Cohort

Background Repeated assessment of cardiorespiratory fitness (CRF) improves mortality risk predictions in apparently healthy adults. Accordingly, the American Heart Association suggests routine clinical assessment of CRF using, at a minimum, nonexercise prediction equations. However, the accuracy of nonexercise prediction equations over time is unknown. Therefore, we compared the ability of nonexercise prediction equations to detect changes in directly measured CRF. Methods and Results The sample included 987 apparently healthy adults from the BALL ST (Ball State Adult Fitness Longitudinal Lifestyle Study) cohort (33% women; average age, 43.1±10.4 years) who completed 2 cardiopulmonary exercise tests ≥3 months apart (3.2±5.4 years of follow-up). The change in estimated CRF (eCRF) from 27 distinct nonexercise prediction equations was compared with the change in directly measured CRF. Analysis included Pearson product moment correlations, SEE values, intraclass correlation coefficient values, Cohen\u27s κ coefficients, γ coefficients, and the Benjamini-Hochberg procedure to compare eCRF with directly measured CRF. The change in eCRF from 26 of 27 equations was significantly associated to the change in directly measured CRF (P\u3c0.001), with intraclass correlation coefficient values ranging from 0.06 to 0.63. For 16 of the 27 equations, the change in eCRF was significantly different from the change in directly measured CRF. The median percentage of participants correctly classified as having increased, decreased, or no change in CRF was 56% (range, 39%-61%). Conclusions Variability was observed in the accuracy between nonexercise prediction equations and the ability of equations to detect changes in CRF. Considering the appreciable error that prediction equations had with detecting even directional changes in CRF, these results suggest eCRF may have limited clinical utility