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Cardiorespiratory fitness (CRF) is associated with mortality and cardiovascular disease, but assessing CRF in the population is challenging. Here we develop and validate a novel framework to estimate CRF (as maximal oxygen consumption, VO2max) from heart rate response to low-risk personalised exercise tests. We apply the method to examine associations between CRF and health outcomes in the UK Biobank study, one of the world’s largest and most inclusive studies of CRF, showing that risk of all-cause mortality is 8% lower (95%CI 5–11%, 2670 deaths among 79,981 participants) and cardiovascular mortality is 9% lower (95%CI 4–14%, 854 deaths) per 1-metabolic equivalent difference in CRF. Associations obtained with the novel validated CRF estimation method are stronger than those obtained using previous methodology, suggesting previous methods may have underestimated the importance of fitness for human health.

BackgroundCardiorespiratory fitness (CRF) was assessed in UK Biobank (UKB) using heart rate response to a submaximal ramped cycle ergometer test that was individualised for participant characteristics including cardiovascular disease risk. Studies have since explored health associations with CRF by estimating maximal oxygen consumption (VO2max) from UKB test data using interpretation methods that have not accounted for this individualisation procedure. Thus, dose-response relationships reported in these studies may be inaccurate. We developed and validated a novel VO2max estimation approach that accounts for the UKB test individualisation procedure and compared dose-response relationships with health outcomes between the novel and previous methods.MethodsIn a cross-over study (n=189), participants completed several UKB tests and VO2max was measured. A multilevel modelling framework was developed that combines heart rate response features from the UKB test to estimate VO2max. Estimates were compared within participants across UKB test protocols, and with directly measured VO2max. Short-term test-retest reliability was assessed in a subsample of participants (n=87). In UKB, we examined associations between estimated CRF and disease endpoints (n=80,259) and compared associations obtained with an unvalidated method. Long-term test-retest reliability was examined (n = 2877).ResultsEstimated and directly measured VO2max were strongly correlated (Pearson’srrange: 0.68 to 0.74) with no mean bias (women bias: −0.8 to 0.4; men bias range: −0.3 to 0.3), outperforming a previous approach for interpreting UKB test data. Agreement between estimated VO2max across different test protocols was strong (Pearson’srrange: 0.94 to 0.99). Short- and long-term reliability was also high (lambda=0.91 and 0.80, respectively). All-cause mortality was 7% (95%CI 4-10%, 2686 deaths) lower and CVD mortality 9% (95%CI 3-14%, 858 deaths) lower for every 1-MET difference in fitness, associations twice as strong as determined by previous methods.ConclusionsWe present a valid and reliable method for estimating CRF in UKB and demonstrate its utility in characterising dose-response relationships with health outcomes. Accounting for the individualisation procedure strengthens observed relationships between CRF and disease and enhances the case for promoting improved fitness in the general population.

AimsResting heart rate (RHR) is inversely associated with cardiorespiratory fitness (CRF) but few studies have investigated the nature of this relationship in large population samples. We examined the association between RHR and CRF in UK adults and explored factors that may influence this relationship.Methods and ResultsIn a population-based sample of 5,143 men and 5,722 women (aged 29-65 years), mean (SD) RHR while seated, supine, and during sleep was 67.6 (9.8), 63.5 (8.9), and 56.9 (6.9) bpm, respectively. The age- and sex-adjusted association with CRF as assessed by submaximal treadmill testing was −0.26 (95%CI −0.27; −0.24), −0.31 (95%CI −0.33; −0.29), and −0.31 (95%CI −0.34; −0.29) ml O2 kg-1 beat-1. Sequential adjustment for objectively measured obesity and physical activity attenuated the RHR coefficient by 10% and 50%, respectively. In longitudinal analyses of 6,589 participants re-examined after 6 years, each 1 bpm increase in supine RHR was associated with 0.23 (95%CI 0.20; 0.25) ml O2 min-1 kg-1 decrease in CRF.ConclusionsAcross all measures, RHR is inversely associated with CRF; half of this association is explained by obesity and physical activity, suggesting CRF changes achieved through altered behaviour could be tracked through changes in RHR, a notion supported by longitudinal results. As well as its utility as a biomarker of CRF at population-level, serial measurements of RHR may facilitate personal goal setting/evaluation and remote patient monitoring.

