The genetic case for cardiorespiratory fitness as a clinical vital sign and the routine prescription of physical activity in healthcare

Hanscombe, Ken B.; Persyn, Elodie; Traylor, Matthew; Glanville, Kylie; Hamer, Mark; Coleman, Jonathan R. I.; Lewis, Cathryn M.

doi:10.1101/2020.12.08.20243337

Cited by 3 publications

(3 citation statements)

References 110 publications

(156 reference statements)

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“…11 The mounting evidence correlating poor cardiorespiratory fitness with all-cause mortality led the American Heart Association to advocate for the use of physical fitness as a clinical vital sign. 12,13 How would this play out in ED, where formal measures of exercise tolerance are not feasible and competing interests are many? Nonexercise-based algorithms have been validated as reasonable predictors of cardiorespiratory fitness.…”

Section: Physical Activity and Healthmentioning

confidence: 99%

All‐star team: Sport and exercise medicine meets emergency medicine

Rogan

Matthews

2022

Emerg Medicine Australasia

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Section: Physical Activity and Healthmentioning

confidence: 99%

All‐star team: Sport and exercise medicine meets emergency medicine

Rogan

Matthews

2022

Emerg Medicine Australasia

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“…It has since been proposed that this might be operationalized and measured using five critical domains -cognitive, sensory, locomotor, vitality, and psychological [10]. Personal traits in these domains are genetically determined [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. However, over the life course, these are modified by complex and dynamic age-related biological changes which themselves are influenced by a range of environmental stimuli.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of an Intrinsic Capacity Score in the UK Biobank Study

Beyene,

Visvanathan,

Ahmed

et al. 2024

Preprint

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Background: In 2015, the World Health Organization introduced the concept of intrinsic capacity (IC) to define the individual-level characteristics that enable an older person to be and do the things they value. This study developed an IC score for UK Biobank (UKB) study participants and validated its use as a tool for health outcome prediction, understanding healthy aging trajectories, and genetic research. Methods: Our analysis included data from 45,208 UKB participants who had a complete record of the ten variables included in the analysis. Factor adequacy was tested using Kaiser Meyer Olkin (KMO), Barthelt, and the determinant of matrix tests, and the number of factors was determined by the parallel analysis method. Exploratory and confirmatory factor analyses were employed to determine the structure and dimensionality of indicators. Finally, the IC score was generated, and its construct and predictive validities as well as reliability were assessed. Results: The factor analysis identified a multidimensional construct comprising, one general factor (IC) and five specific factors (locomotor, vitality, cognitive, psychological, and sensory). The bifactor structure showed a better fit (comparative fit index = 0.995, Tucker Lewis index = 0.976, root mean square error of approximation = 0.025, root mean square residual = 0.009) than the conventional five-factor structure. The IC score, generated using the bifactor confirmatory factor analysis has good construct validity, as demonstrated by an inverse association with age (lower IC in older age; beta = -0.035 (95%CI: -0.036, -0.034)), frailty (lower IC score in prefrail, beta = -0.104 (95%CI: (-0.114, -0.094) and frail, beta = -0.227 (95%CI: -0.267, -0.186) than the robust), and Charlson comorbidity index (CCI) for incident cases (a lower IC score associated with increased CCI, beta, = -0.019 (95%CI: -0.022, -0.015). The IC score also predicted incident CCI (a one-unit increase in baseline IC score led to lower CCI, beta = 0.147 (95%CI: -0.173, -0.121)). Conclusion: The bifactor structure showed a better fit in all goodness of fit tests. The IC construct has strong structural, construct, and predictive validities and it is a promising tool for monitoring aging trajectories. Keywords: Intrinsic capacity, healthy aging, functional ability, physical functioning, mental functioning

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“…As measuring VO 2max is time-consuming and costly, most of the previous studies are based on estimated CRF. Only two previous studies report findings with genome-wide significant P value (5 Â 10 −8 ) on CRF, but neither used directly measured VO 2max (one using an endurance run test and the other using estimated CRF from a submaximal bicycle test (7,8)).…”

mentioning

confidence: 99%

Genome-Wide Association Study Identifies New Genetic Determinants of Cardiorespiratory Fitness: The Trøndelag Health Study

Klevjer¹,

Nordeidet²,

Hansen

et al. 2022

Medicine &Amp; Science in Sports &Amp; Exercise

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Purpose: Low cardiorespiratory fitness (CRF) is a major risk factor for cardiovascular disease (CVD) and a stronger predictor of CVD morbidity and mortality than established risk factors. The genetic component of CRF, quantified as peak oxygen uptake ( VO 2peak ), is estimated to be ~60%. Unfortunately, current studies on genetic markers for CRF have been limited by small sample sizes and using estimated CRF. To overcome these limitations, we performed a large-scale systematic screening for genetic variants associated with VO 2peak . Methods: A genome-wide association study was performed with BOLT-LMM including directly measured VO 2peak from 4525 participants in the HUNT3 Fitness study and 14 million single-nucleotide polymorphisms (SNP). For validation, similar analyses were performed in the United Kingdom Biobank (UKB), where CRF was assessed through a submaximal bicycle test, including ~60,000 participants and ~60 million SNP. Functional mapping and annotation of the genome-wide association study results was conducted using FUMA. Results: In HUNT, two genome-wide significant SNP associated with VO 2peak were identified in the total population, two in males, and 35 in females. Two SNP in the female population showed nominally significant association in the UKB. One of the replicated SNP is located in PIK3R5, shown to be of importance for cardiac function and CVD. Bioinformatic analyses of the total and male population revealed candidate SNP in PPP3CA, previously associated with CRF. Conclusions: We identified 38 novel SNP associated with VO 2peak in HUNT. Two SNP were nominally replicated in UKB. Several interesting genes emerged from the functional analyses, among them one previously reported to be associated with CVD and another with CRF.

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The genetic case for cardiorespiratory fitness as a clinical vital sign and the routine prescription of physical activity in healthcare

Cited by 3 publications

References 110 publications

All‐star team: Sport and exercise medicine meets emergency medicine

All‐star team: Sport and exercise medicine meets emergency medicine

Development and Validation of an Intrinsic Capacity Score in the UK Biobank Study

Genome-Wide Association Study Identifies New Genetic Determinants of Cardiorespiratory Fitness: The Trøndelag Health Study

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