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Age-related frailty and its association with biological markers of ageing.

Mitnitski A, Collerton J, Martin-Ruiz C, Jagger C, von Zglinicki T, Rockwood K, Kirkwood TB - BMC Med (2015)

Bottom Line: Here, we examined whether a biomarker-based frailty index (FI-B) allowed examination of their collective effect in predicting mortality compared with individual biomarkers, a clinical deficits frailty index (FI-CD), and the Fried frailty phenotype.Higher values of each FI were associated with higher mortality risk.The systemic effects of these processes can be elucidated using the frailty index approach, which showed here that subclinical deficits increased the risk of death.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Dalhousie University, Halifax, NS, B3H 2E1, Canada. arnold.mitnitski@dal.ca.

ABSTRACT

Background: The relationship between age-related frailty and the underlying processes that drive changes in health is currently unclear. Considered individually, most blood biomarkers show only weak relationships with frailty and ageing. Here, we examined whether a biomarker-based frailty index (FI-B) allowed examination of their collective effect in predicting mortality compared with individual biomarkers, a clinical deficits frailty index (FI-CD), and the Fried frailty phenotype.

Methods: We analyzed baseline data and up to 7-year mortality in the Newcastle 85+ Study (n = 845; mean age 85.5). The FI-B combined 40 biomarkers of cellular ageing, inflammation, haematology, and immunosenescence. The Kaplan-Meier estimator was used to stratify participants into FI-B risk strata. Stability of the risk estimates for the FI-B was assessed using iterative, random subsampling of the 40 FI-B items. Predictive validity was tested using Cox proportional hazards analysis and discriminative ability by the area under receiver operating characteristic (ROC) curves.

Results: The mean FI-B was 0.35 (SD, 0.08), higher than the mean FI-CD (0.22; SD, 0.12); no participant had an FI-B score <0.12. Higher values of each FI were associated with higher mortality risk. In a sex-adjusted model, each one percent increase in the FI-B increased the hazard ratio by 5.4 % (HR, 1.05; CI, 1.04-1.06). The FI-B was more powerful for mortality prediction than any individual biomarker and was robust to biomarker substitution. The ROC analysis showed moderate discriminative ability for 7-year mortality (AUC for FI-CD = 0.71 and AUC for FI-B = 0.66). No individual biomarker's AUC exceeded 0.61. The AUC for combined FI-CD/FI-B was 0.75.

Conclusions: Many biological processes are implicated in ageing. The systemic effects of these processes can be elucidated using the frailty index approach, which showed here that subclinical deficits increased the risk of death. In the future, blood biomarkers may indicate the nature of the underlying causal deficits leading to age-related frailty, thereby helping to expose targets for early preventative interventions.

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Related in: MedlinePlus

Histograms of the a Clinical Deficit Frailty Index (FI-CD) and b Biomarker Frailty Index (FI-B), and the best fit gamma density functions (solid lines) with the parameters of shape and scale 18.77 and 0.02 for FI-CD and 3.24 and 0.07 for FI-B, respectively
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Fig1: Histograms of the a Clinical Deficit Frailty Index (FI-CD) and b Biomarker Frailty Index (FI-B), and the best fit gamma density functions (solid lines) with the parameters of shape and scale 18.77 and 0.02 for FI-CD and 3.24 and 0.07 for FI-B, respectively

Mentions: The FI-B showed a slightly skewed distribution, fitted by the gamma density function with shape and scale parameters of 18.77 and 0.02, respectively (Fig. 1, Panel b). The 5th centile of the FI-B was 0.24, and the 95th and 99th centiles were 0.48 and 0.60, respectively. The histogram of the FI-CD was more skewed with a longer right tail (Fig. 1, Panel a); the gamma fit shape and scale parameters were 3.24 and 0.07, respectively. The 5th centile of the FI-CD was 0.06, and the 95th and 99th centiles were 0.46 and 0.59, respectively. The mean FI-B was 0.35 (SD, 0.08), higher than the mean FI-CD of 0.22 (SD, 0.12). Individual values of the FI-B were weakly correlated with the FI-CD (r = 0.16, P <0.001). On average, the clinically fittest people (those with 0 or 1 clinical deficits, i.e., FI-CD = 0 or 0.02) had an average FI-B value of 0.33 (CI, 0.32–0.34), compared with an average FI-B value of 0.39 (CI, 0.36–0.41) for the clinically frailest people (FI-CD >0.5).Fig. 1


Age-related frailty and its association with biological markers of ageing.