Background UK Biobank is a large prospective cohort study containing accelerometer-based physical activity data with strong validity collected from 100,000 participants approximately 5 years after baseline. In contrast, the main cohort has multiple self-reported physical behaviours from > 500,000 participants with longer follow-up time, offering several epidemiological advantages. However, questionnaire methods typically suffer from greater measurement error, and at present there is no tested method for combining these diverse self-reported data to more comprehensively assess the overall dose of physical activity. This study aimed to use the accelerometry sub-cohort to calibrate the self-reported behavioural variables to produce a harmonised estimate of physical activity energy expenditure, and subsequently examine its reliability, validity, and associations with disease outcomes. Methods We calibrated 14 self-reported behavioural variables from the UK Biobank main cohort using the wrist accelerometry sub-cohort (n = 93,425), and used published equations to estimate physical activity energy expenditure (PAEESR). For comparison, we estimated physical activity based on the scoring criteria of the International Physical Activity Questionnaire, and by summing variables for occupational and leisure-time physical activity with no calibration. Test-retest reliability was assessed using data from the UK Biobank repeat assessment (n = 18,905) collected a mean of 4.3 years after baseline. Validity was assessed in an independent validation study (n = 98) with estimates based on doubly labelled water (PAEEDLW). In the main UK Biobank cohort (n = 374,352), Cox regression was used to estimate associations between PAEESR and fatal and non-fatal outcomes including all-cause, cardiovascular diseases, respiratory diseases, and cancers. Results PAEESR explained 27% variance in gold-standard PAEEDLW estimates, with no mean bias. However, error was strongly correlated with PAEEDLW (r = −.98; p SR had narrower range than the criterion. Test-retest reliability (Λ = .67) and relative validity (Spearman = .52) of PAEESR outperformed two common approaches for processing self-report data with no calibration. Predictive validity was demonstrated by associations with morbidity and mortality, e.g. 14% (95%CI: 11–17%) lower mortality for individuals meeting lower physical activity guidelines. Conclusions The PAEESR variable has good reliability and validity for ranking individuals, with no mean bias but correlated error at individual-level. PAEESR outperformed uncalibrated estimates and showed stronger inverse associations with disease outcomes.

OBJECTIVES—: Assessing aging muscle through estimates of muscle heterogeneity may overcome some of the limitations of grayscale analyses. The objectives of this study included determining statistical model parameters that characterize muscle echogenicity and are associated with strength in younger and older participants. METHODS—: Thirty-three community-dwelling participants were assigned to younger and older groups. Quantitative B-mode ultrasound scanning of the rectus femoris and isometric grip strength testing were completed. Shape or dispersion parameters from negative binomial distribution, Nakagami, gamma, and gamma mixture models were fitted to the grayscale histograms. RESULTS—: The mean ages ± SDs of the younger and older groups were 24.0 ± 2.3 and 65.1 ± 6.5 years, respectively. Statistical model shape and dispersion parameters for the grayscale histograms significantly differed between the younger and older participants (P = .002–.006). Among all of the statistical models considered, the gamma mixture model showed the best fit with the grayscale histograms (χ(2) goodness of fit = 62), whereas the Nakagami distribution displayed the poorest fit (χ(2) goodness of fit = 2595). Grayscale values were significantly associated with peak grip strength force in younger adult participants (R(2) = 0.36; P < .008). However, the negative binomial dispersion parameter k (adjusted R(2) = 0.70; P < .001) and gamma shape parameter α (adjusted R(2) = 0.68; P < .01) showed the highest associations with peak grip strength force in older adult participants. CONCLUSIONS—: The negative binomial dispersion parameter k and the gamma shape parameter α have clinical relevance for the assessment of age-related muscle changes. Statistical models of muscle heterogeneity may characterize the association between muscle tissue composition estimates and strength better than grayscale measures in samples of community-dwelling older adults.

Aging is associated with impaired upper limb proprioceptive acuity, as reflected by decreased position matching accuracy with increasing task complexity and movement extent. Most studies have primarily used single-joint or planar paradigms to examine age-related changes in proprioception. It is unclear whether these changes can be generalized to more complex multi-joint movements, where additional sensory feedback may affect performance. Since age-related declines in cognitive function may impair the ability to integrate multiple sources of sensory feedback, deficits in position matching ability in older adults may persist when tasks are performed in three-dimensional space. The accuracy with which young and older participants reproduced remembered reference hand positions was assessed under different experimental conditions. Participants matched target locations located directly to the front or 45° to the side relative to the midline using the preferred and non-preferred arms. Either the same (i.e., ipsilateral matching) or the opposite (i.e., contralateral matching) arm was used to reproduce the target location. No differences in matching accuracy were found between young and older participants when matching ipsilaterally. When matching contralaterally, accuracy was worse in older participants for target locations located to the side, which may reflect age-related changes in the perception of peripersonal space. In contrast to previous studies, accuracy did not differ between the preferred and non-preferred arms in either group. These results extend previous findings demonstrating age-related impairments in proprioceptively guided arm movements when interhemispheric transfer is required.

Knee osteoarthritis (OA) is a chronic disease characterized by articular cartilage damage, pain, and weakness. Ambulating stairs is a leading source of pain in people with OA, and disease progression may be marked by asymmetrical gait abnormalities. The purpose of this study was to assess relative peak knee extension torque and Step-Up-and-Over (SUO) test performance asymmetries in individuals with knee OA. Forty-six male Veterans with knee OA (age = 61.6 yrs. ± 5.6) enrolled in the study. Functional performance was assessed via the SUO test, which involves ascending/descending an 8-inch box on a force plate. SUO test outcomes included force-time parameters representing step-up force, step-down force, and force-time curve smoothness. Peak torque was measured using isokinetic dynamometry (180 deg/s). Self-reported symptoms and physical function were evaluated using the Knee injury and Osteoarthritis Outcome Score (KOOS). Force-time curve smoothness was the only SUO test outcome significantly different in the less involved leg (mean = -8.27 ±.55) compared to the more involved leg (mean = -8.48 ±.57, p

The applied use of eccentric muscle actions for physical rehabilitation may utilize the framework of periodization. This approach may facilitate the safe introduction of eccentric exercise and appropriate management of the workload progression. The purpose of this data-driven Hypothesis and Theory paper is to present a periodization model for isokinetic eccentric strengthening of older adults in an outpatient rehabilitation setting. Exemplar and group data are used to describe the initial eccentric exercise prescription, structured familiarization procedures, workload progression algorithm, and feasibility of the exercise regimen. Twenty-four men (61.8 ± 6.3 years of age) completed a 12-week isokinetic eccentric strengthening regimen involving the knee extensors. Feasibility and safety of the regimen was evaluated using serial visual analog scale (VAS, 0–10) values for self-reported pain, and examining changes in the magnitude of mean eccentric power as a function of movement velocity. Motor learning associated with the familiarization sessions was characterized through torque-time curve analysis. Total work was analyzed to identify relative training plateaus or diminished exercise capacity during the progressive phase of the macrocycle. Variability in the mean repetition interval decreased from 68 to 12% during the familiarization phase of the macrocycle. The mean VAS values were 2.9 ± 2.7 at the start of the regimen and 2.6 ± 2.9 following 12 weeks of eccentric strength training. During the progressive phase of the macrocycle, exercise workload increased from 70% of the estimated eccentric peak torque to 141% and total work increased by 185% during this training phase. The slope of the total work performed across the progressive phase of the macrocycle ranged from −5.5 to 29.6, with the lowest slope values occurring during microcycles 8 and 11. Also, mean power generation increased by 25% when eccentric isokinetic velocity increased from 60 to 90° s−1 while maintaining the same workload target. The periodization model used in this study for eccentric exercise familiarization and workload progression was feasible and safe to implement within an outpatient rehabilitation setting. Cyclic implementation of higher eccentric movement velocities, and the addition of active recovery periods, are featured in the proposed theoretical periodization model for isokinetic eccentric strengthening.

Knee osteoarthritis (OA) is a complex condition involving articular cartilage, connective tissue, and skeletal muscle. Diagnostic ultrasound (US) has been proposed as an approach to characterize muscle changes in those with chronic conditions. The purpose of this study was to determine if quantitative US muscle morphology and morphometry measures are associated with clinical markers of knee OA. Male Veterans with knee OA (n=36; age=62.2 ± 5.7 yr; BMI=31.2 ± 6.5) participated in the study. Self-reported symptoms and physical function were evaluated using the Knee injury and Osteoarthritis Outcome Score (KOOS). Knee OA asymmetry was determined by the Kellgren–Lawrence grade and self-reported pain. B-mode quantitative US with a 13–6 MHz linear array transducer was used to obtain tissue echogenicity and muscle thickness values. The primary scanning site was the rectus femoris. Additional sites at the trapezius, deltoid, pectoralis major, and brachioradialis were used as proxy measures of lean body mass (LBM). Lower echogenicity (△ -3.04 grayscale levels, t=2.70, p=.01) and greater muscle thickness (△ .17 cm, t=2.21, p=.03) of the rectus femoris were identified in the less involved limb. Additionally, the summed US muscle thickness values were associated with the Symptom and Sports/Recreation KOOS subscales (r=.37–.39, p=.02–.03), and the deltoid was the only muscle group associated with all 5 KOOS subscales (r=.36–.45, p=.01–.04). In summary, US-derived muscle morphology and morphometry measures identified knee OA asymmetries in Veteran men. Key upper extremity muscle groups and proxy estimates of LBM should not be overlooked as factors that affect the KOOS score.

Proprioception is critical for the control of many goal-directed activities of daily living. While contributions from skin and joint receptors exist, the muscle spindle is thought to play an important role in allowing accurate judgments of limb position and movement to occur. The discharges elicited from muscle spindles can be degraded by simultaneous agonist-antagonist tendon vibration, causing proprioception to be distorted. Despite this, changes in limb perception that may result from sensory adaptation to this stimulus remain misunderstood. The purpose of this study was, therefore, to investigate short-term proprioceptive adaptation resulting from vibration of antagonistic muscle pairs. We measured elbow joint position sense in 21 healthy young adults while 80 Hz vibration was applied simultaneously to the distal tendons of the elbow flexor and extensor muscles. Matching errors were then analyzed during early and late adaptation phases to assess short-term adaptation to the vibration stimuli. Participants committed significant undershoot errors during the early adaptation phase, but were comparable to baseline measurements during the late adaptation phase. When we removed the vibration stimuli and conducted a second joint position matching task, matching variability increased significantly, and participants committed overshoot errors. These results bring into question the efficacy of simultaneous agonist-antagonist tendon vibration to degrade proprioceptive acuity.