Mitnitski A, Collerton J, Martin-Ruiz C, Jagger C, von Zglinicki T, Rockwood K, Kirkwood TB - BMC Med (2015)

Histograms of the a Clinical Deficit Frailty Index (FI-CD) and b Biomarker Frailty Index (FI-B), and the best fit gamma density functions (solid lines) with the parameters of shape and scale 18.77 and 0.02 for FI-CD and 3.24 and 0.07 for FI-B, respectively
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4499935&req=5

Fig1: Histograms of the a Clinical Deficit Frailty Index (FI-CD) and b Biomarker Frailty Index (FI-B), and the best fit gamma density functions (solid lines) with the parameters of shape and scale 18.77 and 0.02 for FI-CD and 3.24 and 0.07 for FI-B, respectively
Mentions: The FI-B showed a slightly skewed distribution, fitted by the gamma density function with shape and scale parameters of 18.77 and 0.02, respectively (Fig. 1, Panel b). The 5th centile of the FI-B was 0.24, and the 95th and 99th centiles were 0.48 and 0.60, respectively. The histogram of the FI-CD was more skewed with a longer right tail (Fig. 1, Panel a); the gamma fit shape and scale parameters were 3.24 and 0.07, respectively. The 5th centile of the FI-CD was 0.06, and the 95th and 99th centiles were 0.46 and 0.59, respectively. The mean FI-B was 0.35 (SD, 0.08), higher than the mean FI-CD of 0.22 (SD, 0.12). Individual values of the FI-B were weakly correlated with the FI-CD (r = 0.16, P <0.001). On average, the clinically fittest people (those with 0 or 1 clinical deficits, i.e., FI-CD = 0 or 0.02) had an average FI-B value of 0.33 (CI, 0.32–0.34), compared with an average FI-B value of 0.39 (CI, 0.36–0.41) for the clinically frailest people (FI-CD >0.5).Fig. 1

Bottom Line: Here, we examined whether a biomarker-based frailty index (FI-B) allowed examination of their collective effect in predicting mortality compared with individual biomarkers, a clinical deficits frailty index (FI-CD), and the Fried frailty phenotype.Higher values of each FI were associated with higher mortality risk.The systemic effects of these processes can be elucidated using the frailty index approach, which showed here that subclinical deficits increased the risk of death.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Dalhousie University, Halifax, NS, B3H 2E1, Canada. arnold.mitnitski@dal.ca.

ABSTRACT

Background: The relationship between age-related frailty and the underlying processes that drive changes in health is currently unclear. Considered individually, most blood biomarkers show only weak relationships with frailty and ageing. Here, we examined whether a biomarker-based frailty index (FI-B) allowed examination of their collective effect in predicting mortality compared with individual biomarkers, a clinical deficits frailty index (FI-CD), and the Fried frailty phenotype.

Methods: We analyzed baseline data and up to 7-year mortality in the Newcastle 85+ Study (n = 845; mean age 85.5). The FI-B combined 40 biomarkers of cellular ageing, inflammation, haematology, and immunosenescence. The Kaplan-Meier estimator was used to stratify participants into FI-B risk strata. Stability of the risk estimates for the FI-B was assessed using iterative, random subsampling of the 40 FI-B items. Predictive validity was tested using Cox proportional hazards analysis and discriminative ability by the area under receiver operating characteristic (ROC) curves.

Results: The mean FI-B was 0.35 (SD, 0.08), higher than the mean FI-CD (0.22; SD, 0.12); no participant had an FI-B score <0.12. Higher values of each FI were associated with higher mortality risk. In a sex-adjusted model, each one percent increase in the FI-B increased the hazard ratio by 5.4 % (HR, 1.05; CI, 1.04-1.06). The FI-B was more powerful for mortality prediction than any individual biomarker and was robust to biomarker substitution. The ROC analysis showed moderate discriminative ability for 7-year mortality (AUC for FI-CD = 0.71 and AUC for FI-B = 0.66). No individual biomarker's AUC exceeded 0.61. The AUC for combined FI-CD/FI-B was 0.75.

Conclusions: Many biological processes are implicated in ageing. The systemic effects of these processes can be elucidated using the frailty index approach, which showed here that subclinical deficits increased the risk of death. In the future, blood biomarkers may indicate the nature of the underlying causal deficits leading to age-related frailty, thereby helping to expose targets for early preventative interventions.

Show MeSH
Related in: MedlinePlus